for Basic Workshop RESEARCH METHODOLOGY€¦ · 09:45-10:15 L-2 Scope of Research Methodology Lecture Dr. Abhay Chowdhary Prof. & Head, Microbiology 10:15-11.00 L-3 Research Question,

SStudy Material for

Basic Workshop on

RESEARCH METHODOLOGY

22 – 24 July 2019 [09:00 AM – 04:00 PM]

Venue Pushpanjali Auditorium, 1st floor,

D.Y. Patil Hospital, Nerul, Navi Mumbai

Jointly Organized by Department of Obstetrics & Gynecology and

Institutional Ethics Committee (IEC), Department of Pharmacology

Organizing Secretary Dr M. N. Satia, Dr. Deepak Langade

Contact: [email protected] / [email protected] 98690 84018 / 99305 50009

This document contains study material and slides for Basic Workshop on Research Methodology conducted on 22 – 24 July 2019. Organizing team thank Dr. Shirish Patil (Vice-chancellor, D Y Patil Deemed to be University, Navi Mumbai), Dr. Surekha Patil (Dean, D Y Patil Deemed to be University School of Medicine, Navi Mumbai), all workshop faculty workshop and the participating delegates. Resource:

Dr. Abhay Chowdhary

Dr. M. N. Satia

Dr. Deepak Langade

Dr. Anant Patil

Dr. Padmaja Samant

Dr. Mrudula Solanki

Dr. Nirmala Rege

Dr. Pratap Jadhav

Dr. Varsha Vyas

Dr. Vaishali Thakare

Dr. Vidita Morepatil

Dr. Kavitha VD

Complied by: Dr. Deepak Langade Prof. & Head, Dept. of Pharmacology Member Secretary, IEC for Clinical Trials Chairman, Pharmacovigilance (PV) Committee Chairman, Institutional Animal Ethic Committee D Y Patil University School of Medicine Nerul, Navi Mumbai 400 706 Contact: [email protected] / 99305 50009

Contact: [email protected] / [email protected] 9930550009

BBasic Workshop on

RESEARCH METHODOLOGY

22 – 24 July 2019 [09:00 AM – 04:00 PM]

Venue Pushpanjali Auditorium, 1st floor,

D.Y. Patil Hospital, Nerul, Navi Mumbai

Organized by Department of Obstetrics & Gynecology and

Institutional Ethics Committee (IEC), Department of Pharmacology

Organizing Secretary Dr M. N. Satia, Dr. Deepak Langade

Contact: [email protected] / [email protected] 98690 84018 / 99305 50009

D.Y. Patil University School of Medicine BASIC WORKSHOP ON RESEARCH METHODOLOGY Organizing Secretary: Dr M.N.Satia, Dr. Deepak Langade


DAY 1, MONDAY 22 JULY 2019

Time Topic Method Faculty 8.30-9.00 Registration & Pretest -

9:00-9:45 L-1 Welcome & Introduction to

Research Methodology Management of Shock and Blood Transfusion in Obstetrics

Lecture Dr. Meena Satia Prof. of Ob. Gyn.

09:45-10:15 L-2 Scope of Research Methodology

Lecture Dr. Abhay Chowdhary Prof. & Head, Microbiology

10:15-11.00 L-3 Research Question, Study Designs & Hypothesis

Lecture Dr. Deepak Langade Prof. & Head, Pharmacology

11.00 - 11.15 Tea 11.15-12.15 L-4 Research Protocol Lecture Dr. Anant Patil

Pharmacology

12.15-12.45 GA-1 (Group Activity) Participants will be divided into 4 groups.

Each group will discuss and come out with at-least 2 research questions and related hypotheses

Indicate why the topic was selected

Type of study of study design

Group Activity

Dr Anant Patil Pharmacology Dr. Kavitha VD Dr. Vaishali Thakare

12.45 - 1.15 pm Lunch 1.15-2.00 L-5 Quantitative Research Methods Lecture M. N. Satia,

Professor Ob. Gyn. Dr Kavitha VD Pharmacology

2.00-3.15 GA-2: Divide into groups and discuss and present

Indicate why the topic was selected, Indicate type of study

Indicate dependent and independent variables in the study

Group Activity

3.15 - 3.30 pm Tea 3.30-4.30 L-6 Principles of GCP Guidelines

Documents in Healthcare Research Lecture Dr. Vidita Morepatil

Abbott India Ltd.

4.30 - 4.45 Day One feedback



DAY 2, TUESDAY 23 JULY 2019 Time Topic Method Faculty

9.00-10.00 L-7 Qualitative Research Methods Lecture Dr. Padmaja Samant Professor Ob. Gyn.

10.00-11.00 L-8 Ethical Issues in Research GA-3: Groups will present

ethical issues in their respective studies

Lecture & Group Activity

Dr. Padmaja Samant Professor Ob Gyn. Seth G.S. Medical College

11:00-11:30 L-9 RPA Lecture Dr. Vijaya Badhwar Professor Ob. Gyn.

11:30 - 11:45 Tea 11:45-12:30 L-10 Sampling Methods Lecture Dr. Mrudula Solanki

Prof. Community Medicine Seth G.S. Medical College

12.30-01.00 L-11 Literature search GA-4: Participants will be

divided into groups Each group will try to search

references related to topics finalized and discussed


Dr. Anant Patil Asst. Prof. Pharmacology Dr Kavitha Vivek Asst. Prof. Pharmacology

01.00 - 1.30 Lunch 1.30-2.15 L-12 Introduction to Biostatistics,

Descriptive Statistics Lecture Dr. Pratap Jadhav

Biostatistician Seth G.S. Medical College

2.15-3.00 L-13 Hypothesis testing & Inferential Statistics GA-5: The groups will discuss

about the inferential statistics (statistical tests) to be applied for the study design discussed in earlier group exercises


Dr. Pratap Jadhav Biostatistician Seth G.S. Medical College

3.00 - 3.15 Tea 3.15-4.30 L-14 Sample size in research

Lecture Dr. Vidita Morepatil

Abbott India Ltd.

4.30 - 4.45 Day Two Feedback



.

DAY 3, WEDNESDAY 24 JULY 2019 Time Topic Method Faculty

09.00-09.30 L-15 Hand hygiene and Management of sharps in labour room & OT

Lecture Dr. Y.S. Nandanwar Asso. Prof. Ob Gyn.

9.30-10.45 L-16 Questionnaire designing Lecture Dr. Nirmala Rege Prof. Emeritus in Pharmacology Seth G.S. Medical College

10.45 - 11.00 Tea 11.00-12.15 L-17 Submission of Synopsis Lecture Dr. Vaishali Thakare

Asso. Prof. Pharmacology

12.15-1.00 L-18 Regulations in Research Lecture Dr. Deepak Langade Prof. & Head, Pharmacology

1.00 - 1.30 Lunch 1.30-2.00 L-19 Roles & Responsibilities of

Researcher / Investigator Lecture Dr. Varsha Vyas

Prof. of Anesthesiology

2.00-3.00 L-20 Critical Evaluation of Journal Article GA-6: Journal articles

(different study designs) will be presented and discussed by members


Dr. Vidita Morepatil Abbott India Ltd.

3.00 - 3.30 Post-test, Day 3 feedback & Workshop evaluation

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INTRODUCTION TO RESEARCH METHODOLOGY

Dr.M.N.SatiaProfessor And Head of Unit Dr D Y Patil School of Medicine Department of obstetrics and gynaecology

WHAT IS RESEARCH

Research is an endeavour to discover answersto intellectual and practical problems throughscientific methods or procedures. It is practically a search for knowledge.

By definition…. Scientific & systematic searchfor pertinent information on a specific topic.

Redman and Mory…..Systematized effort to gain newknowledge.

Advanced learner’s dictionary of current English….. A careful investigation or enquiry specially throughsearch for new facts in any branch of knowledge.

For philosophers and thinkers, research means the outlet for new ideas and insights.

For literary men and women, research means development of new styles and creative work.

For analysts and intellectuals, research means generalizations of new theories.

Research for decision making

SCOPE / SIGNIFICANCE OF RESEARCH

TECHNICAL ASPECTS OF RESEARCH

Define & redefine problems

Formulate hypotheses or suggested solutions

Collect, organize, evaluate data

Make deductions

Reach Conclusions

Careful testing of conclusions to determine whether they conform to the formulating hypothesis.

CHARACTERISTICS OF RESEARCH

Is objective and logical – applying every possible test tovalidate the data collected and conclusions reached.

Involves the quest for answers to unsolved problems.

Requires courage.

Is characterized by patient and unhurried activity.

Is carefully recorded and reported.

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SCIENTIFIC METHOD

‘Science’ refers to the body of systematic and organised knowledge which makes use of scientific method to acquire knowledge in a particular field of enquiry.

Scientific method is the systematic collection of data (facts) and their theoretical treatment through proper observation, experimentation and interpretation.

Scientific method attempts to achieve a systematic interrelation of facts by experimentation, observation, and logical arguments from accepted postulates and a combination of these three in varying proportions.

Purpose clearly defined.

Research process detailed.Research design thoroughly planned.

High ethical standards applied.

Limitations frankly revealed.Adequate analysis for decision maker’s needs.

Findings presented unambiguously.Conclusions justified.

Researcher’s experience reflected.

GOOD RESEARCH CRITERIA

RESEARCH PROCESS

Define ResearchProblem

Review Concepts

And theories

Review PreviousResearchfindings

Formulatehypothesis

DesignResearch

(IncludingSampleDesign)

CollectData

(Execution)

AnalyseData(Test

Hypothesisif any)

Interpretand

report

FF

F

F F

FF

I

II

III IV V VI VII

F

FF

Feed BackFeed Forward

Review the literature

CRITERIA OF A GOOD RESEARCH PROBLEM

Clear and Unambiguous

Empirical

Verifiable

Interesting

Novel and Original

Availability of Guidance

Statement of Research Objectives

Defining Problem, Results inClear Cut Research Objectives..

Analysis of the Situation

Symptom Detection

Problem Definition

ESTABLISHMENT OF RESEARCH OBJECTIVES

Research Objectives should be clear and achievable, as they directly assist in answering the research problem.

The objectives may be specified in the form of either statements or questions.

Generally, they are written as statements, using the word “to”. (For example, ‘to discover …’, ‘to determine …’, ‘to establish …’, etc. )

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• The objective is to design a feasible & inexpensive study that will produce a correct answer to the research question.

• In the pursuit of this objective.1.Choose the research question2.Develop the protocol3.Pretest and review protocol

ESTABLISHMENT of RESEARCH OBJECTIVES

Thank You

♪ EXPLORATION

♪ DESCRIPTION

♪ DIAGNOSIS

♪ HYPOTHESES

♪ INDUCTIONS AND DEDUCTIONS

NEED FOR RESEARCH

RESEARCH OBJECTIVESObjectives Type of Research

To gain familiarity with a phenomenon or to achieve new insights into it

Exploratory or Formulative Research

To portray accurately the characteristics of a particular individual, situation or a group

Descriptive Research

To determine- the frequency with which something occurs -and its association with anyanother factor

Diagnostic Research

To test a hypothesis of a causal relationship between variables

Hypothesis-Testing Research

CHARACTERISTICS OF RESEARCHIs directed towards the solution of a problem.

Is based upon observable experience or empirical evidence

Demands accurate observation and description.

Involves gathering new data from primary sourcesor using existing data for a new purpose.

Activities are characterized by carefully designedprocedures.

Requires expertise i.e., skill necessary to carry outinvestigation, search the related literature and to understand and analyze the data gathered.

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SCIENTIFIC METHODBASIC POSTULATES

It relies on empirical evidence.

It utilizes relevant concepts.

It is committed to only objective considerations.

It presupposes ethical neutrality.

It results into probabilistic predictions.

The methodology is made known.

Aims at formulating scientific theories.

GOOD RESEARCHQUALITIES

• Systematic

• Logical

• Empirical

• Replicable

• Creative

• Use of multiple methods


Throws light on risks and uncertainty

Identifies alternative courses of action

Helps in economic use of resources

Helps in project identification

Contd …..

Solves investment problems

Solves pricing problems

Solves allocation problems

Solves decision making issues in HR

Solves various operational and planning problems of business and industry

contd….


Provides the basis for all government policies in our economic system.

Helps social scientists in studying social relationships and in seeking answers to various social problems.

For students, research means a careerism or a way to attain a high position in the social structure.

For professionals in research, it may mean a source of livelihood.

contd….

SCOPE / SIGNIFICANCE OF RESEARCH PROBLEMS IN RESEARCH

Not similar to science

Uncontrollable variables

Human tendencies

Time and money

Inadequate electronic data facilitiesLack of scientific training in the methodology of research

Contd …

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Insufficient interaction between university research departments and business establishments

Lack of confidence on the part of business units to give information

Lack of code of conduct

Difficulty of adequate and timely secretarialassistance

Contd …

PROBLEMS IN RESEARCH

Poor library management and functioning

Difficulty of timely availability of published data.

Ignorance

Research for the sake of research-limited practical utility though they may use high sounding business jargon.

Contd …

PROBLEMS IN RESEARCH

ROLE OF RESEARCH IN DECISION-MAKING

♪ Decision-making is the process of selecting the best alternative from the available set of alternatives.

♪ Management is chiefly concerned with decision-making and its implementation.

♪ These decisions should be based on appropriate studies, evaluations and observations.

♪ Research provides us with knowledge and skills needed to solve the problems and to meet the challenges of a fast paced decision-making environment.

Contd …

Decision-making involves three activities:

Intelligence Activity - scanning the environment for identifying conditions necessary for the decision.

Designing Activity - identifying, developing and analyzing the alternative courses of action.

Choice Activity - choosing the best course of action from among the alternatives.

- Herbert A Simon

FACTORS THAT AFFECT MANAGERIAL DECISIONS

INTERNAL FACTORS – factors present inside an organisation such as resources, technology, trade unions, cash flow, manpower etc.

EXTERNAL FACTORS – factors present outside the organisation such as government policies, political factors, socio-economic factors, legal framework, geographic and cultural factors etc.

QUANTITATIVE FACTORS – factors that can be measured in quantities such as time, resources, cost factors etc.

Contd …

QUALITATIVE FACTORS –factors that cannot be measured in quantities such as organizational cohesiveness, sense of belonging of employees, risk of technological change etc.

UNCERTAINITY FACTORS –factors which cannot be predicted.

FACTORS THAT AFFECT MANAGERIAL DECISIONS

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TYPES OF RESEARCH

Descriptive vs Analytical Research

Descriptive Research is a fact finding investigation which is aimed at describing the characteristics of individual, situation or a group (or) describing the state of affairs as it exists at present.

Analytical Research is primarily concerned with testing hypothesis and specifying and interpreting relationships, by analyzing the facts or information already available.

Applied vs Fundamental Research

Applied Research or Action Research is carried out to find solution to a real life problem requiring an action or policy decision.

Fundamental Research which is also known as basic or pure research is undertaken for the sake of knowledge without any intention to apply it in practice. It is undertaken out of intellectual curiosity and is not necessarily problem-oriented.

Quantitative vs Qualitative Research

Quantitative Research is employed for measuring the quantity or amount of a particular phenomena by the use of statistical analysis.

Qualitative Research is a non-quantitative type of analysis which is aimed at finding out the quality of a particular phenomenon.

Conceptual vs Empirical Research

Conceptual Research is generally used by philosophers and thinkers to develop new concepts or to reinterpret existing ones.

Empirical Research is a data based research which depends on experience or observation alone. It is aimed at coming up with conclusions without due regard for system and theory.

Other Types of Research..

One-time Research – Research confined to a single time period.

Longitudinal Research – Research carried on over several time periods.

Diagnostic Research – It is also called clinical research which aims at identifying the causes of a problem, frequency with which it occurs and the possible solutions for it.

Contd …..

Exploratory Research – It is the preliminary study of an unfamiliar problem, about which the researcher has little or no knowledge. It is aimed to gain familiarity with the problem, to generate new ideas or to make a precise formulation of the problem. Hence it is also known as formulative research.

Experimental Research – It is designed to assess the effect of one particular variable on a phenomenon by keeping the other variables constant or controlled.

Historical Research – It is the study of past records and other information sources, with a view to find the origin and development of a phenomenon and to discover the trends in the past, in order to understand the present and to anticipate the future.

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RESEARCH PROBLEM

What is a research problem?

The term ‘problem’ means a question or issue to be examined.

Research Problem refers to some difficulty/need which a researcher experiences in thecontext of either theoretical or practical situation and wants to obtain a solution for the same.

HOW DO WE KNOW WE HAVE A RESEARCH PROBLEM?

Customer complaints

Conversation with company employeesObservation of inappropriate behaviour orconditions in the firmDeviation from the business plan

Success of the firm’s competitor’sRelevant reading of published material (trends, regulations)Company records and reports.

The first step in the research process –definition of the problem involves two activities:

Identification / Selection of the Problem

Formulation of the Problem

Definition of the problemIDENTIFICATION / SELECTION OF

THE RESEARCH PROBLEM

This step involves

identification of a few problems and

selection of one out of them,

after evaluating the alternatives against

certain selection criteria.

SOURCES OF PROBLEMS

Reading

Academic Experience

Daily Experience

Exposure to Field Situations

Consultations

Brainstorming

Research

Intuition

CRITERIA OF SELECTION

The selection of one appropriate researchable problem out of the identified problems is based on evaluation certain criteria. They are:

Internal / Personal criteria

Researcher’s Interest,

Researcher’s Competence,Researcher’s own Resource: finance andtime.

Contd….

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CRITERIA OF SELECTION

External Criteria or FactorsResearchability of the problem,

Importance and Urgency,

Novelty of the Problem,

Feasibility,

Facilities,

Usefulness and Social Relevance,

Research Personnel.

DEFINITION / FORMULATION OF THE RESEARCH PROBLEM

Formulation is the process of refining the research ideas into research questions and objectives.

Formulation means translating and transforming the selected research problem/topic/idea into a scientifically researchable question.It is concerned with specifying exactly what the research problem is.

Problem definition or Problem statement is a clear, precise and succinct statement of the question or issue that is to be investigated with the goal of finding an answer or solution.

There are two ways of stating a problem:

1) Posting question / questions

2) Making declarative statement / statements

DEFINITION / FORMULATION OF THE RESEARCH PROBLEM

PROCESS INVOLVED INDEFINING THE PROBLEM

Statement of the problem in a general way

Understanding the nature of problem

Surveying the available literature

Developing ideas through discussions

Rephrasing the research problem

ESTABLISHMENT OF RESEARCH OBJECTIVES

Research Objectives are the specific components of the research problem, that will be answered or completed, in order to answer the overall research problem.

The objectives refer to the questions to be answered through the study. They indicate the aims of the study or the expected results / outcome of the study.

Thank You

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Prof Dr Abhay ChowdharyMD, DHA, DM Virology, FIMSA, FRSTMH

Prof & Head of Microbiology

D Y Patil deemed to be University

School of [email protected]

Outline of PresentationWhat is Research? Why to Research?Need for Medical Research(MR).Characteristics of Research Type of Research-Descriptive/Analytical, Cross sectional, Case control, Cohort, Ecological, Experimental/Interventional, RCT/RT and Non RCT, Blinding- Single, Double…Evidence Based Medicine- Levels of evidenceGlossary of Terms in Research

What is Research: Research derived from French “Recherche” wherein cherchermeans search“A careful consideration of study regarding a particular concern or a problem using scientific methods”. “Research is a systematic inquiry to describe, explain, predict and control the observed phenomenon”. Research is search for knowledge.Research gets generated due to Human curiosity and inquisitiveness.Research involves inductive and deductive methods.Inductive research methods are used to analyze the observed phenomenon . Qualitative methods are used.Deductive research methods are used to verify the observed phenomenon. Quantitative methods are used.PICO- Problems, Intervention, Comparison, Outcome

Research- Why ?One of the most important aspects of research is the statistics associated with it for conclusion or result.It is about the “thought” that goes behind the research. Research is conducted with a purpose to understand:What do organizations or businesses really want to find out?What are the processes that need to be followed to chase the idea?What are the arguments that need to be built around a concept?What is the evidence that will be required that people believe in the idea or concept?

Need for Medical Research(MR)MR to generate new knowledge and improve scientific

understanding for diagnosis of disease, understanding of

disease, causative organisms, investigations, management.

MR to develop a scientific attitude.

MR to enhance career prospects. “Publish or Perish”.

MR for mandatory curriculum requirement.

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Medical Research Question Research topic is broad concept that is generalized and

not clearly defined.

Research question is more specific, logical objective of

doing study and accurate approach to the problem.

Research focus should be narrow ,not broad.

A strong research idea should pass the ”so what” test.

Generating Research QuestionA step ahead based on earlier work.Repeat the work done by other scientists.Serendipity, the accidental discovery.Need of the society or country at that point of time.Question that interests you.Discussion with research guide, colleagues , students.Keen observation of a prepared mind.Persistence on an issue.Intuition.

Characteristics of a good Research Question

FINER criteria by Hulley and Cummings.

Feasible- time, money, materials and expertise

Interesting- you and your guide

Novel-innovative approach

Ethical-moral principles, Respect, Beneficence, Justice

Relevant-current needs at current times

Characteristics of Research1. A systematic approach. Rules and procedures are an

integral part of research that set the objective of a research process.

2. Researchers need to practice ethics and code of conduct while making observations or drawing conclusions.

3. Research is based on logical reasoning and involves both inductive and deductive methods.

4. The data or knowledge that is derived is in real time, actual observations in the natural settings

5.There is an in-depth analysis of all the data collected from research so that there are no anomalies associated with it.

6. Research creates a path for generating new questions. 7. Research is analytical in nature. It makes use of all the

available data so that there is no ambiguity in inference.8. Accuracy is one of the important character of research,

the information obtained while conducting the research should be accurate and true to its nature.

Types of ResearchBasic researchApplied ResearchProblem oriented researchProblem solvingQuantitative ResearchQualitative Research

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Types of Research Descriptive researchAnalytical researchFundamental researchConceptual researchEmpirical researchOne time research or longitudinal researchField-setting research or laboratory research or simulation researchClinical or diagnostic researchExploratory researchHistorical researchConclusion oriented researchCase study researchShort term research

Types of research Quantitative Research: -Describes, infers, and resolves problems using numbers.-Emphasis is placed on the collection of numerical data.

- summary of data and the drawing of inferences from the data.Qualitative Research: - Based on words, feelings, emotions, sounds and other

non-numerical and unquantifiable elements.- Information is considered qualitative in nature if it cannot

be analyzed by means of mathematical techniques. - It also mean that an incident does not take place often

enough to allow reliable data to be collected”

Types of Research Based on Nature of the Study.

Descriptive research-- usually involves surveys and studies that aim - mainly deals with the description of the present

state of affairs as it is. - There is no control over variables in descriptive

research.Analytical research-

-It is fundamentally different ,-Researcher has to use facts or information already available and Analyze these to make a critical evaluation.

Types of Research Based on Basis:Purpose of the Study

Applied research is also referred to as an action research,

Fundamental research is sometimes called basic or pure research.

SR . No.

Applied Research Fundamental Research

1 Tries to eliminate the theory by adding to the basics of a discipline

Aims to solve a problem by adding to the field of application of a discipline

2 Problems are analyzed from the point of one discipline

Often several disciplines work together for solving the problem

3 Generalizations are preferred Often researches individual cases without the aim to generalize

4 Forecasting approach is implemented

Aims to say how things can be changed

5 Assumes that other variables do not change

Acknowledges that other variables are constant by changing

6 Reports are compiled in a language of technical language of discipline

Reports are compiled in a common language

Exploratory Research Descriptive Research Explanatory

Research

Research approach used Unstructured Structured Highly structured

Research conducted through

Asking research questions

Asking research questions

By using research hypotheses.

When is it conducted?

Early stages of decision making

Later stages of decision making

Later stages of decision making

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EBM- Levels of EvidenceIA - Evidence from meta-analysis of RCT (randomized controlled trials)IB - Evidence from at least one RCTIIA - Evidence from at least one controlled study without randomizationIIB - Evidence from at least one other type of quasi-experimental studyIII - Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case-control studiesIV - Evidence from expert committee reports or opinions or clinical experience of respected authorities, or both

EBM- Grades of RecommendationsA-Directly based on Level I evidence

B-Directly based on Level II evidence or extrapolated

recommendations from Level I evidence

C-Directly based on Level III evidence or extrapolated

recommendations from Level I or II evidence

D-Directly based on Level IV evidence or extrapolated

recommendations from Level I, II, or III evidence

organisms, Sir Peter Medawar, won the Nobel Prize with Sir Macfarlane Burnet in 1960 for demonstrating the possibility of transplanting tissues between genetically different organisms.

The Absence of Proofis Not

The Proof of Absence !

Meta-AnalysisA way of combining data from many different research studies.A meta-analysis is a statistical process that combines the findings from individual

studies.Example: Anxiety outcomes after physical activity interventions: meta-analysis

findings.Systematic ReviewA summary of the clinical literature.

A systematic review is a critical assessment and evaluation of all research studies that address a particular clinical issue.

The researchers use an organized method of locating, assembling, and evaluating a body of literature on a particular topic using a set of specific criteria.

A systematic review typically includes a description of the findings of the collection of research studies.The systematic review may also include a quantitative pooling of data, called a

meta-analysis.Example: Complementary and alternative medicine use among women with breast

cancer: a systematic review.

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Randomized Controlled TrialA controlled clinical trial that randomly (by chance) assigns participants to two or more groups. There are various methods to randomize study participants to their groups.

Example: Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

Cohort Study (Prospective Observational Study)A clinical research study in which people who presently have a certain condition or receive a particular treatment are followed over time and compared with another group of people who are not affected by the condition.

Example: Smokeless tobacco cessation in South Asian communities: a multi-centre prospective cohort study. Case-control StudyCase-control studies begin with the outcomes and do not follow people over time. Researchers choose people with a particular result (the cases) and interview the groups or check their records to ascertain what different experiences they had. They compare the odds of having a experience with the outcome to the odds of having an experience without the outcome.

Example: Non-use of bicycle helmets and risk of fatal head injury: a proportional mortality, case-control study.

Cross-sectional studyThe observation of a defined population at a single point in time or time interval. Exposure and outcome are determined simultaneously.

Example: Fasting might not be necessary before lipid screening: a nationally representative cross-sectional study.Case Reports and SeriesA report on a series of patients with an outcome of interest. No control group is involved.

Example: Students mentoring students in a service-learning clinical supervision experience: an educational case report.Ideas, Editorials, OpinionsPut forth by experts in the field.

Example: Health and health care for the 21st century: for all the people. Animal Research StudiesStudies conducted using animal subjects.

Example: Intranasal leptin reduces appetite and induces weight loss in rats with diet-induced obesity (DIO).Test-tube Lab Research"Test tube" experiments conducted in a controlled laboratory setting.

Glossary of Terms Related to Research Design

Before-After StudyA pre-post investigation of a discrete procedure, experience or event that is not managed by the researcher. Data are collected at baseline and one or more times after the procedure, experience or event.

Case Control StudyA study which involves identifying patients who have the outcome of interest (cases) and matching them with individuals who have similar characteristics, but do not have the outcome of interest (controls), and then looking back to see if these two groups differed with regard to the exposure of interest (i.e., the hypothesized causal or contributing factors).

Case Study or Case SeriesA descriptive study of one (case study or case report) or a series of patients (case series) defined by eligibility criteria, and where the unfolding course of events (disease progression, therapies, outcomes, etc.) is described in detail. The study researchers do not manipulate interventions. This study design is used to provide a detailed description of an uncommon disease or condition, a unique situation, or the introduction of a new technique.

Cluster Randomized TrialA special type of a randomized controlled trial (RCT) where groups of individuals (e.g., clinic sites, classrooms, communities), rather than independent individuals, are randomized to the intervention alternatives.

Cohort StudyA study that involves the identification of a group (cohort) of individuals with specific characteristics in common and follows them over time to gather data about exposure to factors and the development of the outcome of interest. Comparison groups can be defined at the beginning or created later using data from the study (e.g., age group, smokers/non-smokers, amount of a specific food group consumed). Prospective cohort studies enroll individuals and then collect data at many intervals. Retrospective cohort studies use an existing longitudinal data set to look back for a temporal relationship between exposure factors and outcome development. In the medical field, many studies labeled a “population-based clinical study” could be classified as retrospective cohort studies.

Cost Benefit Analysis or Cost Effectiveness AnalysisAn analysis that assesses the cost of an intervention in relation to the magnitude of outcome achieved. In cost benefit analysis, the inputs (i.e., intervention alternatives) and the resulting outcomes are quantified and expressed in monetary terms. In cost effectiveness analysis, inputs (i.e., intervention alternatives) are expressed in monetary terms but the outcomes are expressed in a standard unit, such as quality adjusted life years (QALY) or hospitalizations avoided. These are considered a synthesis of primary studies when data from multiple studies are used to derive estimates of inputs and outcomes.

Crossover Study DesignA study where two or more experimental therapies are administered, one after the other, in a specified or a random sequence, to the same group of patients. Usually there is a washout (no treatment) period between therapies. Individuals serve as their own controls. A crossover study is a special type of a randomized or non-randomized trial.

Cross-Sectional StudyA study where exposure factors (e.g., individual or environmental risk factor, nutrition education) and outcomes (e.g., disease occurrence, eating behavior) are observed or measured at one point in time in a sample from the population of interest, usually by survey or interview. In this design, a researcher examines the association among factors and outcomes using a statistical test for association, but cannot infer cause and effect.

Descriptive StudyDescriptive studies, as a research category, use a variety of methods to observe existing natural or man-made phenomena without influencing it (no researcher intervention). Data are gathered, organized and analyzed to depict and describe “what is”. Descriptive studies can be quantitative and/or qualitative and provide an in-depth look at processes, characteristics and patterns. Descriptive studies can result in a theory or framework, but they do not try to determine cause and effect.

Reasons for rejection of manuscripts-related to Study Design

Poor experimental designVague/inadequate method descriptionMethods lack sufficient rigorFailure to account for confoundersNo control or improper controlNo hypothesisBiased protocolSmall sample sizeInappropriate statistical methods, or statistics not applied properly.

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Thank You……..

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21-07-2019 11:00 DR. DEEPAK LANGADE 1

Basic workshop onRResearch methodology, Biostatistics &

Principles of GCP

22 – 24 July 2019Pushpanjali, 3rd floor Auditorium,

D Y Patil Hospital, Nerul

Jointly organized byDept. of Obs. & Gynaecology

Institutional Ethics Committee (IEC)

OBJECTIVES OF THE SESSION

Types of Research

Research Question

Research Hypothesis

Study Designs

Blinding & Randomization

Bias

21-07-2019 11:00DR. DEEPAK LANGADE 2

TYPES OF RESEARCH

23-07-2019RESEARCH METHODOLOGY DR.DEEPAK LANGADE 3

Descriptive Analytical


23-07-2019

RESEARCH METHODOLOGY DR.DEEPAK LANGADE

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QuantitativeQualitative


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Researcher decides what to study;

asks specific, narrow questions,

collects quantifiable data from large number of participants;

analyzes these numbers using statistics;

and conducts the inquiry in an unbiased, objective manner.

Post-positivism – singular reality; objective; deductive

Researcher relies on the views of participants;

asks broad, general questions;

collects data consisting largely of words (or text) from participants;

describes and analyzes text for themes; and

conducts the inquiry in a subjective, biased manner.

Constructivism – multiple realities; biased; inductive

Quantitative research Qualitative research


Conceptual Empirical


Cross-sectional Longitudinal


Field

LaboratoryLibrary


TYPES OF RESEARCH

Descriptive vs. Analytical

Applied vs. Fundamental

Quantitative vs. Qualitative

Conceptual vs. Empirical

Other types:Cross-sectional or longitudinal research

Simulation research

Clinical or diagnostic research

Exploratory or formulative research

Hypothesis-testing research


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Research Methods

Research Methodology


RESEARCH QUESTION


FIRST STEP

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RESEARCH QUESTION ?

First methodological steps towards research

Research question must be accurately and clearly defined

Good research question is the central element of research

A strong research question should never leave room for ambiguity or interpretation


WHAT IS A RESEARCH QUESTION?

Unanswered question Unsolved question Concern Conditions that could be improved Difficulties that need to be eliminatedQuery Statement of inquiry

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WHAT MAKES A GOOD QUESTION?

MotivationInteresting?

FeasibleResearchable?

Have impact on practice/life/outcomeSignificant?

ReachManageable?

UnambiguousClear?

DENTAL -DYP 19

FINER CRITERIA

F • Feasible

I • Interesting

N • Novel

E • Ethical

R • Relevant

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PURPOSE OF RQ ?

Determines where and

what kind of research is

planned

Identifies the specific

objectives of Research


EXAMPLES OF RQ ?

How is Diabetes Mellitus harmful in males?

Unclear:

Clear:

How is male sexual function affected by Diabetes Mellitus?


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EXAMPLES OF RQ ?

What is the effect on the environment from global warming?

Unfocused:

Focused:

How is glacial melting affecting penguins in Antarctica?


EXAMPLES OF RQ ?

How are doctors addressing diabetes in the India?

Appropriately Complex:

What are common traits of those suffering from diabetes in India, and how can these be used in prevention of the diabetes?


SOME RESEARCH TITLES

Observational Study Of Endotracheal Intubation In Emergency Department

Study of thyroid disorders in Diabetes Mellitus

Clinico-radiological profile in patients of Rheumatoid Arthritis

Role of Laparoscopy in Acute Appendicitis

Clinical Study of Acute Pancreatitis and its management

A study on the management of intestinal obstruction 21-07-2019 11:00DR. DEEPAK LANGADE 27

RESEARCH HYPOTHESIS


HYPOTHESISAfter extensive literature survey, researcher should state in clear terms the working hypothesis or hypothesesWorking hypothesis is tentative assumption made in order to draw out and test its logical or empirical consequencesHypothesis should be very specific and limited to the piece of research in hand because it has to be testedThe role of the hypothesis is to guide the researcher by delimiting the area of research and to keep him on the right trackIt also indicates the type of data required and the type of methods of data analysis to be used


APPROACH TO HYPOTHESIS

Study Hypothesis

Discussions with colleagues and experts about the problem, its origin and the objectives in seeking a solution

Examination of data and records

Review of similar studies

Exploratory personal investigation (pilot)


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NULL HYPOTHESIS (H0)

The purpose of most statistical tests, is to determine if the obtained results provide a reason to reject the hypothesis that they are merely a product of chance factors

State a null hypothesis (that there is no effect) and then test whether the obtained data allows rejection of the hypothesis

Alternate Hypothesis (H1)Opposite of null hypothesis

HYPOTHESIS & DESIGN

Non-inferior

Non-equivalenceEquivalenceSuperiority

/ Inferiority


SUPERIORITY HYPOTHESISNull Hypothesis (H0)

‘Test therapy’ is NOT SUPERIOR to ‘Reference therapy’

H0 : ET = ER

Alternate Hypothesis (H1)‘Test therapy’ is SUPERIOR to ‘Reference therapy’

H1 : ET > ER

Superiority defined as at least 10% greater improvement with ‘Test therapy’ relative to “Reference therapy’

EQUIVALENCE HYPOTHESISNull Hypothesis (H0)

‘Test therapy’ is EQUIVALENT to ‘Reference therapy’

H0 : ET = ER

Equivalence is defined as efficacy between 80% to 125% relative to efficacy of ‘Reference’

Alternate Hypothesis (H1)‘Test therapy’ is NOT EQUIVALENT to ‘Reference therapy’

H1 : ET ≠ ER

NON-INFERIORITY HYPOTHESISNull Hypothesis (H0)

‘Test therapy’ is SIMILAR to ‘Reference therapy’

H0 : ET = ER

Alternate Hypothesis (H1)‘Test therapy’ is NOT INFERIOR to ‘Reference therapy’

H1 : ET ≥ ER

Non-inferiority defined as improvement with ‘Test therapy’ similar or greater to “Reference therapy’

HYPOTHESIS & DESIGN

7/23/2019 9:48 AMDR.DEEPAK LANGADE: INTRODUCTION TO STATISTICS 36

SUPERIORITY / INFERIORITY

EQUIVALENCE NON-EQUIVALENCE

NON-INFERIOR

1-SIDED / 2-SIDED

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E.G. WOULD YOU USE QUANTITATIVE RESEARCH HERE?


WE WANT TO STUDY THE PREFERENCES OF PEOPLE FOR

TOOTHPASTE

WE HAVE TO STUDY THE EFFECT OF COUNSELLING ON SMOKING

HABITS & BEHAVIOUR.

STUDY DESIGNS

APPROPRIATE METHODOLOGY?

Quantitative

Qualitative

Mixed

Critical & Action Oriented

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STUDIES

STUDY DESIGNSPilot study

Open

Comparative vs Non-comparative

Parallel group / Cross-over study

Randomised Controlled

Factorial design

Blinded study

Observational vs interventional

Cross-Sectional

Case-Control Study

Cohort Study

PILOT STUDY

Small sample from population

Feasibility and need for the

study

Draw an provisional inferences

Estimate the sample size for a conclusive study

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OPEN STUDY

All participants are aware of the study medication received by the patients.It could be a comparative or non-comparative study

COMPARATIVE STUDY

Also called as Controlled Study Either a

PLACEBO (Placebo controlled) or

ACTIVE drug is used for comparison with the drug under study


PARALLEL GROUP STUDY

Applicable for Comparative studiesAll treatment groups receive the same treatment throughout the study period.

i.e. The study and the control groups run parallel to each other

PARALLEL GROUP STUDY

GROUP I

GROUP II

DRUG A

DRUG B

DRUG A

DRUG B

Study Initiation Study Completion

CROSS-OVER STUDY

Treatment groups receive both study and control medication in the study. There is a cross-over of treatments.E.g.:

Two-Way Crossover Study

Three-Way Crossover Study

2-WAY CROSS-OVER DESIGN


Study Initiation

InterimVisit

Drug free Washout period

GROUP IDRUG A

GROUP IIDRUG B

GROUP IDRUG B

GROUP IIDRUG A

CROSSOVER

Study Completion

FIRST CYCLE

SECOND CYCLE

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4-WAY CROSS-OVER DESIGN


ABCD

DABC

CDAB

BCDA

CASE – CONTROL STUDY


A type of observational study in which two existing groups differing

in outcome are identified and compared on the basis of some

supposed causal attribute.

Used to identify factors that may contribute to a medical condition by comparing subjects who have

that condition/disease (the "cases") with patients who do not have the

condition/disease but are otherwise similar (the "controls").

SMOKING & CANCER


CASE – CONTROL STUDY

They require fewer resources but provide less evidence for causal inference than a randomized controlled trial.

We only get odds ratio from a case–control study which is an inferior measure of strength of association as compared to relative risk.

E.g. Link between tobacco smoking and lung cancer.


RETROSPECTIVE


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COHORT

Prospective

A group of people who share a defining characteristicThose who experienced a common event in a selected period, such as birth or graduation

Cohort studies differ from clinical trials

No intervention, treatment, or exposure is administered

No control group is defined


COHORT STUDY

Define your cohort

Both exposure/treatment and control variables are measured at baseline.

Participants are then followed over time to observe the incidence rate of the disease or outcome in question.

Regression analysis can then be used to evaluate the extent to which the exposure or treatment variable contributes to the incidence of the disease, while accounting for other variables that may be at play.


CASE CONTROL VS COHORT


RETROSPECTIVE CASE-CONTROL STUDYAdvantages:

Useful for rare diseases or unusual exposuresSmaller sample sizesStudies take less time, because the data is readily available (it just has to be collected and analyzed)Costs are generally lower

Disadvantages:Missing dataRecall biasConfounding variables are difficult or impossible to measureCannot make causal statements, although correlations are okay


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PROSPECTIVE COHORT

-BACK-ACHE



BLINDING

Blinding is a procedure by which the participants are kept unaware of the treatment given


SINGLE BLIND

DOUBLE BLIND

TRIPLE BLIND


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RANDOMISATIONRandom numbers

Computer generated charts Rando, True Epistat

Latin square For more than two treatment groups

Types of Randomization:Simple Randomization

Block Randomization

Stratified Randomization

RANDOMISATION

Concealment Of Randomization Code Is The Most Important Aspect Of

A Randomised Controlled Trial (RCT)

FOR OPEN CONTROLLED TRIALS:

Treatment to be received by the patient is provided in SEALED ENVELOPS

with only Patient serial numbers on the cover.

The envelop is opened by the investigator only after a serial number is

allotted to the patient.


OBSERVATIONAL VS INTERVENTIONAL

OBSERVATIONAL

Retrospective / Prospective

Non-experimental

INTERVENTIONAL

Prospective

Experimental


BIAS

Observer / Evaluator

Enrollment / Recruitment / Selection

Detection bias

Instrumentation

Methods to minimize bias:

Matching

Randomization

Blinding


Error in research

Confounding

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GROUP ACTIVITY - 1RESEARCH QUESTION

Each group will discuss and come out with 2 research questions and related hypotheses

Indicate why the topic was selected & the type of study Study design

Objective

Study parameters


Orthopaedics Comparative study of anticoagulants in prevention of pulmonary embolism after Hip & Knee replacement

General surgery Comparative study of open Vs laproscopic appendicectomy


Ophthalmology Evaluation of topical latanoprost for acute congestive glaucoma

AnaesthesiaOndensetron Vs Metoclopramide for PONV


General medicine Tenaligliptine for type 2 DM – Efficacy

DermatologyDrug use pattern in Dermatophytosis


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BASIC WORKSHOP ONRESEARCH METHODOLOGY,

BIOSTATISTICS & PRINCIPLES OF GCP

22 – 24 July 2019Pushpanjali, 1st floor Auditorium,




GROUP ACTIVITY - 1RESEARCH QUESTION

DR. DEEPAK LANGADE

1

2

24-07-2019

Each group will discuss and come out with 2 research questions and related hypotheses

Indicate why the topic was selected & the type of study Study design

Objective

Study parameters

24-07-2019 17:42DESCRIPTVE RESEARCH : DR. DEEPAK LANGADE 3

Orthopaedics Comparative study of anticoagulants in prevention of pulmonary embolism after Hip & Knee replacement

General surgery Comparative study of open Vs laproscopic appendicectomy

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Ophthalmology Evaluation of topical latanoprost for acute congestive glaucoma

AnaesthesiaOndensetronVs Metoclopramide for PONV

General medicine Tenaligliptine for type 2 DM – Efficacy

DermatologyDrug use pattern in Dermatophytosis


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24-07-2019


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1

Research Protocol

Dr. Anant PatilMBBS, MD (Pharmacology), MBA

Department of Pharmacology

Protocol Writing: Dr.Anant Patil 1 Protocol Writing: Dr.Anant Patil 2

The Plan…

To discuss

• What is research protocol?

• Why, when and how to write the research protocol

Protocol Writing: Dr.Anant Patil 3

Protocol definition

• A document containing background, rationale, objective, design, methodology (including matters concerning

performance, management, conduct, analysis), adverse event, withdrawal, statistical consideration and record keeping pertaining to clinical trial

New Drugs and Clinical Trial Rules 2019

Everything and anything that should happen and can happen in a study


Protocol

• Why ?• Where ?• What ? • Who ? • When ?• How ?

• Design• Organization• Execution• Monitoring• Analysis• Reporting

• Design• Organization• Execution• Monitoring• Analysis• Reporting


Science

Ethics and regulations

Compliance with

• Ethics committee (and DCGI*) approved protocol

• Good Clinical Practice (GCP) guidelines• All applicable regulations

*Investigator initiated studies with 'new drugs', DCGI approval is not needed; only an EC approval is required


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Components of protocol

ICMR Guidelines 2017


1. Title page

• Title of the study

• Protocol number

• Date and version

• Signatures of investigators, sponsor and statistician


Other information

• Names, titles, and addresses of

– Sponsor and monitors, if different– Person authorized to sign protocol and protocol amendments for

sponsor– Sponsor’s medical expert– Investigator(s) responsible for conducting the study– Study site(s)– Qualified physician who is responsible for all Study-related

medical decisions, if different than investigator– Clinical lab(s) and other medical and/or technical department(s)



Good Title

“Efficacy and safety of rabeprazole plus itopride in peptic ulcer disease: A randomized, placebo controlled multi-centric trial in Indian patients”


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Poor Title

“Rabeprazole plus itopride in peptic ulcer disease”


2. Background

• Rationale of why study is needed

• Description of population to be studied

• A summary of findings from relevant nonclinical and clinical studies

• Summary of known and potential benefits and risks to human subjects


Background

• Description of and justification for, route of administration, dosage, dosage regimen, and treatment period(s)

• Statement that the study will be conducted in compliance with the protocol, good clinical practices (GCP), and applicable regulatory requirement(s)


3. Eligibility criteria and participant recruitment procedures

• Inclusion criteria

• Exclusion criteria

• Withdrawal criteria


Procedures for subject withdrawal

• When and how to withdraw subjects?

• What is the type and timing of the data to be collected for withdrawn subjects?

• Are subjects replaced? If so, how?

• What is the follow-up, if any, for subjects withdrawn?


4. Justification of inclusion/exclusion of vulnerable population

PrisonersStudents Protocol Writing: Dr.Anant Patil 18

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5. Clinical research objectives

• Primary objectives• Secondary objectives


6. Methodology

• Type of study design (observational, experimental, pilot, randomized, blinded, etc.)

• Types of data collection• Intended intervention (dosages, route of

administration, duration of treatment) • Details of invasive procedures, if any


Study design

• A description of type/design of study to be conducted

• A specific statement of the primary endpoints and the secondary endpoints, if any, to be measured during the study

• A schematic diagram of study design, procedures, and stages

• A description of the measures taken to minimize/avoid biasProtocol Writing: Dr.Anant Patil 21

Intervention

• Description: Randomization, blinding• Dosing• Packaging & labelling• Medication(s)/treatment(s) permitted and not permitted

before and/or during the study• Procedures for monitoring subject compliance• Follow up• Accountability procedures for the investigational

product(s)• Maintenance of study treatment randomization codes and

procedures for breaking codesProtocol Writing: Dr.Anant Patil 22

Placebo use

• Justification for placebo, benefit–risk assessment, plans to withdraw.

• If standard therapies are to be withheld, justification for the same


Assessment of efficacy

• Specification of efficacy (primary and secondary) parameters

• Methods and timing for assessing, recording, and analyzing efficacy parameters


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Assessment of safety

Specification of safety parameters

• Clinical adverse events• Adverse event (AE) reporting• Definition of AE and serious AE

(SAE) • Procedures and timing for assessing,

recording, reporting and analyzing adverse event

• Type and duration of the follow-up of subjects after adverse events


7. Management of risk or injury

• For research involving more than minimal risk, an account of management of risk or injury



8. Compensation/reimbursement

• Proposed compensation, reimbursement of incidental expenses and management of research related injury/illness during and after research period


9. Ancillary care

• Provision of ancillary care for unrelated illness during the duration of research


Duration of study


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10. Statistical analysis

• Data collection and management• Plan for statistical analysis of the study• Statistical methods to be employed• Number of subjects planned to be enrolled

(sample size)• Selection of subjects to be included in the analyses• Level of significance to be used


Statistics

• Criteria for termination of the study

• Procedure for accounting for missing, and unused data

• Interim analysis (if applicable)


11. Ethical considerations

• Ethical considerations and safeguards for protection of participants

• Ethics committee permission


Informed consent

• Procedure for seeking and obtaining informed consent with a sample of the patient/participant information sheet and informed consent forms in English and local languages.

• AV recording if applicable; informed consent for stored samples


Confidentiality

• Plan to maintain the privacy and confidentiality of the study participants


Direct access to source document

• Investigator(s)/ institution(s) will permit Study-related monitoring, audits, IRB/IEC review, and regulatory inspection(s) by providing direct access to source data/documents


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12. Storage and maintenance of data

• An account of storage and maintenance of all data collected during the trial


13. Plan of publication

• Plans for publication of results – positive or negative – while maintaining confidentiality of personal information/identity.


14. Others

• Quality Control and Quality Assurance• Data Handling and Record Keeping• Financing and Insurance (if not addressed in

a separate agreement)• QC and QA procedures• Supplements


Protocol amendment

• A written description of a change(s) to or formal clarification of a protocol


Summary

• Protocol is an essential document in clinical research

• Required for IEC review and approval

• Can be amended (safety reasons, suggestions from IEC, administrative changes)

• Amended version needs to be submitted to IECProtocol Writing: Dr.Anant Patil 41

Thank you


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Group activityNumber of groups: 4

• Prepare a research question and related hypothesis• Indicate why topic was selected• Suggest appropriate study design and methodology in brief

Time: 30 minutes

• Preparation: 10 minutes (all groups together)• Presentation: 05 minutes (each group)


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1

Experimental StudiesDR M.N.Satia

Professor Dept. Of OBGYN

D. Y. Patil Hospital, Nerul, Navi Mumbai

Dr. Meena Satia 2

Session Objectives

3

▪ 1. To enable participants to understand experimental study design

▪ 2. To understand the threats to internal and external validity

▪ 3.To know different types of experimental study designs and their applications

▪ 4.To give hands on experience of designing a study with the help of exercises

Dr. Meena Satia

Experimental Research

Experimental research is an attempt by the researcher to maintain control over all the factors that may affect the result of an experiment. In doing this, the researcher attempts to determine or predict what may occur.

Dr. Meena Satia 4

Types of Clinical Studies

Descriptive•Case report•Case series•Cross sectional (Survey)

Analytic

Observational•Cross sectional•Case-control•Cohort studies

Experimental•Randomized controlled trials

Strength of evidence for causality between a risk factor and outcomeDr. Meena Satia 5

Why Conduct an RCT?

An RCT is conducted to test whether an intervention or treatment works.The key methodological components of an RCT (1) Use of a control condition to which the experimental intervention is compared(2) Random assignment of participants to conditions. Advantages of using an RCT design include:Random assignment ensures that known and unknown person and environment characteristics that could affect the outcome of interest are evenly distributed across conditions..

Dr. Meena Satia 6

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What is a Randomised controlled trial……

Simplest Definition: Individuals are allocated at random to receive one of several interventions (at least two total).

RCT’s are experimental—the intervention is controlled by the investigator

RCT’s are usually comparative studies (“controlled” in the RCT)

Dr. Meena Satia 7

Random allocation means that all participants have a defined probability of assignment to a particular intervention .

Allocation is not determined by the investigator, clinicians, or participants.

Allocation is not predictable based on a pattern

Dr. Meena Satia 8

What purpose is served by random allocation?

Covariates are distributed equally across the groups at baseline

� Affects both measured and, more importantly, unmeasured variables� The risk of imbalance remains even after properly executed randomization� In most RCTs will provide a comparison of treatment and comparison groups, with p-valuesIf randomisation has been performed correctly, chance is the only explanation for any observed difference between groups, in which case statistical tests are considered superfluous Dr. Meena Satia 9

What elements of a trial can be randomized?

Most common unit is individual patientSometimes groups are randomized=cluster randomizationExamples: families, schools, towns, hospitals, communitiesWorry about contamination in cluster randomizationSpecial statistical techniques needed to cope with the loss of independence of the individual units

Dr. Meena Satia 10

Choosing research question-Hulley 1988

▪ Feasible in terms of resources, expertise etc.

▪ Interesting to the investigator

▪ Novel: gen. new data/confirm/ refute earlier findings

▪ Ethical

▪ Relevant

Dr. Meena Satia 11

Experimental Design

Experimental design is a blueprint of the procedure that enables the researcher to test his hypothesis by reaching valid conclusions about relationships between independent and dependent variables.

Dr. Meena Satia 12

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Research Essentials

▪ Manipulation of an independent variable.

▪ All variables except the dependent variable are held constant (control).

▪ Manipulation of the dependent variable by the independent variable is observed (observation).

Dr. Meena Satia 13

Aims of Experimental studies:

To provide scientific proof of aetiological factors which may permit the modification or control of those diseases

To provide a method of measuring the effectiveness and efficiency of health services for prevention, control and treatment of disease and improve health of the community

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In addition to all the advantages and disadvantages of the usual prospective cohort studies, experimental studies have three additional problems of-

1. Cost

2. Ethics &

3. Feasibility

They may be conducted in animals or human beings

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Animal studies

Contributed to our knowledge of anatomy, physiology, pathology, microbiology, genetics, immunology, chemotherapy, etc.Applications:

1. experimental reproduction of human disease in animals to confirm aetiological hypotheses and to study pathogenesis

2. Testing efficacy of preventive and therapeutic measures such as vaccines and drugs

3. Completing the natural history of disease

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Classical Animal Experiments

▪ Webster (USA)

▪ Topley, Wilson, Greenwood ( UK)

▪ Induced epidemics in animals and in studies of herd immunity under lab. conditions

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Advantages:Animals can be bred in laboratories and manipulated

according to the wishes of the investigator

Multiply rapidly and enable investigators to carry out certain experiments which in human population would take several years

Limitations:Not all human diseases can be reproduced in animals

All the conclusions derived may not be strictly applicable to human beings

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Human experiments :

More essential in the investigation of diseases that can not be reproduced in animals

Ethical and logistic considerations prevent its application to study of disease in humans

Benefits of the experiment to be weighed against risks involved

Volunteers made fully aware of all possible consequences of the experimente.g.

James Lind (1747)

Edward Jenner’s (1796) experiment with cowpox

Finlay & Reed - mosquito borne nature of yellow feverDr. Meena Satia 19

Types of experimental studies

A. Randomized controlled trials

B. Non-randomized or non-experimental trials

These depart from randomization for practical purposes Non randomization does not seriously affect theoretical basis of conclusions.

Dr. Meena Satia 20

Randomized controlled trials

▪ Steps:1. Drawing up a protocol2. Selecting reference and experimental

populations3. Randomization4. Manipulation or intervention5. Follow-up6. Assessment of outcome

Dr. Meena Satia 21

Protocol

▪ Aims & objectives of the study

▪ Research Question

▪ Selection criteria for study and control groups

▪ Allocation

▪ Treatments applied- when , where, how

▪ Standardization of working procedures, schedules n responsibilities of parties involved

Protocol aims at preventing bias and to reduce the sources of error in the study

Once the protocol is made we need to strictly adhere to itDr. Meena Satia 22

Selecting reference and experimental populations

a) Reference or target population – to which the findings of the trial, if found successful, are expected to be applicable

b) Experimental or study population –

derived from reference population, randomly chosen criteria:

1. Informed consent

2. Representative of the population to which they belong

3. Qualified or eligible for the trial

Dr. Meena Satia 23

Randomization (Fisher)

▪Heart of a control trial

▪Statistical procedure by which participants are allocated into groups k/a study & control groups

▪Its an attempt to eliminate selection bias & allow comparability

▪“Like can be compared with like”

▪Best done by using table of random numbers

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Manipulation

▪ To intervene or manipulate the study group by the deliberate application or withdrawal or reduction of the suspected causal factor as laid in the protocol

▪ It creates an independent variable whose effect is then determined by measuring final outcome, which constitutes dependent variable

Dr. Meena Satia 25

Mienert 1986- requirements for test and control treatments

▪ They must be distinguishable from one another

▪ They must be Medically justifiable

▪ There must be ethical base for use of either treatment

▪ Acceptable to study patients and to physicians administering them

▪ There must be reasonable doubt regarding efficacy of the test treatment

▪ Reason to believe that benefits outweigh the risks of treatment

Dr. Meena Satia 26

Random assignment equalizes the influence of nonspecific processes not integral to the intervention whose impact is being tested. Nonspecific processes might include effects of participating in a study, being assessed, receiving attention, self-monitoring, positive expectations, etcRandom assignment and the use of a control condition ensure that any extraneous variation not due to the intervention is either controlled experimentally or randomized.That allows the study's results to be causally attributed to differences between the intervention and control conditions.

Dr. Meena Satia 27

In sum, the use of an RCT design gives the investigator confidence that differences in outcome between treatment and control were actually caused by the treatment, since random assignment (theoretically) equalizes the groups on all other variables

Dr. Meena Satia 28

Follow Up

▪ Implies examination of the study and control group subjects at defined intervals of time, in a standard manner, with equal intensity, under the same given circumstances, in the same time frame till final assessment of outcome.

▪ Losses to follow-up are inevitable due to deaths, migration or loss of interest k/a attrition

Dr. Meena Satia 29

Data and Safety Monitoring Committee or Board

Early stopping of trial

▪ Appearance of an effect favoring one treatment so strong as to make it unethical to randomize patient to alternative treatment

▪ Occurrence of adverse events at unacceptable rates given expected benefits

▪ Determination that the reasonably expected results are no longer of sufficient value to continue the trial

Dr. Meena Satia 30

25 26

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6

Assessment :

▪ In terms of –a) Positive results- reduced incidence, severity, costb) Negative results- side effects, complications , death

Techniques are available to analyse the data as they are collected-- Sequential analysis OR at the end of trial analysis

“Intent to treat” principle

Dr. Meena Satia 31

Bias may arise from the errors of assessment due to human element: 3 sources

1.Subject variation:Bais on the part of the participant who may subjectively feel better once he knows he is in the trial .

2.Observer bias:The investigator measuring the outcome may be influenced if he knows before hand what Rx the patient is taking

3.Bias in evaluation: the researcher may subconsciously give a favourable report of the outcome

Dr. Meena Satia 32

Blinding

▪ Randomisation cannot guard against these sorts of Bias & hence in-order to reduce these problems blinding is adopted, which will ensure that the outcome is assessed objectively It can be done in 3 ways1.Single Blind Trial:Participant is not aware whether he belongs to study /control group

2.Double Blind Trial: Participant /Researcher not aware

3.Triple Blind Trial: Participant /Researcher/Analyser are blinded.

Dr. Meena Satia 33

Clinical Trial: Parallel Group Design

Participants screened for entry criteria

ControlTreatment

Experimental

TreatmentWithout

Outcome

WithOutcome

Without Outcome

With Outcome

TimeScreening Baseline Treatment

Dr. Meena Satia 34

Clinical Trial: Crossover Design

Participants screened for entry criteria

Control Treatment

Experimental Treatment

WithoutOutcome

With Outcome

Without Outcome

With Outcome

Control Treatment

Experimental

TreatmentWithout

Outcome

With Outcome

Without Outcome

With Outcome

Screening Treatment (Phase 1)

{Washout}B/L Treatment (Phase 2)Dr. Meena Satia 35

Advantages of Cross- over design

▪ All patients assured to receive new therapy

▪ Economy of numbers at expense of time

▪ Not suitable if drug cures the disease

▪ If drug effective only in certain stage of disease

▪ Disease course radically changes during trial time

Dr. Meena Satia 36

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7

Internal Validity

Internal validity is the extent to which the results of a study

are true ie the intervention really did cause the change in

behavior.

The change was not the result of some other extraneous

factor, such as differences in assessment procedures

between intervention and control participants.

This describes the technical soundness of a study,

particularly concerned with the control of extraneous

influences that might effect the outcomeDr. Meena Satia 37

External Validity

External validity is the extent to which the results can be generalized to a population of interest.

The population of interest is usually defined as the people the intervention is intended to help

Dr. Meena Satia 38

Validity

39

▪ Both are important in a study but they are frequently at odds

with one another in planning and designing a study

▪ Internal validity is considered the basic minimum for

experimental research

▪ To gain internal validity, the researcher attempts to control

everything and eliminate possible extraneous influences

▪ Lends itself to highly controlled, laboratory settings

Dr. Meena Satia

Threats to Internal Validity

40

▪ History – events occurring during the experiment that are not part of the treatment

▪ Maturation – biological or psychological processes within participants that may change due to the passing of time, e.g., aging, fatigue, hunger

▪ Testing – the effects of one test upon subsequent administrations of the same test

▪ Instrumentation – changes in testing instruments, raters, or interviewers including lack of agreement within and between observers

Dr. Meena Satia

Threats continued

41

▪ Statistical regression – the fact that groups selected on the basis of extreme scores are not as extreme on subsequent testing

▪ Selection bias – identification of comparison groups in other than a random manner

▪ Experimental mortality – loss of participants from comparison groups due to nonrandom reasons

▪ Interaction among factors – factors can operate together to influence experimental results

Dr. Meena Satia

External Validity

42

▪ Generalizability of results . . . to what populations, settings, or treatment variables can the results be generalized?

▪ Concerned with real-world applications

▪ What relevance do the findings have beyond the confines of the experiment?

▪ External validity is generally controlled by selecting subjects, treatments, experimental situations, and tests to be representative of some larger population

▪ Random selection is the key to controlling most threats to external validity

Dr. Meena Satia

37 38

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7/23/2019

8

Types of External Validity

43

▪ Population Validity ––refers to the extent to which the results can be

generalized from the experimental sample to a defined population

▪ Ecological Validity ––refers to the extent to which the results of an

experiment can be generalized from the set of environmental conditions in the experiment to other environmental conditions

Dr. Meena Satia

Common Sources of Error

▪ Many possible sources of error can cause the results of a research study to be incorrectly interpreted. The following sources of error are more specific threats to the validity of a study than those described previously

▪ Selected examples:–Hawthorne Effect–Placebo Effect–John Henry Effect–Rating Effect–Experimenter Bias Effect

Dr. Meena Satia 44

Hawthorne Effect

45

▪ A specific type of reactive effect in which merely being

a research participant in an investigation may affect

behavior

▪ Suggests that, as much as possible, participants should

be unaware they are in an experiment and unaware of

the hypothesized outcome

Dr. Meena Satia

Placebo Effect

▪ Participants may believe that the experimental

treatment is supposed to change them, so they

respond to the treatment with a change in

performance

Dr. Meena Satia 46

John Henry Effect

▪ A threat to internal validity wherein research

participants in the control group try harder just

because they are in the control group

Dr. Meena Satia 47

Types of Randomized controlled trials

▪ Clinical trials

▪ Preventive trials

▪ Risk factor trials

▪ Cessation experiments

▪ Trial of etiological agents

▪ Evaluation of health services

Dr. Meena Satia 48

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9

Clinical Trials

▪ Evaluating therapeutic agents

▪ Beta blockers- CVS mortality in MI patients

▪ Folate supplements to prevent recurrent neural tube defects

▪ Tonsillectomy to prevent recurrent throat infections

▪ Ethical, administrative, technical problems

Dr. Meena Satia 49

Preventive Trials

▪ Vaccines and chemoprophylactic drugs

▪ Whooping cough vaccine 3 manufacturers 10 field trials 1946- UK

▪ 6-18 months

▪ Study group-149 cases/ 3801 vaccinees

▪ Control group-687 cases/ 3757 unvaccinated

▪ Attack rate 1.45/1000 Vs 6.72/ 1000

▪ Risk- benefit & Cost

Dr. Meena Satia 50

Risk factor trials

▪ Single factor/ Multi- factors eg :

▪ Clofibrate to lower cholesterol

▪ 15000 men clofibrate Vs Olive oil, 3 centres in Europe

▪ Edinburgh, Prague, Budapest

▪ 9.6 yrs mean follow up

▪ Reduction in non-fatal cardiac infarction

▪ 25% more deaths due to drug toxicity

Dr. Meena Satia 51

Cessation Experiment

▪ Termination of a habit

▪ Removal of a suspected agent

▪ E.g. Smoking cessation- Lung cancer/ primary prevention of CHD

Dr. Meena Satia 52

Trial of etiological agents

▪ Retro- lental Fibroplasia

▪ 50% oxygen for 28 days Vs Oxygen only for clinical emergency was given to premature babies < 1500 gm in 18 hospitals in the USA

▪ All babies in curtailed oxygen group who developed RLF received some oxygen

▪ No cases in those who never received oxygen

Dr. Meena Satia 53

Evaluation of Health services

▪ Domiciliary / sanatorium treatment for TB

▪ Multi-phasic screening trials in UK

Dr. Meena Satia 54

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Non randomized Trials▪

▪ It is not always possible for Ethical ,Administrative or other reasons to resort to RCT in human beings eg

▪ Smoking and lung cancers & induction of cancers by viruses cannot be done in human beings

▪ Crude as compared to RCTs

▪ Useful when disease frequency low , long natural history- cancers

▪ Costs and logistics prohibitive

▪ Some preventive measures can only be applied to groups/ community

Dr. Meena Satia 55

Non-randomized controlled trials

▪ No randomization

▪ Low degree of comparability

▪ Higher chances of spurious results

▪ Control group is predetermined (without random assignment) to be comparable to the study group

▪ Also k/a “quasi experiments”

Dr. Meena Satia 56

57

Non Randomized Controlled Trials

▪ Rely on participants who -1) volunteer to join the study OR2) are geographically close to the study site OR3) conveniently turn up (at a clinic, school) while the

study is being conducted

▪ Because the study groups are opportunistically rather than randomly composed, study group characteristics (age, sex) may not be balanced before (at baseline) the study begins.

▪ Baseline differences between groups may confound the study’s results.

Dr. Meena Satia 57

Typical confounding variables include age, educational level, motivation, severity of illness, social structure, and income.

▪ study groups in non RCT may differ from one another at baseline, and the study’s findings will be compromised.

▪ They aim to create study groups that are as similar to one another as possible (equivalent) at baseline or before “treatment.”

▪ Among the strategies commonly used to ensure equivalence is one called matching.

Dr. Meena Satia 58

Natural Experiments

▪ Where RCT are not possible in human subjects the epdimiologist seeks to identify natural circumstances that mimic an experiment eg :

▪ Smokers/ Nonsmokers

▪ Migrants

▪ Religious or social groups

▪ Atomic bombing of Japan

▪ Famines/Earthquake 1981 Athens- who studied the effects of Acute stress-CVS mortality)

▪ John Snow :discovery that cholera is a water borne disease Dr. Meena Satia 59

Before and after comparison studies

▪ A Before and after comparison studies Without

▪ B Before and after comparison studies with control

▪ Introduction of new treatment- prior group acts as control eg:

▪ Use of seat belt- fall in accident deaths and injuries

▪ Victoria Vs other States with no statutory compulsion for seat belt.

Dr. Meena Satia 60

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11

Criteria

▪ Before – after incidence data must be available

▪ Introduction or manipulation of only one factor e.g. fluorine in water

▪ Diagnostic criteria constant

▪ Preventive measure over wide area

▪ Several trials needed, reduction in incidence must be large

Dr. Meena Satia 61 Dr. Meena Satia 62

Thank you..!!

Dr. Meena Satia 63

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63

Group Activity - Quantitative Research Methods

24-07-2019

1


Basic workshop onResearch Methodology,

Biostatistics & Principles of GCP





RCT EXAMPLES GROUP ACTIVITIES

DR. KAVITHA VIVEK / DR. ANANT PATIL 2

1

2


24-07-2019

2

Discuss in your group and prepare a research protocolDecide your population and how you would recruit participants in control and intervention groupWhat will be the independent and dependent variables and how will you collect data pertaining to themWhat are the likely biases and how will you overcome themDiscuss ethical, administrative and technical issues relevant to your study.


Steps1. Drawing up a protocol2. Selecting reference and experimental populations3. Randomization4. Manipulation or intervention5. Follow-up6. Assessment of outcome


3

4


24-07-2019

3

Group task


Group – 1Prepare a protocol to compare the effect of

Atorvastatin Vs Rosuvastatin in reducing cardiac mortality

Group – 2Draw up a protocol to see the efficacy of citrus fruits for the treatment of scurvy


Group 3 Comparison of intravenous tramadol and intravenous

clonidine for post-spinal shivering in patients undergoing lower limb

orthopaedic surgeries

Group 4 Evaluation of zinc

supplementation in acute diarrhoea in children

5

6


24-07-2019

4

Group 1

What would be the Aims & Objectives of the studyReduce the cardiac mortality

How would you do Randomisation-Study group would receive one drug and control group would receive the other

-How would you randomise the participants Coin flip methods Random No table Odd & even No


How would you do Manipulation or interventionBy using the drugs like Atorvastatin Vs Rosuvastatin


7

8


24-07-2019

5

Follow up of patients in the studyBy monitoring the BP and ECG & lipid profile of the patients in

the study What would be the final outcome of the studyTo check the no of patients dying due to MI


Group 2

Draw up a protocol to see the efficacy of citrus fruits for the treatment of scurvyQuestion to considerAims & objectives Response to the treatment How would you randomise One group of patients who were given lemons and oranges the other group would be given some placebo


9

10


24-07-2019

6

What would be the final outcome??Recovered most quickly, suggesting a beneficial effect of

citrus. ...


GROUP 3

Comparison of intravenous tramadol and intravenous clonidine for post spinal shivering in patients undergoing lower limb orthopaedic surgeries.


11

12


24-07-2019

7

What will the aims and objectives be?

Compare the efficacy and safety of intravenous tramadol and clonidine in controlling post spinal anaesthesia shivering in patients undergoing lower limb orthopaedic surgeries


What will the inclusion criteria be?Patients aged 18–60 years undergoing elective lower limb orthopaedic surgeries who developed Grade III and above level of shivering

Where will the patients be recruited from?Operation theatre

What will the exclusion criteria be?Patients with Grades I and II shivering, patients with cardiac disease (heart blocks, bradyarrhythmias, and left ventricular failure), renal disease, hepatic disease, psychiatric disorder, neuropathies, known history of substance or alcohol abuse


13

14


24-07-2019

8

How will you do randomization?Drawing sequential numbered, sealed envelopes containing a code based on computer generated number list

What will the evaluation parameters?Time taken to stop shivering

Response rate (good if shivering stopped within 15 min)

Recurrence rate (recurrence before the end of surgery)

Side effects such as hypotension, bradycardia, nausea, vomiting, dry mouth, respiratory depression, and deep sedation (Ramsay sedation scale >3).


Group 4

Evaluation of zinc supplementation in acute diarrhoea in children


15

16


24-07-2019

9

What will the aims and objectives be?To evaluate efficacy and safety of daily supplementation of zinc plus oral rehydration solution(ORS) in acute diarrhoea among children


What will the inclusion criteria be?Children aged 6 months to 59 months with acute diarrhoea

Where will the patients be recruited from?A tertiary hospital in Navi Mumbai

What will the exclusion criteria be?Child with severe malnutrition, intractable vomiting, renal failure, respiratory distress, altered sensorium or any such comorbid condition that precludes the use of oral rehydration solution(ORS), severe dehydration (as per standard national guidelines for diarrheal management) or inability to drink


17

18


24-07-2019

10

Intervention: Group A: ORS plus zinc; Group B: ORS plus placebo

How will you do randomization?A computer based random number generator with randomization schedules in permuted blocks

What will the evaluation parameters?Duration of diarrhoea from the time of onset

Number and proportion of patients with diarrhoea >4 days

Mean length of hospital stay

Severity of diarrhoea: use of unscheduled IV fluids, weight loss at discharge

Mortality rate

Adverse events



THANK YOU

19

20

Research Methodology: D Y Patil School of Medicine

22 July 2019

Dr. Deepak Langade / Dr. Vidita Morepatil 1

Good Clinical Practices An Introduction to the ICH-GCP GuidelinesDR. DEEPAK LANGADEMB, MD, PGDASS (APPLIED STATISTICS)

What is GCP?

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provide assurance that the data and the reported results are credible, accurate and that the rights, integrity and confidentiality of trial subjects are protected.

3 Good Clinical Practices

Part of the International Conference on Harmonization (ICH)

ICH-GCP E6 (R2)

Based on the Declaration of HelsinkiAssures protection of human subjects

4

How did it evolve?

The need to harmonizePublic disasters, serious fraud and abuse of human rights.Trials of War criminals-Nuremberg code 1949Thalidomide- Declaration of Helsinki 1964Belmont report 1978 (Ethical Principles and guidelines for the protection of human subjects of research)-Tuskegee syphilis study

5 Evolution

Declaration of Helsinki, 1964 → 2001ICH GCP guidelines, 1996Ethical Guidelines for Biomedical Research in Human Subjects (ICMR), 2000GCP Guidelines, CDSCO, New Delhi, 2001

6

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22 July 2019


What is GCP ? 7

Assures unified, high standards for designing, conducting, recording and reporting trials

GCP

Why GCP?Protect the rights and safety of subjects involved in trialsTrials are based on good science, are well designed and properly analyzedTrial procedures are properly undertaken and documentedAssures integrity of data submitted to regulatory authoritiesPreserves a record of the trial – Source Document

What if GCP is not followed?

Subjects who take part may be at riskData collected may be unreliableApproval of dangerous and ineffective drugsFailure to obtain approval for useful drugsCostly litigation if patients are harmedInvestigator disqualification

9 Scope of GCP

Applies to clinical data intended to be submitted to regulatory authorities

Also applies to clinical interventions and observational studies

10

Stakeholders

CRO

Regulatory Authorities

IRB/IECInvestigator

Investigator Team

11 Declaration of Helsinki

Adapted from the Nuremberg Code by The World Medical Association to address the needs of the biomedical communityFirst published in 1964, revised five time most recently in 2001Lists 31 principlesIs the international standard for the conduct of clinical research

12

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22 July 2019


Key Points: Declaration of Helsinki

Interests of the subjects must always prevail

Protocol must be reviewed by independent committee

Non-therapeutic research

13

13Principles of ICH-GCP

Principles of ICH GCP

1. Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirements.

15 Principles of ICH GCP Continued

2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject & society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

16

Principles of ICH GCP Continued

3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science & society.


4. The available non-clinical & clinical information on an investigational product should be adequate to support the proposed clinical trial.

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15 16

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22 July 2019



5. Clinical trials should be scientifically sound, and describe in a clear, detailed protocol.


6. A trial should be conducted in compliance with the protocol that has received prior IRB (or IEC) approval.

20


7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.


8. Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective tasks.

22


9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.


10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.

24

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21 22

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22 July 2019



11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory compliance.


12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.

26


13. Systems with procedures that assure the quality of every aspects of the trial should be implemented.

27

Areas addressed in GCP

Areas Addressed in the GCP Guidelines

IRB/ECInvestigator ResponsibilitiesInvestigator’s BrochureClinical Trial ProtocolSponsor ResponsibilitiesEssential Documents

29

IEC / IRB

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22 July 2019


IRB/IEC Responsibilities

Should safeguard the rights, safety & well being of all trial subjects.Should obtains following Documents:

Protocol & their amendments, Patient Information sheet & consent form, subject recruitment procedures (e.g. advertisements), Investigator's Brochure (IB), available safety information, Payments and compensation available to subjects, Investigator’s current CV and/or other documentation evidencing qualifications, Any other documents that the IRB/IEC may need to fulfil its responsibilities

31 IRB/IEC Responsibilities

Should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at least once per year. Review Protocol/ ICD/ recruitment procedures/ IB/paymentsContinuing review for Ongoing Progress/Adverse events

32

IRB/IEC Composition

At least 5 membersAt least one non scientific memberAt least one independent memberMaintain list of members and qualificationsOnly independent members to voteQuorum to be present

33 Procedures

The IRB/IEC should establish, document in writing, and follow its procedures, which should include:

CompositionMeeting Scheduling & conductSpecify that trial starts only after IRB reviewSpecify regarding changes in protocolSpecify prompt reporting of adverse events

34

IRB/IEC Records

The IRB/IEC should retain all relevant records for a period of at least 3 years after completion of the trial and make them available upon request from the regulatory authority(ies). The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its written procedures and membership lists.

35 IRB/IEC Summary

All studies must be approved prior to recruiting participants

IRB must review all documents given to participants

Composition of the IRB

Reporting AEs and Deviations from protocol to the IRB

Maintenance of Records

36

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33 34

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22 July 2019


Investigator Responsibilities


Qualifications & AgreementsUp to date CVCompliance with GCPPermission of monitoring by sponsor & regulatory authoritiesMaintenance of a list of qualified personnel who are delegated study responsibilities

38


Adequate ResourcesRecruitmentTimeQualified StaffFacilitiesTraining

39 Investigator Responsibilities

Medical CareA qualified MD (or dentist) responsible for trial-related medical decisionsProvide adequate medical care for AEs or other significant medical conditionInform PCP (Primary Care Physician) about participation in trialMake a reasonable effort to ascertain why participant withdrawals from study

40


Communication with IRBWritten & dated approval prior to initiation of trialProvide IRB with copy of Investigator BrochureProvide IRB with all documents subject to it’s review (amendments, consent form if changed, recruitment material, medical record release forms, etc.)


Compliance with ProtocolInvestigator should sign off on protocolInvestigator should not implement deviations from protocolIf deviations occur, they should be documented and reported at once to the sponsor, the IRB and other regulatory authorities

42

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22 July 2019



Investigational ProductAccountabilityStorageUseMaintenance of records of product delivery, inventory, use by subject, product returned to sponsor & any unused product

Dates, quantities, serial numbers, expiration date, unique code


Informed ConsentReviewed & approved by IRB (all versions)No coercion or unduly influenceNo language of a waiver of legal rightsFully inform participant (or legally authorized representative) of all aspects of the trialWritten in lay languageProvide ample time to review & ask questions

44


Informed Consent Continued…Signed & dated by participant, the legally authorized representative, person administering consent, and a witness if applicableAll contents of an informed consentParticipant should be given a copy


Records & ReportsAccuracy, completeness, legibility & timeliness of data reportedCRF consistent with source documentationChanges to CRF should be dated, initialed & explainedMaintain trial documentsRetention of trial documentsFinancial aspects noted in contractMake available all records for monitor, auditor, IRB, or other regulatory authority

46


Progress ReportsWritten summary of trial status to the IRBWritten reports to the sponsor or regulatory authority of any changes affecting the trial

Safety MonitoringSAEs should be reported immediatelyAEs should be reported according to sponsor guidelinesSupply sponsor & IRB with requested materials on participant deaths


Premature Termination or Suspension

Promptly inform trial subjectsAssure appropriate therapy & follow-upInform sponsor, regulatory authorities & IRB

Final ReportingInform IRB of study completion & a summary of the trial’s outcomeProvide sponsor & regulatory authorities with all required reports

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22 July 2019


IB

Investigator’s Brochure

Defined as a compilation of the clinical and non-clinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects.

50

Study Protocol

Clinical Trial Protocol

General InformationBackground InformationTrial Objectives & PurposeTrial DesignSelection & Withdrawal of ParticipantsTreatment of SubjectsAssessment of EfficacyAssessment of Safety

52

Clinical Trial Protocol Continued

StatisticsDirect Access to Source DataQuality Assurance & Quality ControlEthicsData Handling & RecordkeepingFinancing & InsurancePublication PolicySupplements

53

Sponsor Responsibilities

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22 July 2019


Sponsor Responsibilities

Quality Assurance & Quality ControlProvide written SOPsSecures agreement between all partiesData handling

Contract Research Organization (CRO)Hired by the sponsor to implement trial-related duties

Medical ExpertiseDesignated medical personnel to advise on trial-related medical questions and problems

55 Sponsor Responsibilities contd…

Trial DesignDesigns CRFsPlanning analyses

Trial Management, Data Handling, Recordkeeping, & Independent Data Monitoring Committee (DMC)

Qualified personnel to supervise overall conduct of the studyDMC assesses the progress of the clinical trialMaintain SOPs for electronic data processingInform Investigator of guidelines for record retention

56

Sponsor Responsibilities contd…

Investigator SelectionQualifications by training and experience

Allocation of Duties & FunctionsSponsor should define, establish and allocate all trial-related duties and functions

Compensation Insure investigator/institution against claims arising from the trialCoverage for the cost of treatmentCompensation for the subject

Financing


Notification/Submission to Regulatory Authorities

Submission of required applications to authorities for review, acceptance, and/or permission to begin trial

Confirmation of Review by IRBShould obtain name & address of institutional IRB, statement that they comply with GCPs and applicable laws and regulationsDocumentation of approval

Information on Investigational ProductsSufficient safety & efficacy data from non-clinical studies are available to support human exposureUpdate Investigator’s Brochure as new info becomes available

58


Manufacturing, Packaging, Labeling, & Coding Investigational Products

Manufactured in accordance with GMPsCoded and labeled in a manner that protects blindingPI should be informed of storage informationCoding system for rapid identification of product

Supplying & Handling Investigational ProductsTimely delivery of productMaintenance of records (shipment, receipt, return)System for disposition of unused product


Record AccessSponsor should have access to records

Safety InformationOngoing safety evaluation

Adverse Drug Reaction ReportingReport all adverse drug reactions that are serious and unexpectedSubmit all safety updates and DSM reports

MonitoringRights and well being of human subjects are protectedTrial data are accurate and complete

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22 July 2019



AuditingEvaluate trial conduct and compliance with protocol, SOPs, GCPs and other regulatory requirements

Non-compliancePremature Termination or Suspension

Promptly notify investigators/institution with reason for the termination

Clinical Trial/Study ReportsMulticenter Trials

Communication is facilitated between all investigators

61

Documents

Essential Documents

Before trial

commencement

During conduct

of trial

After completion or termination of

trial

63 Before Commencement

Document Investigator’s Files

Sponsor’sFiles

Investigator’s Brochure

X X

Protocol, Amendments & Consent Form

X X

Recruitment Material

X X

64


Sponsor’sFiles

Financial Docs X X

Contracts X X

IRB Correspondence

X X

IRB Composition X X (where required)

CV/Resume of investigator

X X

65Document Investigator’s

FilesSponsor’s

Files

Normal Values/ Ranges for tests

X X

Lab accreditation X(where required)

X

Medical Certification

X(where required)

X

Sample of label on study drug

X

Instructions for handling drug

X X

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22 July 2019



Sponsor’sFiles

Shipping Records

X X

Certificate of analysis of drug

X

Decoding procedures

X X

Master randomization list

X

Pretrial/Trial initiation monitoring report

X X

67 During the Trial


Sponsor’sFiles

Updates to Investigator’s Brochure

X X

Revisions to Regulatory Docs

X X

Dated approvals from the IRB

X X

Updates to normal values

X X

68


Sponsor’sFiles

Updates to medical/ lab/ technical procedures/tests

X X

Drug shipment information

X X

Certificate of analysis for new batches of drug

X

Monitoring visit reports

X X

Relevant communications

X X

69 Document Investigator’s Files

Sponsor’sFiles

Signed informed consent forms

X

Source documents

X

Signed, dated & complete CRFs

X(Copy)

X(Original)

Documentation of CRF corrections

X(Copy)

X (Original)

Notification of SAEs & related reports

X X

70


Sponsor’sFiles

Notification by sponsor of safety information

X X

Interim or annual reports to IRB

X X(where required)

Subject screening log

X X(where required)

Subject identification code list

X

Subject enrollment log

X

71 Document Investigator’s Files

Sponsor’sFiles

Investigations product accountability log at site

X X

Signature sheet X X

Record of retained body fluids/tissue samples

X X

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Closure/Termination of Trial


Sponsor’sFiles

Investigational product accountability log at site

X X

Documentation of product destruction

X(if at site)

X

73Document Investigator’s

FilesSponsor’s

FilesCompleted subject ID code list

X

Audit certificate X

Close out monitoring report

X X

Treatment allocation & decoding documentation

X

Final report to IRB X

Clinical Study Report

X X

74

Document Storage

Storage of Essential Documents

OHRP Rule: 3 years following study completionNIH Rule: 3 years from date of submission of final expenditure report FDA Rule: 2 options

2 years following marketing of the drug or,2 years after IND application is withdrawn if drug was not marketed

76

Storage of Essential Documents

Sponsor Rule: refer to study protocol

Privacy Rule: Authorizations must be kept for 6 years

Follow rule with the longest time limit!

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Audits

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A systematic and independent examination of trial related activities and documents to determine if these activities were:

RecordedAnalyzed & Accurately Reported

According To:ProtocolSOP’sGCP &Regulatory Requirements

What is an Audit? 79 What does an Site Audit involve?

Introductory Meeting to explain the aims and conduct of the audit Interviews with Study Personnel assessing study conduct Review of:

Facilities - Tour of Lab, Housing Area, Pharmacy etcinvestigator documentation on site and at CRORaw Data such as consent formssource documents including patient notesdrug accountabilitytranscription into CRF/EDC

Close-out meeting to discuss the observations/findings, and also any outstanding questionsFollow-up to review the implementation of the proposed Corrective and Preventive Action

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Latest addendum

ICH-GCP E6 (R2) Step-4 version dt. 09 Nov. 2016

GlossaryApplies to all records (paper or electronic)Investigators/SitesSponsor – Quality management & Risk managementMore active monitoring of CRO’sMonitoring Non-compliance

81 Key changes in new version of E6

Vendors and contract staff (whether used by Investigational Sites or Sponsors) must be qualified and managed to ensure the quality of provided work. The delegation and approval of tasks should be put in writing.Source data should be “attributable, legible, contemporaneous, original, accurate, and complete,” with any changes to the original entry documented (audit trail).Trial Master Files should be searchable and retrievable.Electronic systems should be validated, backed up and safeguarded.A risk-based approach to quality management should be implemented and maintained during the entire life cycle of the clinical trial.Development of a risk-based approach to monitoring should be implemented and the rationale for monitoring plan / monitoring approach documented.CAPA methodology should be used for any identified noncompliance.

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e is one IMPORTANT unwritten Rule in Clinical Trial Study,

DOCUMENT IT DOWN ON PAPER…!

If it is not documented, it did not happen!

Close Out Comment: 83 Differences Between Indian GCP & ICH GCP

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Investigator Qualification

IICH – GCP: (4.1.1)

The investigator(s) should be qualified byeducation, training, experience to assumeresponsibility for the proper conduct of the trial,should meet all the qualifications specified by theapplicable regulatory requirement(s)

Indian GCP: (3.3.1)

The investigator should be qualified by education,training and experience to assume responsibilityfor the proper conduct of the study and shouldhave qualifications prescribed by the MedicalCouncil of India (MCI).

85 Investigator & Sponsor SOP’s

ICH – GCP:

Investigator to comply with the protocol (4.5)and leaves the task of monitoring compliance toSOPs to monitors and auditors (5.19.1).

Indian GCP: (3.1.3)

The Sponsor should establish detailed StandardOperating Procedures (SOP’s). The Sponsor andthe Investigator(s) should sign a copy of theProtocol and the SOPs or an alternativedocument to confirm their agreement.

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PI responsibility for data analysis

ICH – GCP: (4.10)

when the trial is completed, the investigator has toprovide the Independent Ethics Committee (IEC)with a summary of the outcome of trial.

Indian GCP: (3.3.8)

The completion of the study should be informed bythe investigator to the institution, the sponsor andthe ethics committee. The investigator should signand forward the data (CRFs, results andinterpretations, analyses and reports, of the studyfrom his / her centre to the sponsor and the ethicscommittee.

87 Essenttial Documents

ICH – GCP: (8.2)Investigator/ SponsorInstitution

Indian GCP: (APPENDIX V)Investigator / InstituteSponsorCROIEC

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Monitor Responsibilities

ICH – GCP: (5.18..4)Communicating deviations from the protocol,SOPs, GCP, and the applicable regulatoryrequirements to the investigator and takingappropriate action designed to preventrecurrence of the detected deviations.

Indian GCP: (3.2.2)The monitor should promptly inform thesponsor and the ethics committee in case anyunwarranted deviation from the protocol orany transgression of the principles embodiedin GCP is noted.

89 Drug Label

Indian GCP: (2.3.1.6)

In the section on protocol, it ismentioned that drug label shouldinclude name and contact numbers ofinvestigator and name of institution.

This is not a global practice.

This will lead to practical difficulties inglobal trials where the labels areuniform with minor changes made ifrequired by local laws and practice.

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DDocument Retention

ICH – GCP: (5.18.4)Essential documents should be retained untilat least 2 years after the approval of amarketing application in an ICH region.

Indian GCP: (4.9)Indian GCP mandates that the sponsor shouldmake arrangements for safe and securecustody of all study related documents andmaterial for a period of three years after thecompletion of the study or submission of thedata to the regulatory authority (ies)whichever is later.

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Thank You!QUESTIONS?

Resources

http://www.fda.gov/oc/gcp/guidance.htmhttp://www.clinicaltrials.gov/http://www.fda.gov/oc/ohrt/irbs/websites.htmlhttp://ohrp.osophs.dhhs.gov/http://privacyruleandresearch.nih.gov/

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Dr. Padmaja Samant

Introduction to qualitative methods • Basic terms in qualitative research • Sampling and data collection • Data Collection methods – Focus Groups,

Structured interview, etc. • Triangulation, Mixed Methods research • Data analysis and statistical methods, including

software for qualitative data analysis • Challenges Q

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Scientific research ….asks a question,• uses predetermined tools to answer them,• collects evidence & produces findings that were not determined in advance & •that are applicable beyond the immediate boundaries of the study

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• Additionally, seeks to understand a given problem or topic from the perspectives of the local population it involves.

• Effective in obtaining culturally specific information about their values, opinions, behaviors, and social mileau

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Effective in identifying intangible factors, such as social norms, socioeconomic status, gender roles, ethnicity, and religion, whose role in the research issue may not be readily apparent.

• help us to interpret and better understand the complex reality of a given situation and the implications of quantitative data.

• Typically data should not be generalized to other geographical areas or populations.

• In this sense, qualitative research differs from scientific research

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Quantitative research

• Researcher decides what to study;

• asks specific, narrow questions,

• collects quantifiable data from large number of participants;

• analyzes these numbers using statistics;

• and conducts the inquiry in an unbiased, objective manner.

• Postpositivism – singular reality; objective; deductive

Qualitative research

• Researcher relies on the views of participants;

• asks broad, general questions;

• collects data consisting largely of words (or text) from participants;

• describes and analyzes text for themes; and

• conducts the inquiry in a subjective, biased manner.

• Constructivism – multiple realities; biased; inductive

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Generally involves collecting numerical data that can be subjected to statistical analysis

• Data collection methods Performance Tests Personality Measures Questionnaires

( closed-ended or open-ended but transferred to quan data) Not flexible

involves listening to the participants’ narration and subjecting the data to analytic induction (e.g., finding common themes) •Exploratory in nature •Data collection methods InterviewsOpen-ended questionnairesObservations •Focus Groups•Flexible

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• Only a sample ( a subset) of a population is selected for any given study.

• Research objectives and the characteristics of the study population (size and diversity) determine which and how many people to select.

• most common sampling methods used in qualitative research:

purposive sampling, quota sampling, snowball sampling.

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Purposive sampling

Groups participants according to preselected criteria relevant to a particular research question (ie, HIV-positive women in Capital City). • Sample sizes, may or may not be fixed prior to data

collection, depend on the resources and time available, as well as the study objectives.

• Theoretical saturation (the point in data collection when new data no longer bring additional insights to the research questions).

• Purposive sampling is therefore most successful when data review and analysis are done in conjunction with data collection.

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Quota sampling

• we decide while designing the study how many people with which characteristics to include as participants.

• Characteristics might include age, place of residence, gender, class, profession, marital status, use of a particular contraceptive method, HIV status, etc.

• The criteria allow us to focus on people we think would be most likely to experience, know about, or have insights into the research topic.

• Using recruitment strategies appropriate to the location, culture, and study population –

find people who fit these criteria, until we meet the prescribed quotas.

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• In quota sampling, a population is first segmented into mutually exclusive segments. Then number is decided

• This second step makes the technique non-probability sampling. In quota sampling, there is nonrandom selection – The researcher may use accidental sampling

Quota sampling is useful when• Time is limited, • Tight budget• Sample frame not available • Quota sampling is the non probability version of

stratified sampling

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Snowballing • Also known as chain referral sampling – a type of

purposive sampling.• used to find and recruit hidden populations,

i.e. groups not easily accessible to researchers• Participants or informants with whom contact

has already been made; use their social networks to refer the researcher to other people who could potentially participate in or contribute to the study.

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• A recruitment strategy is a project-specific plan for identifying and enrolling people to participate in a research study.

The plan should specify criteria for • screening potential participants, • the location, and• the approach to be used.

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Determined by • the type and number of data collection activities in

the study and• by the characteristics of the study population. Typically flexible and can be modified if• new topics, research questions, or subpopulations

emerge as important to the study, • initial strategies do not result in the desired

number of recruits or method and / or the chosen population does not answer the research question

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• The criteria for selection can also be changed if certain data collection activities or subpopulations of people prove not to be useful in answering the research questions

• Proposed changes in the recruitment strategy must be submitted to the sponsoring organization, and some will require submission of a protocol amendment for approval by the ethics committees

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Data types Include• in-depth or unstructured interviews,• field notes, unstructured field diaries, personal

documents, • Photographs and so on. • initial stages -large mass of data

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The three most common qualitative methods, •participant observation, •In-depth interviews, and• focus groups. •Participant observation is appropriate for collecting data on naturally occurring behaviors in their usual contexts.•In-depth interviews are optimal for collecting data on individuals personal histories, perspectives, and experiences,particularly when sensitive topics are being explored.•Key informant interviews•Focus groups are effective in eliciting data on the cultural norms of a group and in generating broad overviews of issues of concern to the cultural groups or subgroups represented.

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• CAHPS: Consumer Assessment of Health Plan Study

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Researcher administered survey• The questions are read exactly as they appear on

the survey questionnaire. • Close-ended in the beginning though later open-

ended questions can also be included within a structured interview.

• Standardized order in which questions are asked of survey respondents. Q

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• The participant observer – investigator studies the life of a group by sharing in its activities

• an "insider" viewpoint and the information may be much more rich than that obtained through systematic observation.

• Bias and reactivity.• These difficulties are magnified in participant

observation. Events are interpreted through the single observer's eyes.

• Biases-- in taking extensive notes and writing down one's impressions; one's own views can come in to play.

• Going native --sympathy -> objectivity is lost. • Reactivity -- influencing what is being observed.

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• They are qualitative, in-depth interviews of 15 to 35 people selected for their first-hand knowledge about a topic .

• loosely structured, relying on a list of issues to be discussed. allow a free flow of ideas and information.

• Interviewers frame questions spontaneously, probe for information and takes notes, which are elaborated on later.

When Are Key Informant Interviews Appropriate? • This method is useful in all phases of development

activities— identification, planning, implementation, and evaluation

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• When qualitative, descriptive information is sufficient for decision-making.

• When there is a need to understand motivation, behavior, and perspectives of our customers and partners..

• When a main purpose is to generate recommendations. Key informants can help formulate recommendations that can improve a program’s performance.

• When quantitative data collected through other methods need to be interpreted.

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• An essential element of testing reliability nad validity of survey instruments to know whether or not the items or response options are understood or not and interpreted consistently correctly as desired .

• Feed back interview • Think aloud • Probing why

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• formal informed consent is necessary for all qualitative research methods ( except participant observation) regardless of the sampling method used to identify potential participants and the strategies used to recruit them.

• Whether this informed consent is oral or written depends on a number of project-specific factors and ultimately upon approval by the ethics committee.

• Individual informed consent may be written or oral.• During recruitment, obtaining informed consent for qualitative

research involves clearly explaining the project to potential study participants.

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• Gatekeeping influences the research endeavor in a number of ways: by limiting conditions of entry, by defining the problem area of study, by limiting access to data and respondents, by restricting the scope of analysis, and by retaining prerogatives with respect to publication

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A mixed methods research design is a procedure for collecting, analyzing, and “mixing” both quantitative and qualitative research and methods in a single study to understand a research problem.

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Triangulation• Triangulation. : use of more than one approach to the

investigation of a research question in order to enhance confidence in the ensuing findings.

• Since social research founded on the use of a single research method may suffer from limitations associated with that method or from the specific application of it, triangulation offers the prospect of enhanced confidence.

• Triangulation is one of the several rationales for MULTIMETHOD RESEARCH. The term derives from surveying, where it refers to the use of a series of triangles to map out an area.

• triangulation becomes a device for enhancing the credibility and persuasiveness of a research account

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• The two sets of findings may be inconsistent, but, such an occurrence underlines the problem of relying on just one measure or method.

• Equally, the failure for two sets of results to converge may prompt new lines of inquiry relating to either the methods concerned or the substantive area involved.

• Webb et al.

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• Denzin (1970) distinguished four forms of triangulation: • Data triangulation : gathering data through several

sampling strategies, so that slices of data at different times and social situations, as well as on a variety of people, are gathered.

• Investigator triangulation: use of more than one researcher in the field to gather and interpret data.

• Theoretical triangulation : use of more than one theoretical position in interpreting data.

• Methodological triangulation: use of more than one method for gathering data.

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• Analysis also involves breaking down data into bits and then beating the bits together, so that the data is resolved into its components, and its characteristic elements are revealed. In this sense you can say that we split data processing into two activities, namely,

• Checking and converting the data Generating metadata

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The focus on text—on qualitative data rather than on numbers—is the most important feature of qualitative analysis. The text is most often •transcripts of interviews or notes from participant observation sessions,• pictures or other images that the researcher examines.

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1. Analysis of a text as a way to understand what participants reallythought, felt, or did in some situation or at some point in time. The text becomes a way to get behind the numbers that are recorded in a quantitative analysis to see the richness of real social experience.

2. A hermeneutic perspective on texts—that is, a perspective that views a text as an interpretation that can never

be judged true or false. The text is only one possible interpretation among many.

• From a hermeneutic perspective, a researcher is constructing a reality with his or her interpretations of a text provided by the

subjects of research; other researchers, with different backgrounds, could come to markedly different conclusions.

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Qualitative data analysis tends to be inductive—•The analyst identifies important categories in the data, as well as patterns and relationships, through a process of discovery.• There are often no predefined measures or hypotheses

•Emic focus - Representing a setting with the participantsterms and from their viewpoint.•Etic focus - Representing a setting with the researchersterms and from their viewpoint. Q

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• focus on the interrelated aspects of the setting, group, or person under investigation—

• the case— rather than breaking the whole into separate parts.

• The whole is always understood to be greater than the sum of its parts, and so the social context of events, thoughts, and actions becomes essential for interpretation. Q

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An iterative and reflexive process that begins as data are being collected rather than after data collection has ceased ( the meaning of the text and how it might relate to other issues). This process of reading through the data and interpreting them continues throughout the project. The analyst adjusts the data collection process itself when it begins to appear that additional concepts need to be investigated or new relationships explored. This process is termed progressive focusingIf early questions are not working, if new issues become apparent, the design is changed.

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1. Documentation of the data and the process of data collection2. Organization/categorization of the data into concepts3. Connection of the data to show how one concept may

influence another4. Corroboration/legitimization, by evaluating alternative

explanations, disconfirming evidence, and searching for negative cases

5. Representing the account (reporting the findings)• The data for a qualitative study most often are notes jotted

down in the field or during an interview—from which the original comments, observations, and feelings are reconstructed—or text transcribed from audiotapes.

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The various contacts, interviews, written documents, and whatever it is that preserves a record of what happened all need to be saved and listed.

• Documentation is critical to qualitative research for several reasons:

• It is essential for keeping track of what will be a rapidly growing volume of notes, tapes, and documents;

• it provides a way of developing and outlining the analytic process; and it encourages ongoing conceptualizing and

strategizing about the text.

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• Identifying and refining important concepts is a key part of the iterative process of qualitative research.

• Sometimes, conceptualizing begins with a simple observation that is interpreted directly, pulled apart,and then put back together more meaningfully.

• The focus in this conceptualization is to provide a detailed description of what was observed and a sense of why that was important.

• More often, analytic insights are tested against new observations, the initial statement of problems and

• concepts is refined, the researcher then collects more data, interacts with the data again, and the process continues.

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• Matrix : A form on which can be recorded systematically particular features of multiple cases or instances that a qualitative data analyst needs to examine.

• The matrix condenses data into simple categories, reflects further analysis of the data to identify degree of support, and

• provides a multidimensional summary that will facilitate subsequent, more intensive analysis. Direct quotes still impart some of the flavor of the original text.

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• Examining Relationships and Displaying Data• Examining relationships is the centerpiece of the analytic

process,• It allows the researcher to move from simple description

of the people and settings to explanations of why things happened as they did with those people in that setting.

• The process of examining relationships can be captured in a matrix.

• Matrix shows how different concepts are connected, or perhaps what causes are linked with what effects. Q

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• Need for authenticity ; but no set standards• Individual items of information can be assessed in terms of at

least three criteria (Becker 1958):1. How credible was the informant? 2. Were statements made in response to the researcher s

questions, or were they spontaneous? 3. How does the presence or absence of the researcher or the

researcher s informant influence the actions and statements of other group members?

• Reactivity to being observed can never be ruled out as a possible explanation for some directly observed social phenomenon.

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• Comparing conclusions from a qualitative research project to those other researchers obtained while conducting similar projects can also increase confidence in their authenticity.

• Confidence in the conclusions from a field research is strengthened by an honest and informative accountabout

• how the researcher interacted with subjects in the field, • what problems he or she encountered, • and how these problems were or were not resolved.

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• The first activity comprises a) checking out the completeness and quality of data,

• the relationship between data - interviews, field notes, audio visual recordings etc and

• Anonymisationb) converting data or transferring data to a format that is appropriate for dissemination. • checking out the completeness and quality (in terms of

its physical condition, readability audibility, re- usability)• researcher needs to bring to light any problems relating

to confidentiality, anonymity, reusing, suitability for digitisation, etc.

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• Anonymisation. - confidentiality of the respondent or any other person or entity.

• The level of anonymisation used for a dataset depends on the nature of the study

• Sometimes, it is not easy to disguise the identity of the subjects of research without bringing about an unacceptable distortion to the data. Then, the particular data can hardly be reused for any purpose.

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• The second processing activity of generating metadata

• Contextual information that a researcher obtains during processing, for example

• One may create lists of data giving biographical inputs that would make it easier to identify transcripts

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Preparing i) a data list andii) a catalogue of records. iii) a user guide

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• description, interpretation, explanation, understanding, and possibly, prediction.

• Description provides the basis for analysis, which then lays the base for further description.

• Breaking down our data in order to draw concepts from it, which we then use to classify the data.

• We draw connections between different concepts and these connections form the basis of further description. Ian Dey (1993) presents the following diagram, which succinctly represents the circular processes involved

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Comprehensive descriptions of the phenomenon under study. • “Thin description", merely states facts, •thick description includes information abouta ) the context of an act, social, cultural and historical backdrop b) intentions and meaning attributed by the actor to the action subjective meanings imbued by actors to the way of actionc) the process in which the action is embedded.ie consequences of the action Geertz (1973)

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• Ethnography, netnography ethnomethodology; • qualitative comparative analysis;• narrative analysis;• conversation analysis; • case-oriented understanding; and • grounded theory

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• Describing and classifying serve to produce an account of analysis.

• The concepts must be connected together to look for associations between different variables and to see the patterns within the data, so that we can discern regularities and also variation and exceptions.

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• Ethnography The study of a culture or cultures that some group of people shares, using participant observation over an extended period of time.

• Netnography / cyberethnography / virtual ethnography is the use of ethnographic methods to study online communities.

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• The ways in which confidentiality might be breached should be carefully considered before data collection begins and explicit strategies be put in place for protection.

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• the objectivity of a piece of qualitative research is evaluated in terms of the reliability and validity of its observations.

• Reliability - extent to which a measurement procedure yields the same answer however and whenever it is carried out.

• Validity is the extent to which it gives the correct answer.

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The enhancement model • generating hypothesis to be tested by quantitative research,• helping to construct more sophisticated measures of social

phenomena and • explaining unexpected research from quantitative research. The Epistemological Model :• researching parts other research approaches can't reach,• increasing understanding by adding conceptual and

theoretical depth to knowledge, • shifting the balance of power between researchers and

researched and• challenging traditional epidemiological ways of "knowing" the

social world.

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• Sociologists need to establish the usefulness of the data they gather to ensure answers of the following questions.

• How accurate a profile of social life one is able to get • Whether the conclusions reached are representative

enough to be applicable to everyone• Is it possible to repeat the research if others want to

carry it out • and will there be similar results if they did? Q

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• following ideas figure in making data reliable. • consistencye: It is important to obtain consistently similar

responses to the same questions in similar circumstances.

• precision: One has to know how systematic is the form of data that is based on asking people questions about things that they know little about

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Use of open-ended questions and probing –gives participants the opportunity to respond in their own words, rather than forcing them to choose from fixed responses, as quantitative methods do.

Open-ended questions have the ability to evoke responses that are:

• meaningful and culturally salient to the participant

• unanticipated by the researcher• rich and explanatory in nature

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Limitations of Qualitative Research• quality is heavily dependent on the individual skills • easily influenced by personal biases and idiosyncrasies. • Rigor is more difficult to maintain, assess, and demonstrate.• The volume of data makes analysis and interpretation time

consuming.• FGI : Well structured guide, flexible and skilled moderator

required• Not as well understood, accepted as quantitative research

within the scientific community• The researcher's presence during data gathering, often

unavoidable, can affect the subjects' responses. • Issues of anonymity and confidentiality can present problems

when presenting findings• Findings can be more difficult to characterize in a visual way.

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• http://www.referenceworld.com/sage/socialscience/triangulation.pdf

• Claire Anderson Presenting and Evaluating Qualitative Research.Am J Pharm Educ. 2010;74(8):1-7.

• http://www.staff.u-szeged.hu/~magnes/downloads/greetz.pdf

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ETHICS IN MEDICAL RESEARCH

Padmaja Samant: Ethics in Research 2

Session ObjectivesHistoryDefine GCPBrief background to evolution of GCPLandmarksICH GCP Informed ConsentPublication ethics: authorship and plagiarism


Definition: Good Clinical Practices

(GCP) is an international ethical & scientific quality standard for design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials or studies that involve human subjects.

So that …….Positive (or negative) data can lead to a recommendation to use (or not to use) a treatment.

Objectives of GCP

To protect the rights, safety and welfare of humans participating in research consistent with the principles that have their origin in the Declaration of HelsinkiTo assure the quality, reliability and integrity

of collected dataTo provide standards and guidelines for the

conduct of clinical research

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Evolution of GCP

Nuremberg Code, 1947Declaration of Helsinki, 1964 → 2001ICH GCP guidelines, 1996Ethical Guidelines for Biomedical Research in Human Subjects (ICMR), 2000GCP Guidelines, CDSCO, New Delhi, 2001

Background

The Nuremberg code 1947 In May1946 Dr. Leo Alexander had submitted to the Counsel for War Crimes six points defining legitimate medical research.The trial verdict adopted these points and added an extra four. The ten points constituted the "Nuremberg Code".

The Nuremberg Code and the Declaration of Helsinki are the basis for the regulations issued by the US Dept of health & Human Services governing federally funded human subjects research in the United states.

Voluntary ConsentThe experiment should be such as to yield fruitful results for the good of society.and based on the results ofanimal experimentationAvoid all unnecessary suffering and injury.No experiment should be conducted where there is a prior reason to believe that death or disablity will occur.The degree of risk to be taken should never exceed benefit.Proper preparations should be made and adequate.The experiment should be conducted only by scientifically qualified persons. human subject should be free to withdrawscientist prepared to terminate the experiment at any stage, if likely to result in injury, disability or death .

Declaration of Helsinki

Declaration of Helsinki

Founded in 1947, a central objective of the WMA has been to establish and promote the highest possible standards of ethical behaviour and care by physicians. In pursuit of this goal, it adopted global policy statements on a range of ethical issues related to medical professionalism, patient care, research on human subjects and public health

Declaration of Helsinki (1964)

Well-being of subject takes precedence Respect for persons Protection of subjects health and rights

Special protection for vulnerable populations

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Almost every national scientific community hasacknowledged DH as cornerstone of Ethics inHuman Biomedical ResearchIn Israel, Ethics committees are called HelsinkiCommitteesEven though the Declaration of Helsinki is theresponsibility of the World Medical Association,the document should be considered the propertyof all humanity.“National Forum on the Declaration of Helsinki: Brazilian Perspective”

2008

The Belmont Report 1979

The Belmont Report : written by the National Commission for the Protection of Human Services of Biomedical and Behavioral Research.Prompted in part by problems arising from the

Tuskegee Syphilis study(1932–1972) and based on the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974–1978) work

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS

FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE

Background

Need for safe and efficient products for various health problems Drug development is expensive and time consumingNeed for efficient quality systems Global drug marketExistence of national laws and regulations for drug development

ICH - Objective

To provide a unified standard for the EU, Japan & the US to facilitate the mutual acceptance of clinical data by regulatory authorities in these jurisdictionsThe guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).

Should be followed when generating data that are intended to be submitted to regulatory authorities.

ICH GCP: 1996Goals:

Harmonize technical procedures and standards;improve quality of research and products

To provide a unified standard to facilitate the mutual acceptance of clinical data by the regulatory authorities Remove redundancy /duplication in development and review process

In 1997, the FDA endorsed the GCP Guidelines developed by ICH. ICH guidelines have been adopted into law in several countries, but used as guidance for the FDA in the form of GCP

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13 Principles of ICH GCP

Ethics: 1. Ethical conduct of clinical trials 2. Benefits justify risks 3. Rights, safety, and well-being of subjects prevail Protocol and science: 4. Nonclinical and clinical information supports the

trial 5. Compliance with a scientifically sound, detailed

protocol

Responsibilities: 6. IRB/IEC approval prior to initiation 7. Medical care/decisions by qualified physician 8. Each individual is qualified (education,

training, experience) to perform his/her tasksInformed Consent: 9. Freely given from every subject prior to

participation

Data quality and integrity: 10. Accurate reporting, interpretation, and

verification 11. Protects confidentiality of records

Investigational Products 12. Conform to GMP’s and used per protocol Quality Control/Quality Assurance 13. Systems with procedures to ensure quality of

every aspect of the trial

GCP - A Shared Responsibility

Sponsor

Investigator

Regulatory Authority

Ethics Committee

What is an Ethics Committee?• An independent review board or committee comprising of medical

/ scientific and non-medical /non-scientific members, whoseresponsibility is to verify the protection of the rights, safety andwell-being of human subjects involved in a study.

• The independent review provides publicreassurance by objectively, independently and impartially reviewing

and approving the Protocol , the suitability of the investigator(s),facilities, methods and material to be used for obtaining anddocumenting Informed Consent of the study subjects andadequacy of confidentiality safeguards.


Ethics Committee: Composition as perIndian GCP

Heterogeneous group of at least 5-7 members (up to 15)

Qualified

Experienced in their professional field

Proficient to evaluate both scientific & ethical

aspects (familiar with GCP)

Quorum - 5 members should be present for the

meeting

Multidisciplinary, Independent, Competent


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Ethics Committee: Composition –Schedule Y

Chairperson : Outsider

Member – Secretary Quorum- At least 1 member

basic medical scientistclinicianlegal expert social scientist/philosopher/priestlay person


All proposals on

biomedical research involving human subjects

must be cleared

by an

Ethics Committee

Ethics Committee: Role


EC: Type of Studiesprospective / retrospectivepatients / volunteersmodern / alternativedrugs / procedures in physical medicineinterventional/ observational


Types of studies exempt for Ethics Committee review….

• In vitro drug studies ,Cell lines • Research on educational practices effectiveness of or

comparison among instructional techniques, Curricula, classroom management

Exceptionsa) If direct/ indirect identification involvedb) Direct access poses risk of civil/criminal/financial liability or

psychosocial harm in case of disclosure of information outside research


EC: Role & Responsibility

Before the study begins

During the study

After the study



Before the study begins:

Submission of research proposal

Review of proposal

Decision making process

Issuing an approval


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Documents To Be Submitted for ReviewICH-GCP 3.1.2

Trial protocol

Informed consent documents

Subject recruitment procedures (advertisements)

Investigator brochure

Investigator s curriculum vitae & documentation evidencing qualifications and expertise


Submissions to EC

Information: patient payment/ compensation

Regulatory clearances

Details of sponsors & fund allocation

Any other documents specifically requested by

EC that would add to protection of the rights,

safety and/or well being of the subjects.


Reviewing Study DocumentsSuitability of protocol

Background & Justification for study

Objective of the study

Study design and methodology

Risks & benefits to the trial subject

Subject safety measures

Confidentiality of subjects and data

Regulatory aspects

Informed Consent Document


Reviewing Study Documents

ICH GCP: 3.1.3

Competency of the investigator

Qualifications

Experience

Support staff

Available facility

Emergency services


Suitability of the ICF & Pt. Information sheetInformed Consent Form : Contents

Trial involves research PurposeTreatment options in trial, randomisationTrial procedures & durationSubject’s responsibilities / compensationRisk Vs. benefitsReasonably expected benefits

Contact information RIGHT TO WITHDRAW


• Review both amount, schedule and mode of payment

• Payment must be prorated (ICH GCP3.1.8)

• Method of how it is prorated (ICH GCP3.1.9)

27/02/11 ,Shatabdi EC-CON 2011, Nashik

Suitability of the ICF & Pt. Information sheet


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EC : Decision makingTo review within a reasonable time

Projects circulated to members

Comments compiled by member secretary

Decisions taken in formal meetings

by consensus

Documents its views in writing

Approval (schedule Y format)

Modifications required prior to approval

DisapprovalPadmaja Samant: Ethics in Research 37

During the study:

Review of amendments ( Protocol, ICD)

Review of Serious Adverse Events

Protocol deviations

Progress (study status)

ICH GCP 3.1.4

Conduct continuing review for each project atleast

once a year

After the study: Study Report



How an EC functions?

• Documentation requirements• Review procedures• Decision making processes

According to written Standard Operating Procedures


EC procedures• No subject enrolled prior to approval of the study• Amendment must be approved by EC except when necessary

to eliminate immediate hazard or change is administrative• Specify the investigator to promptly report

deviation/ change in protocolchange increases the riskserious and unexpected ADRnew information that may adversely

affect the safetyEC records: Retain records for atleast 3 years post trial

completionPadmaja Samant: Ethics in Research 40

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...Issues faced by Ethical Committee

Why look into Scientific Aspects?‘Me – too’ studiesEnd points not specifiedNo control armDenial of standard of care

Poor Science = Poor EthicsStudy Participants

Incentives?Management of trial related injury?Informed consent document inadequate


INFORMED CONSENT


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Bioethics Principles

• Autonomy: Self determination• Beneficence• Non maleficence• Justice

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Why do we need consent?

• Legal and ethical considerations• Way to minimize potential harm• Avoid unfairness and exploitation. • Protect patients' rights.

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Advantages of Consent

• Enhances Doctor Patient relationship.• Gives a frame work for the doctor to act. • It clarifies the objective of treatment.• Patient may cooperate fully with treatment.

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Definition of informed consentInformed consent is: The process of agreeing to take part in a study based

on access to all relevant and easily digestible information about what participation means, in particular, in terms of harms and benefits.

It is not merely a form that is signed but is a process, in which the subject has an understanding of the research and its risks.

Informed consent is essential before enrolling a participant and ongoing once enrolled.


• It is a process of communication between a patient and physician that results in the patient's authorization or agreement to undergo a specific medical intervention

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Informed Consent must be obtained for all types of human subjects research including; diagnostic, therapeutic, interventional, social and behavioral studies, and for research conducted domestically or abroad.


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Subjects in the study must participate willingly. Vulnerable populations (i.e. prisoners, children, pregnant women, etc.) must receive extra protection.The legal rights of subjects may not be waived and

subjects may not be asked to release or appear to release the investigator, the sponsor, the institution or its agents from liability for negligence.


The key ethical principles- JusticeResearchers must respect diversity when gaining

informed consent and must take into account factors such as:

Ethnicitygenderdisabilityreligious beliefs culture languagelevel of understanding.


Who should administer consent


Some protocols specify the qualifications of the person required to obtain consent. The sponsor is responsible for ensuring that the individual obtaining informed consent is trained to do so.


Consent should be given by someone with the mental ability to do so

Sufficient information should be given to the participant

If any of these requirements is lacking then the consent is invalidated.


Coercion

• Undue benefits • Inappropriate compensation• Connection between the consent taker and

participant• Threat of punishment or harm to patient or

loved ones


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The goal of the processTo provide sufficient information so that a participant can make an informed decision about whether or not to enroll in a study or to continue participation. – Autonomy and Justice


LanguageICD to be written in language easily understood by the participant,it must minimize the possibility of coercion or

undue influence, and the subject must be given sufficient time to consider participation. Translation and Back translation


Scientific, technical, and medical terms must bedefined or explained in lay terms.It is often recommended that the informed consent

be written at the eighth grade reading level. When enrolling minors in a study, related recruitment materials must reflect the reading level of minors.


Types of consentImplied informed consent Implied consent may arise when express written and/or verbal consent is not given; for example, when a participant implies their informed consent by returning a completed anonymised questionnaire. In these circumstances the REC will want to be reassured that there is no way that the researcher will be able to identify the participant from their responses.


Delayed consent usually occurs in emergency situations, when obtaining informed consent might make the study impossible. For example, it may be needed for research undertaken: at the roadside in the event of an accident at a cardiac arrest during the early stages of a patient s emergency

admission to an accident and emergency department.


Verbal – Verbal consent still contains all elements of written consent, however, the participant is verbally read the elements and verbally agrees to participate.


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Potential participants need to know• The purpose of the research, anticipated uses of

the research • How long their participation will last • Who is involved in the research • The practicalities and procedures involved in

participating, what is expected of them • The possible benefits and risks and, when

appropriate, the alternative therapies


• How data about them will be managed and used & how long and where it will be stored

• Names, addresses, and telephone numbers of the sponsors of the research;

• That they are free to ask questions and may refuse to participate;

• They may later withdraw from the research, the consequences of such withdrawal;

• Subjects right to confidentiality

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Additional ElementsDepending on the project and the subject population,

the Informed Consent must also contain information on: Certificate of Confidentiality (if any)/limitations of

certification protection Payment for participation (if applicable)Risks to vulnerable subjects, e.g., embryo, fetus,

pregnancyCircumstances for investigator withdrawing the subject


Additional elements ctd

• Additional costs from participationEarly withdrawal consequencesStatement regarding how significant new findings

will be communicated • Number of subjects participating• Probability of random assignment or placebo

placement• Additional information required by the IRB

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Audiovisual consent


• In the case of Swasthya Adhikar Manch, Indore & Anr Vs. Ministry of Health and Family Welfare &Ors. the supreme court ordered AV recording of IC process of 5 global trials

• CDSCO vide F. No. GCT/20/SC/Clin./2013 DCG1 dated 19.11.2013 - in all clinical trials, audio-visual recording of the informed consent process of each trial subject, including providing information to the subject and his/her understanding on such consent is required to be done while adhering to the principles of confidentiality.

• Such audio-visual recording and related documentation would be preserved..


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Vulnerable participantsEvery recipient of health care is in some way

vulnerable, but those with more limited ability to act autonomously can also be more vulnerable to the impact of research activity . Are those who are relatively or absolutelyincapable of protecting their own interests.They may have insufficient power, intelligence, education,resources, strength, or other needed attributes to protect their own interestsSituational vulnerability: Natural or manmade disasters


Pregnant women

Consent of the spouse unless• it is for health needs of the mother• Partner not traceable• Pregnancy due to rape


ChildrenGaining a child’s views and desires –

use of creative ways of providing information alternative means to express their thoughts.

Children should not receive monetary rewards for participation in research,

Any rewards for participating should benefit the child, not the parents.

In addition, travel costs should be reimbursed for the child and those travelling with them.


Parental Permission – When children/minors are included in research, the parent/guardian must sign a parental permission consent document. Some situations require permission from at least one parent, while other situations require permission from both parents. Assent – Assent is a child s affirmative agreement to participate in research. If the subject is 7- 17 years of age, assent must be obtained.Appropriate reading level of the youngest subject in the age range and use simple terminology.


Old people


Unresponsive peopleUnresponsive patients ( injuries or sedation) can only be

included in research for very specific reasons. Written informed consent to be obtained from a legal

representative.The informed consent given by a LAR should represent that

adult's presumed will.The clinical trial is designed to minimise pain, discomfort, fear

and any other foreseeable risk in relation to the disease and the cognitive abilities of the patient

The risk threshold and the degree of distress are specially defined and constantly monitored

The interests of the patient will always prevail over those of science and society.


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If the patient regains consciousness and capacity, informed consent should be sought as soon as is practical.If the individual refuses consent, all documentation

and data relating them to the study should be destroyed.However in the case of a clinical therapeutic trial, all

documentation must be retained for audit purposes, but it should not be used as part of the research.


Prisoners & army personnelapproval must be sought from the head of health care within the appropriate statutory bodies. A prisoner s participation will be subject to their informed consent in the normal way, particular attention to the need to avoid coercion.

Parole consideration is not subject to partcipationPrisoner advocate on the IRB Risk is not more than that to nonprisonerArmy: articular attention to the need to avoid coercion.


Students Power relationships and the risk of coercion.


Language barrier

• Translator: Name entered in the consent document


WaiverWaiver of one or more elements of informed consent may be obtained from the IRB for-some research projects that could not practically be

done without an alteration to the required elements or for studies where required elements are not applicable.

• The research involves no more than minimal risk;• The waiver or alteration will not adversely affect the

rights and welfare of the subjects;• Whenever appropriate, the subjects will be provided

with pertinent information after participation.Padmaja Samant: Ethics in Research 77

Rules followed in drafting

• National guidelines• Institutional policies• Ethical guidelines• Sponsor requests


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Authorship

ICMJE criteria for authorship 2004

• Authorship credit should be based on(1) substantial contribution to conception and

design, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be published, with authors meeting all of these three conditions.


• ICMJE guidelines also state that each author “should have participated sufficiently in the work to take public responsibility for the content

• “Gift” authorship. This is defined as naming, as an author, a person who does not meet authorship criteria


• A ghost author is defined as a person who is not listed as an author but who made contributions that merited authorship.

• Omitting the name of the true author—for example, the contract researcher—at the time of publication constitutes ghosting.


Plagiarism

Latin plagere=kidnap, plagiatum= “stealing people”

• Plagiarism is the "wrongful appropriation" and "stealing and publication" of another author's "language, thoughts, ideas, or expressions" and the representation of them as one's own.


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Types of plagiarism• Direct form–Fully or partially copy the text, computer files,

audio or video recordings without mentioning the primary source;

• Mosaic form–Borrowing ideas and opinions from the original source, a few words and phrases without citing the source;

• Self-plagiarism–Reuse own work without specifying the primary (own) sources.

• According to data from WAME - World Association of Medical Editors, precise definition of plagiarism is when are copied six consecutive words in a continuous set of 30 used characters.


Most common types of plagiarism• CLONE–Submitting someone else's work as his/hers own;• CTRL-C–Copied from a single source, without alterations;• FIND–REPLACE–Changing key words retaining a substantial part of

the content of the primary sources;• REMIX–Paraphrasing multiple sources;• RECYCLE–The use of already published ; own work • HYBRID–Combine perfectly cited sources with the copied without

citation;• MASH UP–Blending the copied material from multiple sources;• ERROR 404–Includes quoting non-existent or inaccurate source;• AGGREGATOR–Include proper citation of sources, but contains

almost nothing of own work;• RE–TWEET– proper citation, with too much text from the original.


Safeguards to avoid plagiarism Paraphrasing – information read and written with own words.Quote - wording of certain authors and they sentences are always placed in quotes.- Quotation marks should be used if are copied more than six consecutive wordsQuotation or citation and reference Citing own materialAcknowledging ideas taken at conference and formal/informal conversations.


HPV vaccine trial Andhra Pradesh 2009

Andhra Pradesh government brought out an official order (June 2, 2009) asking the deputy medical and health officer in Bhadrachalam block to issue orders to all the hostel wardens and Ashram schools to sign the consent forms on behalf of the parents.In case of 2,763 girls, consent documents were signed en bloc by teachers, hostel wardens and head masters. This is illegal.In another 1948 cases, illiterate parents were asked to put thumb impressions on documents, which they could not understand."


• 13,000 girls in A.P.and 10,000 in Gujarat aged 10–14. The trial halted in March 2010 after seven girls who received the vaccines died during the trial.

• A government enquiry concluded that the deaths were unrelated to the vaccines.

• Adverse events were not recorded or reported and even deaths were not promptly reported.

• Vaccines came free from pharma giants Glaxo Smith Kline and Merck Sharp and Dohme.


DISCUSSION

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THANK YOU

91

D Y Patil School of Medicine, Navi Mumbai

Basic Workshop on Research Methodology 1

DR. MRIDULA SOLANKIASSOCIATE PROFESSORDEPARTMENT OF COMMUNITY MEDICINESETH G.S.MEDICAL COLLEGE & KEM HOSPITAL

1Mridula Solanki: Sampling Methods

Learn the concept of sampling.

Develop an understanding about differentsampling methods.

Distinguish between probability & non

probability sampling.

Discuss the relative advantages &

disadvantages of each sampling methods.


• “Scientific research is systematic, controlled,empirical, and critical investigation of naturalphenomena guided by theory and hypotheses aboutthe presumed relations among such phenomena.”– Kerlinger, 1986

• Research is an organized and systematic way of

finding answers to questions.


Problem statement, research questions, purposes,benefits

Theory, assumptions, background literature

Variables and hypotheses

Operational definitions and measurement

Research design and methodology

Instrumentation, sampling

Data analysis

Conclusions, interpretations, recommendations


A Sample is “a smaller (but hopefully representative)collection of units from a population used to determine truthsabout that population”. (Field, 2005)

Sampling is the process of selecting some members of thestudy population to represent the population as a whole.

The Sampling frame is the list from which the potentialrespondents are drawn : e.g.◦ Registrar’s office◦ Class rosters

However, Must assess sampling frame errors like universityversus personal email addresses; changing class rosters; are allstudents in your population of interest represented?


Study of entire population what is called as census is difficultand almost impossible for infinite populations.

Costly, time consuming and not feasible.

Accurate and reliable estimates and inferences possible byproper sampling.

Since size is small in depth study can be done easily

Better supervision hence better data.

There are more risks for making interviewer and other errorsdue to the high volume of persons contacted and the numberof census takers, some of whom may not be well-trained.

Mridula Solanki: Sampling Methods 6

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What is your population of interest?To whom do you want to generalize yourresults?

All doctorsSchool childrenIndiansWomen aged 15-45 yearsOtherHRGs

Can you sample the entire population?


3 factors that influence sample representativenessSampling procedure

Sample size

Participation (response)

When might you sample the entire population?When your population is very small

When you have extensive resources

When you don’t expect a very high response

9Mridula Solanki: Sampling Methods 10

SAMPLING BREAKDOWN

Mridula Solanki: Sampling Methods

11

Defining the Population

Developing a Sampling Frame

Determining Sample Size

Specifying Sample Method

SELECTING THE SAMPLE


The sampling process comprises several stages:◦ Defining the population of concern.◦ Specifying a sampling frame, a set of items or events

possible to measure.◦ Specifying a sampling method for selecting items or

events from the frame.◦ Determining the sample size◦ Implementing the sampling plan◦ Sampling and data collecting◦ Reviewing the sampling process


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A population can be defined as including all

people or items with the characteristic one

wishes to understand.

Because there is very rarely enough time or

money to gather information from everyone or

everything in a population, the goal becomes

finding a representative sample (or subset) of

that population.


Note also that the population from which the sample isdrawn may not be the same as the population aboutwhich we actually want information. Often there is largebut not complete overlap between these two groups dueto frame issues etc .

Sometimes they may be entirely separate - for instance,we might study rats in order to get a betterunderstanding of human health, or we might studyrecords from people born in 2008 in order to makepredictions about people born in 2009.


A sampling frame is the list of all elements in

the population from which the samples are

drawn.

Sample frames for an entire target population

rarely exists and are too impractical to

construct. (Here cluster sampling is done).


In the most straightforward case, such as the sentencing of a batchof material from production (acceptance sampling by lots), it ispossible to identify and measure every single item in thepopulation and to include any one of them in our sample. However,in the more general case this is not possible. There is no way toidentify all rats in the set of all rats. Where voting is notcompulsory, there is no way to identify which people will actuallyvote at a forthcoming election (in advance of the election)

As a remedy, we seek a sampling frame which has the propertythat we can identify every single element and include any in oursample .

The sampling frame must be representative of the population


Sampling methods can be split into two distinct

groups:

1. Probability samples

2. Non-probability samples


Probability Samples

Probability samples offer each respondent an equal

probability or chance at being included in the sample.

They are considered to be:

• Objective

• Empirical

• Scientific

• Quantitative

• Representative

Sampling


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A probability sampling scheme is one in which everyunit in the population has a chance (greater than zero) ofbeing selected in the sample,

And this probability can be accurately determined.

When every element in the population does have thesame probability of selection, this is known as an 'equalprobability of selection' (EPS) design. Such designs arealso referred to as 'self-weighting' because all sampled

units are given the same weight.


Non Probability Samples

A non probability sample relies on the researcher selecting the respondents.

They are considered to be:

• Interpretive

• Subjective

• Not scientific

• Qualitative

• Unrepresentative

Samplling


Any sampling method where some elements of population have no chance of

selection (these are sometimes referred to as 'out of coverage'/'under covered'),

or where the probability of selection can't be accurately determined. It involves

the selection of elements based on assumptions regarding the population of

interest, which forms the criteria for selection. Hence, because the selection of

elements is non random, non probability sampling does not allow the estimation

of sampling errors..

Example: We visit every household in a given street, and interview the first

person to answer the door. In any household with more than one occupant, this

is a non probability sample, because some people are more likely to answer the

door (e.g. an unemployed person who spends most of their time at home is

more likely to answer than an employed housemate who might be at work when

the interviewer calls) and it's not practical to calculate these probabilities.


Probability (Random) Samples◦ Simple random sample

◦ Systematic random sample

◦ Stratified random sample

◦ Multistage sample

◦ Multiphase sample

◦ Cluster sample


Non-Probability Samples◦ Convenience sample

◦ Purposive sample

◦ Quota sample

◦ Snowball Sample

• In addition, non response effects may turn any probabilitydesign into a non probability design if the characteristics ofnon response are not well understood, since non responseeffectively modifies each element's probability of beingsampled.


• Applicable when population is small, homogeneous &readily available

• All subsets of the frame are given an equal probability.Each element of the frame thus has an equal probabilityof selection.

• It provides for greatest number of possible samples. Thisis done by assigning a number to each unit in thesampling frame.

• A table of random number or lottery system is used todetermine which units are to be selected.


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Advantages

Estimates are easy to calculate.

Simple random sampling is always an EPS design, but

not all EPS designs are simple random sampling.

Disadvantages

If sampling frame is large, this method impracticable.

Minority subgroups of interest in population may not be

present in sample in sufficient numbers for study.


Sampling schemes may be without replacement ('WOR' - noelement can be selected more than once in the same sample)or with replacement ('WR' - an element may appear multipletimes in the one sample).

For example, if we catch fish, measure them, and immediatelyreturn them to the water before continuing with the sample, thisis a WR design, because we might end up catching andmeasuring the same fish more than once. However, if we donot return the fish to the water (e.g. if we eat the fish), thisbecomes a WOR design.


Systematic sampling relies on arranging the target populationaccording to some ordering scheme and then selecting elements atregular intervals through that ordered list.

Systematic sampling involves a random start and then proceedswith the selection of every kth element from then onwards. In thiscase, k=(population size/sample size).

It is important that the starting point is not automatically the first inthe list, but is instead randomly chosen from within the first to thekth element in the list.

A simple example would be to select every 10th name from thetelephone directory (an 'every 10th' sample, also referred to as'sampling with a skip of 10').


As described above, systematic sampling is an EPS method, because

all elements have the same probability of selection (in the example

given, one in ten). It is not 'simple random sampling' because different

subsets of the same size have different selection probabilities - e.g. the

set {4,14,24,...,994} has a one-in-ten probability of selection, but the set

{4,13,24,34,...} has zero probability of selection.


ADVANTAGES:

Sample easy to select

Suitable sampling frame can be identified easily

Sample evenly spread over entire reference population

DISADVANTAGES:

Sample may be biased if hidden periodicity in population

coincides with that of selection.

Difficult to assess precision of estimate from one survey.


Where population embraces a number of distinct categories,the frame can be organized into separate "strata." Eachstratum is then sampled as an independent sub-population, outof which individual elements can be randomly selected.

Every unit in a stratum has same chance of being selected.

Using same sampling fraction for all strata ensuresproportionate representation in the sample.

Adequate representation of minority subgroups of interest canbe ensured by stratification & varying sampling fractionbetween strata as required.


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Finally, since each stratum is treated as an independentpopulation, different sampling approaches can be applied todifferent strata.

Drawbacks to using stratified sampling.

First, sampling frame of entire population has to be preparedseparately for each stratum

Second, when examining multiple criteria, stratifying variablesmay be related to some, but not to others, further complicating thedesign, and potentially reducing the utility of the strata.

Finally, in some cases (such as designs with a large number ofstrata, or those with a specified minimum sample size per group),stratified sampling can potentially require a larger sample thanwould other methods.


Draw a sample from each stratum


Cluster sampling is an example of 'two-stage sampling' .

First stage a sample of areas is chosen;

Second stage a sample of respondents within thoseareas is selected.

Population divided into clusters of homogeneous units,usually based on geographical contiguity.

Sampling units are groups rather than individuals.

A sample of such clusters is then selected.

All units from the selected clusters are studied.


Advantages :Cuts down on the cost of preparing a sampling frame.

This can reduce travel and other administrative costs.

Disadvantages : Sampling error is higher.

Often used in epidemiologic research for eg to evaluate vaccination coverage in EPI, studies on

HRGs etc..


Two types of cluster sampling methods.

One-stage sampling. All of the elements within

selected clusters are included in the sample.

Two-stage sampling. A subset of elements within

selected clusters are randomly selected for

inclusion in the sample.


• Identification of clusters– List all cities, towns, villages & wards of cities with their

population falling in target area under study.

– Calculate cumulative population & divide by 30, this gives

sampling interval.

– Select a random no. less than or equal to sampling interval

having same no. of digits. This forms 1st cluster.

– Random no.+ sampling interval = population of 2nd cluster.

– Second cluster + sampling interval = 3th cluster.

– Last or 30th cluster = 29th cluster + sampling interval36Mridula Solanki: Sampling Methods

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• Freq c f cluster• I 2000 2000 1• II 3000 5000 2• III 1500 6500• IV 4000 10500 3• V 5000 15500 4, 5• VI 2500 18000 6• VII 2000 20000 7• VIII 3000 23000 8• IX 3500 26500 9• X 4500 31000 10• XI 4000 35000 11, 12• XII 4000 39000 13• XIII 3500 44000 14,15• XIV 2000 46000• XV 3000 49000 16

• XVI 3500 52500 17• XVII 4000 56500 18,19• XVIII 4500 61000 20• XIX 4000 65000 21,22• XX 4000 69000 23• XXI 2000 71000 24• XXII 2000 73000• XXIII 3000 76000 25• XXIV 3000 79000 26• XXV 5000 84000 27,28• XXVI 2000 86000 29• XXVII 1000 87000• XXVIII 1000 88000• XXIX 1000 89000 30• XXX 1000 90000• 90000/30 = 3000 sampling interval


Although strata and clusters are both non-overlapping subsets ofthe population, they differ in several ways.

All strata are represented in the sample; but only a subset ofclusters are in the sample.

With stratified sampling, the best survey results occur whenelements within strata are internally homogeneous. However,with cluster sampling, the best results occur when elementswithin clusters are internally heterogeneous.


Complex form of cluster sampling in which two or more

levels of units are embedded one in the other.

First stage, random number of districts chosen in all states.

Followed by random number of talukas, villages.

Then third stage units will be houses.

All ultimate units (houses, for instance) selected at last

step are surveyed.


This technique, is essentially the process of taking random samples of

preceding random samples.

Not as effective as true random sampling, but probably solves more of

the problems inherent to random sampling.

An effective strategy because it banks on multiple randomizations. As

such, extremely useful.

Multistage sampling used frequently when a complete list of all

members of the population does not exist and is inappropriate.

Moreover, by avoiding the use of all sample units in all selected

clusters, multistage sampling avoids the large, and perhaps

unnecessary costs associated with traditional cluster sampling.


Part of the information collected from whole sample & part from

subsample.

In Tb survey MT in all cases – Phase I

X –Ray chest in MT +ve cases – Phase II

Sputum examination in X – Ray +ve cases - Phase III

Survey by such procedure is less costly, less laborious & more

purposeful


A method of assigning participants to groups in which pairs of participantsare first matched on some characteristic and then individually assignedrandomly to groups.

The Procedure for Matched random sampling can be briefed with thefollowing contexts,

Two samples in which the members are clearly paired, or are matchedexplicitly by the researcher. For example, IQ measurements or pairs ofidentical twins.

Those samples in which the same attribute, or variable, is measured twiceon each subject, under different circumstances. Commonly called repeatedmeasures.

Examples include the times of a group of athletes for 1500m before andafter a week of special training; the milk yields of cows before and afterbeing fed a particular diet.


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The population is first segmented into mutually exclusive sub-groups, justas in stratified sampling.

Then judgment used to select subjects or units from each segment basedon a specified proportion.

For example, an interviewer may be told to sample 200 females and 300males between the age of 45 and 60.

It is this second step which makes the technique one of non-probabilitysampling.

In quota sampling the selection of the sample is non-random.

For example interviewers might be tempted to interview those who lookmost helpful. The problem is that these samples may be biased becausenot everyone gets a chance of selection. This random element is itsgreatest weakness and quota versus probability has been a matter ofcontroversy for many years


Conveniencee SSampling• This involves selecting the nearest

and most convenient people toparticipate in the research.

• This method of selection is nnotrepresentative and is considered avery unsatisfactory way to conductresearch.


Sometimes known as grab or opportunity sampling or accidental orhaphazard sampling.A type of non probability sampling which involves the sample being drawn fromthat part of the population which is close to hand. That is, readily available andconvenient.

The researcher using such a sample cannot scientifically make generalizationsabout the total population from this sample because it would not be representativeenough.

For example, if the interviewer was to conduct a survey at a shopping centerearly in the morning on a given day, the people that he/she could interview wouldbe limited to those given there at that given time, which would not represent theviews of other members of society in such an area, if the survey was to beconducted at different times of day and several times per week.

This type of sampling is however most useful for pilot testing.


◦ Use results that are easy to get


Snowball Sampling• This type of sampling is used when the research is focused

on participants with very specific characteristics such asbeing members of a gang.

• Having identified and contacted one gang member theresearcher asks to be put in touch with any friends orassociates who are also gang members.

• This type of sampling is not representative however isuseful, especially where the groups in the research are notsocially organised i.e. they do not have clubs ormembership lists.


The researcher chooses the sample based on

who they think would be appropriate for the study.

This is used primarily when there is a limited

number of people that have expertise in the area

being researched


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Method of first selecting a group of participants through a random samplingmethod and then asking that group for the same information again several timesover a period of time.

Therefore, each participant is given same survey or interview at two or more timepoints; each period of data collection called a "wave".

This sampling methodology often chosen for large scale or nation-wide studiesin order to gauge changes in the population with regard to any number ofvariables from chronic illness to job stress to weekly food expenditures.

Panel sampling can also be used to inform researchers about within-personhealth changes due to age or help explain changes in continuous dependentvariables such as spousal interaction.

There have been several proposed methods of analyzing panel sample data,including growth curves.

49Mridula Solanki: Sampling Methods 50Mridula Solanki: Sampling Methods

THANK YOU


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1

Literature search

Dr. Anant PatilMD Pharmacology

Department of PharmacologyDr DY Patil Medical College, Navi Mumbai

Content

• Why (& when), where and how of literature search

• Effective literature search

• Examples

Content

• Why, where and how of literature search


• Examples

“A researcher cannot perform significant research without first understanding the

literature in the field”

Boote and Beile, 2005: 3

Why?

• F• I• N• E• R

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2

“If you have no destination, you’ll never get there”

Harvey Mackay

Other reasons

• Writing introduction, review of literature and discussion sections in thesis

• Manuscript writing

• Writing systematic reviews and meta-analysis

Content



• Examples

Literature search is not just Googling

Sources of literature source

• Textbooks

• Journals (open access, subscription)

• Websites

Databases• PubMed• IndMed• MedInd• Scopus• Index Copernicus• EMBASE• Google Scholar• Cochrane database• Science direct• Springer link• Informa world• IngentaConnect

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• It is free search engine

• MELINE + PubMed Central

• Available since 1996

• United States National Library of Medicine (NLM)

• Has more than 28 million references

• Articles published in >5000 journals

• https://www.ncbi.nlm.nih.gov/pubmed/

PubMed

• Database of articles from journals related to medicine, nursing, pharmacy, dentistry, veterinary medicine and healthcare

• Over 26 million records

• Temporal coverage: since 1946

MEDLINE

• Selected peer reviewed medical journals published from India

• About 100 journals indexed from 1985 onwards

• MedIND: Full text articles of selected Indian medical journals indexed in IndMED or PubMed

• http://indmed.nic.in/

IndMED and MedIND Embase

• 1947 onwards

• Over 32 million records, including MEDLINE articles

• Over 8,500 journals

• https://www.elsevier.com/en-in/solutions/embase-biomedical-research

• Elsevier’s database

• Available since 2004

• About 69 million articles

• About 36,377 titles

• https://www.scopus.com/

Scopus

• International indexation database of scientific journals

• Registered scientific journals: 44,929

• http://en.indexcopernicus.com/

Index Copernicus

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4

Content



• Examples

Principles for effective search

• Planning: Understanding the research framework/paradigm

• Identify key search terms

• Preliminary research followed by focused research

Steps

• Research problem

• Resources

• Principles for effective literature search

How do we approach?

• Basic information

• Research related information

• Meta-analysis/guidelines

How do we approach?

• Basic information: Textbook, handbook, manuals

• Research related information: Journals, clinical trial registries

• Meta-analysis/guidelines: Cochrane database, association’s websites, journals

http://library.downstate.edu/EBM2/2100.htm

In vitro researchAnimal research

Ideas, Editorial, Opinion

Case reportsCase series

Case control study

Cohort study

RCT

Meta-analysis

Evidence pyramid

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5

Which is the most commonly searched database for scientific/medical

literature?

PubMed gives different types of articles

Content



• Examples

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6

How to get best results with minimum efforts?

Search/key word

1

Tagging

2

Methods of PubMed search

PubMed search by words

1. Your choice of word

2. MeSH

3. Specific word search in the article

4. Combination of words

PubMed search by words

1. Your choice of word (e.g. diabetes)

2. MeSH (diabetes mellitus)

3. Specific word search in the article (title, abstract, journal name, author name etc)

4. Combination of words (e.g. Diabetes AND India)

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1. MeSH terms

2. Synonyms

3. Filters

4. Boolean operators

Content



• Examples

Type 2 diabetes in elderly patients Type 2 diabetes in elderly patients

Who tags what?

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Short forms for search words in…

Area of search

[Ti] Title

[tiab] Title plus abstract

[Jour] Journal name

[Au] Author

[MeSH] Mesh terms

[page] Page number

[pdat] [dp] Year

Title

Author Journal

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9

Combining terms

• Renal disease in diabetes

Combining terms

Do not use words like “of”, “in”, “with” etc.

• Prevalence of renal disease in diabetes

• Renal disease in patients with diabetes

Use “Boolean” terms

• Boolean logic

• George Boole (British-born Irish mathematician)

• Relationships between search terms

“Boolean” terms

Command Purpose

AND

OR

NOT

Boolean operators

Command Purpose

AND Articles that include all search terms/keywords

OR Articles that include any of the search terms

NOT Excludes articles that include specific keyword

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What does it mean?

Boolean operator Searchresult

Why?

1 Diabetes X2 Diabetes AND hypertension3 Diabetes OR hypertension4 Diabetes NOT hypertension

What does it mean?


Why?

1 Diabetes X2 Diabetes AND hypertension < X Both terms3 Diabetes OR hypertension4 Diabetes NOT hypertension

What does it mean?


Why?

1 Diabetes X2 Diabetes AND hypertension < X Both terms3 Diabetes OR hypertension > X At least one term4 Diabetes NOT hypertension

What does it mean?


Why?

1 Diabetes X2 Diabetes AND hypertension < X Both terms3 Diabetes OR hypertension > X At least one term4 Diabetes NOT hypertension < X Diabetes but not

hypertension

What does it mean?Boolean operator Search

resultWhy?

1 Diabetes X2 Diabetes AND hypertension < X Both terms3 Diabetes OR hypertension > X At least one term4 Diabetes NOT hypertension < X Diabetes but not

hypertension

DM HTBoth

Specific search

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Articles published by Anant Patil in“Perspectives in Clinical Research”

Which search words will I put in PubMed?

Patil[Au] AND Perspect Clin Res[jour]

How would the result look like?

Enalapril in diabetes as well as hypertension

Search words

• Diabetes OR hypertension AND enalapril

Diabetes OR hypertension AND enalapril…anywhere in the article

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Diabetes OR hypertension AND enalapril

Diabetes OR hypertension AND enalapril…in the title or abstract

Diabetes[tiab] OR hypertension[tiab] AND enalapril[tiab]

Diabetes OR hypertension AND enalapril…only in the title

Diabetes[ti] OR hypertension[ti] AND enalapril[ti]

MeSH

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MeSH

• Medical Subject Headings

• Standard terms to describe the article

Where do we get the MeSH term?

Articles on diabetes published in 2017

Boolean search

Diabetes[MeSH] AND 2017[dp]Diabetes[MeSH] AND 2017[pdat]

Diabetic nephropathy

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Treatment of gastroesophageal reflux disease in children

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Finding incomplete reference

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Patil Indian J Endocrinol Metab2014

Patil Indian J Endocrinol Metab2014

Advanced search

Diabetic retinopathy

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More customization for search

Customize your search

Getting correct reference style

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We are done with…



• Examples

Summary

• Research problem

• Resources

• Principles for effective literature search

• Use correct Boolean terms

• Advanced search helps to get you specific articles

Thank you

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1

Group ActivityLiterature search

Dr. Anant PatilMD Pharmacology

Department of PharmacologyDr DY Patil Medical College, Navi Mumbai

Exercise 1You attended a lecture in a conference on the topic

“Heart failure in pre-diabetes” and one of the slides of the speaker had following reference

“Nielsen R, et al 2018”

Search the article in PubMed

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2

2

Exercise 1

J Nucl Cardiol. 2018 Feb;25(1):169-176. doi: 10.1007/s12350-016-0622-0. Epub 2016 Jul 29.Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism.

Nielsen R1, Jorsal A2,3, Iversen P4, Tolbod L4, Bouchelouche K4, Sørensen J4, Harms HJ4, Flyvbjerg A3, Bøtker HE2,3, Wiggers H2.Author information

Abstract

You attended a lecture in a conference on the topic “Heart failure in pre-diabetes” and one of the slides

of the speaker had following reference

“Nielsen R, et al 2018”

Search the article in PubMed

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4

Exercise 2

• Search articles related to diabetes authored by Dr. Mohan which are published in 2017 and 2018

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Exercise 3

• Search clinical trials related to gastroesophageal reflux disease published in 2017 and 2018

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Exercise 4

• Search clinical trials related to zinc in pediatric diarrhea published between 2016 to 2018

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Thank you

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24-07-2019

1

Pratap L JadhavAssistant Professor Statistics & Demography

Department of Community MedicineSeth G.S. Medical College & K.E.M. Hospital

Data Primary DataSecondary Data

Data Qualitative DataQuantitative Data

Data Discrete dataContinuous Data

STATISTICAL DATA

DATA

QUANTITATIVE

CONTINUOUS DISCRETE

QUALITATIVE

DISCRETE

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24-07-2019

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Measurement Scales for Statistical Data

Measurement scales

Nominal

Ordinal

Interval

Ratio

Sr no Name of variable Type of data Measurement scale

1 Diagnosis of patients admitting in psychiatry ward

2 Range of motion of elbow joint

3 APGAR score

4 Temperature

5 Religion

6 Haemoglobin level of IV year medical students

7 Pain measured on Vas

8 Grades of anaemia

9 IQ score

10 Birth weight

Data Representation

Contingency table

Frequency distribution Table

Graphical presentation

Contingency TableA group of 3579 person was protected against post-traumatic tetanus. Of the 1546 who were given Benzathine penicillin intramuscularly, 578 had punctured wounds, 271 had lacerated or contused wounds and 306 had incised wounds. Of the 962 with other type of injuries, 561 received A.T.S. which was administered to 767 with punctured wounds and 381 with incised wounds. Present the information in tabular form.

Contingency table

Type of wound

Treatment mode

Total

Benzathinepenicillin

ATS

Punctured wounds 578 767 1345

Lacerated wounds 271 314 585

Incised wounds 306 381 687

Other type of injuries

391 571 962

Total 1546 2033 3519

578

271

306

391

0 100 200 300 400 500 600 700

Punctured wounds

Lacerated wounds

Incised wounds


Punctured wounds Lacerated wounds Incised wounds Other type of injuriesBenzathine penicillin 578 271 306 391

Simple Bar diagram

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24-07-2019

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Frequency distribution Table Hemoglobin values in grams percentage of 100 first MBBBS first term Medical students are given below.

11.4 12.4 12.8 13.0 12.0 11.0 12.9 12.4 11.5 11.2

11.3 10.8 12.4 12.7 11.5 13.0 12.8 11.0 10.5 12.4

13.2 11.9 11.4 12.7 12.8 12.5 12.1 13.0 11.8 12.3

11.8 12.2 12.3 12.4 12.1 12.4 12.9 13.0 11.0 11.5

12.9 13.2 13.1 12.0 12.5 12.8 13.4 12.5 12.2 10.9

11.3 11.5 12.1 10.8 13.9 13.5 13.2 11.8 12.8 12.5

12.0 11.5 11.9 11.8 11.7 11.6 12.2 11.9 11.3 10.6

10.5 12.0 13.1 10.9 13.8 13.6 11.5 11.9 10.8 10.1

12.3 12.6 13.9 10.1 10.9 11.1 10.9 11.8 12.5 12.7

11.8 11.9 11.4 11.9 12.0 13.4 12.2 13.6 12.3 13.4

Frequency distribution tableClass interval Frequency Relative

frequency

< Cumulative frequency

> Cumulative frequency

10.0 – 10.5 2 0.02 2 100

10.5 - 11.0 10 0.10 12 98

11.0 – 11.5 11 0.11 23 88

11.5 – 12.0 20 0.20 43 77

12.0 – 12.5 22 0.22 65 57

12.5 – 13.0 17 0.17 82 35

13.0 – 13.5 12 0.12 94 18

13.5 – 14.0 6 0.06 100 06

Graphical presentation for Quantitative data

HistogramFrequency polygon Line diagramOgive curveScatter diagram Box plot

Graphical presentation for Qualitative data

Bar diagram a) Simple bar diagramb) Multiple bar Diagramc) Subdivided bar diagram

Pie diagram

578

271

306

391

0 100 200 300 400 500 600 700

Punctured wounds

Lacerated wounds

Incised wounds


Punctured wounds Lacerated wounds Incised wounds Other type of injuriesBenzathine penicillin 578 271 306 391

Simple Bar diagram

0

100

200

300

400

500

600

700

800

Benzathine penicillin ATS

578

767

271

314306

381391

571

freq

uenc

y

Axis Title

Multiple Bar Diagram

Punctured wounds Lacerated wounds Incised wounds Other type of injuries

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24-07-2019

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Subdivided Bar diagram

0

500

1000

1500

2000

2500

Benzathine penicillin ATS

578767

271

314306

381391

571

freq

uenc

y

Mode of treatment


Incised wounds

Lacerated wounds

Punctured wounds

57837%

27118%

30620%

39125%

Pie Diagram showing Frequency Distribution for type of Wounds

Punctured wounds Lacerated wounds

Incised wounds Other type of injuries

0

5

10

15

20

25

10 10.5 11 11.5 12 12.5 13 13.5

2

1011

20

22

17

12

6

freq

uenc

y

Hemoglobin Level

Histogram showing frequency Distribution for hemoglobin levels

02

12

23

43

65

82

94

100

0

20

40

60

80

100

120

10 10.5 11 11.5 12 12.5 13 13.5 14

cum

ulat

ive

freq

uen

cyOgive Curve or cumulative frequency curve

0

2

1011

20

22

17

12

6

00

5

10

15

20

25

10 10.5 11 11.5 12 12.5 13 13.5 14 14.5

freq

uenc

y

FREQUENCY POLYGON

y = 0.6286x + 21.124R² = 0.9429

81.5

82

82.5

83

83.5

84

84.5

85

85.5

96 97 98 99 100 101 102 103

Pul

se ra

te

Temperature 0 F

Scatter diagram

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Research Methodology 23 July 2019

D Y Patil University School of Medicine 1

Inferential Statistics

PRATAP L . JADHAVAssistant Professor Statistics & DemographySeth G.S. Medical College & K.E.M. Hospital

STATISTICAL DATA

DATA

QUANTITATIVE

CONTINUOUS DISCRETE

QUALITATIVE

DISCRETE

Measurement Scales for Statistical Data

Measurement scales

Nominal

Ordinal

Interval

Ratio

Summary values

Summary value Population Sample

Mean μStandard Deviation σ S

Variance

Proportion P p Complementary proportion Q q

Standard Error P = {x1, x2, x3,……….xn} = μ σ РS1= {x1, x2, x3, …….,x50} = p1S2= {x1, x2, x3, …….,x100} = p2S3= {x1, x2, x3, …….,x60} = p3...Sn= {x1, x2, x3, …….,x40} = pn

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Inferential StatisticsInferential statistics provides the procedure to draw inference about the conditions which exist in a large population. For e.g.- to test the efficacy of a new hypertensive drug in which the physician will have only a limited number of hypertensive patients with whom to work.The methods of inferential statistics are those of making inference from a sample about a large population, from which the sample is drawn.

Inferential statisticsInferential statistics has two aspects

Estimation of population valueTesting of hypothesis

Purpose of Estimation To provide an estimate of a population parameter.In theory, the parameter value could be computed if a measurement could be obtained from every subject in the population. In practice, that is too expensive, and sometimes operationally impossible

To give an idea of the precision of the estimate and reliability of the estimation procedure

This is possible only if the estimate is obtained from a “probabilistic sample”. In probabilistic sampling every subject in the population has a known probability of being selected .

The sample mean is the natural estimator of the population mean. We will use the mean of a sample (statistic) as an estimate of the mean of the population (parameter).

The difference between the sample mean and the population mean is called “sampling error” of the estimation.

Estimation SEM SEPSEDMSEDP

Estimating with Confidence

That chance (95%) is what gives the researcher “confidence” in the method. He will present his sample mean as an estimate of the population mean in the form

Sample mean ± 1 SEM Covers 68.27 % Samples Sample mean ± 2 SEM Covers 95.45 % Samples Sample mean ± 3 SEM Covers 99.73 % Samples

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Confidence interval (CI)

Indicates the ammount of random error in the estimateCan be calculated for any ‚ “test statistic e.g.: means, proportions,

ORs, RRs "

e.g. CI for means95% CI = x – 1.96 SE up to x + 1.96 SE

1 - αα/2 α/2

Lower limit upper limitof 95% CI of 95% CI

= 5%

s

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Intervals for large samples with different confidence level

Important Note

This procedure is valid when the sample is large (n≥ 30) and it is small with respect to the population (no more than 5% of it)

Confidence interval for a Population MeanSuppose a researchers wish to estimate the mean of some normally distributed population.They draw a sample of size n from the population and compute sample mean ( )which they use point estimate of μAlthough this estimator of μ possesses all qualities of good estimator, we know that random sampling inherently involves chance, sample mean can not be expected to be equal to μIt would be much more meaningful, therefore, to estimate μby interval that somehow communicates information regarding to the probable magnitude of population mean μ

Confidence interval for a Population mean

In particular, when sampling is from normal distribution with known variance, an interval estimate of population mean μ may be expressed as

Population estimate range =

At different level of significance we can estimate interval for μ using following properties

Sample mean ± 1 SEM Covers 68.26 % Samples meansSample mean ± 2 SEM Covers 95.45 % Samples meansSample mean ± 3 SEM Covers 99.73 % Samples meansSample mean ± 1.96 SEM Covers 95 % Samples meansSample mean ± 2.58 SEM Covers 99 % Samples means

Confidence interval for a Population meanIn a situation such as, that the population variance as well as population mean is unknown then confidence interval for population mean is given by statistics

Range =

When we construct a confidence interval for a population mean, we must decide whether to use value of Z or value of t as the reliability factor To make an appropriate choice we must consider sample size, whether the sampled population is normally distributed, and whether the population variance is known.

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Confidence interval for the difference between Two Population Means

Sometimes there arise a case in which we are interested in estimating the difference between two population mean The confidence interval for difference between two population mean If the population variances are known the CI of difference given by


From examination of confidence interval for the difference between Population means provides information that is helpful in deciding whether or not it is likely that the two population means are equal.When constructed interval does not include zero (0) we say that interval provides evidence that the two population means are not equal.When interval includes zero, we say that the population means may be equal.


A research team is interested in the difference between serum uric acid levels in patients with and without Down’s syndrome. In a large hospital for a treatment of mentally retarded, a sample of 12 individual with Down’s syndrome yielded a mean of 4.5 mg / 100 ml. In a general hospital a sample of 15 normal individual of the same age and sex were found to have a mean value of 3.4 mg/100 ml. If it is reasonable to assume, that the two populations of values are normally distributed with variance equal to 1 & 1.5. Find the 95 % CI for difference between two population mean


For a point estimate of we use= (4.5 – 3.4 )= 1.1 reliability coefficient is

corresponding to .95 is 1.96 so the value of

SEDM= .4282 so 95 % CI is given by= 1.1 ± 1.96 ( 0.4282)= 1.1 ± 0.84 = ( 0.26 , 1.94)Since the interval does not include zero, we conclude that the two population means are not equal


When population variances are unknown and we wish to estimate the difference between two population mean with a confidence interval, we can use a t distribution as a source of reliability factorAssuming that the two sampled populations are normally distributed.With regard to the population variance we distinguish between two conditions a) Population variances are equalb) Population variances are not equal


The confidence interval is given by

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Confidence interval for a Population ProportionMany questions of interest to the health worker relate to population proportionsWhat proportion of patients who received a particular type of treatment?What proportion of some population has certain disease?What proportion of the population are immune to certain disease?To estimate population proportion we proceed in the same manner as when estimating a population mean

Confidence interval for a Population proportionCI for population proportion is given by

Where p = probability of occurrence and q = (1- p )

n= no of observation in a given sample

Confidence interval for the difference between two population proportion

The magnitude of the difference between two population proportion is often of interest We may want to compare two age groups, or two diagnostic groups with respect to the proportion possessing some characteristic of interestCI for (p1-p2) is given by

Confidence interval for the difference between two population proportion

Testing of Hypotheses.Hypothesis is usually considered as the principal instrument in research.In fact many experiments are carried out with the deliberate object of testing of hypotheses.Decision makers often face situations wherein they are interested in testing hypotheses on the basis of available information and then take decisions on the basis of such testing.

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Testing of Hypotheses.In social since, where direct knowledge of population parameter(s) is rare, hypothesis testing is often used strategy for deciding whether a sample data offer such support for a hypothesis that generalization can be madeThus hypothesis testing enables us to make the probability statement about population parameter.The hypothesis may not be prove absolutely, but it is accepted if it is withstood a critical testing.

What is a Hypothesis?Hypothesis is a formal question that researcher tend to resolve.Hypothesis may be defined as proposition or a set of proposition set forth as an explanation for the occurrence of some specified group of phenomena.E.g.:- students who receive counseling will show greater in creativity than students not receiving A hypothesis states what we are looking for and it is a proposition which can be put to a test to determine its validity.

Characteristics of good HypothesisHypothesis should be clear and precise.Hypothesis should be capable of being tested.Hypothesis should state relationship between variablesHypothesis should be limited in scope and must be specific.Hypothesis should be consistent with most known facts.Hypothesis should be amenable to testing within reasonable time.

Basic concepts concerning testing of HypothesesNull hypothesis and Alternative hypothesis :-

Null hypothesis (H0)- If we have to compare method A with method B about it superiority and if we proceed on the assumption that methods are equally good then this assumption is termed as Null Hypothesis.As against this, we may think that the method A is superior or method B is inferior, we are then stating what is termed as Alternative Hypothesis (H1).

Basic concepts concerning testing of Hypotheses

In simple word Null hypothesis is simple statement of no difference stating no difference in population parameter and sample statistics.Alternative hypothesis is usually the one which one wishes to prove and the null hypothesis is one wishes to disprove.Thus null hypothesis represents the hypothesis we are trying to reject and alternative hypothesis presents all other possibilities.


Level of significance:- it is always some percentage (usually 5 % ) which should be chosen with great care, thought and reason.In case we take LS 5 % implies that H0 will be rejected when the sampling result has less than 0.05 probability of occurrence if H0 is true Level of significance is the maximum probability of rejecting null hypothesis when it is true.Level of significance determined in advance before testing of hypothesis.

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Basic concepts concerning testing of HypothesesDecision rule or test of hypothesis:-Given a hypothesis H0 and H1, we make a rule which is known as Decision rule according to which we accept or reject Ho. E.g.:- if Ho- is that a certain lot is good (there are very few defective items in it ) against H1- that the lot is not good ( there are too many defective items in it )then we must decide the number of items to be tested and the criterion for accepting or rejecting the hypothesis.


Type-I and Type-II error:-There are basically two types of errors we can make.We may reject H0 when it is true is called as type-I error. Type one error means rejection of hypothesis which should have been accepted. Type –I error can also be called α (alpha) error or level of significance of test.If we accept H0 when it is false is called Type-II error. it means accepting the hypothesis which should have been rejected and also called β (beta) error.

Errors in testing of Hypothesis

Your Statistical Decision

True state of null hypothesis

H0 True(example: the drug doesn’t

work)

H0 False(example: the drug works)

Reject H0(ex: you conclude that the drug works) Type I error (α) Correct

Do not reject H0(ex: you conclude that there is insufficient evidence that the drug works)

Correct Type II Error (β)

Steps involve in testing of hypothesesMaking formal statement i.e. Null Hypothesis and Alternative HypothesisSelection of level of significanceDeciding distribution to be used Calculation of critical ratioInference on the critical ratio.Final Conclusion

Testing of hypothesis or tests of significanceThere are different types of problems for which tests of significance are use to drawing results.Different types of problem needs different tests but basis of all the tests and steps involve in procedures are the same. The common types of problems are:

Compare sample mean with population meanCompare two sample meansCompare sample proportion with population proportion Compare two sample proportions

Parametric test of significance The statistical methods of inference which make certain assumption about the population from which the samples are drawn.e.g.: assumption may be that populations are normally distributed, have the same variance etc. The statistical techniques which make assumption about the parameter are called parametric techniques.

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Non-parametric or Distribution free test of significance

More recently large no of techniques of inference have been develop which do not make any assumption about population parameter or their distribution

Parametric Vs Nonparametric BASIS FOR

COMPARISON PARAMETRIC TEST NONPARAMETRIC TEST

Meaning A statistical test, in which specific assumptions are made about the population parameter is known as parametric test.

A statistical test used in the case of non-metric independent variables, is called non-parametric test.

Basis of test statistic

Distribution Arbitrary

Measurement level Interval or ratio Nominal or ordinal

Measure of central tendency

Mean Median

Information about population

Completely known Unavailable

Applicability Variables Variables and Attributes

Correlation test Pearson Spearman

Parametric tests of significance

The most commonly used test of significance areZ- Testt-test F test One way ANOVA & Two way ANOVARepeated measure ANOVA

Non-parametric or Distribution freetest of significance

Chi-square testWilcoxon’s Signed rank testMann Whitney U- TestKruskal -wallis testMedian test Freidman ANOVA testFisher exact testMc Nemar testSpearman rank correlation

Correlation & Regression

Types of correlation Correlation coefficient (r )Regression Types of regression

simple Multiple Logistic

Which test should I use?

Outcome Variable

Are the observations independent or correlated?

Assumptionsindependent correlated

Continuous(e.g. pain scale, cognitive function)

TtestANOVALinear correlationLinear regression

Paired t testRepeated-measures ANOVAMixed models/GEE modeling

Outcome is normally distributed (important for small samples).Outcome and predictor have a linear relationship.

Binary or categorical(e.g. fracture yes/no)

Relative risksChi-square test Logistic regression

McNemar’s testConditional logistic regression

Sufficient numbers in each cell (>=5)

Time-to-event(e.g. time to fracture)

Kaplan-Meier statisticsCox regression

n/a Cox regression assumes proportional hazards between groups

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Continuous outcome (means)

Outcome Variable

Are the observations independent or correlated?

Alternatives if the normality assumption is violated (and small sample size):independent correlated

Continuous(e.g. height ,weight

Ttest: compares means between two independent groups

ANOVA: compares means between more than two independent groups

Pearson’s correlation coefficient (linear correlation): shows linear correlation between two continuous variables

Linear regression: multivariate regression technique used when the outcome is continuous; gives slopes

Paired t-test: compares means between two related groups (e.g., the same subjects before and after)

Repeated-measures ANOVA: compares changes over time in the means of two or more groups (repeated measurements)

Mixed models/GEE* modeling: multivariate regression techniques to compare changes over time between two or more groups; gives rate of change over time

*Generalized estimating equations

Non-parametric statistics

Wilcoxon sign-rank test: non-parametric alternative to the paired ttest

Wilcoxon sum-rank test (=Mann-Whitney U test): non-parametric alternative to the ttest

Kruskal-Wallis test: non-parametric alternative to ANOVA

Spearman rank correlation coefficient: non-parametric alternative to Pearson’s correlation coefficient

Binary or categorical outcomes

Outcome Variable

Are the observations correlated? Alternative to the chi-square test if sparse cells:independent correlated

Binary or categorical(e.g. fracture, yes/no)

Chi-square test: compares proportions between more than two groups

Relative risks: odds ratios or risk ratios

Logistic regression: multivariate techniqueused when outcome is binary; gives multivariate-adjusted odds ratios

McNemar’s chi-square test: compares binary outcome between correlated groups (e.g., before and after)

Conditional logistic regression: multivariate regression technique for a binary outcome when groups are correlated (e.g., matched data)

GEE* modeling: multivariate regression technique for a binary outcome when groups are correlated (e.g., repeated measures)*Generalized estimating equations

Fisher’s exact test: compares proportions between independent groups when there are sparse data (some cells <5).

McNemar’s exact test: compares proportions between correlated groups when there are sparse data (some cells <5).

Time-to-event outcome (survival data)

Outcome Variable

Are the observation groups independent or correlated? Modifications to Cox regression if proportional-hazards is violated:independent correlated

Time-to-event (e.g., time to fracture)

Kaplan-Meier statistics: estimates survival functions for each group (usually displayed graphically); compares survival functions with log-rank test

Cox regression: Multivariate technique for time-to-event data; gives multivariate-adjusted hazard ratios

n/a (already over time)

Time-dependent predictors or time-dependent hazard ratios (tricky!)

P- VALUE VS CI Which approach should be used?

Researchers have become polarized on this issue. Some statistician favor only hypothesis testing approach and some epidemiologist favors only confidence interval approach.CI are always based on the observed or estimated effect and convey useful information regarding the direction of effect and precision of the estimate .Hence more descriptive and useful than p- values, especially while interpreting and reporting of Negative studies.

P- VALUE VS CI Which approach should be used?P-values tell precisely how significant the results are.However, Statistically significant results need not always be clinically important.Further the non significant results (p < 0.05) does not necessarily imply that there is no effect in the population It means that the effect observed in the sample is small compared with what could have occurred by chance alone Both P- values and CIs provides complementary information and both should be reported, where possible

THANK YOU !THANK YOU !

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Page 1 of 2

For the following examples identify the appropriate test of significance (Parametric or Nonparametric) and prepare Null and Alternative Hypothesis.

Lebranchu et al. conducted a study in which the subjects were 9 patients with common variable immunodeficiency (CVI) and 12 normal controls among the data collected were the following on CD4+ T cell per cubic mm of peripheral blood. May we conclude, on the basis of this data the CVI patients have a reduced level of CD4 + cells?

CVI Patients

623 437 370 300 330 527 290 730 1000

controls 710 1260 717 590 930 995 630 977 530 710 1275 825

The following table shows the duration of endurance of pain by eleven mice before and after administration of drug (adrenaline 0.04 mg/20 gm body-weight). Is there sufficient evidence in the data to say that the drug increases the duration of endurance of pain?

Before drug 15 12 14 16 20 22 20 18 17 17 19 After drug 21 20 17 22 20 20 20 19 18 24 19

In a study of cerebrovascular disease the patient from three socioeconomic back-ground were thoroughly investigated. One characteristics measured was diastolic blood pressure in mm/Hg. Is there is any reason to believe that three groups differ with respect to this characteristic? Sr. no

Group-A

Group-B Group-C

1 100 92 81 2 103 97 102 3 89 88 86 4 78 84 83 5 105 90 99 6 --- 95 --- Total obs.

05 06 05

In a survey on hearing level of school children with normal hearing it was found that in the frequency 500 cycle/ second , 62 children tested in the soundproof room had a mean hearing threshold of 15.5 decibels with SD of 6.5. In a sample of 76 comparable children who were tested in the fields had a mean threshold of 20 decibels with SD of 7.1. Test, if there is any difference between the hearing levels recorded in sound-proof room and in the field.

Page 2 of 2

Thirty percent of children enrolled in particular school are known to have been fully immunised. In a class 7th c of this school, there are 56 pupils. At-least how many of these would be fully immunised at 95% confidence interval.

An experiment was conducted to test the efficacy of chloromycetin in checking typhoid. In the certain hospital chloromycetin was given to 285 out of 392 patients suffering from typhoid. The numbers of typhoid cases were as follows: test the effectiveness of Chloromycetin in checking typhoid

Use of Drug Typhoid No Typhoid Total Chloromycetin 35 250 285 No Chloromycetin 50 57 107 Total 85 307 392

An IQ test was administrated to 5 persons before and after they were trained. Test whether there is any improvement in IQ after the training program.

Sr no 1 2 3 4 5 IQ before Training 110 120 123 132 125 IQ after Training 120 118 125 136 130

Systolic blood pressure (SBP) measured in mm of Hg and Pulse Rate/ min was measured

for 10 individuals as follows: Estimate pulse rate for SBP = 130

SBP 120 140 128 142 110 148 132 126 158 100 PR/MIN 70 78 72 74 66 76 80 68 84 60

A survey was carried out in a state amongst the doctors belonging to Rural Health service

cadre (500 Doctors) and among the medical education directorate cadre (300 teaching doctors). They were asked a question, “would it be acceptable to you, if the government proposes to hire all the doctors on a fixed period contractual basis?” The doctors were to answer either as ‘Acceptable’ or ‘Not Acceptable’. There was not third category ‘Undecided’. For the following data test an appropriate hypothesis.

Doctors Acceptable Not Acceptable Total Rural cadre 195 305 500 Teaching cadre 140 160 300 Total 335 465 800



Basic workshop onResearch Methodology, Biostatistics &

Principles of GCP





Determination of Sample Size

Dr. Deepak Langade

7/24/2019 5:25 PM Sample Size Estimation 2

Objectives

List the factors influencing the sample size

Appreciate importance of incorrect sample size in research

Calculate the sample size using appropriate formulae


Factors affecting sample size

Size of populationResources – subjects, financial, manpowerStudy Design – Crossover / Parallel / Paired Method of Sampling – random, stratifiedDegree of difference ( ) to be detectedMargin of Error (ME)Variability (S.D.) – pilot study, historical


Factors affecting sample size

Degree of Accuracy (or errors)- Type I error (alpha) p<0.05- Type II error (beta) less than 0.2 (20%)- Power of the test (1 – β): more than 0.8 (80%)Statistical FormulaeDropout rate, non-compliance to Rx


Correct ( ) decisions and Types of Errors (X) in hypothesis testing

X

X

Difference exists (H1) No Difference (H0)

Difference exists (H1)

No Difference

Do not reject (H0)

TRUE Situation

CONCLUSION hypothesis test

(Power or 1-beta)

Type II error or

Beta error

Type I error or

Alpha error


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Approach to sample sizeDetermine the expected difference

Find out the Standard deviations of both groups

Set alpha error to be tolerated viz. P = 0.05

Decide the power of the study desired viz. 80%, beta error 0.2

Select the appropriate formula

Calculate the sample size using the formula

Give allowance for drop-out rate

Give allowance for non-compliance of treatment if possible7/24/2019 5:25 PM Sample Size Estimation 7

Incorrect sample size

Wrong conclusions

Poor quality research (Errors) Type II error can be minimized by increasing the sample size

Waste of resources

Loss of money

Ethical problems

Delay in completion


Formulae for Sample Size


Comparison of means (two groups)

Alpha=0.05,

Beta=0.2, (power 80%)

Between group comparison (Unpaired)

n = 16 X (S.D./M1-M2)2

Within group comparison (Paired)n = 8 X (S.D. of differences/M1-M2)2


2

2/2

2

difference)Z(2 Z

n

Formula for difference in means

Sample size in each group (assumes equal sized groups)

Represents the desired power (typically .84 for 80% power).

Represents the desired level of statistical significance (typically 1.96).

Standard deviation of the outcome variable Effect Size (the

difference in means)7/24/2019 5:25 PM Sample Size Estimation 11

Comparison of percentages (two groups)

Alpha=0.05,


n = 8 X p1q1 + p2q2

---------------(p1-p2)2


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221

2/2

)(p)Z)(1)((2

pZpp

n

Formula for difference in proportions

Sample size in each group (assumes equal sized groups)

Represents the desired power (typically .84 for 80% power).

Represents the desired level of statistical significance (typically 1.96).

A measure of variability (similar to standard deviation)

Effect Size (the difference in proportions)


Comparison of one mean only

Alpha=0.05,


n = 8 X (S.D./M1-M0)2


Sample Size Example

Effect on sleep


Sleep Aid Example : 1 Sample

Study the effect of new sleep aid1 sample testParameter – Sleep time after taking the medication for one weekTwo-sided test, α = 0.05, power = 90%Difference = 1 (4 hours of sleep to 5)Standard deviation = 2 hr


Sleep Aid Example

1 sample test2-sided test, α = 0.05, 1-β = 90%σ = 2hr (standard deviation)δ = 1 hr (difference of interest)

2 2 2 21 / 2 1

2 2

( ) (1.960 1.282) 2 42.04 431

Z Zn


Effect of Difference

Change difference of interest from 1hr to 2 hrn goes from 43 to 11

2 2

2(1.960 1.282) 2 10.51 11

2n


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Effect of Power

Change power from 90% to 80%n goes from 11 to 8(Small sample: start thinking about using the t distribution)

2 2

2(1.960 0.841) 2 7.85 8

2n


Effect of S.D.

Change the standard deviation from 2 to 3n goes from 8 to 18

2 2

2(1.960 0.841) 3 17.65 18

2n


Sleep Aid Example: 2 Sample

2 2 2 21 / 2 1

2 2

2( ) 2(1.960 1.282) 2 84.1 85 170 total!1

Z Zn

Original design (2-sided test, α = 0.05, 1-β = 90%, σ = 2hr, δ = 1 hr)Two sample randomized parallel designNeeded 43 in the one-sample designIn 2-sample need twice that, in each group!4 times as many people are needed in this design


Conclusion

2 21 / 2 1

2

4 ( )2

Z ZN

Changes in the detectable difference have HUGE impacts on sample size20 point difference → 25 patients/group 10 point difference → 100 patients/group 5 point difference → 400 patients/groupChanges in α, β, σ, number of samples, if it is a 1- or 2-sided test can all have a large impact on your sample size calculation


Group Activity


Group Task 1 - Question

The cure rate of disease is 20% with a known drug treatment. It is claimed that yoga is better than the drug and a trial is to be conducted find out the truth. It is decided that a even 10% increase in cure rate would be clinically important.

The alpha and beta were set at 0.05 and 0.2.

The results will be analysed using Chi Square test.

How many patients would be required for the trial?


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Task 1 - Answer

Aim – To see whether yoga is better than standard drug Rx in curing the pt.Analysis type- comparison of proportion Parameters- cure rate 20% vs 30%No. of groups – 2 p1=20 q1=80, p2=30 q2=70Set alpha=0.05, beta=0.2, Power=0.8Statistical formula to be used

n = p1q1 + p2q2 X 8(p1-p2)2 Ans. 296


Group Task No. 2 - Question

The mean(+SD) hospital stay of patients after a conventional surgical procedure (CP) is 12.3 ( 4.8) days. A modified procedure (MP) is to be tried to reduce the hospital stay.

Their hospital stay will be compared using unpaired t test at p<0.05 with power of 80%.

The minimum clinically important difference in the duration of hospital stay is expected to be 3.

Calculate the sample size for each group ?


Task 2 - Answer

Aim – To see whether modified procedure reduces the hospital stay as compared to conventional procAnalysis type- comparison of mean, unpaired dataParameters- duration of hospital stay 12.3 vs 9.3 No. of groups-2Given M1=12.3, M2=9.3, SD= 4.8 Set alpha=0.05, beta=0.2, Power=0.8Statistical formula to be used

n = 16 X (S.D./M1-M2)2

Ans 40.967/24/2019 5:25 PM Sample Size Estimation 27

Group Task 3 - Question

The mean fruit juice consumption in the population is 5 oz./day.

Dennison and colleagues wanted to know whether mean juice consumption in 2 year old children is different from 5 oz./day – either more or less by1 oz/day.

SD is 3 oz/day.

Calculate the sample size required ?


Task 3 - Answer

Aim – To see whether fruit juice consumption differs by 1 from the population (Normal standard) mean of 5oz./dayAnalysis type- comparison of mean, paired dataParameters- fruit juice/day 5 vs 6 or 4 No. of groups-1Given M1= 4 or 6, M0=5, SD= 3

Set alpha=0.05, beta=0.2, Power=0.8Statistical formula to be used

n = 8 X (S.D./M1-M0)2

Ans 727/24/2019 5:25 PM Sample Size Estimation 29

Hands – on

SamplePower (IBM SPSS)NCSS PASSMedcalcStataSASStatisticaGraphpad


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Exercise-1

A survey estimated that 20% of all people aged 16 to 20 from UP drove under the influence alcohol.A similar survey is planned for Maharashtra. They want a 95% confidence interval to have a margin of error of 0.04.

Find the necessary sample size if they expect to find results similar to those in the UP.


One proportion

P = 20%Margin of error (difference) = 4%Z-score

1.645 90%1.96 95%2.58 99%

N = 384.27/24/2019 5:25 PM Sample Size Estimation 32

Exercise-2

A researcher wants to assess the mean change in blood sugar with a oral antidiabetic drug. An earlier study reported a mean and standard deviation of 140 mg% and 100 mg%.

How many patients should be included for a 95% C.I. to have a margin of error of 20?


One mean

S = 100Margin of error (difference) = 20t = 1.96 for 95% confidence (t-distribution)

N = 199


In reality, the SD is now 10. Using the sample size you used above, would the margin of error for a 95% C.I. be -

<20, 20, or >20

Margin of error decreased to 10in same proportion of SD


Thank You !


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For the following data identify the study design and using appropriate formula calculate minimum sample size required for given studies

1) A local health department wishes to estimate the prevalence of tuberculosis among children under five years of age in the locality. How many children should be included in the sample so that the prevalence may be estimated to within 5 % points of the true value with 95 % CI if it is known that the true rate is unlikely to exceed 20%?

2) In a pilot survey in a developing country, an epidemiologist compared a sample of 50 adults suffering from a certain neurological disease with a sample of 50 comparable control subjects who were free of the disease. Thirty of the subjects with the disease and 25 of the control were involved in fishing related occupations. If the proportion of the population involved in fishing related occupation in the entire population is similar to that observed in pilot survey. How many subject should be included in a larger study in each of the two group if the epidemiologist whishes to be 90% CI detecting the true difference between the two group at the 5 % LS

3) A health department nutritionist, wishing to conduct a survey among population

of teen age girls to determine their average protein intake, he would like an interval about 10 unit wide ie he would like his estimate to be within 5 unit of the true value in either direction at 5 % LS. From the past experience he feels that the population standard deviation is probably about 20 gms.

4) Suppose we want to test the hypothesis that, mothers with low economic status

deliver babies whose birth weights are lower than normal. To test this hypothesis a list of birth weights from 100 consecutive, full term, live-born deliveries from the maternity ward of a hospital in low SES area is obtained. The mean birth weight is found to be 2.4 kg with SD = 0.24 kg suppose we know from nationwide survey based on millions of deliveries that the mean birth weight is 2.8 kg with standard dev of 0.35 kg

5) In a hypothetical disease the fatality rate is 40%. A new remedy is available and preliminary experiments suggest that it reduces the fatality rate to 35 % it is decided to carry a careful clinical trial with an equal no of patients in each group. What is the smallest number that must be included in each group if the drop of 5% in the fatality rate is to be statistically significant at 95% confidence limit.

6) An epidemiologist is planning the study to investigate the probability that the certain lung disease is linked with exposure to a recently identified air pollutant. What sample size should be needed in each of the two groups exposed and non-exposed, if epidemiologist wishes to estimate the relative risk within 50 % of the true value (which is believed to be approximately = 2 ) with 95 % confidence. The disease is present in 20 % of people who are not expose to the air pollutant.

7) Given that Westoff and Bumpass (1973) approximately 30% women of childbearing age will have exposure to OC within three months of conception P0 = 30 % or 0.3 Alpha (α) = 0.05 Beta (β) = 0.10 RR = 3 Calculate sample size for given study

For RCT with Equal Allocation

2

12

2

( * (2(p*q) )c c t t

c t

Z z p q p qnc

p p

Sample size for continuous outcome measure

2 2

12

2

( ) ( )t c

c t

z znc

(Case control ) P0 = RR = Alpha = Beta =

21 1 0 01

22

1 0

( * (2(p*q) )Z z p q p qn

p p

01

0

( *R)[1 (R 1)]

ppp

Cohart study RR= P(e) / P(c)

2

2[(1 ) (1 ) / ]

log (1 )e e c c

e

z p p p pn

24-07-2019

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2

Questionnaire Designing

Nima Rege

:Questionnaire Designing: Nima Rege

Session ObjectivesAt the end of this session, participants will be able to:

Select questionnaire as a tool for collecting information

Enumerate types of questions

Describe care to be taken while wording questions

Select appropriate response format

Appreciate importance formatting a questionnaire

State importance of pretesting a questionnaire

Describe strategies to increase response rate3:Questionnaire Designing: Nima Rege

Questionnaire

Is a tool/Instrument to collect data systematically

when survey is selected as a method of

obtaining information

4:Questionnaire Designing: Nima Rege

Survey

Method to obtain information

- for a specific purpose

- from or related to a specific population

- that is analyzable to meet the purpose.


Survey types

Interview

Individual- Face to face- Telephonic

Focus group

Mail surveyGroup administeredDrop off surveyElectronic survey

e-mailonline

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Self-completion


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Questionnaire is NOT the method of choice

when little is known about the subject

:Questionnaire Designing: Nima Rege 8

1. Decide the information required- Research question

2. Define the target respondents3. Choose the method(s) of reaching your target

respondents4. Decide on question content5. Develop the question wording6. Put questions into a meaningful order and format7. Check the length of the questionnaire8. Pre-test the questionnaire9. Develop the final survey form

Questionnaire designing steps


9

Questions and questionnaire are

vital to successful survey.


How to get 'right' questions?

10

Thinking of a question is not a problem; coming up with right question is.

Questions


'Right' questions

11

List variablesSources include patients/subjects (focus groups, key informant interviews), clinical observation, your prior research, and expert opinion

Literature search: theory or conceptual framework, published work of others

Borrow from other instruments

Solicit input from peers:Questionnaire Designing: Nima Rege 1212

Questionnaire Design

Introduction

Instructions

Questions

Closing


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INTRODUCTION


INTRODUCTIONMention the purpose of the questionnaire Provide reason for selection of participantsInform what the participants are supposed to do and request for timeExplain how the information obtained will be usedAssure research ethics: right of non- acceptance, anonymity, confidentialityWhere and when to return, whom to contact for queriesPromise sharing of resultsAcknowledge participant's co-operationUse language appropriate for participants selectedGive researcher's details

Establishes rapport


INSTRUCTIONS


INSTRUCTIONS

DirectionsWhat the respondents are supposed to do?

Transitional statementsTo signal that a new topic is about to begin

To start new pages

To break up the monotony of a long series of questions

In this next section of the survey, we'd like to ask youabout your personal relationships. Remember, we do

not want you to answer any questions if you are

uncomfortable doing so.


Questions

:Questionnaire Designing: Nima Rege 17 1818

Question design

Type

Wording

Response format

Placement and Sequence


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Types of QuestionsOpen ended

Closed endedTwo option responses

Single best response

With multiple answers

Ordered responses –rating scales

Ranking

Filter questions

Partially closed ended:Questionnaire Designing: Nima Rege 20

Have you used computer for graphical presentation?

Yes No

If yes, How often?DailyNot daily but at least twice a weekNot twice weekly, but at least 4 times a monthLess than 4 times a monthNever used till now


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Types of QuestionsPlease indicate your level of agreement/disagreement with the following statements by circling the number that best describes your opinion (PLEASE NOTE: 5=Strongly Agree; 1=Strongly Disagree)

Strongly Agree Agree Neutral Disagree Strongly

Disagree

Some professors are much more interesting than others

5 4 3 2 1

Lengthy lectures can be tiring

5 4 3 2 1

Bipolar scale : Likert response scale:Questionnaire Designing: Nima Rege 22

Question Wording


Question Wording

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SimpleSpecific Avoid jargon, abbreviationUnambiguousAvoid biasAvoid unnecessary repetitive, leading questionsCareful phrasing:Questionnaire Designing: Nima Rege 24

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Phrasing Questions1. Use clear wording

“Often? Sometimes? Regularly?”

2. Be specific

"In general, how good is your health?"

Would you say your health, in general, is-------

3. Avoid making assumptions

How many children do you have?

Do you have children?

4. Include all necessary information

Do you agree or disagree with the assessment

strategy mentioned in vision 2015?:Questionnaire Designing: Nima Rege 25

5. Double-Barreled Questions Do you think the patients should visit OPD regularly and contact doctors telephonically time to time?How satisfied are you with your treatment and the advice about diet?

6. Double NegativeWould you say that your doctor is not inattentive?

7. Casting Too Big of a NetIs Gynaecology department efficient ?

8. Sensitivity

Funneling questions to introduce sensitive topics 26:Questionnaire Designing: Nima Rege

9. Avoid “deceptively short” questions or those with high respondent burden- complex tables - rank ordering- mental calculations- “check all that apply”

10. Language as understandable by the target participants

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Recently a survey was conducted by the United Nationsusing a sample from several different countries. Thequestion asked was:

" Would you please give your opinion about the foodshortage in the rest of the world?"

The survey was a huge failure. Why?• In Africa they did not know what 'food' meant.• In Western Europe, they did not know what 'shortage'

meant.• In Eastern Europe they did not know what 'opinion'

meant.• In South America they did not know what 'please'

meant.• And in the U.S., they did not know what 'the rest of the

world' meant. :Questionnaire Designing: Nima Rege

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I can’t decide whether to have ticks in boxes, crosses, circling or underlining

Response format

:Questionnaire Designing: Nima Rege 30Anchored or categorized VAS :Questionnaire Designing: Nima Rege

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31Checklist :Questionnaire Designing: Nima Rege

Broad or General Questions

Narrow or Specific Questions

The Funnel Approach to Ordering Questions


Questions: Placement

Group questions on one topicGroup similar type of question based on response formatPlace instructions where needed, not just at the beginning

:Questionnaire Designing: Nima Rege 33 34

• Simple, friendly, closed ended, easy to respond and should convey the theme of the survey

Early Questions

• Target questionsMiddle

Questions

• Optional questions like related to demographic data

• Sensitive questions on difficult or uncomfortable aspects

• open ended questions

Late Questions


Have you copied other students' MCQ answers in a degree exam?

By the way, do you happen to have copied other students' answers in a degree exam?Please tick one or more of the following items which correspond to how you have answered degree examination questions in the past.As we all know, most medical students have copied other students' answers in degree exams. Do you happen to be one of them?Give a scenarioComment and have you done or would you consider doing the above? 35:Questionnaire Designing: Nima Rege

CLOSING


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Questionnaire Design

Introduction

Instructions

Questions

Closing

Length of the questionnaire and time required for answering : keep that is absolutely necessary (2-4 pages)


The Golden Rule

Be sensitive to the needs of the respondent

Do unto your respondents as you

would have them do unto you!


Visual designAttractive, uncluttered formatConsider light pastel colorsAvoid excessively small or unusual fontsNumber and carefully align (vertically) questions and response optionsAvoid loose pages; booklet format if possible.Avoid splitting questions across columns/pages.Minimize the number and abruptness of format changes; use transitional sentences.


Response rate:50% to 90% is preferable but this may be unrealistic.

Telephone, mail and computer methods may result in much lower response.

Questionnaires don’t reach!

3–8% of items in any questionnaire are usually left blank.

Response rate for Survey


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1) Advance personalized invitation

2) Make the participants feel that they are

stakeholder in the study

3) Stamped, addressed, return envelope

4) Follow-up reminders

5) Incentives or prizes in return for completion

Strategies to increase response rate


Pretesting of Questionnaire

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Essential step!


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Participants fail to respond because they

Don’t understand questions Can’t complete the questionnaire Get bored or offended by questionsDislike how the questionnaire looks



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Purpose

To maximize the proportion of subjects answering

questionnaire - that is, the response rate.

To obtain accurate relevant information



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Questions that a pretest should answer:

Does a question measure what it is intended to measure?

Do respondents understand all the words?

Are questions interpreted similarly by all respondents?

Are the answers respondents can choose from correct?

Does any aspect of the questionnaire suggest bias on the part of the researcher?


DetermineValidity: How well the test measures what it supposed to measure?

Reliability : Whether the test produces stable and consistent results


Validity and reliabilityConstruct validity : Literature review to verify concepts and assumptionsContent validity : Expert judgment, other documents, keep some open questionsConcurrent validity: Compare responses with validated questionnaire

Back up with other evidencesPredictive validity: Predicting performanceFace validity: Whether questions ‘look’ right? Reliability: Test-retest reliability

Inter-rater reliabilityInternal consistency

Cronbach's coefficient 47:Questionnaire Designing: Nima Rege

Pretesting

Feedback on questions, response format and impression created by the questionnaire

Try tabulation and analysis procedures

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Revise


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Online survey programsHere are two online products for survey design and data collection:

SurveyMonkey: www.surveymonkey.comQuestionPro: www.questionpro.com


Critical appraisal checklist for a questionnaire study

BMJ. 2004 May 29; 328(7451):1312–1315


51

ReferencesCrawford IM. Questionnaire Design. Chapter 4. In, Marketing

Research and Information Systems. By Food and agricultural

Organization of United States. 1997 http:/www.fao.org

Taylor-Powell E. Questionnaire Design: asking questions with

purpose. In, Programme Development and Evaluation.

Cooperative Extension Publications. University of

Wisconsins. 1998; 1-17.

Boynton PM. Selecting, designing and developing your

questionnaire. BMJ 2004;328: 1312-1315

http:/ www statcan.gc.ca51:Questionnaire Designing: Nima Rege 52

Additional resourcesLinks to useful articles/guidelines on sampling

and survey methods:http://gsociology.icaap.org/methods/surveys.htmhttp://gsociology.icaap.org/methods/sampling.htmlhttp://gsociology.icaap.org/methods/

ICAAP is The International Consortium for the Advancement of Academic PublicationICAAP is supported by Athabasca University


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Thank You !:Questionnaire Designing: Nima Rege

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Synopsis Submission Process: Research Methodology

7/24/2019

Dr. VaishalI thakare 1

INSTITUTIONAL ETHICS COMMITTEE FOR BIOMEDICAL AND HEALTH RESEARCHD. Y. Patil School of Medicine

SUBMISSION OF RESEARCH PROPOSAL

Dr Vaishali Thakare

Member Secretary -IECBH

Institutional Ethics Committee :

• As per New clinical trial rules & regulations –

March 2019

• Two different registered ethics committee

– 1. IEC for Clinical trial

– 2. IEC for Biomedical & health

research – ACADEMIC

– ICMR guidelines

Plagiarism check


INSTITUTIONAL ETHICS COMMITTEE FOR BIOMEDICAL AND HEALTH RESEARCH D. Y. Patil School of Medicine

IEC for Clinical trial “New drug” means,1. A drug

Active pharmaceutical ingredient Phyto-pharmaceuticalNot been used in the country to any significant extent

2. A drug approved Modified or New indicationNew route of administrationNew dosage New dosage form

3. A fixed dose combination of two or more drugs To be combined for the first time in a fixed ratioRatio of ingredients in an approved combination - To be changed

4. Any drug approved Modified or sustained release form of a drug Novel drug delivery system

5. Vaccine

Academic clinical trialA clinical trial of a drug

already approved for a certain claim Initiated by any investigatorAcademic or research institution

For a New indication New route of administration New dose New dosage form

The results of such a trial Intended to be used only for academic or research purposes Not for seeking approval for marketing or commercial purpose

Biomedical and health research • Research Studies on

– Basic, applied and operational research – Clinical research

• Designed primarily – To increase scientific knowledge – about diseases and conditions– Their detection and cause – Evolving strategies for – health promotion &Prevention– Amelioration of disease and rehabilitation

• Does not include clinical trial as defined in clause

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IEC – Institutional Ethics CommitteeAll research proposals from Biomedical, social and behavioural

scienceInvolving

• Human participants• Their biological material & Data

To be reviewed & approved – Appropriately constituted EC To safeguard

Dignity , rights, safety and well-being - Research participants.

Approval Prior to their initiationContinuing - Ensure ethical complianceEC - Competent and independent in its functioning


MEMBERS Contact number Email ID

•Dr Hemlata Iyer 9820391401 [email protected]

•Chairperson•Dr.Vaishali Thakare 9869366927 [email protected]

•Member Secretary•Dr. Sharmila Patil 8850635503 [email protected]

•Dr. Abhay Chowdhary 9869009050 [email protected]

•Dr.Anant Patil 9920449433 [email protected]

•Dr. Ketan Vagholkar 9821341290 [email protected]

•Dr Sangita Sawant 9321214832 [email protected]

•Dr. Rochna Bakshi 9323272151 [email protected]

•Dr. Baishali Bhattacharya 9820268795 [email protected]

•Dr. DeepaliVidhate 9869687771 [email protected]

•Dr. Balasaheb Khadbade 9967294847 [email protected]

•Usha More 8108236868 [email protected]

•Tanmay Sinnarkar 9820466919 [email protected]

•Lakshmi Patro 9833632967 [email protected]

•Rajesh Dhoke 9320925899 [email protected]


• Modification & Innovation of submission process

• PG admission – 2019-2020

• Process of submission – Online

• LMS – Platform

• Portal is created


Process Of Synopsis / Research Proposal Submission For IEC Approval

Go to http://mydy.dypatil.edu

Dash board will come IECBH – Assignments 1. Form 2. Annexures

Download the form & annexures

Complete the form & annexuresapllicable to you and complete

Approval of the HOD & Guide Is mandatory

Upload the approved form & completed annexures back

Submit 1 hard copy to IECBH Pharmacology department


Circular for uploading (8/8/19- 10/8/19)

Completion of uploading of Proposal and AnnexureApproved by HOD and Guide (15/8/19)

Submission to IECBH (20/8/19)

Department Of Pharmacology - Ms. Poonam and Mr. Bahadur

Proposal for discussion

Submitted through website, approved by HOD and guide, hardcopies submitted to IECBH

Tentative dates for IEC meeting (22/8/19)

Pre-clinical and para-clinical (22/8/19 and (23/8/19)

Medicine and allied (24/8/19 to 27/8/19)

Surgery and allied (28/8/19 - 31/8/19)


If no changes – 20 days

Email communication in – 2weekChanges – Chairperson/Secretary

Resubmission – 2 weeks Communication 2 weeks

Submission of approved protocol – HOD & Guide

HARD COPY -IECBH Meeting in 3 days


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• Information required for

• Online submission of

• Synopsis/Research proposal

• Registration of your thesis – Mandatory

• CTRI - Separate portal – Thesis / Dissertation

• http://ctri.nic.in/Clinicaltrials/news.php?lid=17


Scientific title of the study Carry maximum information about the study In a few word(within 12-15 words) -seven elements

study setting, location, or both

Patients, organism, event, or relationship studied;

Intervention, treatment, or exposure;

Comparator or control group(s);

Outcomes or end points;

Study design, and sometimes

Duration of the study

Ex : 1. Evaluation of safety & efficacy if ITRA Vs Terbinafine

2. “Prospective randomized open lable clinical trial in Dermatology outpatient department

of tertiary care teaching hospital to evaluate the efficacy & safety of Itraconazole Vs

Terbinafine in resistant cases of various types of cutaneous dermatophytosis “

2.Principle investigator –

Name, Department, Designation, Email ID, Contact No.

3.Name of the guide & Co- Guide ( If it is) –

Details as above

4.Contact Person

5.FundingYes No

Self Organization – Govt. Non govt

6.Sponsor

7.Study site : Hospital , Additional site, School, Other sites

8.Health condition /Problem studied

Diabetic, Hypertensive, Post menopausal, Breast cancer, Peptic ulcer, Psoriasis,

Depression

9.Study population –

Healthy volunteers -

Diseased ( specify details – Stage, Duration etc)

• Type of the study –• Observational -• Simply Observing – collecting the data

• May be about intervention - Routinely practiced intervention

• “Comparative study to evaluate safety & efficacy of intrathecal lignocaine(2%) &

Bupivacaine in a patient undergoing caesarean section”

• Longitudinal – Following over a period of time ( Exposure & outcome – different time)

• Prospective - From exposure – Outcome

• Smoking to Lung cancer

• Retrospective - Outcome – Exposure

• Lung cancer to Smoking

• Cross-sectional - Same time (Snap shot picture)

• Ex: Random sample of schools across London may be used to assess the prevalence of

asthma among 12-14 year olds.

• Interventional

– Drug – Pharmacological Name , Dose, duration, Frequency,

– Who will bear the cost, what is to be done with once the trial is

over

– Lifestyle modification – Diet , Exercise

– Operative procedure – Standard of care, Newly introduced

– Other

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Study arm

o Single arm

o Double arm/Multiple arm

Parallel group - Running parallel

Cross over

Randomized - Method of randomization

Computer generated chart/Table

Flipping of coin

Nonrandomized

Control/Comparator group

Placebo - Ethical issues – explained

Standard drug/Method

Other

Blinding

Open label

Complete study design

• Inclusion criteria

• Exclusion criteria

• Primary outcome

• Secondary outcome

• Sample size

• Too large – resources waste

• Too small – No inference

• Method of sampling

• Calculation

• Phase of trial

• Material & method

– Groups

– Enrollment

– Data collection method

– Estimated duration

– Study procedure

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• Statistical details

– Test

– Level of significance

• Brief summary

• References : Vancouver style only

• Recent one – Last 5 years

• Please upload the following annexureMandatory• Informed consent form

– Download the format – English – Hindi, Marathi,English– Translation form

• Case record sheet/Patient proforma• Patient information Sheet –

– Download the format – English– Hindi,Marathi,English

IF APPLICABLE

1. Other –Questionnaires - Validation is MUST

2. Waiver of consent form

3. Checklist for Research Involving Pregnant Women & Foetus

4. Checklist for Research Involving Cognitively Impaired Adults

5. Checklist for Research Involving Students, Employees or Residents6. Checklist for Genetic Research

• Group activity• 1. Metformin + Glipizide Vs Metformin + Sitagliptin

In Type 2 DM• 2. Standard vs modified nailing & plating method

for open reduction of # forearm bones• 3. Observational study to analyze prescribing

pattern in dermatology department• 4. Evaluation of efficacy of misoprostol

Versus Dinoprostone Gel For Induction of Labour

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Basic workshop onResearch methodology, Biostatistics &

Principles of GCP22 – 24 July 2019

Venue: Pushpanjali, 3rd floor Auditorium, D Y Patil Hospital, Nerul

Jointly organized by

Dept. of Obs. & GynaecologyInstitutional Ethics Committee (IEC)

7/23/2019 9:53:39 AM I.E.C. - GCP WORKSHOP 1

Regulations in Clinical Research DR. DEEPPAK LANGADE M B B S , M D , P G D A SS ( A P P L I E D S TAT I S T I C S )

PROF. & HEAD, PHARMACOLOGYSECRETARY, INNSTITUTIONAL ETHICS COMMITTEE ( IEC)CHAIRRMAN, IAECCHAIRRMAN, PHAARMACOVIGILANCE COMMITTTEE

7/23/2019 9:53:40 AM DR. DEEPAK LANGADE 3

Drugs & Cosmetics Act 1940, and Drugs & Cosmetic Rules 1945

Regulatory body in India

Central Drugs Standard Control

Organisation(CDSCO)

Drug Marketing Approval

Import of Drugs

Clinical Trials for New drugs

Drug Safety in India (Pharmacovigilance)

Materiovigilance

Haemovigilance

Drugs Controller General (I)

(Centre)

FDA (State)


Schedule ‘Y’CDSCO & DTAB in 2005

7/23/2019 9:53:40 AM DR. DEEPAK LANGADE 5 7/23/2019 9:53:40 AM DR. DEEPAK LANGADE 6

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New Drugs and Clinical Trials Rules, 2019

G.S.R. 104(E) 02ND FEB. 2018

G.S.R. 227(E) 19TH MARCH 2019


New Drugs and Clinical Trials Rules, 2019


• Preliminary & DefinitionsChapter-I• Authorities & OfficersChapter-II• EC for Clinical Trial, BA and BE studiesChapter-III• EC for Biomedical and Health ResearchChapter-IV• CompensationChapter-VI• MiscellaneousChapter-XIII

Chapter - I


Rules shall come in to force from the date of

their publication in the Official Gazette

Except Chapter IV which shall come in to force after 180

days

Biomedical and Health ResearchResearch including studies, designed primarily to increase scientific knowledge about diseases and conditions (physical or socio-behavioral); their detection and cause; and evolving strategies for health promotion, prevention, or amelioration of disease and rehabilitation but does not include clinical trial as defined in clause (j) of Rule 2.


Academic Clinical Trial

7/23/2019 9:53:40 AM

A clinical trial of a drug already approved for a certain claim and initiated by any investigator, academic or research institution for a new indication or new route of administration or new dose or new dosage form, where the results of such a trial are intended to be used only for academic or research purposes not for seeking approval of the regulatory authority of any country for marketing or commercial purpose

DR. DEEPAK LANGADE 11

New Drug(i) a drug, including API or phytopharmaceutical drug, which has not been used in the country to any significant extent, and has not been approved as safe and efficacious by the Central Licencing Authority with respect to its claims; or

(ii) a approved drug with modified or new claims including indication, route of administration, dosage and dosage form; or

(iii) a FDC of two or more drugs; or(iv) a modified or sustained release form of a drug or novel drug delivery system; or(v) a vaccine, r-DNA derived product, living modified organism, monoclonal antibody, stem cell derived product, gene therapeutic product or xenografts, intended to be used as drug;


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The new drugs shall continue to be new drugs ..for a period of FOUR years from the date of their permission granted by the Central Licencing Authority and the drugs referred to in sub-clauses (iv) and (v) shall always be deemed to be new drugs;


Clinical trialAny systematic study of a new drug or Investigational New Drug (IND) in human subjects to generate data for discovering or verifying its,-

i. clinical or;ii. pharmacological including pharmacodynamics,

pharmacokinetics or;iii. adverse effects,with the objective of determining the safety, efficacy or tolerance of such new drug or investigational new drug;


Orphan Drug

7/23/2019 9:53:40 AM

A drug intended to treat a condition which affects not more than five lakh persons in India




EC FOR CLINICAL TRIAL, BIOAVAILABILITY AND

BIOEQUIVALENCE STUDY

• To review and oversee the conduct of research for New Drugs and BA/BE Studies

EC BIOMEDICAL & HEALTH RESEARCH

• To review and oversee the conduct of such research as detailed in National Ethical Guidelines for Biomedical and Health Research Involving Human Participants


Composition of IECMinimum 7 members from: medical, non-medical, scientific and non-scientific areas …

At-least ….

(i) one lay person;

(ii) one woman member;

(iii) one legal expert;

(iv) one independent member from other related field - social scientist


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Rules

New Drugs & Clinical Trials Rules, 2019, Good Clinical Practice (GCP) Guidelines, and other regulatory requirements to Safeguard the rights, safety and well-being of study subjects,


Role of IEC

All proposals on research involving human subjects must be reviewed and approved by an Ethics Committee (EC)


Functions of Ethics CommitteeNEW DRUGS & CLINICAL TRIALS RULES 2019


(i) review and accord approval to a clinical trial or BA/BE study

protocol and other related documents,

Oversee the conduct of clinical trial to safeguard the rights, safety

and wellbeing of trial subjects in accordance with these rules,

GCP Guidelines and other applicable regulations;


(ii) make at appropriate intervals, an ongoing review of the

clinical trials for which it has accorded approval and such

review may be based on periodic study progress reports

furnished by the investigators or

monitoring and internal audit reports furnished by the sponsor or

by visiting the study sites;

(iii) indicate the reasons that weighed with it while rejecting or

asking for a change or notification in the protocol in writing and a

copy of such reasons shall also be made available to the Central

Licencing Authority;


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(iv) where any Serious Adverse Event (SAE) occurs to a study

subject,

the Ethics Committee shall analyse the relevant documents

pertaining to such event and forward its report to the DCGI and

comply with the provisions of Chapter VI;


(v) where at any stage of a clinical trial, it comes to a conclusion

that the trial is likely to compromise the right, safety or well-being

of the trial subject,

the IEC may order discontinuation or suspension of the study

and the same shall be intimated to the head of the institution and

the DCGI;



(vi) allow any officer authorised by the Central Licencing Authority to enter, with or without prior notice, to inspect the premises, any record, or any documents related to clinical trial, furnish information to any query raised by such authorised person, in relation to the conduct of clinical trial and to verify compliance with the requirements of these rules, Good Clinical Practices Guidelines and other applicable regulations for safeguarding the rights, safety and well-being of trial subjects;


(vii) comply with the requirements or conditions in addition

to the requirements specified under the Act and these rules

as may be specified by the Central Licencing Authority with

the approval of the Central Government,

to safeguard the rights of subjects.

Vulnerable subjects


STUDENTS EMPLOYEES CHILDREN ELDERLY MENTALLY CHALLENGED

Sources of funding


ICMR - Indian Council of Medical Research

Department of Biotechnology

Department of Science and Technology

CSIR - Council for Scientific and Industrial Research

Pharmaceutical Industry

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Collaboration outside India

Additional approval from the Health Ministry Screening Committee, a committee that works out of ICMR


CompensationTRIAL RELATED INJURY


Chapter - VI


Rule 39. Compensation in case of injury or death in clinical trial or bioavailability or bioequivalence study of new drug or investigational new drug.

Where any death of a trial subject occurs during a clinical trial or bioavailability or bioequivalence study, the legal heir of the trial subject shall be provided financial compensation by the sponsor or its representative who has obtained permission

Compensation: 7th Schedule

7/23/2019 9:53:41 AM

DeathCompensation = (B x F x R) / 99.37Where,B = Base amount (i.e. 8 lacs)F = Factor depending on the age of the trial subject as per Annexure 1 (based on Workmen Compensation Act)R = Risk Factor depending on the seriousness and severity of the disease, presence of co-morbidity and duration of disease of the trial subject at the time of enrolment in the clinical trial between a scale of 0.5 to 4.0


(1) 0.5 terminally ill patient (expected survival not more than (NMT) 6 months)

(2) 1.0 Patient with high risk (expected survival between 6 to 24months)

(3) 2.0 Patient with moderate risk

(4) 3.0 Patient with mild risk

(5) 4.0 Healthy Volunteers or trial subject of no risk.


High mortality

However, in case of patients whose expected mortality is 90% or more within 30 days, a fixed amount of Rs. 2 lacs should be given.


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Permanent disability

Compensation = (C x D x 90) / (100 x 100)

Where :D = Percentage disability the trial subject has suffered.C = Quantum of Compensation which would have been due for payment to the trial subject's nominees) in case of death of the trial subject.


Congenital anomaly or birth defect

Lump sum amount - Fixed deposit or alike, which shall bring a monthly interest amount equivalent to half of minimum wage of the unskilled worker (in Delhi). The quantum of compensation in such cases of SAE shall be half of the base amount as per formula for determining the compensation for SAE resulting into death.The medical management of the child as long as required shall be provided over and above the financial compensation.


Insurance


Other Guidelines

•Good Clinical PracticesGCP•Good Manufacturing PracticesGMP•Good Laboratory PracticesGLP•Good Documentation PracticesGDP


Thank You


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Research Methodology Workshop 24-07-2019

Dr. Varsha Vyas 1

ROLE AND RESPONSIBILITIES OF PRINCIPAL INVESTIGATOR [PI]

Dr Varsha Vyas Professor in Anaesthesia

Principal Investigator[PI]

The PI has primary responsibility for achieving the success of the research

Varsha Vyas 3

ELIGIBILITY of PI

• Preferably from an post-graduate medical institute or specialty/super-specialty hospital.

• Adequate training and experience in his/her specialty.

• Interested in conducting the study.• Up-to-date Resume/CV should be

submitted to IEC.• Familiar with the use of investigational

product and should comply with norms of GCP and the applicable regulations.

Varsha Vyas 4

Responsibilities of PI

Varsha Vyas 5

Adequate Resources

Adequate medical care of the subjects

Communication with IRB/IEC

Protocol compliance

Accountability of trial supplies

Randomization procedure & un-blinding

Written informed consent

Master file (Maintenance of Records)

Progress of trial

Reporting of Adverse drug reactions (Safety Reporting)

Premature study termination

Final report

ADEQUATE RESOURCES

• Have adequate number of staff to assist in conduct of study.

• Should have adequate facilities for the conduct of study.

• Should be able to recruit required number of subjects for study.

• Should have sufficient time to properly conduct and complete the study.

• Should permit monitoring and auditing by sponsor.• Maintain a list of qualified persons (Investigating

team) to whom study related duties are assigned.• Should inform all persons assisting in the study about

the protocol, investigational product and study related duties

Varsha Vyas 6

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Dr. Varsha Vyas 2

Role of PI

Varsha Vyas 7

Delegate responsibilities to team.

Team memebrs should be qualified and trained.

Supervising entire study activities.

MEDICAL CARE OF SUBJECTS

• Responsible for all study related medical decisions

• Ensure adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory values related to the study.

MEDICAL CARE OF TRIAL SUBJECTS

PI should inform a subject when medical care is needed for intercurrent illness of which the investigator becomes aware

Varsha Vyas 9

MEDICAL CARE OF SUBJECTS

Varsha Vyas 10

The PI should inform the subject’s primary physician about the subject’s participation in the study if the subject agrees to the primary physician being informed.

If the subject is withdrawing prematurely from a trial, the PI should ascertain the reason(s), while fully respecting the subject’s rights


Varsha Vyas 11

PI should apply to the IEC for approval of the study.

Documents for IRB/IEC approval:• Study protocol• Investigator’s brochure• Screening & case report forms• Subject recruitment procedures• Details of the tests to be performed• References and literature supporting the• need & design of the study • Informed consent forms• Patient Information Sheet


• PI should initiate a study only after obtaining a written and dated approval to conduct the study from IEC.

• PI should provide all updated documents subject to review.

• If the protocol has to be amended, the proposed protocol amendment should be submitted as soon as possible to:

(a) IRB/IEC for review and approval.(b) The sponsor for agreement.(c) The regulatory authorities.

Varsha Vyas 12

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Dr. Varsha Vyas 3

COMPLIANCE WITH PROTOCOL

Varsha Vyas 13

Should conduct the trial in compliance with the protocol approved by the

IEC

Should not implement any

deviation from the protocol without

approval from IEC

IPINVESTIGATIONAL

PRODUCT

• Accountability of study medication.

• Maintain all records for medication.

• Medicine should be stored as specified by the law.

• Medication should be used in accordance with the approved protocol.

• Correct use of investigational products is explained to each subject.

Varsha Vyas 14

Randomization Procedures & Unbinding

• Follow the randomization procedures as per the protocol.

• Ensure that the blinding is broken (Unblinding) only in accordance with the study protocol.

Varsha Vyas 15

Informed Written Consent• Written informed consent should be

obtained from each and every patient before participating in the study.

• Informed Consent Forms (ICF) should also be approved by the IEC.

• Consent should be obtained in compliance with GCP and ethical principles laid out in Declaration of Helsinki.

• Participation in the trial should be voluntary and neither the PI nor the trial staff should force the subject to participate in the study.

Varsha Vyas 16

Informed Consent Process• PI should inform to the

subject all pertinent aspects of the study.

• Language should be non-technical and understandable to the subject (Vernacular).

• Should not contain any language that causes the subject to waive any legal rights or appears to release the PI, institution or sponsor from liability for negligence.

• PI should provide ample time and opportunity to the subject to decide whether to participate in the study or not.

Varsha Vyas 17

Informed Consent Process

• If the subject is illiterate, a legally acceptable representative or an impartial witness should be present during discussion.

• In such case the consent form should be signed by the person present during the discussion.

• The informed consent should also be signed by the person who conducted discussion with time and date.

• The informed consent discussion and the written informed consent form should include explanations to all aspects of the study.

• The subject should receive a copy of the signed and dated written informed consent form prior to participation in study.

Varsha Vyas 18

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Dr. Varsha Vyas 4

Informed Consent Process

Varsha Vyas 19

In emergency - Consent of subject’s legally acceptable representative should

be taken.

In case of children - Legally Acceptable Representative [LAR]

Contents of Informed Consent

• That the study involves research• Purpose of the study• Trial treatments and the probability of random assignment• Procedures to be followed• Subjects responsibilities• Aspects of the study that are ‘experimental’• Anticipated risks and inconveniences to the subject or

nursing infant• Expected benefits• Alternative modalities of treatment available to the subject• Compensation and/or treatment available to the subject in

case of study related injuryVarsha Vyas 20

Contents of Informed Consent

• Anticipated expenses to the subject due to participating in the study

• That the subjects participation is entirely voluntary, and that the subject can withdraw from the study at any time, without penalty or loss of benefits to which the subject is otherwise entitled

• Records identifying the subject will be kept confidential• Information about the persons to be contacted in case of

study related injury• Foreseeable circumstances or reasons under which the

subjects participation may be terminated• Expected duration of the subjects participation in the study• Approximate number of subjects involved in the studyVarsha Vyas 21

Records & Documents

• The PI/institution should maintain adequate and accurate source documents and trial records that include all pertinent observations on each of the site's trial subjects.

• Source data should be attributable, legible, contemporaneous, original, accurate, and complete.

Varsha Vyas 22

Correction of records

• Changes to source data should be traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an audit study)

Varsha Vyas 23

Records to be maintained

• Screening forms• Patient screening log• Patient information sheets & ICF• Adverse event forms• Communication records• Updated record of the study

medication• All original records of the subjects

(laboratory, clinical, ECG, X-ray, Scan, USG, Doppler etc.)

Varsha Vyas 24

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Dr. Varsha Vyas 5

Safety reportingAll SAE should be reported immediately to the concerned authority.

Varsha Vyas 25

Final Study Reports

• Upon completion of the trial, the PI should inform the IEC with study summary.

• The final report to be prepared.• PI should sign the final report.

Varsha Vyas 26

Questions ??Varsha Vyas

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Research Methodology: D Y Patil University School of Medicine

1

How to write and appraise an original scientific paper


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Objectives• Types of publication• Primacy of research question• Structure of a scientific paper

TitleSummary / AbstractIntroductionMethodologyResultsDiscussion

• Critical appraisal (check list)Research Methodology: D Y Patil

University School of Medicine3

Types of Publication

• 2 Primary Types

(A) Original Research Articles(B) Reviews

(Other than original research)


4

Types of Publications

• Original article • Short communication• Case report • Review • Editorial • Letter/• Correspondence·

• Technical note • Pictorial essay • Commentary • Non- scientific

material • Others


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Original Research Article• Report of a study written by the researchers

who actually did the study.• The researchers describe their

– hypothesis– the purpose of the study – the research methods.– Interpretation of results – Discussion of possible implications.


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Original Research Article• Most important and common• Provides new information based on original

research. • Supported by in-depth statistical analysis of

the data provided in the results. • Structure IMRAD


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Primacy of the research question• Central organizing principle of the paper

• Key attributes:1. specificity2. originality or novelty3. relevance to a broad scientific community


8

Formal structure of scientific journals and types of Scientific papersDavid Sharp


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7 RULES


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Rule #1-

Create time blocks in your daily schedule for writing


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Rule #2• Create a outline and discuss it with your

mentors or peers

• Outline (level1):-What is the topic of my paper?-Why is this topic important?-How could I formulate my hypothesis?-What are the necessary outcomes to bemeasured?


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The Basic Structure(SIMRAD)

TitleSummary (Structured Abstract)Introduction (What Question was asked?)Methods (How was it Studied?)Results (What was Found?)Analysis (How data was analysed?)Discussion (What Do the Findings mean?)

Figures, Tables, References, AcknowledgementsResearch Methodology: D Y Patil


Structure of a PaperScientific writing follows a rigid structure –A paper can be read at several levels:

• Some • refer to the title • only the title and abstract • the paper for a deeper understanding

• Hence each section should be complete, accurate and self explanatory


14


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• Start writing as rough drafts

• Do not get tempted to edit your writing during the first draft

• Revise later, followed by feedback from colleagues.


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Rule #3

Material and methods

• Most important part of the manuscript

• Flaws in this section are most common reasons for rejection of an article


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To describe the study in sufficient detail so that other competent researchers canrepeat the study

what was done?which type of study – its locationwhat is the duration?how was it done?how will the data be analyzed?

Main Purpose


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When should you write material and methods ?

• Before start of the study

• After completion of study, material and methods are written first during manuscript preparation.


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Grammar

• Avoid complex sentence structure

• Use simple and clear English

• Passive voice

• Past tense


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Use of past tense and passive voice

I incubated the sample at 37 C for 3 days

The sample was incubated at 37 C for 3 days .

We used ANOVA to compare the means.

ANOVA was used to compare the means.


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Describe the method used

Describe the materials used

Describe the research methodology


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1 . Materials • Patients /volunteers/subjects/ animals• Drugs , chemicals, reagents, plant extract• Cell lines, tissue cultures, immune sera, culture

medias, etc• Kits • Questionnaires• Instruments• Softwares


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Material - Animal studies

• Species, Strain• Number of animals• Age• Gender• Weight • Physiological or pathological status• Diet • Housing conditions • Name of the supplier• Ethics committee approval


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Material - Clinical study

• Subjects - patients , volunteers• Approval from ethics committee• Informed consent• Source of the population• How were they recruited ? • Exclusion and inclusion criteria• Sample size and randomization in detail• Relation between control and study group – whether

matching was done ?


25

Material - Drugs / chemicals

• Generic name• Chemical name of non standard drugs• Suppliers name• Dose and dosage form• Route of administration• Schedule of administration


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Material cont..

Plant extract

• Species • Part of the plant • Plant identification by a botanist• Method of extraction


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Material cont..

Questionnaire• Validated or pretested questionnaireInstruments (in case of animal studies) -

•model details• manufacturer• city of manufacture• any modification • illustrations if required


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2. Methods • Study design• Study location • Masking / blinding • Exact methodology of the study • Approved method• If the method is new, all details must be provided

/ any modifications• Questions such as “how” or “how much” must be answered

and not left to be puzzled over


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Task - 1

• "135 microliters of sample one was diluted with 330 microliters of buffer to make the protein concentration 2 mg/ml.“

• samples were diluted to a final concentration of 2 mg/ml protein;"


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Task - 2

• First pour agar into six petri plates. Then inoculate the plates with the bacteria. Then put the plates into the incubator . . .

• Six petri plates were prepared with agar and inoculated with the bacteria. The plates were incubated for ten hours.

DO NOT write this section as though it were directions in a laboratory exercise book.


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3. Evaluation method • Number of observers• Independent/consensus assessments• Time period between readings• Any grading system/ measurement of parameters • Any specially designed form• Follow ups – duration of follow up


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Statistical methods • How is the data expressed ?• Which test ? • Why – for which data ?

The data was expressed as Mean One way ANOVA was used to compare the mean

weight gain in the five groups.

• Significance level• Any software used with version


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• Enough information must be given so that the experiments could be reproduced by a competent colleague

• Be meticulous and accurate in describing material and methods. Do not change the voice within one paragraph

Materials and methods (in short)


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# Rule 4

Be clear , concise and objective in describing your results


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The ResultsText

TablesFigures

StatisticsResearch Methodology: D Y Patil


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ResultsProvide the answers to..

What was found?

Usually expected results

REPORT unexpected findingsREPORT negative findings


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Data Vs Results• Data – Factual findings – Eg. Numbers

– Raw data (Eg: B.P.)– Summarised (Eg: Mean and S.D.)– Transformed (Eg: Percentage of baseline)– Reader is forced to draw their own conclusions

• Results: What do the data mean?• The authors clearly state what is their interpretation

of the dataResearch Methodology: D Y Patil


Text• Describe study groups, participants

• How was your sample representative of the study population

• Were the groups comparable (Baseline characteristics)

• Characteristics of the subjects

• How many completed study, lost follow up or withdraw from study Research Methodology: D Y Patil


TextEach parameter (Efficacy & safety)–

• One parameter per paragraph

• Logical sequence as methods

• Most important to least important

• Delineate topic and message clearly

• Avoid repetition Research Methodology: D Y Patil University School of Medicine

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Text - IncludeDescriptive data e.g. no. of patients meeting- inclusion criteria, died and lost to follow up.

Statistical significance

Highlight important data from tables & figures

Negative association, unexpected outcome and their statistical significance at the end


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Table

Eye catching, preferred by readersAccommodates MORE extensive and exact data compared to graphs & illustrationsMORE efficient in summarizing results than text

If a table does not convey anything more than the ABSENCE of a statistically significant difference between

two experimental groups –

Table is NOT requiredResearch Methodology: D Y Patil


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Age wise Prevalence of Anemia

Age (Years) Prevalence of Anemia(%)<8 33.3

9-10 38.510-11 48.511-12 49.812-13 52.913-14 50.214-15 51.215-16 49.316-17 47.817-18 49.218+ 37Total 50.1

Multicentric Study on Adolescent Girls (Gujarat, Mumbai, Delhi)N=150


43 Research Methodology: D Y Patil University School of Medicine

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Figures

• Better visual impact than Tables in

showing

trends,amounts, frequencies relationship in data

GraphsPhotos

Technical Diagrams

Maps



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#Rule 5:Introduction• Be clear in describing the benefit of the paper• Should be brief (250-600 words)

Interest the reader in your Introduction by signalling all its elements and stressing on its novelty and significance


49

Introduction• Structure your introduction using the 3 way

approach:


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Discussion

• Typically should move from specific to general (opposite of introduction)

• In some journals, is followed by a Conclusions section

• In some short papers, is called “Comment” rather than “Discussion”


51

DISCUSSION• The Discussion is harder to define than other sections.

Thus, it is usually the hardest section to write.

– Many manuscripts are rejected by journal editors because of a faulty Discussion, even though the data of the paper might be both valid and interesting.

– Many if not , most discussion sections are too long and verbose.


52

Structure for Discussion (Steps) of scientific papers.

• Statement of principal findings.

• Meaning of the study finding : Possible mechanisms & implications for clinicians or policymakers.

• Strengths & weaknesses in relation to other studies, discussing particularly any differences in results.

• Unanswered questions & future research.


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Limitations : Part of discussion

– For example: small sample size, short follow-up, incomplete data, possible sources of bias, problems with experimental procedures

– Better to mention limitations yourself than for peer reviewers and readers to think that you’re unaware of them


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Word choice

• Avoid prove.

• Use show, demonstrate, indicate, support, suggest, imply, appear.

• Hedging terms such as may be, might be, could be, probably, possibly may be used as needed, but avoid using too many hedges in one sentence.Research Methodology: D Y Patil


Verb Tenses (active!):

Past, when referring to study details, results, analyses, and background research:

• We found that • They lost more weight than• Subjects may have experienced

Present, when talking about what the data suggest … The greater weight loss suggests The explanation for this difference is not clear. Potential explanations include


56

# Rule 6:

Present the implications of principle findings, relationships and generalizations in a concise and convincing tone


57

How frequently do editors encounter manuscript problems?

Seldom Occasionally Frequently

Poorly written, excessive jargon

Inadequate/inappropriate presentation

Poor description of design

Excessive zeal and self promotion

Rationale confused, contradictory

Essential data omitted, ignored

Boring

Important work of others ignored

Byrne DW, Publishing Medical Research Papers, Williams and Wilkins, 1998

Research Methodology: D Y Patil University School of Medicine 58

Conclusions• After the Discussion section the main conclusions

of the study are summarized.

How to write it• Nothing new is presented here. Each conclusion is based

on previously discussed information.• Each conclusion is brief.• The focus is on importance, validity of results, limitations of

the study.


59

# Rule 7

Revise your paper at macrostructure and microstructure level.


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Title• Content of title - Title and short describing subtitle

AuthorsCorresponding authorAffiliation

• When is the best time to choose a title? – After you finish the paper– Must accurately reflect the paper s content and emphasis

• The title must:– Brief & grammatically correct – Complete AND be able to stand alone.

• A good title should be able to let the reader knows content of the paper.



62

Oral progesterogen in threatened miscarriage

Efficacy of dydrogesterone versus standard care in threatened miscarriage in an Indian population: a prospective randomized double blind study


63

Exactly what are you planning to do?

PICOTP - who are the patients or what’s the problem?

disease or conditionstage, severitydemographic characteristics (age, gender, etc.)

I - what is the intervention or exposure?type of intervention or exposuredose, duration, timing, route, etc.

C – what is the comparison group?risk or treatmentplacebo or other active treatment

O - what is the outcome or endpoint?frequency, risk, benefit, harmdichotomous or continuoustype: mortality, morbidity, quality of life, etc.

T – what time limit ?Research Methodology: D Y Patil


Key words

• Number – 3-10

• Should select in such a way – that reflect the content of your article

• Necessary for retrieval of published data

• Characteristics – 1) Patient type2) Interventions3) Comparison4) Outcome


65

Summary /Abstract• Earlier – Abstracts was short, uninformative, written at the

end

• Now they are at the start of an article.

• Longer, structured or unstructured

• Busy reader – read only abstract and decide


66

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Abstract• Start with a statement describing the

purpose/problem of the research• Show theoretical/experimental plans used for the

research• Summarize principle findings• Indicate major conclusions• No data evaluation, no references, table, figures• Length: 80 to 300 words (Optimal_1 paragraph)• It should be able to stand on its own and published

separately.• Write it last! Research Methodology: D Y Patil

University School of Medicine67 Research Methodology: D Y Patil



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• http://www.consort-statement.org/(Schulz KF, Altman DG, Moher D, the CONSORT Group(2010) CONSORT 2010 Statement: updated guidelines forreporting parallel group randomised trials. BMJ 340:c332. )• Amor S, Baker D. Checklist for reporting and reviewing studies

of experimental animal models of multiple sclerosis and related disorders. Multiple sclerosis and related disorders 1. (2012) 111-115

• https://www.nc3rs.org.uk/arrive-guidelines (Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research. PLoS Biol 8(6): e1000412. doi:10.1371/journal.pbio.1000412 )

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887790/

Adv Biomed Res. 2018; 7: 55.

Levofloxacin-containing versus Clarithromycin-containing Therapy for Helicobacter pylori Eradication: A Prospective Randomized Controlled Clinical Trial Vahid Sebghatollahi, Maryam Soheilipour, Mahsa Khodadoostan, Alireza Shavakhi,1 and Ahmad Shavakhi

Background: This study evaluated the clinical efficacy and tolerability of a 14-day course of bismuth-based quadruple therapy including tinidazole and levofloxacin in compare to a 14-day bismuth-based quadruple therapy including clarithromycin as first-line treatment for Helicobacter pylori infection in Iranian adults.

Go to:

Materials and Methods: The study was a prospective, parallel group, randomized controlled, clinical trial that conducted on 150 patients with H. pylori infection. Patients were randomly assigned to the two groups as follows: first group received pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, and clarithromycin 500 mg (PBAC group), and other group received pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, tinidazole 500 mg for 7 days, followed by levofloxacin 500 mg for the second 7 days (PBATL group). Main outcomes were eradication rate, tolerance of treatment, and dyspepsia severity.

Go to:

Results: The eradication rates for PBAC regimen was 81.1% (95% confidence interval [CI]: 71.9–90.2) and for PBATL regimen was 70.8% (95% CI: 60.1–81.6), which was not significantly different (P = 0.147). Tolerance of treatment was similar between groups. The median of severity of dyspeptic after treatment in PBAC group was 10 [9–14.75], which was similar to PBATL group 10 [9–13.5] (P = 0.690).

Go to:

Conclusion: There is no significant difference between PBAC and PBATL regimen, and efficacy was similar in both groups. The overall rate of treatment failure suggests that up to 18%–30% of patients will fail bismuth-based quadruple therapy and require retreatment for the infection.

Keywords: Clarithromycin, Helicobacter pylori, levofloxacin, tinidazole

Introduction

2

Helicobacter pylorus has been linked conclusively to various disorders of the upper gastrointestinal tract, including peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer.[1,2] Approximately over half of the world's population is reported to have H. pylori infection and depending on the population studied, infects 7% to 87% of adults.[3,4] A global systematic review shows that approximately 4.4 billion people in the world were estimated to be infected with for H. pylori in 2015. This infection is more common in developing countries, and in Asia, 54.7% reported to be positive for H. pylori. In Iran, analyses of reports show that 59% of people were infected by H. pylori.[5]

Choosing a treatment for H. pylori eradication depends on different factors, such as the local availability of antimicrobial agents, the pattern of primary antibiotic resistance, and the therapeutic cost.[3] The most commonly recommended for first-line treatment of H. pylori included 7- to 14-day triple therapy with a proton-pump inhibitor (PPI), amoxicillin, and clarithromycin with cure rates of 80%–90%.[6,7] These rates were reported for many years ago, and studies from different parts of the world have raised some important concerns about the current success of this regimen, especially with regard to increasing clarithromycin resistance.[8,9] Thus, bismuth-containing quadruple therapy is recommended as first-line treatment for the eradication of H. pylori infection in regions with a high clarithromycin resistance rate. In Iran with increasing in clarithromycin resistance rate, bismuth-containing quadruple therapy has been strongly recommended.

Levofloxacin and tinidazole have been shown to be effective for the treatment of H. pylori infection, and some studies have also shown that these drugs are effective as the first-line treatment for H. pylorieradication.[10,11,12] The optimal duration for H. pylori eradication therapy is controversial, with recommendations ranging from 7 to 14 days whereas the duration of therapy with the pattern of H. pyloriantibiotic resistance, and the patients’ compliance is known as the main factors in the success rate of eradication regimens.[13] In regard to the high resistance to metronidazole and clarithromycin in patients infected by H. pylori in Iran and controversial findings on the therapy, the present study was designed to investigate effective treatment duration for 14-day bismuth-based quadruple therapy including tinidazole (for 7 days), followed by levofloxacin (for 7 days) in compare to 14-day bismuth-based quadruple therapy including clarithromycin by comparing eradication rate, compliance, and adverse event rate between the regimens as first-line treatment for H. pylori eradication.

Go to:

Materials and Methods The study was a prospective, parallel group, randomized controlled, clinical trial that conducted on 150 patients, referrals to the gastroenterology clinics of Isfahan University of Medical Sciences (IUMS) from February to November 2016. Ethical approval was obtained from the Research Ethics Committee of IUMS before recruitment.

One hundred fifty consecutive patients were included in the study according to the following inclusion criteria: (1) patients in both genders with age 18 and over and (2) patients with peptic ulcer disease. H. pylori infection was confirmed by serologic and gastric tissue. The participants with known gastrointestinal malignancy, MALT lymphoma, Zollinger–Ellison syndrome, immunodeficiency disorders, liver or renal diseases, clinical conditions that need antibiotic therapy, history of gastric surgery, and history of H. pylorieradication or using PPI, antibiotic, or probiotics within 4 weeks before the study and pregnant women were not included in the study. The exclusion criteria were serious side effects that require immediate

3

discontinuation of therapy. Furthermore, patients who did not use their study medications regularly were excluded from the study.

All eligible patients were voluntary and gave written informed consent to participate in the study. The sampling method was consecutive, and randomization was performed by generating a random list of patient allocations before the start of intervention, by Random Allocation Software.

Enrolled patients were randomly assigned to one of the two equal groups. Group I (PBAC) had 75 patients who received treatment regimen included pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, and clarithromycin 500 mg; all given twice daily (q12 h) for 14 days. Group II (PBATL) had 75 patients who received treatment regimen included pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, twice/day for 14 days, tinidazole 500 mg twice daily for the first 7 days, followed by levofloxacin 500 mg daily for the second 7 days.

Collected data included age, sex, dyspepsia symptoms, medicinal effects of each regimen (bad taste, nausea, bloating, diarrhea, constipation, skin rash, and epigastric pain); intolerance of treatment which was assessed at the end of treatment as none, mild, moderate, and severe; and eradication rate. To assess the eradication rate of H. pylori in studied patients, 13C urea breath test with 94% of sensitivity and 95% of specificity, respectively, was use 1 month after the end of treatments.[14] Dyspepsia severity was evaluated by the short-form leeds dyspepsia questionnaire (SFLDQ), which evaluates frequency and interference of four symptoms including epigastric pain/discomfort, retrosternal burning, regurgitation, and nausea. The total score of the SFLDQ ranges from 0 to 32 and was completed by patients in both groups at baseline and after treatment.[15]

Statistical analyses were done using SPSS software for Windows (SPSS, Inc., Chicago, IL, USA, version 24). Descriptive data are reported as mean ± standard deviation, median (IQR), or number (percent) as appropriate. Independent sample t-test, Chi-square test, Mann–Whitney U-test, Wilcoxon signed-rank test, and analysis of covariance (ANCOVA) were used as appropriate. All hypothesis testing was two tailed, and level of significance was considered to be <0.05 in all tests.

Go to:

Results One hundred sixty patients were reviewed to selected eligible patients; ten patients did not enter (nine refused informed consent and one was not eligible). One hundred fifty eligible patients randomly allocated into two intervention groups. Four patients were lost during follow-up period. Finally, 74 patients in PBAC group and 72 patients in PBATL group completed the study and analyzed [Figure 1].

4

Figure 1

Flow diagram of patient's recruitment

The mean age of studied participants was 47.3 ± 12.8 years; 44.5% (65 patients) were male and 55.5% (81 patients) were female. Other demographics and clinical characteristics of the participants by treatment regimens are shown in Table 1.

Table 1

Demographic and clinical characteristics of studied population by intervention groups

5

As shown in Table 2, there has been significant reduction in the LDQ score in both regimens. The result of ANCOVA was not found any difference between groups.

Table 2

The summary results of both frequency and severity of dyspeptic symptoms based on Leeds dyspepsia questionnaire score according to treatment regimens

6

There was no significant difference of H. pylori eradication rates between the studied regimens. The eradication rate for PBAC regimen was 81.1% (95% confidence interval [CI]: 71.9–90.2) and for PBATL regimen was 70.8% (95% CI: 60.1–81.6) (P = 0.147).

In this study, overall HP eradication rate was significantly associated with age. The whole observations indicate that younger patients had a significantly better response [Table 3 and Figure 2]. However, there was no significant difference between the regimens by age for the H. pylori eradication rates (P > 0.05).

Table 3

Helicobacter pylori eradication in studied population by age group

7

Figure 2

Overall Helicobacter pylori eradication in studied population by age group

Go to:

Discussion In this study, PBAC regimen included 14-day treatment with bismuth, amoxicillin, clarithromycin, and pantoprazole which was associated with higher rates of H. pylori eradication in compare to PBATL regimen included 14-day treatment with bismuth, amoxicillin, tinidazole (followed by levofloxacin in the second 7 days), and pantoprazole. Eradication rate for PBAC regimen was 81.1% and for PBATL regimen was 70.8%, which did not significantly differ between groups. There is no significantly different for adverse event between groups, and both studied regimens were well tolerated based on patients’ reports in two studied groups. The rates of eradication in our studied regimens were low, and according to Graham classified efficacy of H. pylori treatment,[15,16] success rate in PBATL regimen is poor and for PBAC regimen is unacceptable. The lower rate of eradication in our study might be related to the prevalence of antibiotic resistant of H. pylori strains in our studied patients, where we did not assess pretreatment antibiotic resistant in these patients.

In a meta-analysis, it is reported that sequential therapy was superior to a 7-day standard triple therapy regimen, but when compared with a longer duration of standard triple therapy, the difference disappeared.[17] In the other studies, the duration of sequential therapy has been assessed to determine whether longer therapy will help improve the eradication rates of H. pylori infection. In Warrington et al. study, it is shown that regardless of the treatment duration, sequential regimens are not better than standard triple therapy. In this study, the eradication rate was 83.7% in the standard triple therapy, 80.0% in the 10-day sequential therapy, and 79.1% in the 14-day sequential therapy regimen.[18] In a large study by Liou et al., it is suggested that longer therapy with a sequential regimen would provide better eradication rates. In these study for 10- and 14-day of sequential therapy, the eradication rate of 90.7% and 87.0% is reported, respectively, and in a 14-day standard triple therapy group,

8

the eradication rate was 82.3%.[19] In Ergül et al.'s study, eradication rate of 90.7% is reported for a 14-day bismuth-containing quadruple therapy as first-line therapy.[20] Su et al. in their study showed an eradication rate of 80.2% and 89.7% for 1-week two regimens of bismuth-based quadruple-containing clarithromycin or levofloxacin, respectively.[21] One study in Iranian patients reported 82.3% of eradication rate of H. pylori for quadruple therapy after 2 weeks.[22] In another report from Iran, after 10-day quadruple therapy, eradication rate was 84.0%.[23] In the Mousavi et al. study, 14 days of bismuth-based quadruple regimen had eradication rate of 75.7%.[24] Aminian et al. reported 85.7% of H. pylori eradication rate after 4 days of bismuth-based quadruple with metronidazole.[25] In a randomized clinical trial, Metanat et al. evaluated 10- and 14-day nonbismuth-based quadruple regimen for H. pylori treatment and reported eradication rate 83.5% and 92.8% for studied regimens, respectively.[26] In the present study, in both bismuth-based quadruple therapy, eradication rates were lower than reported previously (81.1% for PBAC regimen and 70.8% for PBATL regimen). The prevalence of antibiotic resistance, differences in the studied regimens, and does of drugs might be explain the differences between study findings.

In the present study, the eradication rate was decreased with increase in age group; patients in older age group had a lower rate of eradication though this difference was not statistically significant. In other study, in Iran, it is reported that patients’ age and gender are associated with H. pylori eradication rate.[22] Another study reported that occupation, gender, and protocol compliance were positively associated with H. pylori eradication rate.[27] Silva et al. report a significant association between age and H. pylorieradication rate but did not report a significant difference between patients’ characteristics and eradication rate.[28]

The present study has some limitations. First is the lack of any analysis of antibiotic resistance relative to the eradication rates and treatment regimens, whereas antibiotic resistance is known as the most important cause of treatment failure. Second, this trial was not a double-blind placebo-controlled trial in which the detection bias was minimized. Third, this study was a single-center study and its results need to be externally validated.

Go to:

Conclusion This randomized trial showed that a 14-day bismuth-based quadruple regimen-containing amoxicillin, tinidazole (followed by levofloxacin in the second 7 days), and pantoprazole is statistically effective as well as 14-day bismuth-based quadruple regimen-containing amoxicillin, clarithromycin, and pantoprazole in the eradication of H. pylori infection, and there is no significant difference between PBAC and PBATL regimens. The overall rate of treatment failure suggests that up to 18%–30% of patients will fail bismuth-based quadruple therapy and require retreatment for the infection. More studies are needed to draw meaningful conclusions for optimal duration of H. pylori eradication regimens.

Financial support and sponsorship

This study was supported by a grant from Isfahan University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.

Go to:

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Acknowledgments This study was supported by a grant from Isfahan University of Medical Sciences.

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8. Dib J, Jr, Alvarez B, Mendez L, Cruz ME. Efficacy of PPI, levofloxacin and amoxicillin in the eradication of Helicobacter pylori compared to conventional triple therapy at a Venezuelan hospital. Arab J Gastroenterol. 2013;14:123–5. [PubMed]

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10. Federico A, Nardone G, Gravina AG, Iovene MR, Miranda A, Compare D, et al. Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection. Gastroenterology. 2012;143:55–610. [PubMed]

11. Shah A, Javid G, Zargar SA, Teli F, Khan BA, Yattoo GN, et al. Safety and efficacy of 1-week levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori-related peptic ulcer disease in Kashmir, India. Indian J Gastroenterol. 2013;32:32–6. [PubMed]

12. Fakheri H, Taghvaei T, Hosseini V, Bari Z. A comparison between sequential therapy and a modified bismuth-based quadruple therapy for Helicobacter pylori eradication in Iran: A randomized clinical trial. Helicobacter. 2012;17:43–8. [PubMed]

13. Yuan Y, Ford AC, Khan KJ, Gisbert JP, Forman D, Leontiadis GI, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2013;11(12):CD008337. [PubMed]

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14. Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection – The maastricht IV/florence consensus report. Gut. 2012;61:646–64.[PubMed]

15. Fraser A, Delaney BC, Ford AC, Qume M, Moayyedi P. The short-form Leeds Dyspepsia Questionnaire validation study. Aliment Pharmacol Ther. 2007;25:477–86. [PubMed]

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18. Warrington E, López-Román O, Tirado Montijo R, Urbina R, Cruz-Correa M, Toro DH, et al. Neither 10- nor 14-day sequential treatment is better than standard triple therapy for Helicobacter pylorieradication. P R Health Sci J. 2016;35:203–8. [PubMed]

19. Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: A multicentre, open-label, randomised trial. Lancet. 2013;381:205–13. [PubMed]

20. Ergül B, Doǧan Z, Sarikaya M, Filik L. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicillin, clarithromycin on Helicobacter pylori eradication: A prospective study. Helicobacter. 2013;18:454–8. [PubMed]

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25. Aminian K, Farsad F, Ghanbari A, Fakhreih S, Hasheminasab SM. A randomized trial comparing four Helicobacter pylori eradication regimens: Standard triple therapy, ciprofloxacin based triple therapy, quadruple and sequential therapy. Trop Gastroenterol. 2010;31:303–7. [PubMed]

26. Metanat HA, Valizadeh SM, Fakheri H, Maleki I, Taghvaei T, Hosseini V, et al. Comparison between 10- and 14-day hybrid regimens for Helicobacter pylori eradication: A Randomized clinical trial. Helicobacter. 2015;20:299–304. [PubMed]

27. Cai W, Zhou L, Ren W, Deng L, Yu M. Variables influencing outcome of Helicobacter pylorieradication therapy in South China. Helicobacter. 2009;14:91–6. [PubMed]

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28. Silva FM, Zaterka S, Eisig JN, Chehter EZ, Chinzon D, Laudanna AA, et al. Factors affecting Helicobacter pylori eradication using a seven-day triple therapy with a proton pump inhibitor, tinidazole and clarithromycin, in Brazilian patients with peptic ulcer. Rev Hosp Clin Fac Med Sao Paulo. 2001;56:11–6. [PubMed]

Basic Workshop on RESEARCH METHODOLOGY 2019 Name: ……..………………………. (optional)

1

Pre / Post - TEST No. ITEM (Please tick appropriate) 1. In the FINER criteria for assessing the research question “I” stands for

A. Innovative B. Interesting

C. Inspiring D. Inclination

2. The authority to whom permission for conducting a clinical is to be asked for in India is A. Director, Indian Council of Medical Research B. Director General Health Services C. Drug Controller General of India D. Chairman, Medical Council of India

3. Among the following types of studies which one can be a “Hypothesis generating study?” A. Clinical trial

B. Case control study C. Cohort study D. Cross sectional study

4. Sampling frame is nothing but describing the A. Sampling method B. Procedure of calculating sample size

C. Population itself D. Inclusion & exclusion criteria

5. Making estimate about dependent variable from the independent variable for values beyond the observed range of independent variable is:

A. Interpolation B. Extrapolation

C. External validation D. Internal validation

6. The drawback/s of the open-ended question is/ are A. Likely hood of blanks B. Time consuming for coding C. Neither A nor B D. Both A & B

7. Harvard and Vancouver are the names for styles of A. Questionnaires B. Protocol writing C. Reference citation D. Sampling


2

No. ITEM (Please tick appropriate) 8. Focus group discussion is a tool/ method used for

A. Qualitative research B. Quantitative research C. Questionnaire designing D. Sampling

9. Ability of a test to detect disease in those who have it is its A. Sensitivity

B. Specificity C. Predictive power of positive test D. Predictive power of positive test

10. In Likert type of questions (in questionnaire) respondent is asked to indicate: A. How much he/she agrees with the statement B. Which of the statements he/she agrees C. Rank order of the statement D. Correct/ false answers.

11. One type of medical research in which informed consent may not be required and may not be feasible is

A. Survey B. Case control study C. Cohort study D. None of the above

12. For testing the hypothesis about disease causation of a rare disease, the epidemiological study of first choice is

A: Cross sectional study B: Case control study

C: Cohort study D: Experimental study

13. The theoretical range of sensitivity of a screening test when compared with gold standard is A: Zero to one B: Minus 1 to plus 1 C: Zero to infinity

D: 1 to 100

14. For testing etiological hypothesis for a disease wherein you want to test more than one cause (risk factor) the epidemiological study of choice will be

A: Cross sectional study B: Case control study



3

No. ITEM (Please tick appropriate)

15. When information in qualitative study is validated by collecting it from more than one source, it is called

A. Duplication B. Triangulation

C. Confirmation D. None of the above

16. In questionnaire, the type of questions that do not have a preset answer and respondent is provided with a blank space for response are called:

A. Close ended questions B. Open ended questions

C. Likert type of questions D. Babbie format style questions

17. In a class, students’ height does not show much variation. For this variable the population will be considered as

A: Homogenous B: Heterogenous C: Dynamic D: Static

18. Data of 1000 patients is grouped into 3 groups as per severity of anemia: mild, moderate and severe and is presented in tabular form. What is the scale of measurement here?

A. Nominal B. Ordinal

C. Interval D. Ratio

19. In a hospital, due to turnover, patients stay for a brief period only. As such the age/sex structure of patients shows variation over time. Thus, for these variables this will be

A: A homogenous population B: A heterogenous population C: A dynamic population D: A static population

20. In statistics, the word "Parameter" refers to A: The constant that describe population characteristic B: The constant that describe sample's characteristic C: A property of normal curve D: A measure of variation used in advanced statistics


4

No. ITEM (Please tick appropriate) 21. Median is almost equal to ……….. percentile.

A: 25 th B: 50 th

C: 80 th D: 90 th

22. In clinical trial "Reference Population" is the population A: To which the results of the study are applicable B: Which actually participates in the trial C: Which receives new drug being tested D: None of the above

23. As per ICMR guidelines, the responsibility of screening of the research proposals coming to institutional ethics committee is assigned to:

A. Chairman B. Secretary

C. Medical expert in the group D. Legal expert in the group

24. You are planning a clinical trial and you want to search if similar trials are planned anywhere in world. The best and authentic source for this information is:

A. World Health Organization: www.who.int/clinical trials B. Pubmed: www.ncbi.nlm.nih.gov/pubmed/clinicaltrials C: US National Institute of Health www.clinicaltrials.gov D: Google: www.google.com/ clinical trials

25. Assigning alphabetical/ numerical identifiers to responses from respondents in a questionnaire is:

A. Data editing B. Data reduction

C. Data coding D. Data embedding

26. Triangulation is a method of - A. Data collection B. Data presentation

C. Data validation D. Data analysis

27. In clinical trial "Study Population" refers to the population - A: To which the results of the study are applicable B: Which is eligible to participate in the trial C: Which receives new drug being tested D: None of the above


5

No. ITEM (Please tick appropriate)

28. According to ICMR guidelines a new drug is defined as - A. a new chemical entity (NCE); B. a drug which has been approved for a certain indication, by a certain route, in a certain

dosage regimen, but which is now proposed to be used for another indication, by another route, or in another dosage regimen

C. Both A & B D. Neither A nor B

29. A table in which first column represents labels (names) of groups and second column represents the number corresponding to each group is

A: Simple table B: Frequency distribution table C: Master table D: Two by two table

30. When testing the association of one cause (Risk factor) with two or more diseases (or outcomes) is the objective of the study, the epidemiological study of first choice is

A: Descriptive study B: Case control study
