Introduction to clinical research

An introduction of: Investigator initiated research (IIR)

DR NOR HIDAYAH ZAINOOL ABIDINDepartment of Anaesthesiology and Critical care

HRPZ 2, Kota Bharu

What is research?

• A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalize knowledge

Research is best learnt by actually conducting the research project rather than reading or attending lecture

“A journey of a thousand miles begin with a single step.”

Simple study base on questionnaire

• KNOWLEDGE, ATTITUDE, AND PRACTICE (KAP) STUDY OF DENGUE AND CHIKUNGUNYA DISEASE AMONGST ADULT POPULATION OF KAMPUNG TANJUNG API, KUANTAN, PAHANG, 2009

Why research? – The right mindset!

• Untuk mengambil hati boss. • Untuk mendapat markah SKT yang tinggi.• Untuk naik pangkat. • Untuk orang ramai kenal saya. • Untuk menang dalam pertandingan. • Untuk mengisi masa lapang. • Dipaksa/ Dipaksarela. • Saya nak belajar lebih

Data is power……

• Vital to the understanding of problems

• Translate basic sciences to human studies, and subsequently to clinical practices. • New drug/ technology development • New diagnostic techniques • To compare effectiveness • To compare safety profile • To study the healthcare systems • Economic evaluation • Applied research

Research impact

• Build the scientific foundation for clinical practice

• Prevent disease and disability • Manage and eliminate symptoms caused by

illness • Enhance end-of-life and palliative care • To help the decision making processes

Examples of Clinical Research Types

• Clinical trials or therapeutic research Clinical epidemiology: disease diagnosis and prognosis, clinical decision making

• Clinical Economics; cost-effectiveness of healthcare

• Disease epidemiology: incidence, prevalence, distribution of and risk factors for disease X

What is Clinical trial/clinical study?

• It is any investigation in human subject intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigation product(s), with the object ascertaining its safety and/or efficacy

General type of research

• Commercialized (ISR – industry sponsored research)– Pharmaceutical companies provide protocol and

funds for the researcher to recruit patients and implement the study

• Non-commercialized (IIR – investigator initiated reasearch)– Investigator initiates clinical trials with or without

the involvement of the drug companies

Why should we be involve in clinical trials?

• Reinforcement or our clinical practice– Clinical trial does not differ much with daily

practice apart from following protocols stringently– Application of research findings

• Continuous medical education (CME)– Well verse with the topic/areas involve in the trial• A lot more readings, literiture search and discussion

with expert of the area

• Advantages to clinician/ investigators

• Benefits to patients• Advantages to the

institutions• Advantages to

pharmaceutical companies

• Benefits to the country

Advantages of doing

clinical trials

Advantages to the clinician/investigator

• Extra money• Travel overseas• Academic achievement• Experience in well planned clinical trial• Practice better medicine• Experience working with experienced clinician

and peer recognition• Experience with pre release drugs

Benefits to the patient

• Better monitoring of patient’s medical problems

• Managed by most experienced and dedicated people

• Better relationship with physician resulting in better outcome of medical problem

Disadvantages in clinical trials

• Clinician/investigators– Time consuming– Extended commitment

• Patient– Risk of developing side effects– Sereious Adverse event & adverse reaction

• Pharmaceutical companies– Risk of great financial loss if outcome of trial not

favour them

Requirement to become investigators

• Clinician• GCP certified• Ready to give full commitment to

make it successful

What is Good clinical practice (GCP)?

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

GCP- provisions and prerequisites for a clinical trial

• Ethical principle• Declaration of Helsinki• Justice• Respect for person• Beneficience (maximize benefits and minimize

harms and wrongs)• Non maleficence (do no harm)• Fully informed

Ethical principles & requirements

• Safeguards the rights, safety and well being of all trial subjects– Trial protocol/ amendments– Written informed consent– Subject recruitment procedures– Written informations to be provided to subject

PATIENT INFORMATION SHEET AND INFORMED CONSENT FORM

1. Title of study: 2. Name of investigator and institution: 3. Name of sponsor: 4. Introduction:

1. You are invited to participate in a research study (brief introduction why they are selected and what the study is all about)

5. What is the purpose of the study6. What kind of study products will I receive7. What will happen if I decide to take part? (need to fill up medical history data, or questionnaire, or

follow the treatment schedule (just a give a brief what patient need to do, can be in numbering or phrases form.)

8. What are my responsibilities when taking part in this study?9. What kind of treatment will I receive after my participation in the trial?10. What are the potential risks and side effects of being in this study?11. What are the benefits of being in this study?12. Who is funding the research13. Can the research or my participation be terminated early14. Will my medical information be kept private15. Who should I call if I have questions

Protocol

• A document that prescribes the – objectives– design– methodology– statistical considerations– organisation of trial– background and rationale for the trial

• Throughout the ICH-GCP guideline the term protocol refers to protocol and protocol amendments (a written description of changes to or formal clarification of a protocol

• Generate ideas • Review related literatures • Formulate research questions/ objectives • Design research & study proposal Conduct study • Analyse data • Interpret results • Determine implications of research (conclusion

and recommendations) • Publication/ presentation

Complicated????

CRC Malaysia

• Perkhidmatan• Pengenalpastian pesakit• Pemilihan subjek• Pegurusan projek

– Registry pesakit– Menjalinkan usahasama dalam kajian

• Kursus dan latihan– Program bimbingan

• Pendaftaran dan permohonan geran penyelidikan• Pembentukan protocol kajian• Analisa statistik• Pembentangan hasil kajian• Penulisan saintifik hasil penyelidikan• Analisa statistik

– Pembentangan GCP• Khidmat rundingan

– Pendaftaran penyelidikan– Rekabentuk dan metodology kajian

CRM

Research in Ministry of health (MOH)

Current MOH policy on research, as specified in the guideline, requirement

Policy statement 1

• All research require prior registration with the approval by MOH

• National medical research registry (NMRR)• To upload – Agreement from investigators– Agreement of HOD– Agreement of director of institutions/hospital

• NIH review and approval

Policy statement 2

• Research involving human subjects require prior review and approval by the medical research @ ethical committee (MREC)

Policy statement 3

• All research publications and presentations must have DG of health approval

• Submit cover letter + form + draft to NIH secreteriats

• Prior review by NIH panels• NIH sec DDG (P&ST) DG

National Medical Research Register (NMRR)

The NMRR is thus specifically designed to enable:• Online registration of research. to be registered in publicly accessible research registers. • This is to ensure transparency and to increase public trust in the conduct of medical research; as well

as to inform physicians and prospective volunteers about ongoing research in which they may wish to enroll.

• Online submission to an appropriate authority for approval, as well as online review of the submitted research by relevant appointed reviewers. The online system ought to reduce the research review time as well as to enable investigators to track the status of their research online

• Online submission of research publication to the NIH for approval• Finally, the NMRR also enable MOH management to document the level of research activity in the

MOH, and also to track the progress of the research it has approved and/or provided support such as funding.

• The title of all registered research and its associated publications where available will be published in the Directory of Medical Research on the NMRR website.

• In the process of registering a research, participating investigators are required to be registered on NMRR too. All such registered investigators shall also be published in a Directory of Clinical Investigator & Medical Researchers on the NMRR website. The Directory should be of help to investigators to locate other potential collaborators, and to sponsor of clinical trial to identify suitably qualified clinical investigators to participate in their multi-centre trials.

Documents for submission

• Research documents– Protocol synopsis– Protocols/ amendments– Investigator broshure– Patient informed consent

• Investigators documents– CVs– GCP certificate– Investigator’s agreement and HOD approval– Professional indemnities

Research tools• to create dataset and data analysis– SPSS – Epi-info

• Endnote– Search, organize and share research. And

automatically format bibliographies with the only patented bibliography technology.

• Epical 2000 software– statistical calculator that works with pre-

tabulated data

Because bunches and guesswork is not enough

Thank you for your attention…………