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WRITI NG A RESEARCH PROTOCOL
Dr. Mirza Shi raz Baig
Department of Pharmacology
Govt. Medical College
Aurangabad.
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Kind Instructions to Dear
Delegates
Please switch off your mobiles
I will be speaking for around 45 min as per
allotted time & may exceed 15 minutes !
Please dont leave the hall when I am
speaking this will definitely disturb me.
Total 69 slides remaining including thank U
slide Thanks for your kind reading .
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Outline.
Protocol Draft & references
Case report form
Essential formats(appendices)
Professional Negligence
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WHAT DO WE MEAN BY A STRONG
RESEARCH TEAM?
Research Team: A group of people
working together in a systematic and
scientific manner to establish facts Strong Research Team: Committed to
applying the principles of Good Clinical
Practice (GCP).
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GOOD CLINICAL PRACTICEMUST KNOW
A standard for the design, conduct, performance,
monitoring, auditing, recording, analyses, and reporting
of clinical trials that provides assurance that the data
and reported results are credible and accurate, and that
the rights, integrity and confidentiality of trial subjects
are protected.
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Study Protocol: What? Describes every step of a study
Identification of the problem
Application of the results
Answers relevant questions
Public health problem: Important?
Study question: relevant to the problem?
Objectives: consistent with the study question?
Study design: achieves objectives?
Public health impact of the findings?
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DEVELOPMENT OF A CLINICAL
STUDY PROTOCOL
Idea with ReferencesReviews from the experts with references
First planning meeting (basic design features)
Second planning meeting (draft protocol)
Final protocol (ethical and scientific, statistician)
Evaluation (scientific review, IEC/IRB)Implementation
Final analysis and publication 7
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MAIN PROTOCOL FEATURES
1. Background and rationale (wi th support ing studies & references)
2. Specific objectives (Pr imary and Secondary)
3. Patient selection criteria (I nclusion and Exclusion)
4. Study Design & Randomization
5. Study population & recruitment
6. Detail procedures/Methodology
7. If Drug used then treatment schedules (details)8. Methods of patient evaluation (detail study Procedure)
9. Patient information sheet & informed consent (I n Vernacular language)
10. Discontinuation /Withdrawal/Follow up criterias
11. Sponsors details/Forms and data handling
12. Declaration of Helsinki /Data Safety/Quality assurance/Patient privacy.
13. Compensation to patients and all other financial aspects (must)
14. Protocol deviations & Amendments(Approval fr om IEC)
15. Plans for statistical analysis (Must Know)
16. Publication Plans & References (Compulsory)
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PRINCIPAL INVESTIGATOR
Also known as the PI
An individual who actually conducts the
clinical trial
Is the leader of the research team at the
site
Is responsible for the conduct of the study
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QUALIF ICATIONS OF THE PI
An appropriately qualified person
Trained and experienced in clinical
research
Familiar with the background of the study
and the requirements of the study
Has high ethical standards and
professional integrity
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RESPONSIBI L I TI ES OF THE PI
Obtain IRB/IEC approval of the protocoland informed consent prior to initiation ofstudy
Enroll eligible patients as per protocol
Obtain informed consent from patients orparents/guardians of children
Observe, measure and document alleffects of study (response, AEs, etc)
Record all data pertinent to study
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RESPONSIBI L I TI ES OF THE PI
Evaluate, manage (treat) all toxicities Report toxicities as specified in protocol
Submit protocol changes or amendments tothe IRB/IEC for approval
Notify IRB/IEC of any issues that pose a threat tothe welfare of the patients on the study
Maintain study documentation and make this
available for data verification Comply with all procedures specified in
protocol in accordance with GCP.
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CO-INVESTIGATORS
Investigators who share responsibility
along with the PI through out the study
period. They are equally responsible for
study..
PI should take meeting and disclose all fine
details of the study to the co-investigators
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Title Full title of protocol
Short Title Shortened title, if one is typically used by you or your Center/Dept.
Protocol Number The standard protocol number used to identify this study.
Phase Clinical study phase (e.g. Phase 1, 2, 3 or 4)
Methodology
Design attributes such as single blind, double blind or open label; Randomized, placebo or active
placebo control; cross-over design, etc.
Study DurationEstimated duration for the main protocol (e.g. from start of screening to last patient processed and
finishing the study)
Study Center(s) Single-center or multi-center. If multi-center, note number of projected centers to be involved.
Objectives Brief statement of primary study objectives
Number of Subjects Number of subjects projected for the entire study (e.g. not for simply one site, rather for entirestudy, all sites combined)
Diagnosis and Main
Inclusion Criteria
Note the main clinical disease state under study and the key inclusion criteria (i.e. not the entire
list that will appear later in the protocolrather only the key inclusion criteria)
Study Product,
Dose, Route,
Regimen
Study drug name (generic name, though can also state marketed name if name-brand used in the
study). Also dose, dose route and dose regimen
Duration of
administrationTotal duration of drug product administration (including any open-label lead-in, if applicable).
Reference therapyNote if there is a standard reference therapy against which the study product is being compared,
or if the reference is a placebo
Statistical
Methodology
A very brief description of the main elements of the statistical methodology to be used in the
study. (As few lines as possible).15
SY
N
OP
S
I
S
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Begin with sentence of GCP
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19. Publication Plans
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CRUCIAL ROLES OF STATI STICIANS
Study Design
No of Subjects
Data Analysis
Reporting
New statistical methodology
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WHY A DATA ANALYSIS PLAN ?
Prevents collection of data that will
not be used
Prevents failure to collect crucialinformation
Better estimates of sample size for
analysis of sub groups
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CASE REPORT FORM
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A LEGAL DOCUMENT
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TYPICAL I NCLUSION CRITERIA
Subject must have disease of interest
Subject must have a certain amount
of disease
Subject must understand study and
agree to participate
Other
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TYPICAL EXCLUSION CRITERIA
Subject must not be on an active
treatment
Subject must not be allergic tointervention
Pregnancy, breastfeeding, child
Other
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Poorly Designed CRF
Data not collected
Database may require modificationNotallowed
Data Entry process impeded
Target dates are missed OR
Collected too much dataWasted resourcesin collection and processing
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APPENDICES
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SAFETY & ADVERSE EVENT
What are Adverse Events?
Any untoward medical occurrence in a
clinical trial participant who has received
test article/intervention that may or may
not have a causal relationship with this
treatment
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SAFETY & ADVERSE EVENT
MONITORING
Post-study adverse events (instructions at lastscheduled visit)
To be followed till resolved / subject is lost to
follow-up or otherwise explained ..
Abnormal laboratory values.
Hospitalization, Prolonged hospitalization or
Surgery.
Recording of adverse events.(AE module of CRF)
Reporting of serious adverse events:
Sponsor/IEC/FDA.
Unblinding procedures.
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WHAT IS A CLINICAL
TRIALS GREATEST ENEMY?
BIAS59
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HOW DO WE MINIM IZE BIAS?
Make sure groups are equivalent Standardize outcome assessment
Randomization
Blinding single- or double-blind versus open-
label
role of placebo
?? triple-blind
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COMMON PROBLEMS IN STUDY
PROTOCOLS ??
Too ambitious: too many questions !!
Insufficient attention to previous literature
Poor justification
why is it important to answer this question?what impact does it have on public health?
Poorly formulated objectives! Unspecific.
Inappropriate analysis Inadequate description
Absence of pilot or test
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If above all followed No Problems
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If NOT followed !!! Then
possibility ?
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PROFESSIONALNEGLIGENCE :
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PROFESSIONAL NEGLIGENCE :
- Breach of duty/ subject has suffered damage-
the relatives may approach-
* Civil court to claim compensation.
* Criminal court demanding punishment to
the doctor.
- Under civi l law: The physician is liable forUnlimited monetary claim from patient or
successor in case of damage/death. Indian contractact, 1872 can be filed.
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- UNDER CRIM INAL LAW:
Investigator may be charged under section.
1. 304 A of IPC : In case of death - imprisonment upto2 years or fine or both(it is a bailable offence).
2. 336 of IPC : Rash/negligent act endangers the life imprisonment upto 3 months or fine upto Rs.200/-
or with both(it is a bailable offence).
3. 337 of IPC : Rash/negligent act causes hurt -imprisonment upto 6 months or fine upto Rs.500/- or
both (it is a bailable offence).
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4. 338 of IPC : Rash/negligent act causes grievous
hurt imprisonment upto 2 years or fine upto
Rs.1000/- or both (it is a bailable offence).
There are provisions under section 406 of IPC
to charge the investigator for criminal breach of
trust and under section 420 of IPC to charge theinvestigator for cheating.
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SUMMARY
Protocol lays out who, what,
why, when, where, how...
Safeguards participants.
Safeguards study integrity.
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I S PROTOCOL WRITING ! ! !
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WHY PROTOCOL
DESIGNING !!
Higher quality protocol =
More efficient study execution
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Thank you .