WRITING A RESEARCH PROTOCOL

Dr. Mirza Shiraz Baig Department of Pharmacology Govt. Medical College Aurangabad.

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Outline.
Protocol Draft & references Case report form Essential formats (appendices) Professional Negligence

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).

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.

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?

DEVELOPMENT OF A CLINICAL STUDY PROTOCOL

Idea with References Reviews 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
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MAIN PROTOCOL FEATURES

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Background and rationale (with supporting studies & references) Specific objectives (Primary and Secondary) Patient selection criteria (Inclusion and Exclusion) Study Design & Randomization Study population & recruitment Detail procedures/Methodology If Drug used then treatment schedules (details) Methods of patient evaluation (detail study Procedure) Patient information sheet & informed consent (In Vernacular language) Discontinuation /Withdrawal/Follow up criterias Sponsors details/Forms and data handling Declaration of Helsinki /Data Safety/Quality assurance/Patient privacy.

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14. 15. 16.

Compensation to patients and all other financial aspects (must)

Protocol deviations & Amendments(Approval from IEC) Plans for statistical analysis (Must Know) 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

QUALIFICATIONS 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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RESPONSIBILITIES OF THE PI

Obtain IRB/IEC approval of the protocol and informed consent prior to initiation of study Enroll eligible patients as per protocol Obtain informed consent from patients or parents/guardians of children Observe, measure and document all effects of study (response, AEs, etc) Record all data pertinent to study

RESPONSIBILITIES OF THE PI

Evaluate, manage (treat) all toxicities Report toxicities as specified in protocol Submit protocol changes or amendments to the IRB/IEC for approval Notify IRB/IEC of any issues that pose a threat to the 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 Short Title

Full title of protocol Shortened title, if one is typically used by you or your Center/Dept.

Protocol Number

The standard protocol number used to identify this study.

Clinical study phase (e.g. Phase 1, 2, 3 or 4) Design attributes such as single blind, double blind or open label; Randomized, placebo or active placebo control; cross-over design, etc. Estimated duration for the main protocol (e.g. from start of screening to last patient processed and finishing the study) Single-center or multi-center. If multi-center, note number of projected centers to be involved. Brief statement of primary study objectives Number of subjects projected for the entire study (e.g. not for simply one site, rather for entire study, all sites combined)

S Y N O P S I S

Phase Methodology Study Duration Study Center(s) Objectives Number of Subjects

Diagnosis and Main Note the main clinical disease state under study and the key inclusion criteria (i.e. not the entire Inclusion Criteria list that will appear later in the protocol rather only the key inclusion criteria) Study Product, Dose, Route, Regimen Duration of administration Reference therapy Statistical Methodology

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

Total duration of drug product administration (including any open-label lead-in, if applicable). Note if there is a standard reference therapy against which the study product is being compared, or if the reference is a placebo A very brief description of the main elements of the statistical methodology to be used in the study. (As few lines as possible). 15

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Begin with sentence of GCP

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Publication Plans

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CRUCIAL ROLES OF STATISTICIANS

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 crucial information Better estimates of sample size for analysis of sub groups

CASE REPORT FORM

A LEGAL DOCUMENT
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TYPICAL INCLUSION 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

must not be on an active treatment Subject must not be allergic to intervention Pregnancy, breastfeeding, child Other
Subject

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Poorly Designed CRF

Data

not collected Database may require modificationNot allowed Data Entry process impeded Target dates are missed OR Collected too much data Wasted resources in collection and processing

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 last scheduled 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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SAFETY & ADVERSE EVENT RELATIONSHIP TO STUDY PRODUCTS

All adverse events must have their relationship

to study product assessed using the following

terms:
Definitely Related

Probably Related
Possibly Related Probably Not Related Not Related

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WHAT IS A CLINICAL TRIALS GREATEST ENEMY?

BIAS
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HOW DO WE MINIMIZE BIAS?

Make

sure groups are equivalent Standardize outcome assessment Randomization Blinding single- or double-blind versus openlabel 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

If above all followed No Problems

If NOT followed !!! Then possibility ?

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PROFESSIONAL NEGLIGENCE :

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PROFESSIONAL NEGLIGENCE :
- Breach of duty/ subject has suffered damagethe relatives may approach* Civil court to claim compensation. * Criminal court demanding punishment to the doctor. - Under civil law : The physician is liable for Unlimited monetary claim from patient or successor in case of damage/death. Indian contract act, 1872 can be filed.

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- UNDER CRIMINAL LAW: Investigator may be charged under section.

1. 304 A of IPC : In case of death - imprisonment upto 2 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 the investigator 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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IS PROTOCOL WRITING !!!

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WHY PROTOCOL DESIGNING !! Higher quality protocol = More efficient study execution

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Thank you .
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