writing research protocol...2007

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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?

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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 .

writing research protocol...2007

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