RESEARCH ETHICS COMMITTEESCOMPOSITION AND FUNCTIONS

Dr. Tamer Hifnawy MD. Dr. “PH”Associate Professor of Public HealthFaculty of Medicine BSU. University- Egypt.College of Dentistry- Taibah University- KSA.

By the end of this lecture:

What is an IRB/REC? The need for established REC`s When do I need REC? Roles and composition of REC. Ethics Review process…. Rrole of Central or National IRBs The interactions between IRBs from

different countries Composition & Function of DSMB

WHO TO DECIDE WHAT IS AN ETHICAL RESEARCH???

Research Ethics committee (REC)Institutional review board (IRB)

Tamer Hifnawy MD. Dr.PH

Research Ethics Committee (REC)

=Institutional Review Board

(IRB)Tamer Hifnawy MD. Dr.PH

WHY REC/IRB?

Advancement of ScienceProtection of

Subject Welfare/Rights

Balancing Two Goals

Why Do I need an REC to review my protocol?

Tamer Hifnawy MD. Dr.PH

International guidelines1

require that an independent committee perform an Ethical and Scientific review of biomedical research.

1Declaration of Helsinki/CIOMS

Tamer Hifnawy MD. Dr.PH

Make research studies better!! Enhance study design Enhance protection of

subjects Enhance researcher reputation Increased requirements for

ethical approval in different scientific bodies

More likely to get published in good journals

More likely to get funding/ grants.

Tamer Hifnawy MD. Dr.PH

When to Apply to REC/IRB

When to apply?

Before any research activity At least 2 weeks before meeting date Allow at least 1 month “for full board

review”

No post-conduction approval

TOO LATE !

!

No post Conduction approval

HOW & WHAT TO APPLY?

Essential Documents:

1. A signed and dated application form2. Full protocol.3. Informed consent4. CV`s for the PI and co-investigators.5. Additional tools for the study”6. For clinical trials…safety reports,

previous studies.. 7. Arabic Summary

Tamer Hifnawy MD. Dr.PH

Composition of Ethics Review Boards

Qualifications & experience

At least oneWith the scientific

background

Include men and women

A community representative

At least 5 members

There are minor variations between guidelines on composition

Types of ReviewLevel of Risk Determines Type of Review

Low Risk Higher Risk

Expedited Full

Tamer Hifnawy MD. Dr.PH

REC decisions:

Conditioned approval, after clarifications, modifications.

Unconditioned approval

Defer till more information be

availableDisapprove

REC/IRBDecision

Sleem, H., El-Kamary, S., & Silverman, H. J. (2010). Identifying structures, processes, resources and needs of research ethics committees in Egypt. BMC Medical Ethics,11(12), 1–8.

Frequent Issues with REC Applications

Incomplete/insufficient description of purpose, methods/procedures, subject selection

Incomplete cover page, lack of contact information

Typographical errors

Tamer Hifnawy MD. Dr.PH

Inappropriate language on the informed consent document (too technical)

Research-related documents are not included in the application (questionnaires, advertisements, surveys, informed consent, etc.)

Proposals are delivered at the last minute

Post Conduct application

Frequent Issues with REC Applications

Tamer Hifnawy MD. Dr.PH

Clinical trials in developing countries

Increase

Research Landscape: Clinical Trials

Health research in the Middle East

The national budget devoted to research in small

How does one explain the discrepancy between the increase in the clinical trial activity with the small amount of funding for research by the national government?

Tamer Hifnawy MD. Dr.PH

Outsourcing clinical trialsDeveloped world to developing world

Advantages to Pharma Large population Disease pattern:

Cancer Diabetes Shistosomiasis, HCV

Lower cost Faster patient recruitment Avoid regulatory restrictions Avoid elaborate safety and compensation

requirements

Outsourcing clinical trialsDeveloped world to developing

worldAdvantages to Host Countries: Exposure to recent technologies and

recent drug therapies. Training to local health professionals. A road paving to upgrade local drug/

biotech industry

Problems faced in developing countries

National regulation Research Ethics Committee Investigators Study subjects Translation Informed consent

Tamer Hifnawy MD. Dr.PH

Alahmad, Ghiath, Mohammad Al-Jumah, and Kris Dierickx. "Review of national research ethics regulations and guidelines in Middle Eastern Arab countries." BMC medical ethics 13.1 (2012): 34.

Research Ethics in the Middle East Statistics between 2006 and 2010 show

a 4 % rise in the global number of drug trials conducted in the Middle East, which was the largest increase in any region of the world.

Many factors make the Middle East attractive for clinical research: Patient diversity, Good medical facilities, Cost advantages, and Favorable infrastructure, Many new universities and research centers

have appeared

Research Ethics in the Middle East

After the establishment of the first international and Western clinical research guidelines, it required a few decades for decision makers in the Arab countries in the Middle East to begin thinking about their own guidelines.

The first attempts at crafting clinical research regulations appear as summarized chapters in the general medical ethics guidelines: in Lebanon, the “Law of Medical Ethics” (1994)

Research Ethics in the Middle East

in Saudi Arabia, the “Ethics of the Medical Profession” (1998; renewed, 2007) and

in Egypt, the “Profession Ethics Regulations” (2003)

The Jordanian “Law of Clinical Studies” (2001)

Ten years after establishing universal ICH-GCP guidelines (1995), the first local GCPs began to appear in the region through the Saudi Food and Drug Authority’s (SFDA)

“Clinical Trial Requirement Guidelines” (2005; renewed, 2008)

Research Ethics in the Middle East

The UAE’s “Guidance for Conducting Clinical Trials Based on Drugs/Medical Products & Good Clinical Practice” (2006)

Kuwait’s “Ethical Guidelines for Biomedical Research” (2009)

Qatar’s “Guidelines, Regulations and Policies for Research Involving Human Subjects” (2009)

The Saudi law, “System of Ethics of Research on Living Subjects” (2010)

Tamer Hifnawy MD. Dr.PH

Saudi Arabia is the only country that has three different documents referring to the regulation

of research ethics

The first existing documents that dealt with medical ethics are the Egyptian

papyrus (~16th century BC)

Flow Chart for Approval to Conduct Clinical TrialInvestigator / SponsorInvestigator / Sponsor

Submission of ResearchProtocol & Required

Documents to IRB

Submission of ResearchProtocol & Required

Documents to IRB

National Scientific & Research Ethical

Committee

National Scientific & Research Ethical

CommitteeRejection

Modification

Prior to Approval

Yes

Approval

Negative opinion

Protocol Amendment

Protocol Amendment

Modification

Prior to ApprovalProtocol

Amendment

Protocol Amendment

Checklist fulfilled

Yes

Approval LetterApproval Letter

InvestigatorInvestigator

Commencement of the study

Commencement of the study

Approval

No

What about Interactions between different IRBs/RECs in

the same country?

Up to your knowledge; is there any Interactions

between different IRBs/RECs in the MENA

region?Tamer Hifnawy MD. Dr.PH

Central IRB/REC?

No common definition of what is meant by a Central IRB Model

Centralization of IRB reviews have been increasing in the US and elsewhere, but many questions about it remain. In the US, a few centralized IRBs (CIRBs) have been established, but how they do and could operate remain unclear

Klitzman, Robert. "How local IRBs view central IRBs in the US." BMC medical ethics 12.1 (2011): 13.

DATA AND SAFETYMONITORING BOARD

Also termed DMC= Data Monitoring Committee in some countries

Independent body appointed for most clinical trials

Major role is to ensure safety of participants Assures validity of results by overseeing

conduct of a trial Protects investigators Advises investigators (often the Steering

committee) and the sponsor

DSMB – Data Safety Monitoring Board

Tamer Hifnawy MD. Dr.PH

Monitor data throughout a trial

Only group that has access to unblinded data before the end of a study

Analyzes data by treatment arm Are there concerns about safety? Is there already enough proof that the

intervention works?

Also considers New evidence that might be relevant to the trial Practicalities -is it still feasible to continue?

Role of a DSMB

Tamer Hifnawy MD. Dr.PH

Composition of the DSMB:

Generally at least three members Clinicians and statisticians Sometimes ethicists and community representatives Other members to address specific issues

Ideally independent of sponsor and investigators Clinicians and biostatisticians

relevant expertise clinical trials experience freedom from conflicts of interest

Tamer Hifnawy MD. Dr.PH

Safety Long term trials that compare mortality or major morbidity

outcomes A priority reasons for safety concerns

Intervention is invasive or has serious toxicity “fragile” population – elderly, children Population is at higher risk SAEs are expected Study is large, of long duration, and multi-center

Practicality• Not required for short duration trials

Scientific validity• External consideration might warrant changes in trial

design

When Is an External DSMB Required?

Responsibilities of the DSMB

Interim monitoring: efficacy safety study conduct external data

Making recommendations: protocol changes termination

Tamer Hifnawy MD. Dr.PH

• Sources of data CRFs, SAE data, Randomization codes Up-to-date enrollment information Protocol violations/exemptions Special assays/lab tests that could un-blind

sponsor Last-minute endpoint or mortality data

prepared via endpoint sweep Timely data more important than totally

clean data.

Data Quality is Vital to the DSMB

Tamer Hifnawy MD. Dr.PH

• Monitoring for effectiveness• Estimates of treatment effect unstable at

early points• Futility analysis: benefit is unlikely

• Monitoring for Safety • Subjects given the investigational

intervention are experiencing worse outcome Demand less rigorous proof of harm to justify

early stopping

Interim Analysis

Tamer Hifnawy MD. Dr.PH

Possible decisions: Continue with trial as planned Stop: safety problem Stop: efficacy established Stop: new knowledge (usually from other

trials suggesting risks) Stop: futile. Trial unlikely to show a result Modify trial design

Decisions

Tamer Hifnawy MD. Dr.PH

Need to be absolutely sure that you are making the correct decision

Need to adjust the p value if you are doing multiple interim analyses

Establish these “stopping rules” at the beginning of the study

Issues to consider in interim analyses

Tamer Hifnawy MD. Dr.PH

• No commonly accepted standards for composition and functions of DSMBs

• Not entirely independent in all situations

• Might not be responsible for data monitoring plan if formed late

• Little communications directly with IRBs

Concerns

Tamer Hifnawy MD. Dr.PH

• Provide monitoring plan to institutional review boards

• Provide summaries of study safety to institutional review boards at agreed-upon intervals

Relationship Between IRBs and DSMBs

Tamer Hifnawy MD. Dr.PH

Thank YOUTamer Hifnawy MD. Dr PH.Associate Professor of Public Health & Community MedicineFaculty of Medicine, Beni Suef University, EgyptCollege of Dentistry, Taibah University, KSAAssistant Vice Dean for Quality and DevelopmentCertified Trainer in International Research Ethics

Email: tamer.hifnawy@bsu.edu.eg thifnawy@yahoo.comMobile: +201114130107 Egypt +966564356123 KSA