research ethics committees (recs- irbs)
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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
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