Dr. Tamer Hifnawy MD. Dr.

“PH”
Associate Professor of Public Health
Faculty of Medicine BSU. University- Egypt.
College of Dentistry- Taibah University- KSA.
 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
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
 Balancing Two Goals

Protection of
Advancement of Science Subject Welfare/Rights
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

 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

1. A signed and dated application form
2. Full protocol.
3. Informed consent
4. 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
 At least one
With the scientific
Qualifications & experience
background

At least 5
members

Include men and women A community representative

There are minor variations between guidelines on composition

Level of Risk Determines Type of Review

Low Risk Higher Risk

Expedited Full

Tamer Hifnawy MD. Dr.PH

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.
 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

Tamer Hifnawy MD. Dr.PH
Increase
 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

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
Advantages 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
 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.
 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
 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)
 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)
 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

 Investigator / Sponsor

Submission of Research
Protocol & Required Negative opinion
Documents to IRB

Protocol Modification Approval

Amendment Prior to Approval

National Scientific &
Research Ethical Rejection
Committee

Protocol Modification
Amendment Prior to Approval

Checklist fulfilled
No
Yes

Approval

Yes

Approval Letter

Investigator

Commencement of the
study
Up to your knowledge; is there
any Interactions between
different IRBs/RECs in the
MENA region?
Tamer Hifnawy MD. Dr.PH
 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.
 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
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?

Tamer Hifnawy MD. Dr.PH

 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
 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.

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

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
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

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

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

Tamer Hifnawy MD. Dr.PH

Tamer Hifnawy MD. Dr PH.
Associate Professor of Public Health & Community Medicine
Faculty of Medicine, Beni Suef University, Egypt
College of Dentistry, Taibah University, KSA
Assistant Vice Dean for Quality and Development
Certified Trainer in International Research Ethics

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