International Dialogue on Bioethics

Ethical Rules in Egypt

Lamis Ragab, MD, MHPEProf of Pediatrics & Medical Education

Former DeanFaculty of Medicine

Cairo University

Copenhagen 19/6/2012

Present Regulations in Egypt

• Egypt Constitution 1971 (part 3), Egypt Constitution 1971 (part 3), Article 43 Any medical or scientific experiment may not

be undergone on any person without his free consent.

• Profession Ethics RegulationsProfession Ethics Regulations issued by the Resolution of the Minister of Health & Population No. 238/2003, Articles 52-61

Copenhagen 19/6/2012

Copenhagen 19/6/2012

•Egyptian clinical trial directive: assuring the rights & benefits of subjects participating in clinical research

•National law for clinical research

•National committee formed by the Ministry of Research

•Law is under processing

The Standard Operating Procedures on CT Submission & Privacy-Confidentiality

Copenhagen 19/6/2012

• Ministry of Health & Population• Central Directorate for Research & Health

Development• Required documents and procedures for the

proposal to the REC• Application form code• 3 files + 5 files + 3 CDs• rhd@mohp.gov.eg

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• Approval of the site• Approval of the ethics committee• Type of the study: Interventional (non-

pharmaceutical) Observational Health System Research• Amendment• Annual follow up• Timeline

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Copenhagen 19/6/2012

Faculty of Medicine

Cairo University Since 1827

Copenhagen 19/6/2012

9684 undergraduate & 8300 postgraduate students

2702 faculty members & 2000000 patients

UC Davis October 2009

9684 undergraduate & 8300 postgraduate students

2702 faculty members & 2000000 patients

UC Davis October 2009

Cairo University hospitals comprise more

than 5200 beds (over 9 premises)

UC Davis October 2009

Research Ethics Committee

Faculty of Medicine

Cairo University

Cairo University MREC

• Established in 2003

• Current committee was formed in 2008

• Most recent regulations were approved in 2011– Rules governing research protocol evaluation

– Required documents

– Details of consent form

• REC convenes monthly

• The protocol to be submitted 1 month before REC meeting Copenhagen 19/6/2012

International Guidelines

• Professional Membership• USA Office for Human Research Protections

registration • IORG0002878- IRB00003475- FWA00005111• Egyptian Network of Research Ethics

Committee ENREC Founding Member

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Members

• Prof .Dr. Mohsen Ibrahim Professor of Cardiology- Chairman President of the EHS • Prof.Dr.Lamis Ragab Professor of Pediatrics- Vice dean for post graduate studies &• research • Prof.Dr.Sohier Mahfouz Professor of Pathology-Head of Pathology department • Prof.Dr.Samia Rizk Professor of clinical Pathology Certified trainer of human subject research ethics

• Prof.Dr.Maha El Rabbat Professor of Public Health • Prof.Dr.Omar El Khashab Professor of Internal Medicine• Prof.Dr.Adel Zaki Professor of Cardiology

• Prof.Dr.Maher fawzy Professor of Anesthesiology• Dr.Hany Sleem Consultant of Dermatology and Andrology National Institute for tropical and Liver diseases Certified trainer of human subject research ethics• Dr.Abdel Rahman El Nagar Professor of Pharmacology-Head of the national center for toxicology

• Dr.Noha Assem Assistant Lecturer of Public Health Certified trainer of human subject research ethics• Mr.Ahmed Darwish Manger of legal affaires in Kasr Al Aini

Training • Four committee members are internationally

certified form Maryland University USA • All members attended training sessions held

during REC meetings

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Study Title:

Principal investigator &Department name

Source of Funding Governmental Non governmental Self

Sponsor :

Background and Rationale (no more than 5 lines )

Objectives:

Study population & Sample size :

Study Design :

Interventions :

Possible Risk (s):

Outcome parameter (s):

Statistical analysis plan:

Time plan:

Cairo UniversityFaculty of MedicineMedical Research Ethics Committee

Protocol summary

البحث عنوان  جامعة: الباحثون دكتور استاذ

جامعه دكتور استاذجامعه دكتور استاذ

الدراسة من :الغرضالمشارك / من المطلوبة األعمال :اإلجراءات

  للمشاركة المطلوبة الزمنية :الفترة

.المخاطروالمجتمع للمشارك :الفوائد

  البيانات سرية و المشارك خصوصية :حماية

تطوعية :المشاركة

البحث فى المشاركة :تكاليف :التعويض 

  االنسحاب فى :الحق : المشاركة فى الرغبة عدم حالة فى المتاحة يمكنك  البدائل الدراسة هذه عن المزيد لمعرفة

بالدكتور .--------------االتصال02ت: ------------- .

بالدكتور االتصال يمكنك الدراسة فى المشاركة نتيجة صحية متاعب حدوث حالة .------------فى02ت:---------- - .

/ محسن الدكتور البحوث اخالقيات مراجعة لجنة بمكتب االتصال يرجى شكوى، وجود حالة فىرقم إبراهيم تليفون

0103657120

إذا كنت توافق على االشتراك فى هذه الدراسة، قم •باإلشارة فى المكان المناسب فى الجزء التالى:

____: لقد تم شرح كل المعلومات الواردة فى هذه •االتفاقية.

____: لقد قرأت وفهمت المعلومات الواردة فى هذه •االتفاقية.

اسم المشارك: _________________________ توقيعه: •______________________

شاهد علي إجراءات الموافقة : ____________________ •توقيعه: _______________________

توقيع مسئول الدراسة: •________________________________________________

التاريخ: _______________________•ال تعتمد إال إذا كان خاتم لجنة مراجعة اخالقيات البحوث •

عليها . 201 / / إلى 201 / / سارية من : •تسلم نسخة للمشارك وتحفظ النسخة األصلية مع •

الباحث فى ملف المشارك

• Application for REC Review • Section One: Application Information • Principal Investigator/s:• Department:• Title:• Phone/Pager:• Fax:• E-mail address:• Mailing Address: • Title of Project• Purpose of Project (one or two sentences)

REC ID

Summary of Reviewers Evaluation (cont.)

Research Ethics CommitteeReview Procedure/ Check List

• Thoroughness and completeness of the information submitted

• Suitability of the protocol and the data collection forms in relation to the objectives of the study

• Suitability of the investigator for the proposed study

• Adequacy of the site, including the supporting staff and available facilities

• Adequacy of medical supervision and follow-up

• Sources of funding, sponsor and other potential conflict of interest

Copenhagen 19/6/2012

Research Ethics Committees Review Procedure/ Check List (cont)

• Provisions made for monitoring and auditing the conduct of the research

• Means by which initial recruitment is to be conducted

• Vulnerable subjects

• Content and the wording of the informed consent form

• Provisions for compensation/treatment in the case of disability

• Confidentiality of personal subject information

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• Establishment of REC filing system and database for activities

• Documents produced by the committee • Standard operating procedures SOP`s• Standardized Kasr Al-Ainy REC application form• Standardized Kasr Al-Ainy REC review form• Standardized letters for REC decisions • Continuing review requirements and review form• Conflict of interest management plan• Confidentiality agreement form• Release of REC annual report• Complete list of REC advisory board.

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Number of submitted protocols:

Year 2008 2009 2010 2011

No. 21 42 49 104 applications

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Decisions of REC for submitted protocols:

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Source of Funding

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Types of Research Projects

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Multicenter trials

• Lack of harmonization of procedures among countries

• Difficult approach• Trials in developing countries and the risk of

double standards• From a purely economical or utilitarian

perspective developing countries represent a unique, cheaper and large source of subjects

Categories of submitted studies

Compensation

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Applied Studies

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Presence of Data Safety Monitoring Board

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Previous Scientific Review

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Type of Consent

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Pediatric Clinical Research in Egypt

Experience of the FMCU

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• The pediatric population has the right to use medicines that have been appropriately evaluated and tested.

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•Protection of children FROM research

•Protection of children THROUGH research

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Scientifically and ethically sound methodological standards:

•Benefit/risk balance

•Consent/Assent

•Placebo

•Interventional vs observational

•Therapeutic vs non-therapeutic

•Compensation/Insurance

•Legal guardian

•Post-trial benefitCopenhagen 19/6/2012

Research involving children

2008 2009 2010 2011

N. % N. % N. % N. %

4 33.4 15 35.7 10 25.7 20 22

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2008N.=4

2009N.-15

2010N.=10

2011

N=20

N. % N. % N. % N. %

Peculiar to

pediatric age2 50% 11 73.3% 8 80% 16

8

0

%

Children and

adults 2 50% 4 26.7% 2 20% 4

2

0

%

Research category Single site project 1 25.0

4 26.7

5 50.0 6

Multi-center project 2 50.0

8 53.3

3 30.0 12

National collaborative project

1 25.0

2 13.3

0 0 1

International collaborative project

0 0 5 33.3

3 30.0 5

Research type

Research type Experimental study 1 25.0 7 46.7 5 50.0

12

Observational Descriptive Study

0 0 2 13.3 2 20.0

2

Observational Analytic study 3 75.0 5 33.3 3 30.0

4

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Phase of Experimental studies

Phase I 0 0 1 14.3

1 20.0 2

Phase II 0 0 0 0.0 0 0 3Phase III 1 10

06 85.

74 80.0 5

Phase IV 0 0 0 0.0 0 0 2

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Insurance

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Consent form

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Assent 2011 applications

2011

Assent 4No Assent 16

Clinical Research at the Pediatric Department

• An open-label, multi-center trial on efficacy and safety of lon-term treatment with ICL670 (10 to 20 mg/kg/day) in beta-thalassemia patients with transfusional hemosiderosis

May 2004

• An open-label, multi-center trial on efficacy and safety of long-term treatment with ICL670 (10 to 20 mg/kg/day) in beta-thalassemia patients with transfusional hemosiderosis ( Extension Phase)

June 2005

• A one year, open-label, single arm, multi-center trial on evaluating the efficacy and safety of oral ICL670 (20 mg/kg/day) in patients diagnosed with transfusion dependent iron overload

April 2005

Clinical Research at the Pediatric Department

A one year, open-label, single arm, multi-center trial on evaluating the efficacy and safety of oral ICL670 (20 mg/kg/day) in patients diagnosed with transfusion dependent iron overload (Extension Phase)

July 2006

A one Year, open label, single arm, multi- center trial evaluating the efficacy and safety of oral ICL670 (20 mg/ kg/day) in patients diagnosed with transfusion dependent iron overload

May- 2007

Clinical Research at the Pediatric Department

A five year observational study (registry) of children aged 2 to ≤ years at enrollment with transfusional hemosiderosis treated with deferasirox

Aug- 2007 Inhibitor development in previously untreated PUPs) or

minimally blood component treated patients ( MBCTPs) when exposed to plasma derived von Willebrand factor containing factor concentrate and to recombinant factor VIII :An International Independent Multicenter Prospective Controlled Randomized Open label Clinical Trial

March- 2009

Clinical Research at the Pediatric Department

• A multicenter, randomized open label phase II trial evaluating deferasirox compared with deferoxamine in patients with cardiac iron overload due to chronic blood transfusion (CORDELIA)

Mar- 2010

• Phase II, open label single arm, multicenter study to evaluate the efficacy and safety of deferasirox in combination with deferoxamine followed by deferasirox monotherapy in patients with severe cardiac iron overload due to chronic blood transfusion (HYPERION)

Jul- 2010 January 2011 • International sentinel site surveillance of patients with transfusional

hemosiderosis treated with Exjade in actual practice setting September 2010 February 2012

Clinical Research at the Pediatric Department

 

• A phase 3, randomized multi-center, open- label, active comparator study to evaluate the efficacy and safety of Genz- 112638 in patients with Gaucher disease Type 1 who have reached therapeutic goals with enzyme replacement therapy

Nov- 2010 • A multi- center, open-label, phase III study to evaluate the safety and efficacy of

ISU302 (Imiglucerase for injection) in patients with type 1 Gaucher disease Apr- 2011

• A randomized, open- label, multi-dose study of HQK-1001 in subjects with sickle cell disease

Oct- 2011 • Multicenter, randomized, open label, non- inferiority active controlled trial to

evaluate the efficacy and safety of deferiprone compared to deferasirox pediatric patients aged 1 month to less than 18 years affected transfusion dependent hemoglobinopathies

Development phase

• 12 recruiting European Centres (from Italy, Greece, Cyprus) and 3 recruiting non-European Centres (from Egypt, Albania, China) with scientific partners from EU

• DEEP intends to guarantee the respect of ethical rules, regardless of the country in which the research is carried out, in compliance with the current European and international legal frameworks.

• Reflection Paper on ethical & GCP compliance in clinical trials conducted in Third Countries:

Ethical principles applied to the clinical trials in the EEA should also apply to trials conducted in non-EU Countries, taking into account local legal requirements and cultural background.

“International Ethical Guidelines for Biomedical Research Involving Human Subjects”

• Double standards are not acceptable.

• Ethical principles applied to clinical trials should supervene everywhere,

considering local legal requirements and cultural backgrounds.

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• Ethics and science:

hand in hand

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International Cooperation• Cooperation

• Information sharing

• Training

• Sharing best practice

• Regulatory authoritiesCopenhagen 19/6/2012