Case Study: Research Ethics Committee

at Cairo University, Egypt

Noha Asem

Introduction

The Faculty of Medicine at Cairo University in Egypt has a responsibility to

ensure that scientifically valid research is conducted according to accepted ethical
practices that promote the rights and welfare of research subjects. As such, in 2002,
the Dean of the Faculty of Medicine established a research ethics committee
(REC) to review human subject research conducted by staff at Kasr Al Ainy
hospital. Also, Cairo University obtained an FWA from the United States Office of
Human Research Protections (OHRP) and the REC registered at OHRP.
The Cairo REC had encountered many challenges during its inception
phase. This included insufficient training for its members, lack of diverse member-
ship, and limited resources. All of these challenges have been documented for other
RECs in Egypt (Sleem et  al. 2010). In addition, at the time of its establishment,
there was a lack of awareness among the faculty regarding research ethics and
the functions of the REC. A survey study that involved medical staff members
of Cairo University showed that many of the faculty had limited knowledge
regarding research ethics and that only 31.4% (27 of 88) had previously sub-
mitted a protocol to REC (Asem and Silverman 2009). Raising awareness about
research ethics and the roles of the REC became an important mission that the
REC achieved primarily through the conduct of several workshops in research
ethics, including a faculty conference in 2013. In addition, REC members made
presentations in different departments of the faculty about the roles and
responsibilities of the REC.
Originally, the faculty were not required to submit their researches to the
REC. Only internationally sponsored clinical trials were required as per the
sponsor’s country regulations to seek site specific REC approval. Beginning in

N. Asem (*)
Faculty of Medicine, Cairo University, Cairo, Egypt
e-mail: noha_asem@yahoo.com

© Springer International Publishing AG 2017 295

H. Silverman (ed.), Research Ethics in the Arab Region, Research Ethics Forum 5,
https://doi.org/10.1007/978-3-319-65266-5_30
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180
160
153
129
140
116
120
108
100
80
60
49
41
40
21
20
0
Y 2008 Y 2009 Y 2010 Y 2011 Y 2012 Y 2013 Y 2014

Fig. 1  Numbers of applications to REC from 2008 to 2014

Rheumatology 0.7%
Psychiatry 0.7%
Orthopedics 0.7%
Neurosurgery 0.7%
Neurophysiology 0.7%
Family Medicine 0.7%
derma 0.7%
Public Health 1.3%
Critical Care 2.0%
Clinical Pathology 2.0%
Urology 2.6%
ophthalmology 3.9%
Neurology 3.9%
Anesthesia 5.9%
Obstetrics & Gynecology 6.5%
Tropical Medicine 11.1%
Internal Medicine 11.8%
Pediatrics 20.3%
Oncology 24.2%
0.0% 5.0% 10.0% 15.0% 20.0% 25.0%

Fig. 2  Applications in 2014 categorized by specialty

2010, the Faculty of Medicine made it mandatory for faculty to submit other
types of research for REC approval; these included all master’s and doctoral
theses that represent high risk interventional studies. This change led to
increased applications to the REC, as shown in Figs. 1 and 2. In 2008, 21 applica-
tions were submitted, whereas in 2014 the number of applications reached 153
(Fig. 1), representing submissions from 19 departments as shown (Fig. 2).
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Governance

The REC is under the governance of the Faculty of Medicine. In 2009, the Vice
Dean for Research appointed a senior professor as chair of the REC. Subsequently,
the chair made recommendations for who could serve as members, which was pre-
sented to the faculty council for approval. The composition of the REC represents a
gender-balanced committee comprised of faculty from medicine and other depart-
ments. In response to the increased number and diversity of protocol submissions to
the REC, an advisory board of 34 staff members from several faculty departments
was established. An advisory board member can be invited to review a protocol
application and attend certain REC meetings based on the domain of the applied
research protocol.

Structure and Operations

Regulations and Guidelines

The REC operates according to Declaration of Helsinki, the WHO Standards and
Operational Guidance for Ethics Review of Health-Related Research with Human
Participants, the Council for International Organizations of Medical Sciences
(CIOMS) and the International Conference of Harmonization, Good Clinical
Practice.

Administrative Staff

The increased numbers and complexity of applications to REC raised the need to

hire an administrative secretary for the REC office. An REC coordinator has also
been assigned since 2010, who has qualifications in research ethics and Good
Clinical Practice (GCP).
The main responsibilities of the REC coordinator are as follows:

• Serves as liaison to the research community;

• Conducts initial review of all submissions for completion and identifies regula-
tory and ethical concerns prior to full board review;
• Gives presentations about the REC to departments at the university;
• Provides consultation to faculty regarding the review process and the technical
and ethical requirements for conducting research involving human subjects;
• Helps with designing culturally relevant informed consent forms;
• Works in partnership with the REC chairperson and members to develop and
upgrade written guidelines and templates to improve communication and under-
standing of human research requirements among the faculty;
• Tracks status of submitted and approved studies;
• Records the meeting minutes; and
• Coordinates expedited review of eligible submissions.
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Documents

The REC developed several documents and templates to enhance transparency.

These include the following: Standard Operating Procedures (SOPs); a standardized
REC application form; standardized REC review form; standardized letters for the
PI to communicate REC decisions; conflict of interest management plan; confiden-
tiality agreement; continuing review submission form and review form; and amend-
ments submission and review form.

Meetings

The REC meets monthly on Saturdays. A quorum (half of REC membership plus
one) is required for a meeting to be held.

Member Training

Four members of the REC received advanced training in research ethics from the
Fogarty International Health/NIH -sponsored Middle East Research Ethics Training
Initiative (MERETI) that is administered at the University of Maryland University.
Other members receive training from the following variety of resources: (1) educa-
tional sessions held during REC meetings, (2) online training, including the
MERETI, WHO, and CITI programs, and (3) workshops and conferences held at
Cairo University. All advisory board members attended a full day workshop in
research ethics that was organized by the REC in 2010. Future workshops are
planned.

Conflict of Interest Policy

Members are required to reveal their conflict of interests before their first REC
meeting. In addition, members are required to declare any professional conflict of
interest at the outset of the meeting and if present, do not participate in the subse-
quent review of that research.

Submissions of Applications

Researchers are requested to complete a standardized REC application form (see

Appendix III) accompanied by supporting documents, including their curriculum
vitae, study protocol, data collection sheet and informed consent form. All materials
must be delivered to the REC office at least 2  weeks before the monthly
meeting.
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Type of Submissions

Table 1 shows the major research designs of the submissions to the REC between
2011 and 2014. Interventional studies represent the main type of research submitted
to the REC, which has increased yearly since 2011, reflecting the increased number
of industry sponsored clinical trials conducted at the Faculty of Medicine. Also,
masters and doctoral theses are increasingly involving experimental studies. Table 1
also shows that phase III clinical trials represents the main category of submitted
experimental studies; 63.3% in 2011 and 71.1% in 2014. The percentage of Phase
II and Phase IV studies range between 10% and 20%, while the number of Phase I
studies is no more than 1 or 2 studies per year. Beginning in 2013 and 2014, slightly
more than half of the applications to REC represented multicenter studies (data not
shown). Also, international collaborative studies represented 50.4% and 49.0% of
the total number of submitted proposals for years 2013 and 2014, respectively (data
not shown).
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Table 1  Clinical designs of researches submitted to the REC 2011–2014

2011 2012 2013 2014
Research category n % n % n % n %
Interventional studies 60 55.6 77 66.4 92 71.3 114 74.5
Phase of Phase I 2.0 3.3 1.0 1.3 2.0 2.2 1.0 0.9
experimental Phase II 10 16.7 16 20.8 17 18.5 20 17.5
studies Phase III 38 63.3 51 66.2 62 67.3 81 71.1
Phase IV 10 16.7 9 11.7 11 12.0 12 10.5
Observational 48 44.4 39 33.6 37 28.7 39 25.5
Total 108 100.0 116 100.0 129 100.0 153 100.0

Table 2  Specific issues included in studies submitted to REC 2011–2014; total n = 108
2011 2012 2013 2014
Research category n % n % n % n %
Biological specimens collection 31 28.7 52 44.8 57 44.2 65 42.5
Genetic testing 9 8.3 17 14.7 30 23.3 33 21.6
Stem cell research 1 0.9 6 5.2 2 1.6 2 1.3

Table 2 shows specific research issues involved with many of the submitted pro-
posals. As shown, there has been an increase in number of studies involving biologi-
cal samples/specimens; 31 applications (28.7%) in 2011, which increased to 65
(42.5%) in 2014. Application involving genetic testing progressively increased from
9 (8.3%) in 2011 to 33 (21.6%) in 2014. The number of submissions for stem cell
research has not increased, which reflects the concerns of REC regarding aspects of
stem cell research.

Informed Consent

Guidelines emphasize that written consent is required for human subject research
with few exceptions, e.g., to waive the documentation of signature or waive any or
all of the basic elements of informed consent. Table 3 shows that documentation by
a written signature has increased from 77.8% of studies in 2011 to 97.4% in 2014.
The increase in documentation by written consent is mainly attributed to the
increased number of interventional studies. Very few studies are performed in which
a waiver of consent is granted.
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Table 3  Types of informed consent in research submitted to REC 2011–2014

2011 2012 2013 2014
n % n % n % n %
Written 84 77.8 106 91.4 118 91.5 149 97.4
Verbal 20 18.5 8 6.9 5 3.9 4 2.6
Waiver 4 3.7 2 1.7 6 4.7 0 0.0
Total 108 100.0 116 100.0 129 100.0 153 100.0

Table 4  REC decisions: 2011–2014

2011 2012 2013 2014
n % n % n % n %
Unconditional approval 63 58.3 62 53.4 66 51.2 83 54.2
Conditional approval 34 31.5 44 37.9 51 39.5 61 39.9
Deferral 9 8.3 8 6.9 9 7.0 7 4.6
Disapproval 2 1.9 2 1.7 3 2.3 2 1.3
Total 108 100 116 100 129 100 153 100

Decisions of the REC

One of the four following decisions is made after protocol review:

1. Unconditional approval;
2. Conditional approval with clarifications or modifications;
3. Deferral due to insufficient information to make a decision
4. Disapproval when a proposal lacks sufficient social values or present major
safety concerns that does not appear to be remedial.

Table 4 shows the REC decisions from 2011 to 2014. It shows that the most com-
mon decisions are unconditional approval (above 50%) followed by conditional
approval. Deferral decisions are less frequent (less than 10%). Common reasons for
deferrals include: unacceptable study design, insufficient supportive documents or
published papers related to the safety of study intervention, or insufficient pre-­
clinical data, pharmacological or pharmacokinetics of a study drug. Disapproval
decisions are the least common decision given for the submitted studies (less than
3%). Most common reasons for disapproval includes an unfavorable assessment of
the risk benefit ratio and the prospect of risky adverse events.

Monitoring of REC Approved Studies

The REC monitors approved studies through continuing review, which is required
on a yearly basis for most protocols and more frequently for high risk protocols with
potential major safety concerns. Monitoring is also achieved by mandatory
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reporting requirements that includes safety reports, progress reports, protocol devia-
tions, end-of-study notification, and clinical study reports. Local serious adverse
events must be reported within 24 h to the REC. The auditing role of the REC is still
limited to individual cases where protocol deviations are reported or complaints are
received from research participants.

Special Considerations

International Research

There has been an increased number of international studies submitted to the REC
during the past few years. Concerns regarding these studies are mainly related to
research design issues and the nature and extent of post-trial benefits. Specifically,
the most common concerns are as follows: relevance of the research to the health
needs of the local population; applicability of the research design to the local cul-
tural context, especially among socially or economically disadvantaged people;
presence of insurance coverage; presence of Data Safety and Monitoring Board
(DSMB), including national and international clinical trials; informed consent that
is sensitive to the local setting; post-trial benefits to research participants and to the
local population.

Stem Cell Research

Standard practice in clinical stem cell research necessitates specific regulations to

ensure the biological safety of the infused stem cells, including consideration of
long range side effects and minimizing exposure to unknown risks. As such, there
are additional regulatory requirements for stem cell research that uses ex-vivo
expanded stem cells that regulates methods of stem cell preparation in the labora-
tory. For example, stem cells for human use must be collected and expanded ex vivo
in dedicated facilities, with filtered laminar flow of environmental air and controlled
access in compliance with Good Manufacturing Practice (GMP) rules. Oversight
and regular auditing of these processes are necessary (“ISSCR Guidelines for the
Clinical Translation of Stem Cells” 2009).
Based on REC responsibility in ensuring safety and welfare of patients who par-
ticipate in stem cell studies, while promoting ethical research in the institute, the
REC requires the following actions to be implemented before clinical stem cell
researches can proceed:

• Examining the available stem cell laboratory for compliance with the facility
requirements of stem cell research regulations and recommending the required
improvements if any.
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• Establishing the critical preparatory requirements for cells to be infused into

patients including sampling, culture and growth factor, cell infusion, in vivo cell
tracking and follow up issues.
• Establishing the necessary quality control and biosafety measures to be imple-
mented and monitored.
• Establishing the frequency and requirements for regulatory audit of stem cell
clinical studies.
• Establishing an institutional policy and procedures that ensure and enforce the
above measures.

Research Involving Storage/Exportation of Biological Samples

There was an increase in number of studies submitted to REC that involved collec-
tion of biological samples/specimens (Table 2). There are compelling scientific rea-
sons for the collection, export, storage and reuse of human biological samples for
research purposes (Tindana et  al. 2014). However, the practice of exporting and
sharing human biological samples from Africa and the Arab region have raised con-
cerns about appropriate mechanisms to safeguard the interests of sample donors and
their communities (Zhang et al. 2010). Specific issues involve safeguarding confi-
dentiality, benefit-sharing, and informed consent, particularly for future use of
stored samples. Obtaining appropriate consent for sample export and reuse that
allows research participants to put limits for using of their stored samples in future
research is the most frequent concern. Finally, approval is required from the
Egyptian National Security Agency before exportation of any biological material
outside the country.

Informed Consent

Inform consent forms for international researches have usually led to the use of
lengthy and complex consent documents, especially after translation into the Arabic
language. A large proportion of the narrative in such consent forms are usually due
to the input of legal language required by sponsors. Such language is complex and
makes comprehension problematic for many potential research participants, thus
presenting difficulties for the consent process.
This issue was discussed in several REC meetings and accordingly, a site specific
consent form template was developed (see Appendix IV). It provides a guide to the
essential components of the consent form, as well as site specific contact informa-
tion for research participants. When an applied consent document is more than five
pages, the principal investigator may be required to submit a consent form that
provides potential research participants with the most essential and site specific
information they need to know in a simpler more reader friendly form in the begin-
ning of the ICF. Subsequently, the full consent document is presented.
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Challenges Facing the Cairo University REC

The following represent challenges to the REC at Cairo University:

Lack of National Regulations for Research Ethics

To date, there are no national regulations for research ethics in Egypt to provide
specific guidance to RECs in its review of research that is responsive to the local
context. However, a draft law for guiding clinical research has been drafted and
waiting for the parliament to discuss, make any necessary changes, and grant
approval.

Resources

A lack of human and physical resources represents a common challenge, as men-

tioned before and identified for other RECs in Egypt (Sleem et al. 2010). Initially,
the REC had no dedicated office space, supplies, computer or other IT facili-
ties. In 2008, the Dean and Vice Dean for Research and Postgraduate Studies pro-
vided additional meeting space and office equipment in 2010.
Current efforts are directed to the development of a complete management infor-
mation system. This has been a priority for the REC’s plan of improvement in
response to the increased numbers and complexity of applications. On the other
hand, continuous updating and capacity building among all members of REC to
keep the pace with advancements of research is important for continuous capacity
building.

 wareness and Knowledge of Researchers Regarding Issues

A
in Research Ethics

Concerns have been expressed about the awareness and knowledge of researchers
regarding issues in research ethics. For example, a study conducted among 135
medical researchers from Cairo University in 2008 showed that they desired more
training on the principles of research ethics and writing a proper informed consent
(Asem and Silverman 2009). Another study performed in south Egypt showed that
the academic medical staff had deficient knowledge about research ethics and that
they desired more research ethics training (Shabrawy et al. 2014). Template submis-
sion forms for researchers applying to REC were developed to overcome some of
their knowledge-based challenges. Also, the REC has organized several faculty
annual conferences aimed at raising awareness and knowledge regarding research
ethics among staff and students.
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Monitoring and Auditing Role

Parties responsible for the oversight of multi-centre clinical trials include research-
ers, institutions, sponsors of research, and RECs. It remains controversial regarding
best practices for a monitoring role for RECs (Pickworth 2000). Currently, REC
monitoring is limited to specific studies and occurs only after being notified of
adverse events and protocol violations. Extension of the monitoring role of REC
beyond the mere receipt of reports will require additional human and capital
resources.

Next Steps
The REC is taking steps towards expanding its role in raising awareness and build-
ing capacity among the staff and students at Kasr Al-Ainy. Intense efforts are also
planned to enhance the service it provides to researchers, e.g., faster turnaround
times of ethical review. Finally, strengthening the REC’s information system as well
as automation of several of its functions will be more cost-effective.

References
Asem, N., and H.J. Silverman. 2009. Perspectives of faculty at Cairo University towards research
ethics and informed consent. Abstract Presentation at PRIM&R, Nashville, Tenn.
ISSCR Guidelines for the Clinical Translation of Stem Cells. 2009. Current Protocols Stem Cell
Biology., Appendix 1, Appendix 1B. https://doi.org/10.1002/9780470151808.sca01bs9.
Pickworth, E. 2000. Should local research ethics committees monitor research they have approved?
Journal of Medical Ethics 26 (5): 330–333.
Shabrawy, E., T. Hifnawy, and H. Reda. 2014. Applying ethical guidelines in clinical researches
among Academic Medical Staff: An experience from South Egypt. British Journal of Medicine
and Medical Research 4 (10): 2014–2024.
Sleem, H., S. El-Kamary, and H.J. Silverman. 2010. Identifying structures, processes, resources
and needs of research ethics committees in Egypt. BMC Medical Ethics 11: 12.
Tindana, P., C.S. Molyneux, S. Bull, and M. Parker. 2014. Ethical issues in the export, storage and
reuse of human biological samples in biomedical research: perspectives of key stakeholders
in Ghana and Kenya. BMC Medical Ethics 15: 76. https://doi.org/10.1186/1472-6939-15-76.
Zhang, X., K.  Matsui, B.  Krohmal, A.A.  Zeid, V.  Muthuswamy, Y.M.  Koo, … R.K.  Lie. 2010.
Attitudes towards transfers of human tissue samples across borders: an international survey of
researchers and policy makers in five countries. BMC Medical Ethics 11: 16. ­doi:https://doi.
org/10.1186/1472-6939-11-16.