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Module 2.
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Part 1. Research Ethics Committees (RECs)
Several international guidelines have developed ethical and scientific standards for carrying out
research involving human participants. Compliance with these guidelines helps to ensure the
dignity, rights, safety and well-being of participants who participate in research. These guidelines
require, amongst many other things, that an independent research ethics committee (REC)
conducts an ethical review of biomedical research involving human participants.

1.1. Authority, role and mandate of RECs
Research Ethics Committees (RECs) are sometimes referred to as Institutional Review Boards
(IRBs), Research Ethics Boards (REBs), Independent Ethics Committees (IECs) or simply Ethics
Committees (ECs). The legal status of RECs varies from country to country and they may be set
up, and operate, according to different models. Most frequently, RECs will be set up by a
government or an institutional authority (such as a hospital, research institution or university).
In some countries, RECs may be set up by private organizations. However, some countries
prohibit “private RECs” that are not publicly accountable in some way (such as through
accreditation). There is, however, little hard data to suggest that the quality of ethics review
conducted by private RECs is worse that that of institutional or national RECs.
A REC that has authority and responsibility over research projects that are conducted under the
auspices of its constituting authority, be it national, regional or institutional, is considered the
“competent REC” for that organization.
The competent REC is the one to which researchers should submit their protocols. Identifying the
competent REC may help to avoid protocols being submitted to another committee considered to
be more lenient than the competent REC. This practice - sometimes called “REC shopping”-
undermines the protection of research participants.
On REC shopping:
“… commercial IRBs have a fundamental conflict of interest. They are in a client–provider business
relationship with the commercial entities whose studies they review. Because commercial IRBs
generate their income from clients with a direct financial interest in obtaining approval, they are
affected by the very problem they are expected to curtail. The financial interests involved are huge.
Pharmaceutical companies pay CROs [Contract Research Organizations] for their speed and
efficiency. Clinical trials are a crucial step in the drug development process. Any delay in approval
by an IRB affects the sponsor's profit margins.
The countries that have allowed these private IRBs to flourish have also failed to regulate them
carefully… Anyone who can bring together five people, including a community representative, a
physician, a lawyer and an “ethicist,” can set up shop and start competing for business.
Moreover, regulations in those countries fail to prevent CROs from selecting the IRB least likely to
reject the trial or delay approval by imposing too many restrictions. If one IRB is too stringent, they
can simply go to the one next door.”
Lemmens & Elliot in “Should Society Allow Research Ethics Boards to Be Run As For-Profit
Enterprises?” Ezekiel J. Emanuel, Trudo Lemmens, Carl Elliot , PLoS
Despite legal and operational differences, the primary role of RECs remains the same:
to ensure the well-being, safety and protection of persons who participate in all types of
research involving humans.
Ensuring the protection of humans who participate in research involves collaboration between
RECs and researchers to ensure that research meets the highest ethical standards.

RECs will typically accomplish this goal by the combination of the following activities:
The ethics evaluation and approval of protocols before they commence

The continuing review of ongoing research
The active promotion of principles of ethics through education and training.
WHO GUIDELINES Section 2: “ECs are responsible for acting in the full interest of potential
research participants and concerned communities, taking into account the interests and needs of
the researchers, and having due regard for the requirements of relevant regulatory agencies and
applicable laws”
Emanuel E.J., Lemmens T., Elliot C., 2006.

WMA, Declaration of Helsinki, 2013, Para. 23.
WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 2.
ICH-GCP, 1996, Sec.1.27, 1.31, 2.3, 3.1.
CIOMS, International Ethical Guidelines for Biomedical Research Involving Human
Subjects, 2002, Guideline 2.
COUNCIL OF EUROPE, Additional Protocol to the Convention on Human Rights and
Biomedicine, concerning Biomedical Research, 2005, Art. 9,10.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 2(k).
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.108, 46.109.

Question 1
The legal framework applicable to ethics review (and to RECs) varies from one country to the
next.
True or False?
In countries where RECs are not formally recognized by law, RECs only need to be consulted by
researchers when their project poses more than minimal risk.
True
False

1.2. Independence of ethics committees and committee members: a
key feature
In order to properly perform their protective function, RECs must be independent from research
sponsors, investigators and from any other undue influence, such as political, institutional,
professional or commercial influences.
REC independence is critical to ensuring that research participants’ interests always come first
and are not secondary to other interests such as scientific advancement or economic gain. REC
independence is one of the four requirements for standardized ethical review. The others are
constitution, competence and standard operating procedures.
Achieving REC independence is a challenge in many situations and is often a question of ensuring
proper accountability and balanced membership. REC independence is promoted when they are
made accountable as will be discussed in section 1.6 below. In many countries, it is standard
practice to exclude from REC membership all institutional authorities (chief executive officer, legal
counsel, Deans and directors, most notably of research centres) in order to maintain REC
independence.
A common example of a potential conflict of interest is when an international institution wishes to

conduct a collaborative research project. The foreign collaborating institution typically discusses
the issue with the CEO/head of the local institution. When there is potential for local institutional
gains from participation in a trial sponsored by the foreign institution (e.g., a laboratory, equipment,
employment), the potential conflict is manifest. The judgment of the CEO in the ethics evaluation of
such a proposal if s/he sits on an ethics committee will not appear to be objective (and for this
reason many countries do not allow CEOs to sit on RECs). Undue influence may also be placed on
the REC.
REC members must also be in a position to conduct independent reviews of protocols. This means
that they must be free from, or have properly managed, any conflicts of interest. More concretely,
“A conflict of interest arises when a member (or members) of the [REC] holds interests with
respect to specific applications for review that may jeopardize his/her (their) ability to provide a free
and independent evaluation of the research focused on the protection of the research participants.
Conflicts of interests may arise when an EC member has financial, material, institutional, or social
ties to the research.”
WHO, Operational Guidelines, Glossary
If members have particular links with a given protocol, they should not participate in decisions
concerning that protocol. Current practice requires them to declare the conflict of interest and they
may be requested to leave the meeting room when that protocol is being discussed.
CIOMS, International Ethical Guidelines 2002, commentary on Guideline 20. On potential

conflicts and capacity strengthening activities:
REC independence becomes a challenge again during strengthening capacity for ethical and
scientific review and biomedical research by collaborating institutions as well as sponsors. “The
specific capacity-building objectives should be determined and achieved through dialogue and

negotiation between external sponsors and host-country authorities. External sponsors would be
expected to employ and, if necessary, train local individuals to function as investigators, research
assistants or data managers, for example, and to provide, as necessary, reasonable amounts of
financial, educational and other assistance for capacity-building. To avoid conflict of interest and
safeguard the independence of review committees, financial assistance should not be provided
directly to them; rather, funds should be made available to appropriate authorities in the host-
country government or to the host research institution.
The independence of RECs from government agencies, commercial entities, researchers and
supporting institutions, among others, varies depending on the country’s research review
structure, the types of RECs and their sources of funding. In general there seem to be no specific
safeguards to address this issue. There is a need to adopt measures to protect the independence
of RECs.

ICH-GCP, 1996, Sec.1.7, 1.31, 3.2.1.
Biomedicine, concerning Biomedical Research, 2005, Art. 9,10.
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.107.

Question 2
Recall the VanTx case discussed in Module 1. The ethics review of trials to be conducted by
VanTx, the contract research organization (CRO), was conducted by a private research ethics
committee. The fact that the chief executive officer (CEO) of the private REC was also the CEO of
the organization conducting the trials raised serious concerns and prompted regulatory responses
to preclude such situations.
Why did this raise concerns? Choose the BEST answer.
CROs are in the business of conducting trials and as such will employ physicians who can
act as qualified investigators for the trials. The fact that the CEO of both the REC and of the
CRO was the same person signified that the REC was not independent of the investigator.
The fact that a single person holds interests in both the organization conducting the trial
(the CRO) and in the body ensuring its ethical oversight (the REC) jeopardizes that
person’s ability to provide a free and independent evaluation of the research focused on
the protection of the research participants. The competing financial interest constitutes a
conflict of interest.
It is critical that public trust in the ethics review system be maintained. The primary role of
the REC is to protect the interests of persons who participate in trials. Thus, the REC’s
duty towards research participants cannot be secondary to any commercial interests.
All of the above.

1.3. Composition and operational aspects

1.3.1 Composition
RECs are multi-disciplinary committees, drawing on the strengths of its members with varied
backgrounds. The goal of a diversified membership is to ensure that RECs can collectively conduct
a thorough and independent ethics evaluation of research projects.
Although there may be more specific requirements in some countries, there is a core of minimal
requirements for REC membership:
At least 5 members who collectively have the qualifications and experience required to
ensure proper review of the ethical, scientific, medical and financial aspects of a trial
At least one non-scientific member
At least one member who is independent of the institution or study site.
In many countries, it is further required that there be 3 non-scientific members: one legal, one
ethical and one representing the community.
REC members should be appointed for a fixed term by the recognized authority according to an
established procedure. The REC may choose to invite outside experts who are not members to
assist on particular aspects (often scientific) of a project.
In order to conduct a thorough review of proposed research, REC members need to have a sound
knowledge of research ethics acquired through training and continued education.

ICH-GCP, 1996, Sec.3.2.1.
Biomedicine, concerning Biomedical Research, 2005, Art. 9.

1.3.2.Properly constituted RECs and standard operating
procedures
The REC must be properly constituted and function according to applicable guidelines and
regulations. It must also perform its functions according to its own written operating procedures.
Minimally, the following elements of any REC should be clearly established:
the authority which established the REC (Terms of Reference)

the RECs mandate (function and duties) (Standard Operating Procedures)
the REC composition, minimum quorum requirements
the procedure for appointing members
Guidelines, and in some countries regulations, specify that REC operating procedures should
cover at least the following aspects:
How meetings will be conducted (including scheduling and notifying members) and the
need to keep detailed minutes of meetings
Procedures for submitting an application including the Submission Form
That the REC will make its decisions at announced quorate meetings
Internal procedures for ethics review such as how it will conduct initial review and
continuing review of studies, expedited review procedures, and target time for notification of
the decision to investigators
A rule that no participant should be admitted to a study before the REC has issued its
written approval or favourable opinion of the trial
That no deviations from, changes of or amendments to the protocol be initiated without
prior review and approval by the competent REC except when necessary to eliminate
immediate hazards to participants or when changes are simply logistical or administrative in
nature
How minor changes of ongoing trials will be reviewed (expedited review if in accordance
with applicable regulations)
The investigator’s duty to promptly report to the REC: deviations from the protocol to
eliminate immediate hazards to participants, changes that affect the initial balance of risks
and benefits, serious and unexpected adverse drug reactions, and any new information that
may have an impact on safety of participants or the conduct of the study.
RECs may need to ensure their written procedures comply with their national, local or institutional
requirements.

ICH-GCP, 1996, Sec. 3.2.1, 3.2, 3.3.
Biomedicine, concerning Biomedical Research, 2005, Art. 9.3, 11.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 6.1, 6.5, 6.6, 6.7.

Question 3
You are the Chair of an REC. Your REC has a policy requirement for “someone with knowledge of
relevant law to be part of the ethics review process.” On the day of a regularly scheduled REC
meeting, the lawyer member of the REC informs you that she will not be able to attend the meeting
due to a re-scheduled court date. She sends her regrets and includes her comments based on her
review of the protocols that will be reviewed by the REC.
As chair of the REC, you are not sure if you should still have your REC meeting or not. Which of
the following is the best option:
If the legal member cannot attend the meeting in person, the REC will not have a quorum.
So you must postpone the meeting even if this means that all of the projects will be delayed
until your meeting next month.
You decide to hold the meeting anyway because you don’t think it really matters which
members actually attend the meeting as long as there is a quorum.
You consult your institution’s policy on research and operating procedures for the REC to
verify if the quorum requirement can be met by sharing the written comments of your legal
member. Since this is an exceptional situation, you decide to hold your REC meeting
anyway.

1.4. Ethical deliberation & decision-making
Decision-making involves two distinct phases:
1. Deliberation and
2. Reaching a decision
The legitimacy of decisions reached by RECs rests on valid deliberation and respect of rules of
due process. REC members should take an active part in both phases when reviewing a research
project. In addition, the REC should adopt a proportionate approach when deliberating and making
a decision regarding a given project based on the risks and potential benefits. The greater the
potential for harm, the greater should be the care in its review.

1.4.1. Ethical deliberation
For members of the REC, ethical deliberation refers to reflection and discussion of research
projects in light of the ethical principles and values of research ethics as reflected in relevant local
and international guidelines. It requires the participation of all present to contribute and provide
their expertise and perspectives during the discussion. In order for each member of the committee
to do this in a meaningful way, all documentation relevant to the review must be received and
reviewed by all members prior to their discussion. Members must have adequate time to
communicate their points of view during the discussion. Each member must be familiar with the
ethical norms and regulations that govern research in order to be able to determine whether a
protocol complies with the ethical norms and regulations. Furthermore, ethical deliberation requires
a significant amount of reflection when different ethical norms and concepts appear relevant but
lead to contradictory conclusions.
In order for deliberations to lead to valid ethical decisions, RECs need to establish clear procedural
rules that include:
Listening and openness

Expressing everyone’s opinion
Reaching out to those who hesitate to participate in the discussion
Taking all factors into consideration
Highlighting disagreements and analyzing them
Achieving consensus.
Some have proposed procedural methods of deliberation that are useful when RECs face a moral
conflict that needs resolving. For example, each member should be given an equal opportunity to
initiate and continue communication, an equal opportunity to present recommendations or
explanations, and the opportunity to request justification or a rationale for any portion of the
research project.
These rules of procedure and dialogue require all REC members to recognize the importance of
each member’s contribution to the ethics review process and to manifest openness, tolerance and
dialogue. Here, the chairperson of the REC plays a critical role.
Glazer J.W., 1989.

Moreno J.D., 1991.
Durand G., 1999.
Amdur R., Bankert E., 2011.

1.4.2. Reaching a decision
Reaching a decision is the second phase of decision-making, which logically follows the
deliberation phase.
In conducting their review, as will be discussed in sections ahead, RECs usually evaluate the
scientific validity and value first and then evaluate the ethical and financial aspects of the project,
the consent documentation, risk/benefit ratio and any other documents to be provided to
participants. The goal of ethics review is to ensure that the project is ethically acceptable and
properly protects research participants. When there are ethical issues or concerns, the REC must
discuss these fully and use their collective judgment to reach a decision that protects participants
without unduly restricting research. REC decisions should be preceded by extensive discussion of
the ethical concerns and of possible means of improving the research project (e.g., research
design, information provided in the informed consent process).
The REC has the authority to approve, reject, require modifications to, as well as terminate or
suspend approval of any proposed or ongoing research under their jurisdiction according to
whether it meets ethical requirements.
Consensus
Ideally, the REC deliberates and eventually comes to a collective opinion (or consensus) that all
members find ethically satisfactory. Consensus reached by a REC is valid to the extent that it
emerges out of deliberations that are honest, factually well-informed, follow standard operating
procedures, and are fair.
“The members of bodies whose deliberations issue in consensus will all agree that the outcome is,
if not the very best in the opinion of each, at least thoroughly acceptable to each” (Caws, p.378).
However in reality it doesn’t always work this way. Sometimes a decision is not “thoroughly
acceptable” to some members, but those members agree their concerns were heard and
discussed, and they deem the process of deliberation and decision-making fair.
Voting
Making decisions by vote, as opposed to consensus, should be restricted to exceptional

circumstances, since voting gives priority to the number of people who hold a certain opinion but
does not take into account the reasoning behind the opinions held.
Dissenting and abstaining
It may be necessary for a REC’s operating procedures to provide that, in the event that a minority
of members consider the project or some aspect of the project unethical, an effort must be made to
reach consensus. However, when a decision reached is not unanimously acceptable, the number
of members dissenting and/or abstaining should be recorded in the minutes. Dissenting or
abstaining members may also be offered the opportunity to join their opinion to the REC’s decision
in a minority report.
Caws P., 1991.

1.4.3. Due process
As mentioned above the moral authority of consensus rests in part on due process, or procedural
justice, being respected within the work of the committee. This also holds true with respect to
investigators who submit their projects for review.
From a practical perspective, due process implies that the REC will be impartial, and will make its
decisions at announced meetings with a quorum and that only members who participate in
deliberations should take part in decisions. This also means that investigators should have a fair
opportunity to be heard (although not participate in the deliberation and decision).
REC decisions must also be communicated to the investigator in writing, ideally within 2 weeks of
the meeting. Decisions should contain a number of items (See BOX A: Key Elements When
Communicating a REC Decision) and provide reasons justifying negative decisions.
Appropriate archiving also promotes due process. The REC should ensure that it stores, and be
ready to make available, relevant records of its decisions, procedures, etc., for the required time
period. Archives should be retained for at least 3 years after completion of the study. Many
countries will require longer archiving for records of clinical drug trials.
WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 7, 8, 10.

ICH-GCP, 1996, Sec. 3.2.3, 3.2.4, 3.2.5, 3.3.9, 3.4.
Biomedicine, concerning Biomedical Research, 2005, Art. 9.3.

Question 4
Which ONE of the following statements regarding ethical deliberation in an REC meeting is TRUE?
All research projects must be discussed and receive the same thorough level of scrutiny.
Each member must have an equal opportunity to present and discuss her/his point of view.
The REC chairperson should discourage the use of rules of dialogue since this would
encourage discussion and make the meetings too long.
All of the statements above are false.

1.5. Follow up of ongoing research
In fulfilling their responsibility for protecting human research participants, RECs evaluate research
projects initially and re-evaluate approved projects at regular intervals. With consideration of the
researcher’s suggestions, it is left to the discretion of the REC to determine the frequency of follow-
up - or continuing review - of ongoing research based on the level of risk the project poses to
human participants. However, RECs are required to conduct a continuing review of projects at
least once a year. Researchers will be requested to submit written summaries of the study’s status
to the REC for this annual review, or more frequently if requested by the REC.
As part of the continuing review process, some events or instances trigger the need for follow-up
by the REC:
a. any protocol amendment;

b. serious and unexpected adverse events related to the conduct of the study or study
product, and the response taken by investigators, sponsors, and regulatory agencies;
c. any event or new information that may affect the benefit/risk ratio of the study;
The goal of continuing ethics review
The purpose of continuing ethics review is to determine if the project (including recruitment and
informed consent process) is being conducted in compliance with the protocol approved by the
REC, and that the potential benefits and risks to research participants remain acceptable. If the
risks and/or potential benefits have changed, re-consent by the research participants indicating
their continued choice to participate in the research after having been informed of the change may
be required.
REC decisions during continuing review
If any of the above is deemed unacceptable, the REC might:
Suspend or withdraw ethical approval of the project (until further information is provided
and reviewed)
Request that new information, changes to the project, or changes to the balance of
risk/potential benefits be communicated to research participants to enable an informed
choice or refusal to continue in the research.
Request modifications to the project or to the informed consent document, which will
require re-approval by the REC and a new informed choice or refusal from participants.
WMA, Declaration of Helsinki, 2013, Para. 18, 23.

WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 8.12, 9.
ICH-GCP, 1996, Sec. 3.1.4, 3.3.3, 3.3.9.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 10, 16.3, 17.
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.109 (e),
46.110, 46.113.

Question 5
(adapted from WHO, case 24))
Laboratory studies suggest that microbicides are effective against many sexually transmitted
pathogens. A vaginal microbicide could potentially offer women the potential to protect themselves
from HIV and other STIs. While the protective benefits of microbicides for men have not been
studied, a woman’s male partner might also be protected from infection by her use of a vaginal
microbicide.
An REC has approved a phase II trial to further assess the safety and efficacy of a potentially
effective microbicide. The trial will take place in a population of 300 women who are not sex
workers and will be the first to use a formulation that is not contraceptive. A local women’s
organization will collaborate with researchers and representatives from the host-country university
to hold meetings at local clinics to explain the study to potential participants and to elicit their
feedback.
The study participants will apply the gel or a placebo vaginally at least three times a week and
before intercourse for approximately 1 year, during which time they will receive monthly
examinations at a clinic to check for signs of irritation and test for STIs, safe-sex counselling, free
condoms, counselling to ensure that they understand the trial requirements and objectives, plus
modest monetary compensation for time and transport for each visit.
However, a group of women from the community health committee register their disagreement with
the researchers’ decision not to obtain informed consent from the partners of women in the trial.
They believe that this action might place women at risk for sexual and physical abuse if their
partner discovers their use of the product without their approval.
Should the researchers inform the REC of the potential for this previously unknown risk of harm?
Yes
No

1.6. Accountability
Research ethics concerns everybody: patients, researchers, sponsors, policy makers, regulators,
and members of the general public. It is relevant at different organizational levels, from the
international stage to the institution that is hosting the research to the individual household.
RECs are a critical component of the research process to ensure high quality research and
appropriate protection of patients participating in clinical trials. RECs are independent bodies
whose responsibility is to ensure the protection of the rights, safety and well-being of human
participants involved in a trial. Given their important role, RECs must be accountable for their work.
This can be achieved in several ways.
First, RECs are immediately accountable to their constituting authority which may (and should)
require annual reports of activities. The constituting authority must also be committed to not
overriding a negative REC decision.
Second, RECs must demonstrate accountability towards researchers and the broader public. This
can be achieved by promoting the transparency of its activities and decisions. For example,
guidelines for applications should be freely accessible. REC members should evaluate projects at
officially announced meetings to allow researchers the opportunity to be heard. Decisions of RECs
should be justified and communicated. As a matter of policy, RECs should also require the
registration of clinical trials on official websites such as the one at WHO or the one at the US NIH.
Third, public bodies that sponsor clinical trials and research generally may audit a trial site
including the REC that reviewed the project. In such cases, auditors will look through minutes of
meetings as well as records related to the project.
Finally, when research receives public funding from the United States or when it contributes data
for a new drug submission to the Food and Drug Administration, additional assurances are
required:
The REC may need to be pre-approved through mechanisms such as the Federal Wide
Assurance
Researchers must ensure that the REC will operate according to US regulations by
completing FDA Form1572

ICH-GCP, 1996, Sec. 3.2.3.
WHO, International Clinical Trials Registry Platform (ICTRP).
US, ClinicalTrials.gov.

Question 6
Your are the chief executive officer (CEO) of a community-based hospital. Until last year,
physicians at your institution were occasionally contacted by pharmaceutical companies to conduct
clinical trials, mostly to test new diabetes drugs. Diabetes appears to have a significantly higher
prevalence in one of the communities in your region. In the past year, the number of trials
proposed to your physicians has significantly increased and many have a pharmacogenomic or a
genetic analysis component added on. Until now, your institution used the ethics review services of
your National REC as most non-teaching hospitals do in your country. However, given the increase
in number of trials and the particularly delicate issues raised by the genetic component, you have
decided to create your own REC to make sure that local issues get properly considered.
You are quite determined to set up a state of the art REC that complies with international and
national requirements. You are reviewing your institution’s research policy from which the authority
of the new REC will flow. Ensuring accountability of the review process is critical; yet you wonder
how far you should go in terms of transparency. More precisely, you cannot decide if you should
make public the list of members of the REC by posting them on the website.
Which of the following statement(s) is (are) relevant? Choose the best answer.
Transparency of the ethics review process is critical. Names of REC members should be
made public to promote public trust in the review process. Some local communities will be
suspicious if they do not know who is on the committee.
Ensuring the independence of the REC is critical. Names of REC members should be kept
confidential to avoid any pressure being placed on them to approve or refuse given
protocols.
Independence and transparency are both critical to a robust ethics review programme and
so a balanced solution needs to be found.

Part 2. Research and ethics evaluation

2.1. What research requires ethics evaluation
Generally speaking, all research that involves humans must be evaluated and approved by a
competent REC before the research begins or, more precisely, before any prospective participants
are contacted for recruitment. This is often referred to as the ethics review requirement. The ethics
review requirement also applies to research conducted with personal information found for
example in medical files, or with human tissue and products such as genetic material. Research
with gametes, embryos and fetal tissue also requires prior ethics review in addition to a number of
other requirements.
The ethics review requirement is found in many international guidelines and in many national
regulations and/or guidelines and it applies to all types of research involving humans.
The ethics review requirement is triggered when an activity constitutes research and will involve
humans. Research is a term that is difficult to define and there are many grey zones. Generally
speaking “research” aims at developing generalizable knowledge. It can be conducted by different
types of researchers, in many different fields of inquiry (health, social sciences, humanities, etc.)
and using different methodologies (clinical trials, record review, observation, participation, and
other qualitative approaches).
In some countries, certain types of research may be exempted from the REC review requirement
under certain conditions. The REC will assess if a project qualifies for one of the exemptions. A
researcher cannot issue his/her own exemption for a study. An exemption must be issued by an
REC.

ICH-GCP, 1996, Sec. 2.6.
COUNCIL OF EUROPE, Convention on Human Rights and Biomedicine, 1997, Art. 16(iii).
Biomedicine, concerning Biomedical Research, 2005, Art. 2, 7, 9(1).
EU Directive 2001/20/EC on Clinical Trials, Art. 2(a), 6(2), 9(1).

Question 7
“Research” is a systematic investigation conducted in order to establish and communicate facts,

principles, or generalizable knowledge. In other words, it is an activity in which information is
gathered and analyzed and designed to develop or contribute to knowledge through dissemination
of results.
Research involving humans as participants can include observation of people going about their
daily activities, evaluation of a new teaching method, or testing of new drugs or medical devices. It
can also involve interviewing individuals in public life for a scholarly purpose, or use of information
originally collected to treat individuals or administer a publicly funded service to them. It includes
the use of human remains, cadavers, tissues, biological fluids, embryos or foetuses.
In health care settings, there are a variety of activities that involve human participants. These
include research as well as quality assurance (QA), chart reviews, innovative care and surveys.
Only research projects require REC review and approval.
Medication error reporting: Is it research?
Hospital staff recently noticed a packaging issue with a medication that is routinely administered
only to critically ill patients. The ink on the new package labels tend to run and become blurred
when it comes in contact with liquids. This has not yet led to any errors, though there was a recent
near-miss incident with one patient who was almost given an incorrect dosage. The ICU director
has notified the pharmaceutical company that makes the drug and wants to look through ICU logs
and write an article about the problem to submit to a medical journal. The article will describe the
near-miss incident and make recommendations for other hospitals that use this drug.
Should the director submit a research plan to the REC?
Yes
No

2.2. Particular cases
Some kinds of research require, in addition to ethics evaluation, other reviews and approvals. In
addition, some kinds of activities may well resemble research but do not constitute research
involving humans and thus do not require evaluation and approval by a REC. This section provides
examples of these two types of activities.
Clinical trials are a good example of a type of research that has additional requirements. In many
countries, sponsors of drug trials must ask the competent government authority (or regulatory
body) for authorization to use an experimental drug in a trial. Investigators are legally required to
have both the government approval for use of an experimental drug and REC approval before a
trial can start. In other countries, there is a system of notification of all drug trials to the national
drug agency.
In countries where it is not forbidden to undertake research involving human reproductive material
(stem cells, gametes, embryos), there will often be a requirement that national oversight
committees review the research project in addition to the competent REC.
Other types of research that may need additional approvals are studies involving school children.
In some countries, in order to engage school children in research, a proposal may need to be
approved by relevant Government authorities such as the Ministry of Education at the national
level and other authorities at the regional, district and schools levels.
The important point here is that whatever the additional requirement, it does not replace ethics
evaluation and approval by the competent REC. Nor should a positive approval from the other
authority influence the conduct of ethics evaluation. Both reviews are necessary.
Some activities may be conducted for purposes such as quality assurance, education or research.
Chart reviews are one such activity. For example, a person may wish to have access to medical
charts to assess the quality of a certain type of procedure. When conducted for quality assurance
purposes only, chart reviews do not require REC approval, although other types of approval may
be necessary. When it is not clear whether or not an activity requires ethics committee approval,
the Chair of the REC should be consulted.

Question 8
The program for delivery of pre-natal care at a large clinic is being evaluated to determine what
improvements might be made to services provided and the relationship between pre-natal and post-
natal care. Staff at the clinic will access the records of women who were seen at a clinic while
pregnant and who presented with a condition related to the pregnancy. In order to evaluate the
methodology that will be used to assess clinical care, as well as to provide computer training to
staff who will be conducting the reviews, clinic physicians want to begin the process by reviewing
the records of women who presented with vitamin A deficiency. Because it is not known which
women had deficiencies during pregnancy until this is noted from their records, it is not feasible to
obtain prior consent from patients to review their records.
Does this project require prior ethics review by a REC
Yes
No

2.3. What aspects get evaluated and why
Ethics evaluation of research projects generally aims at ensuring that projects are – or can be
modified to become - ethically acceptable. Among other criteria, RECs will ensure that projects
offer a favourable risk-benefit ratio and are consent-worthy for prospective participants. This
requires that the science and ethics of projects be evaluated and found acceptable.
2.3.1. Scientific aspects
All protocols involving human participants should undergo an independent and rigorous scientific
review to assess the scientific quality, the potential of the research to increase knowledge, the
appropriateness of the study methodology to answer a precisely articulated scientific question, the
qualifications of the applicants to conduct the research, and in some cases, clinical questions. For
example, the design of clinical trials should be based on sound statistical principles and
methodologies, including sample size, use of controls, randomization, population stratification,
stopping rules, and the feasibility of relating endpoints to objectives. Ensuring that the chosen
study design minimizes bias and generates data that will answer the scientific question requires
some understanding of the research process and the topic to be studied. These issues are pivotal
to a successful study and must be evaluated before considering the ethical aspects of the
proposed study.
The scientific evaluation can be conducted by the REC if it has membership with appropriate
scientific expertise. Otherwise, a separate scientific review committee should conduct the scientific
review, the results of which can then be communicated to the REC. It should be noted that the
approval provided by government authorities to authorize the use of an experimental drug in a trial
is not considered an appropriate scientific review. Even if the REC does not conduct the scientific
evaluation, it can always consider scientific issues as they relate to the ethical acceptability of the
project (see below 3.3)
There will always be some level of overlap between scientific and ethical review, most notably on
the issue of the importance of the research question (see below 3.2 & 3.3)
2.3.2. Ethical aspects
Once a project has received a favourable scientific review, the REC will then evaluate its ethical
acceptability. The ethics evaluation involves examining the scientific and financial as well as the
ethical aspects of a project. There are several ways of breaking down the scope of ethics
evaluation. Generally, the REC must conduct the ethics evaluation of projects according to the
following criteria:
Community participation or collaborative partnership

Social value: relevance of research to local health needs & expectations
Scientific validity
Qualifications of investigators
Participant selection process
Acceptable balance of risks and potential benefits
Informed consent
Privacy and confidentiality
Fair compensation/reimbursement
Conflicts of interest
Scientific integrity
Ongoing respect for research participants and collaborating communities

These are discussed in more detail below (part 3).
It is particularly important to note that a project that is not scientifically sound is not ethically
acceptable because it will expose participants to the risks and potential harms of research without
having the possibility of yielding benefits to the participants and/or to society. Thus, the REC must
ensure that appropriate scientific evaluation has occurred even if it does not conduct the scientific
assessment itself. If a project does not pass scientific evaluation, then it should be denied ethics
approval as well.
2.3.3. Financial aspects
Another important aspect of ethics evaluation is the assessment of the financial components of
projects. This requires that the REC ensure that the investigator is free of conflicts of interests or
that these are properly managed, and that prospective participants will not be unduly influenced to
participate.
Emanuel E.J., Lemmens T., Elliot C., 2006

Question 9
You are the Chairperson of an REC. Discussion during the REC meeting raises the following
issues about a project that is intended to determine whether or not health care workers will
continue working in hospitals should there be a new outbreak such as SARS. The project involves
responding to a questionnaire anonymously and will expose participants to minimal risk. However,
the social scientist on your committee considers that the project has major methodological flaws
and the inquiry will not provide reliable results for the objectives of the study. As Chair of the REC
you wish to guide your REC as to the various options for a decision about the project.
Which of the following statements is the best option:
You propose to refuse the project.
Since participants will be exposed to minimal risks and that the prospective participants are
not vulnerable you propose to approve the project despite concerns over scientific validity.
You decide to defer your decision and request that an independent scientific review of the
project be conducted.
You decide to request modifications to the protocol that are conditional to the approval.

2.4. Levels of evaluation
It is generally accepted that RECs can adopt a proportionate approach to ethical evaluation: the
greater the risks of a project, the greater the scrutiny. In practice this means that RECs can use
two approaches to ethics evaluation:
Evaluation by the full committee

Evaluation by a sub-committee which is also called “expedited review”
Projects that pose only minimal risk can undergo expedited review, if the REC operating
procedures so provide. Projects that pose greater risks deserve attention by the full REC to ensure
proper safeguards are in place.
Full committee evaluation will involve all members’ comments and discussion of all ethical issues
arising from the proposed study and the deliberations thereof and reaching a consensus on an
REC decision. This will take place in an ordinary REC meeting, scheduled according to the
standard operating procedures.
RECs should establish procedures for expedited review of research proposals. These procedures
should specify the following:
1. The nature of the applications, amendments and other considerations that will be eligible
for expedited review
2. The quorum requirements for expedited review
3. The status of decisions (that is, whether or not subject to confirmation by the full REC)
In some countries national regulations establish categories of research that pose no more than
minimal risk that can receive expedited review.

WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 6.3.

Question 10
You are the administrator of a REC and as such you are not a member of the committee although
you do attend meetings to take minutes. This week you received a new project and the researcher
specifies in her cover letter that the project should receive expedited review since it involves
minimal risks to potential participants. You know that the REC’s next meeting is particularly heavy.
So you decide to:
Choose the correct answer:
Do as the researcher requests since she has the best knowledge of her project.
Show the project to the chair of the REC.
Review the project yourself.
None of the above

2.5. Ethics review of international collaborative research
International collaborative research, sometimes referred to as externally sponsored research

requires two ethics evaluations:
One in the country of the sponsor of the research (usually from the investigator’s
organization), and
One in the host country (i.e. where the trial will be conducted and participants recruited)
In these situations, both approvals must be obtained before the research can start. Both RECs will
conduct a full review of the project.
The REC in the sponsoring country must ensure that the research meets its own national as well
as international ethical standards.
The REC in the host country has a special responsibility to determine whether the objectives of the
research are responsive to the health needs and priorities of that country. The ability to judge the
ethical acceptability of various aspects of a research proposal requires a thorough understanding
of a community's customs and traditions. The REC in the host country, therefore, must have as
either members or consultants persons with such understanding; it will then be in a position to
determine the acceptability of the proposed means of obtaining informed consent and otherwise
respecting the rights of prospective participants as well as the means proposed to protect the
welfare of the research participants. Such persons should be able, for example, to indicate suitable
members of the community to serve as intermediaries between investigators and participants and
to advise on whether material benefits or inducements may be regarded as appropriate in the light
of a community's gift-exchange and other customs and traditions.
The European Union explicitly requires that all clinical trials that are to be taken into account for
market authorization be conducted in accordance with the principles of the Declaration of Helsinki
whether they are conducted in the EU or elsewhere.

ICH-GCP, 1996, Sec. 2.1.
Biomedicine, concerning Biomedical Research, 2005, Art. 9.1, 29.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 7.

Question 11
Professor Green works at a Swiss University and has been conducting pre-clinical research on a
vaccine for leishmaniasis – a disease caused by parasites found in tropical countries. Moving into
the clinical trial phase, the researcher has made contacts with colleagues in countries where the
risk of leishmaniasis is significant. She has developed the study protocol and is considering various
recruitment sites in Africa and India. Funding for the clinical trials has been secured from a not-for-
profit organization that is based in the United States where she intends to eventually submit the
trial data in support for market approval of the vaccine.
You are the chairperson of an REC in one of the African countries to which the protocol for the
vaccine trial on the leishmaniasis vaccine has been submitted for review. Which of the following
statements is relevant for the ethics evaluation by your REC?
Choose the best answer.
You must receive a copy of the REC review and approval from Professor Green’s
competent research ethics committee in Switzerland.
Scientific review of the protocol is necessary.
You will need the authorization from a drug regulatory agency in the host country that
approves the use of the experimental vaccine in a clinical trial.
All of the above.

Part 3. Ethics evaluation of research projects
This part discusses core issues that ethics committees need to address when conducting ethics
review of research projects. For this purpose, questions that need to be addressed when reviewing
projects are identified. Before providing ethics approval of a project , the REC must be satisfied
that the issues raised by these questions have been properly addressed.

3.1. Community participation or collaborative partnership
Community participation, or collaborative partnerships, refers to several elements that should be

part of the research process to avoid, or at least minimize, the possibility of exploitation.
“A exploits B when B receives an unfair level of benefits or unfair burden of risks as a result of
interacting with A.”
(Emanuel et al, 2004)
Research in developing countries has a greater potential for exploitation of local participants than
research in developed countries. For example, local communities who participate in, and bear the
risks and burdens of, research designed to be conducted in developing countries would be
considered as having been exploited if the benefits accrue mostly to people in developed
countries.
Does the proposed project involve a collaborative partnership?
Ethics guidelines as well as the ethics literature agree that community participation is key to
diminishing the risks of exploitation.
Of direct interest to RECs, this involves:
Ensuring that the research is responsive to the health needs of the community to be
involved. This means that the importance of a problem and the setting of priorities for
research will be determined in partnership with local communities.
Ensuring that successful interventions are reasonably made available to the community.
This requires the sponsor of the research to initiate a negotiation with stakeholders in the
host country, representatives of the communities from which participants are drawn and
non-governmental organizations such as health advocacy groups to determine the practical
implications of making the products of research available to the local community.
Developing local capacities.
Ensuring that the participants and communities receive benefits.
Ezekiel E.J., Wendler D., Killen J., Grady C., 2004.
WMA, Declaration of Helsinki, 2013, Para. 22, 20, 34.

WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 6.2.6.
Subjects, 2002, Guidelines 3, 10, 20, 21.

Question 12
(Adapted from WHO case 47)
A team of molecular biology researchers wishes to study features of alcoholism in selected native
peoples of North America. This research is based on reports of a significant correlation between
alcoholism and several forms of brainwave activity that are measurable by
electroencephalography. Other ethnic communities with these brainwave patterns have a higher
risk of alcoholism. There is also some evidence of a genetic linkage between the brainwaves and
traits of alcoholism.
Since the prevalence of alcoholism is high in many North American indigenous communities, this
research team believes that it is important to ascertain whether there is a genetic linkage between
brainwave patterns and alcoholism in this population. The researchers propose to select 300
families that have high incidences of alcoholism. Compensation to participants will average US$
300 for 2 days of participation. A preliminary survey in the native communities indicates that many
hundreds of individuals are interested in participating.
A week before the research ethics committee was to meet to review the proposal, the committee’s
chair received the following memorandum from a representative body for the selected community:
“The XX native community urges the Research Ethics Committee to reject this study. No native
community or representative body has been contacted to discuss the concerns that our members
might have with the study. This oversight fails to recognize our community’s legitimate concerns
about how the information this may produce will be used scientifically and whether the methods
used are in keeping with our religious and cultural values. For example, the research plan does not
describe how blood samples will be treated. Like most indigenous communities, the XX Tribe
traditionally considers all parts of the body sacred, including materials derived from the body (such
as blood products or organs). Of equal concern, we believe that both our community as a whole
and individuals within the community may be stigmatized by the proposed research. We point to
the history of discrimination and stigmatization that has burdened our people, particularly in relation
to alcoholism, as proof of this concern. Since this study offers no immediate benefits and poses
significant risk, it should not be approved.”
How should the REC respond?
The REC should review the project without considering the memorandum.
The REC should request that the potential concerns about discrimination and
stigmatization are included in the consent form and let potential participants decide
whether or not they wish to participate.
The REC should defer its decision and request that the research team meet with the
indigenous community to discuss their concerns. Any changes to the project that might
result would need to be communicated to the REC.

3.2. Social value: relevance of research to local health needs &
expectations
In order for research involving humans to be ethical, it must have social value. Demonstrating the
social value of a proposed project is a critical component of the REC review process. Concretely
this means that in order to justify including humans in research, researchers must convince the
REC of the importance of the research objective(s) for society.
Without demonstration of this element, a REC will have no choice but to suspend its review or
reject the project.
Does this project have social value?
Generally, research will be considered as having social value when the hypotheses or questions
being researched will have potential benefits for the individuals and/or community where the
research takes place. This value may accrue to individuals, to advancing knowledge in relation to
an important topic or issue for that society, or to some combination of these benefits.
Another example of social value, or lack thereof, involves phase 4 clinical trials. These trials occur
once a drug is marketed. In many cases, they will aim to increase safety data about a drug.
However, in some cases when drugs are already well documented, the objectives of such trials
have little or no social value since they are no more than marketing initiatives, aiming to get
patients to take a given drug rather than another. In this latter situation, the study may lack social
value and the REC should refuse it.
In the context of international collaborative research agreements, or of externally sponsored

research, RECs must be particularly careful to ensure that the proposed project is relevant to local
health needs and addresses issues that are perceived by the community as needing to be
addressed. In other words, the prospective research community should consider the question
being addressed as a problem that deserves to be investigated. For example, the knowledge
generated could contribute to diminishing the morbidity or the mortality of certain patients or to
improving the quality of life of the local population by solutions that are reasonably made available
to local communities and are socio-culturally acceptable.
What is the social value of student research?
Student research does not always generate new knowledge or original work. Rather, the value of
student research consists in their education and training on how to conduct research involving
humans. Although student research mainly benefits the students themselves, it can be considered
to benefit society indirectly because the students may eventually become fully qualified
researchers who can undertake research on issues of direct relevance to their community.

Question 13
So-called “meal replacement bars” have become widely available and are very popular among
teenagers in one African country. The bars can be high in sugar and fat and are believed to be a
contributing factor to teenage obesity, a growing problem in many local communities. A group of
international investigators (including biomedical, nutritional science and sociology researchers)
want to conduct a study about the impact of this phenomenon on teenage obesity. Their research
will include determinations about whether a bar that is affordable, sugar-free, low-fat and high
nutrient might be appealing enough to teenagers that they would choose it over other available
options. It will also include interviews with teenagers at a local school.
True or False? The proposed project is essentially a marketing initiative and should therefore be
rejected by the REC.
True
False

3.3. Scientific validity
In addition to having social value, in order for a research project involving humans to be ethical, it
must be scientifically valid. Research that is deemed to lack scientific validity is considered
unethical since such research would not allow for meaningful conclusions, while unnecessarily
exposing participants to risks of inconvenience, or even of harm. This contravenes the overarching
principle of respect for persons and human dignity and wastes society’s resources.
Is the proposed project scientifically valid?
Scientific validity is attained when research has the potential to result in facts, reproducible
observations, or generalizable information in relation to the question under study. In other words,
the project proposes a sound methodology and protocol design that is likely to lead to reliable
conclusions and is adequate to answer the research question(s). (See also Section 2.3.1)
(Freedman, 1987)
A scientific committee, a sub-committee of the REC, or the REC itself, can perform the scientific
evaluation. Regardless of who performs the evaluation, ultimately the responsibility to ensure that
an appropriate scientific evaluation is performed on all research projects involving humans is that
of the REC. Even if a scientific committee reviews and provides approval of a given project, RECs
can raise questions about the scientific aspects of the project and ultimately have the final say on
the project’s approval.
During a scientific review, the REC may review or request to review any information and
documentation that is judged as relevant for a proper evaluation. This might include but is not
limited to the following:
a. Name and qualifications of the researcher(s): in order to evaluate whether the

researcher(s) is competent and qualified to conduct the research.
b. Objectives and/or hypothesis: determine whether they are clear, well-designed, and
reasonably attainable.
c. Comprehensive literature review: to outline the knowledge available in the discipline’s
scientific literature and demonstrate how the project will add to this knowledge. Based on
this information, the REC determines whether the project has sufficient scientific merit.
d. Results of the pre-clinical laboratory and animal studies (when applicable): provides
important information for the REC on potential benefits and risks.
e. Justification for the use of human participants: the reason for the research, how the
research contributes to the advancement of knowledge and/or the well-being of humans,
scientific assessment of risks for participants
f. Method: to evaluate whether the study is designed in such a way that it could lead to valid
and meaningful scientific conclusions, applicable and pertinent to the discipline and at the
same time is designed to minimize risks and maximize the potential benefits.
Freedman B., Scientific value and validity as requirements for research: a proposed
explication, 1987.

ICH-GCP, 1996, Sec. 2.5.
Subjects, 2002, Guidelines 1, 2.

COUNCIL OF EUROPE, Convention on Human Rights and Biomedicine, 1997, Art. 16(iii).
Biomedicine, concerning Biomedical Research, 2005, Art. 7, 8.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 6(3).

Question 14
Investigators in Europe and sub-Saharan Africa are working together to design a program of study
that will include the development of a new multi-stage DNA vaccine for malaria. If effective, the
vaccine could reduce deaths due to malaria in children younger than 5 years, particularly in infants.
Vaccines are one of the most cost-effective and sustainable ways to control this type of infectious
disease. In sub-Saharan Africa, malaria is a serious public health threat.
The first protocol in this program of study involves conducting chart reviews across a network of
urban clinics to determine malaria rates among children specific to the local population. The project
will also provide an infrequent opportunity for local nursing students to learn how to review charts
for the purposes of this type of project. The project has been reviewed and approved by an
international scientific committee; however, an expert on a local REC has some concerns about
the methodology. What elements should be considered by the REC?
Choose the BEST answer:
Chart review studies are inherently low risk and it is a reassuring sign for the REC that the
protocol has been reviewed by an international scientific committee.
The opportunity for local nursing students to benefit from the study is a good reason to
permit the study to proceed.
The REC is responsible for ensuring that an appropriate scientific evaluation is performed
on all research projects involving humans.

3.4. Qualifications of researchers
Is the researcher qualified?
Research should only be conducted by qualified researchers or under their supervision. This is
critical for two reasons: to ensure the safety of participants and to ensure that the project will be
conducted appropriately and lead to results. Researchers, whether or not they are from licensed
professions, should demonstrate they have competence acquired through appropriate education,
training and experience to conduct the proposed project.
In addition, when reviewing clinical trials, RECs should ask for relevant documents and medical
licenses from investigators to ensure regulatory requirements are met.

ICH-GCP, 1996, Sec. 2.8, 3.1.2, 4.1.
WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 6.2, 3.1.
Biomedicine, concerning Biomedical Research, 2005, Art. 8, 21(2).
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 2(f), 2(k), 3(3), 6(3)d).

Question 15
(From WHO Case 26)
Micronutrient supplementation for pregnant women
A new community based trial will take place in a South Asian country to determine whether a
weekly low-dose supplement of vitamin A to women of reproductive age will reduce deaths and
illness related to pregnancy and improve the survival and growth of young infants. In South Asia,
premature births and small size for gestational age are leading risk factors for stillbirths and for
neonatal and early childhood death and have been linked to insufficient levels of vitamin A during
pregnancy, particularly in poor communities. While studies show a 30% reduction in the mortality
rates of preschool children receiving vitamin A supplements, it is not known if supplementation to
pregnant women will have a positive impact on the health of women and/or their infants.
The three nurses who are part of the research team will supervise and train a number of
community health workers to seek informed consent from women to be monitored and distribute
the test intervention to the women’s homes. The community health workers will also invite
pregnant women to have more detailed clinical examinations to assess them for malaria, anaemia,
parasitic infections and diet. Their babies will be weighed and measured within 10 days of birth and
at 6 months of age. Babies’ blood samples will be taken at 3 months of age.
Which of the following statements is true?
As licensed health care professionals, nurses on the research team may take blood
samples of babies, because nursing training and credentialing give nurses the expertise
and authorization to take blood samples safely.
Community health workers may learn to take blood samples by self-learning for the
purposes of the study. Because of the large number of participants in the study, the study
will not be possible without a large team to implement the blood collection process as set
out in the protocol.
Both statements are true.

3.5. Participant selection process
3.5.1. Is the proposed participant selection process fair?
The fair distribution of the anticipated risks and potential benefits of participating in research is a
concrete way of applying the principle of justice in research ethics.
The selection of research participants must be fair. When reviewing the choice of the study
population and inclusion and exclusion criteria for research participants, RECs should ensure that
the choice of the study population is based on scientific considerations, minimizes risk, and
involves the participation of the targeted community. They should also try to ensure that the
individuals and communities who share in the risks of the research participation also share in the
benefits, and vice-versa.
3.5.2. How does a REC ensure proper consideration when populations in situations of
vulnerability are proposed as study populations?
Populations in situations of vulnerability include persons incapable of consenting to research

participation (e.g., children, incapable adults), persons unduly susceptible to harm (e.g. migrant
populations, the homeless, sex trade workers and drug abusers), and persons in situations where
a voluntary consent is questionable (e.g., prisoners, soldiers, patients who do not have access to
health care and students who are invited to take part in the research project conducted by their
supervisor). RECs must ensure special protections for such populations.
For example, people who are not legally competent to consent to research participation must only
be involved in research projects that require using people from those groups to answer the
research question. In addition, they or members of their group must potentially benefit from the
research, and their legal representatives must authorize their participation in the research.
WMA, Declaration of Helsinki, 2013, Para. 5, 7, 28, 30.

ICH-GCP, 1996, Sec. 4.8.13, 6.5.
Subjects, 2002, Guidelines 9, 12-17.
COUNCIL OF EUROPE, Convention on Human Rights and Biomedicine, 1997, Art. 17.
Biomedicine, concerning Biomedical Research, 2005, Art. 15, 18-20.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 4(e), 5(e).
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, art. 46.111 (a) (3),
46.204-205, 46.305-306, 46.404-409.

Question 16
A group of western researchers establish an affiliation with clinics in a South-East Asian country
where a recent natural disaster has impacted local communities. The researchers are exploring the
psychiatric diagnosis and assessment of traumatized populations. They will conduct interviews with
patients who come to the clinics for medical treatment. The researchers have decided not to
interview any persons with mental disabilities who cannot give consent to the research.
Does the planned approach and rationale raise concerns?
Yes
No

3.6. Acceptable balance of risks and potential benefits
Principles of doing good (i.e., beneficence) and of not doing harm (i.e., non-maleficence) come
together in research ethics in an effort to bring about more good than harm in the research
process. In doing this, researchers should try to optimize the potential benefits and minimize risks
for participants and others affected by the research.
What are the potential benefits of a project?
Potential benefits can take a number of forms and involve a number of people. There can be
physical benefits (e.g., better health), psychological benefits (e.g., satisfaction of participating in the
development of knowledge), social benefits (e.g., new drug formulation, a cheaper drug, new
scientific knowledge), and economic benefits (e.g., free access to drugs or profits). Researchers,
institutions, sponsors, research participants and society as a whole can share in these benefits,
either directly or indirectly.
Benefits can be further classified as:
Direct benefits to participants when the research procedures have the potential of
benefiting them. For example, a study offering a new treatment of hypertension offers the
possibility of a direct benefit of treating the hypertension.
Indirect benefits to participants when benefits result to them from aspects other than the
research procedures themselves. For example, if as part of a drug trial participants get a
full medical check-up, they may have health-benefits as a result of the check-up (indirect
benefits) rather than from the experimental drug.
Benefits to society such as the prospect of a healthier population, a better trained health
workforce or infrastructure improvements (e.g., a new community clinic).
What are the risks raised by a project?
A risk is the potential for an adverse outcome (harm) to occur. Harms associated with a research
project can take a number of forms and affect a number of people. There can be physical (e.g.,
injury, illness, disability, side effects), psychological (e.g., anxiety, emotional distress, reactivation
of trauma, embarrassment), social (e.g., stigma, breach of confidentiality) or economic (e.g., loss of
income due to time away from work).
Most research risks will be direct risks to research participants. In some cases, there may also be
potential harms to “third-parties” such as to the unborn fetus or to communities.
RECs need to identify all risks of research.
What is the probability and gravity of the risks and potential benefits?
Risks and potential benefits vary in probability and gravity. For example, the risks in a given
research project might include a high probability for a minor harm (e.g., small bruise at an injection
site), a low probability for a serious harm (e.g., disability, death), and/or risks with some other
combination of probability and gravity.
Similarly, potential benefits may be highly probable but rather minor (e.g., satisfaction from sharing
one’s opinion about something one cares about), highly unlikely but quite significant (e.g., control
of HIV infection), something in between the two, or there may be no benefit at all.

How are risks and benefits assessed?
RECs need to clarify who bears research risks and to whom potential benefits will accrue. To be
acceptable, the research risks to participants must be considered reasonable in relation to the
potential direct and indirect benefits to participants. This requires careful consideration and
judgment by the REC. This process is often called the balancing of risks and potential benefits.
(see next section).

3.6. Acceptable balance of risks and potential benefits (continued)
The centrality of risk-benefit evaluations
A critical part of the work of RECs involves the balancing or evaluating of the risks and potential
benefits of a project. In effect, the REC strives to ensure that no potential research participant –
sick or well, young or old – is offered participation in research that is an unreasonable choice and
unworthy of consent.
Declaration of Helsinki, Paragraph 18:

“Every medical research study involving human subjects must be preceded by careful assessment
of predictable risks and burdens to the individuals and communities involved in the research in
comparison with foreseeable benefits to them and to other individuals or communities affected by
the condition under investigation.”
What is an acceptable balance of risks to benefits?
Requirements for acceptable balance of risks to potential benefit are addressed in various ways in
regulation and guidelines. National regulations may establish thresholds of risk to benefit
assessments that must be respected locally for certain types of populations. Guidance provided by
leading instruments can be summarized as follows:
Declaration of Helsinki 2008
In medical research involving human subjects, the well-being of the individual research
subject must take precedence over all other interests (paragraph 6).
Medical research involving a disadvantaged or vulnerable population or community is only
justified if the research is responsive to the health needs and priorities of this population or
community and if there is a reasonable likelihood that this population or community stands
to benefit from the results of the research (paragraph 17).
CIOMS
The potential benefits and risks are reasonably balanced and risks are minimized
Risks of 'beneficial' interventions or procedures must be justified in relation to expected
benefits to the individual subject
Risks of interventions without the prospect of direct benefits to subjects must be reasonable
in relation to the importance of the knowledge to be gained (benefit to society)
Despite this guidance, RECs around the world struggle with this issue. There are no categorical
answers, thus the importance of the work of RECs. It is generally considered that there is an
asymmetry between who bears risks and who bears the benefits: on the whole it is the research
participant who bears the burden of research risks while the benefits usually accrue to society as
well as to researchers.
Declaration of Helsinki (2008)
Paragraph 21. “Medical research involving human subjects may only be conducted if the
importance of the objective outweighs the inherent risks and burdens to the research subjects.”
Paragraph 27: “For a potential research subject who is incompetent, the physician must seek

informed consent from the legally authorized representatives. These individuals must not be
included in a research study that has no likelihood of benefit for them unless it is intended to
promote the health of the population represented by the potential subject, the research cannot
instead be performed with competent persons, and the research entails only minimal risk and
minimal burden.”
Paragraph 32. “The benefits, risks, burdens and effectiveness of a new intervention must be
tested against those of the best current proven intervention except in the following circumstances:
The use of placebo, or no treatment, is acceptable in studies where no current proven

intervention exists; or
Where for compelling and scientifically sound methodological reasons the use of placebo is
necessary to determine the efficacy or safety of an intervention and the patients who
receive placebo or no treatment will not be subject to any risk of serious or irreversible
harm. Extreme care must be taken to avoid abuse of this option.
CIOMS, International Ethical Guidelines for Biomedical Research Involving Human Subjects
GL8. Benefits and risks of study participation

“For all biomedical research involving human subjects, the investigator must ensure that potential
benefits and risks are reasonably balanced and risks are minimized.
Interventions or procedures that hold out the prospect of direct diagnostic, therapeutic or
preventive benefit for the individual subject must be justified by the expectation that they
will be at least as advantageous to the individual subject, in the light of foreseeable risks
and benefits, as any available alternative. Risks of such 'beneficial' interventions or
procedures must be justified in relation to expected benefits to the individual subject.
Risks of interventions that do not hold out the prospect of direct diagnostic, therapeutic or
preventive benefit for the individual must be justified in relation to the expected benefits to
society (generalizable knowledge). The risks presented by such interventions must be
reasonable in relation to the importance of the knowledge to be gained.”
GL9. Special limitations on risk when research involves individuals who are not capable of giving
informed consent
“When there is ethical and scientific justification to conduct research with individuals incapable of
giving informed consent, the risk from research interventions that do not hold out the prospect of
direct benefit for the individual subject should be no more likely and not greater than the risk
attached to routine medical or psychological examination of such persons. Slight or minor
increases above such risk [minimal risk] may be permitted when there is an overriding scientific or
medical rationale for such increases and when an ethical review committee has approved them.”
Are the risks of the project reasonable in relation to the potential benefits?
Generally, a project will be considered acceptable if, in the judgment of the REC, the risks are
reasonable in relation to the benefits. In conducting this risk to benefit assessment for specific
projects, RECs repeatedly stumble on questions like what kinds of risks must be considered and to
whom benefits should accrue. As well, the notion of “reasonable” is quite vague. This evaluation
involves a complex judgment call that brings together various concepts.
A method for systematically assessing risks, called component analysis, has been developed to
assist in this evaluation and to promote a more consistent evaluation by, and amongst, RECs.
Component analysis is summarized in BOX B: Overview of component analysis as a tool for RECs
and researchers.

(Adapted from Weijer & Miller, 2004)
Whether or not RECs choose to use the component analysis approach, they need to ensure that
the following aspects are adequately addressed (see BOX B: Overview of component analysis for
more detail):
If the research proposes to recruit patients into a clinical trial, does the clinical trial satisfy
clinical equipoise?
Are the risks minimized?
If the project involves vulnerable populations, is the threshold of acceptable risk respected?
Are the research risks reasonable in relation to anticipated benefits (direct and indirect)?
Prior to approving a project, RECs must be satisfied that the balance of risks and benefits is
acceptable. The REC should bear in mind than in many studies there is an ‘asymmetry’ of risks
and benefits: the risks are borne by research participants while the benefits often accrue to society
at large. This asymmetry should be offset as far as possibly achievable.
Weijer C., Miller P., 2004.

WMA, Declaration of Helsinki, 2013, Para. 8, 16, 17, 20, 28, 33.
ICH-GCP, 1996, Sec. 2.2.
COUNCIL OF EUROPE, Convention on Human Rights and Biomedicine, 1997, Art. 16(ii).
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 3(2)a), 6(3)b).
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.111 (a).
Brazil,National Council of Health, Resolution No. 466, 2012.

Question 17
(Adapted from WHO CASE 9)
As described above in Question 14, investigators in Europe and sub-Saharan Africa are working
together to design a program of study that they hope will lead to a multi-stage DNA vaccine for
malaria. If effective, the vaccine could reduce deaths due to malaria in children younger than 5
years, particularly in infants. Vaccines are one of the most cost-effective and sustainable ways to
control this type of infectious disease. In sub-Saharan Africa, malaria is a serious public health
threat.
The investigators have developed another protocol as part of this program of study in which they
will monitor patients who come to clinics or hospitals with malaria symptoms. They will also access
an effective epidemiological surveillance system used in the district that will be the site for the
study. They will randomly select potential participants (infants) for the vaccine trial from the
surveillance database and collect data on subsequent illness and death due to malaria from
hospital records, and if required, verbal autopsies. Infants whose parents consent to their
participation on the trial will receive a dose of the experimental vaccine.
The experimental vaccine has been tested several times in humans, so its toxicity has been
documented somewhat. This, however, is the first trial to test for efficacy. Known potential adverse
effects include becoming infected with malaria. There is always a chance that there will be
unknown and unexpected adverse events.
If the vaccine is found to be safe and effective, it will benefit research participants by preventing
morbidity or mortality due to malaria. Then the vaccine can be administered to all infants. If the
outcome of the study shows that the vaccine is not effective, then this will be known and research
resources can be put towards other possible treatments
Which statement correctly describes how the risks to potential benefits should be evaluated?
Given the significant potential for benefit to the general population (vaccine for malaria),
any level of risks to study participants can be justified.
Given the significant potential for benefit to research participants (infants receiving the
vaccine for malaria before it is accessible to the general), any risks to study participants
can be justified by these benefits.
The risks to participants must be minimized to the greatest extent possible; then the
remaining risks must be justified by the potential benefits to participants and to the general
population.
All of the above.

3.7. Informed Consent
Researchers show respect for autonomy by enabling potential research participants to make
informed choices about whether to participate in research. Likewise, by informing research
participants about any new information learned during on-going research that could affect their
willingness to participate, researchers respect research participants’ autonomy since participants
are given the opportunity to choose to continue to participate or exercise their right to withdraw.
Respect for autonomy is so important that violations to people’s personal integrity, for instance, by
using them in research (or even touching them!) without their consent or authorization, are in
principle forbidden by law.
Is the proposed consent process appropriate?
Obtaining valid consent is critical in showing respect for autonomy since it allows prospective
participants the opportunity to choose to take part in research and to voluntarily expose themselves
to the research risks involved. In conducting ethical evaluation, RECs will want to ensure the
project and consent documentation are appropriate for obtaining valid consent. In order to assess
the appropriateness of the proposed consent process, RECs must understand the key elements of
valid consent. These are:
1. Persons must be capable: Capacity refers to the mental capacity of the participant to
consider alternatives in light of personal goals, values, and preferences.
2. Persons must be competent: Competence refers to the legal capacity to authorize or
refuse participation.
When prospective participants lack capacity and/or competency to consent additional

safeguards are required. Minimally, the permission of a legally authorized representative is
required and in some countries, national law requires assent of the prospective participant
when possible. In many countries, when able to express oneself, an incompetent person’s
refusal to participate must also be respected
3. Persons must be informed: During the conduct of research, participants may be exposed
to risks without any potential personal benefits. In this context, it is necessary that
participants be informed of all the potential risks. Various guidelines provide lists of
essential information that must be communicated to prospective participants. [See BOX C:
Some key elements that should be disclosed] In addition to disclosing information to
prospective participants, researchers must also ensure that prospective participants
understand and have an appreciation of the information. The role of the REC is critical as it
needs not only to assess whether all the pertinent information is included but also whether
the language used in consent documents suits the prospective participants’ level of
language, whether translations are needed, whether the process is culturally appropriate,
etc.
4. Consent must be voluntary: Prospective participants must be free to choose whether to
participate in a given project and subsequently whether to withdraw from the project. In
general, this means that consent should be free from undue influence, undue inducement,
coercion or manipulation that may influence the person’s free choice.
Nuremberg Code: Article 1
The voluntary consent of the human subject is absolutely essential. This means that the person
involved should have legal capacity to give consent; should be so situated as to be able to exercise
free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-

reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and
comprehension of the elements of the subject matter involved as to enable him to make an
understanding and enlightened decision. This latter element requires that before the acceptance of
an affirmative decision by the experimental subject there should be made known to him the nature,
duration, and purpose of the experiment; the method and means by which it is to be conducted; all
inconveniences and hazards reasonable to be expected; and the effects upon his health or person
which may possibly come from his participation in the experiment.
The Nuremberg Code, 1949, Principle 1.

WMA, Declaration of Helsinki, 2013, Para. 25, 26, 31.
ICH-GCP, 1996, Sec. 2.9, 4.8.
WHO, Operational Guidelines for Ethics Committees, 2000, Sec 6.2.5;
Subjects, 2002, Guidelines 4, 5, 6.
COUNCIL OF EUROPE, Convention on Human Rights and Biomedicine, 1997, Art.
16(iv)-(v).
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 3(2)b).
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.109 (b) (d),
46.111 (a) (4), 46.116.

3.7. Informed Consent (continued)
Waiver of consent
Researchers should not enrol participants in a trial prior to obtaining their individual consent. In
some very limited and specific circumstances, the consent requirement can be waived by the REC
after careful consideration. This may be the case for emergency or intensive care research. In such
situations, necessary measures should be taken to seek the patient’s informed consent to
participate in the research as soon as s/he has recovered her/his full capacity. Both investigators
and RECs must verify this waiver of consent to research is allowed by law.
A process
Consent should be understood as a process, not a single event. Thus, information about the
research can be disclosed and discussed on several occasions and in a variety of ways before
someone chooses to participate in the research project. The process should continue after the
participant chooses to participate until the completion of the research project. This requires
communication of any new information that may affect willingness to continue to participate.
Participants can also choose to withdraw from research participation for any reason. Withdrawal
from a project should not compromise the rights of the participant in any way – e.g. to access
ongoing health services from a research site normally offering health care. In some circumstances,
participants’ ongoing consent to continue participating in research should be sought (either
formally or informally) throughout the research project.
Written or documented consent
In principle, participants should sign a consent form to indicate their choice to participate in a
research project. In some countries, this is a legal requirement. Written consent may also be
necessary if researchers wish to have access to participants’ medical files for research purposes.
However, in some situations, written consent is not possible since prospective participants may not
be able to read or write. In these cases documentation, including the consent form, should be
explained verbally (possibly by a third party not involved in the research). Consent may be
expressed in a number of ways. In some rare situations, it is preferable to not have written consent
since without any identifiable records participants can remain anonymous. When exceptions to
written consent are required, researchers must provide justification to the REC which will decide if
the exception is warranted.
Involving communities and families or spouses within the consent process
In some cultures, researchers may enter a community to conduct research or approach

prospective participants only after having obtained permission from the community leader, family
leader or other authority. Investigators should strive to understand and respect such customs.
However, community or family leader permission does not in any way replace the need to obtain
individual consent from prospective participants.
Consent by special populations
Consent is a process that raises a number of issues when special populations are considered for
research: persons with mental disorders, prisoners, military, pregnant women, children, orphans or
child-headed households. Populations such as these may also be in situations of vulnerability and
deserve additional protections because being in a situation of vulnerability can diminish a person’s

ability to participate meaningfully and independently in the consent process or can expose them to
risks. If after careful consideration of the proposed study population the REC considers that there
is sufficient scientific justification for including vulnerable populations, then the REC must ensure
that the consent process is appropriate. When prospective participants lack the capacity to consent
(minors, incompetent adults) then consent from the legal representative must be sought. When
prospective participants are competent, but are in situations that affect the voluntary nature of their
consent, special measures may be required.
Consent for the use or re-use of personal health information and biological material
In principle, individual consent is necessary to collect, use and/or store personal health information
and biological material for research purposes. Consent is also required for any additional uses of
these data. However, there may be situations where consent would be impossible or impractical to
obtain for such research or would pose a threat to the validity of the research. In such situations,
and as local regulations provide, it may be possible to conduct such research after REC approval
that confirms that individual consent need not be obtained.
When reviewing projects involving the collection, use/re-use and or storage of personal information
and biological material, RECs must ensure that either consent will be obtained or that the
conditions for waiver of consent are present. To be granted a waiver of subject consent,
researchers should minimally demonstrate that consent is either impracticable or impossible, or
that the validity of research would be compromised by a consent requirement. RECs and
researchers will also need to consider applicable regulatory requirements as well as guidelines on
epidemiological research such as the International Ethical Guidelines for Epidemiological Studies,
2009.
CIOMS, International Ethical Guidelines for Epidemiological Studies, 2009.

Question 18
A researcher from your institution in a West African city consults you as chair of the REC. The
researcher is a local investigator for an international multi-centre trial that will look into the impact
of vitamin supplements on the well-being of women following child birth. The researcher
appreciates the potential benefits of this project for women in your country. However, she has
concerns with the consent process. Study procedures require that written consent be obtained
from all women who choose to participate. Given traditions and culture in your country, you
anticipate that asking women to sign consent forms individually could raise problems for several
reasons. For example, women will expect their husbands to engage in such a procedure with them
or even on their behalf and some may perceive that having to sign a document signifies that the
investigator does not trust their word.
Given the potential benefits of the research for women, the researcher is consulting you in order to
find possible options to make the consent process more appropriate locally and considering that it
is a multi-centre trial.
Which of the following considerations should guide your discussions with the researcher on this
issue? Choose the BEST answer.
The key consideration is to ensure that women choose to participate freely. If the fact of
asking for a signature is problematic there may be other ways of ensuring and documenting
voluntary participation.
It is critical that women who live in communities where spousal consent is the tradition not
be systematically excluded from research that could potentially be of benefit to them or to
other women like them.
Consent to participate may be expressed in various ways: verbally, implicitly or explicitly

with a signature. The requirement for signed consent serves as a means for participants to
express their consent. Written consent also serves as a means for investigators to
document the consent process that is open to audit. Explaining to communities these other
purposes of signed consent may help reassure them that by asking for a signature the
investigator is not doubting their word but rather meeting other obligations.
All of the above
None of the above. As chair of the REC you should not engage in any discussions with a
researcher.

3.8. Fair compensation / reimbursement
It is acceptable to offer a certain level of compensation, reimbursement or payment to research

participants for their expenses or travel costs due to participation in a trial. They may also receive
free medical services in addition to any medical treatment considered necessary for the safe
conduct of a trial. Some guidelines even allow payment for lost earnings although this practice is
sometimes prohibited by national regulations. When a clinical trial involves healthy volunteers who
receive no direct benefit, they may be paid for inconvenience and the time spent participating to
the trial. It is not acceptable to pay for risks taken in research.
Does the proposed compensation constitute undue inducement?
However, proposed compensation or reimbursement must be fair and not constitute ‘undue
inducement’. Inducement will be considered undue if it could lead to persons undertaking actions
they would not ordinarily accept. Undue inducement occurs for example, when the payments are
so large or the medical services so extensive as to induce prospective participants to consent to
participate in the research against their better judgment. Undue inducements make consent
involuntary.
Is the compensation fair?
RECs must use their judgment to assess whether or not compensation is acceptable or unduly
affects voluntary nature of consent. What constitutes fair compensation varies according to the
particular context of each trial and of each type of person being solicited for participation.
“Monetary and in-kind recompense must, therefore, be evaluated in the light of the traditions of the
particular culture and population in which they are offered, to determine whether they constitute
undue influence. The ethical review committee will ordinarily be the best judge of what constitutes
reasonable material recompense in particular circumstances.” (CIOMS comment to GL 7)
Compensation offered to prospective participants must be documented and approved by the REC.
The REC must also consider the compensation arrangements that will apply if a participant
withdraws from the study or is withdrawn by the investigator. It is usually considered inappropriate
to make full compensation dependent on completion of a trial.
ICH-GCP, 1996, Sec. 3.1.2, 3.1.8, 5.8.3.

WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 5.3.12, 6.2.3.10.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 6(3)(j).

Question 19
Mother-to-child transmission of HIV through breastfeeding
A research group based at a medical research institute in a central African country is studying risks
related to HIV in pregnancy and risks to newborns. The research is being undertaken at the city’s
general hospital during a 1-year period. At the third trimester prenatal visit for an in-hospital
delivery, every participant has blood drawn to determine her HIV status. Those found to be
seropositive receive counselling and are advised not to breastfeed their infants. The counsellors
assure them that all the infant formula they need will be provided to them free of charge. Some
mothers accept the offer of free formula and do not breastfeed, while others choose to breastfeed
their newborns. The HIV status of every child is assessed at birth and every 6 months up to 18
months; the mother’s status is reassessed at 18 months. All children in the study are seen at least
every 2 weeks in a special clinic where drugs for common childhood illnesses, as well as for HIV-
associated opportunistic infections, are available free of charge.
Does the promise of free formula and the provision of free clinic visits and medication constitute a
form of undue inducement to participate?
Yes
No

3.9. Privacy and confidentiality
Respect for privacy requires keeping secret or hidden what is not intended for public view. An
important aspect of privacy in research ethics is confidentiality, which requires keeping personal
information secret or hidden. Respect for privacy and confidentiality are important ways to promote
human dignity.
Confidentiality of information gathered during research
As with any information collected during care by a health professional, personal information
collected during research must be held confidential. The researcher has a duty not to share
personal information about the research participant with others without the participants’ consent or
a legal authorization to do so. The duty of the researcher to treat private information in a respectful
and confidential manner is an internationally recognized norm and ethical standard.
Does the project properly protect privacy and confidentiality?
RECs play a critical and essential role in balancing the importance of the activities of research
against the respect for privacy. RECs also play an important role in ensuring that invasions of
privacy are minimized. Privacy involves the “right to be left alone”. Recruitment procedures of
project should respect prospective participants’ privacy.
One way to protect the confidentiality of personal information and records is to anonymize them
(i.e., remove all identifiers). However, access to personal identifying information is essential for
many research projects in order to advance knowledge that benefits the participant and society as
a whole. When personal information will be recorded, research participants have a right to know
who will have access to their information. RECs protect this right and protect participants from
harm that may be caused by unauthorized use of personal data by ensuring that participants are
informed, via the consent process, of the extent of the confidentiality that can be promised.
Therefore, participants must be informed about who may potentially have access to their identifying
information (e.g. the REC, regulatory agencies, the sponsor of the study or funding agencies).
Furthermore, during the ethics review of a research project, the REC should verify that data
collected is stored by the researcher with all appropriate measures necessary to protect
confidentiality based on the sensitivity of the information and see to it that when data is released it
does not contain names or identifying information.
In its review of research that obtains personally identifiable information about research participants,
the REC should consider:
The type of data to be collected

The purpose for which the data will be used
Limits on the use, disclosure and storage of the data
Appropriate safeguards for security and confidentiality
Visual and sound recordings that allow identification of particular participants
Who will have access to the data and whether they promise to respect confidentiality
Any anticipated secondary use of identifiable information from the research
Any anticipated linkage of the research data with other data about participants, and
Provisions for confidentiality of data in research reports.

WHO, Operational Guidelines for Ethics Committees, 2000, sec 6.2.4.
ICH-GCP, 1996, Sec. 2.11.
EU Directive 2001/20/EC on Clinical Trials, 2001, Art. 3(2)c).
US 45 CFR 46 Protection of Human Subjects - Common Rule, 2009, Art. 46.111 (a) (7).

Question 20
Researchers conducting interviews with traumatized populations have stated in the study protocol
that no names or addresses will be used on the answers recorded from each interview. Interview
results will be coded with a special identifier for each participant and the coding key will be kept
separate from the results by the lead researcher.
True or False? This procedure alone will be sufficient to protect privacy and confidentiality, so any
additional security processes are not necessary.
True
False

3.10. Researcher conflicts of interest
Properly managing conflicts of interests of researchers, as well as of REC members as seen above
in 1.2, is an important mechanism for promoting the protection of research participants.
What counts as a conflict of interest?
Conflicts of interest can be generally defined as:

“a set of conditions in which one’s judgment concerning a primary interest tends to be unduly
influenced by a secondary interest.” (Thompson 1993)
Primary interests of researchers include, for example, patient/research participant welfare or
conducting valid research. Secondary interests of researchers could include, for example, financial
gain, acknowledgment and professional advancement, or other personal interests. Secondary
interests are not necessarily illegitimate in themselves but what is problematic is the influence they
exert on decisions. A common conflict of interest arises when the researcher also has routine
clinical care responsibilities for the persons he or she recruits into a research study.
Conflicts of interest can be actual, potential or perceived. The appearance of conflict may be as
damaging as a real conflict. While being in situations of conflict does not imply that people are
dishonest, it is important that these situations be managed properly in order to promote the
integrity of judgment, to ensure transparency and to preserve the trust relationship researchers
hold with research participants.
Can researcher conflicts of interests be managed properly?
As a general rule, researchers are required (often on REC submission forms) to disclose actual,
perceived or potential conflicts of interest to the REC. Institutions may develop mechanisms to
address and resolve conflicts of interest. In order to properly evaluate a project, the REC should be
provided with details on budgets, commercial interests, contractual relationships and other relevant
information.
A conflict of interest can be assessed as severe or not by evaluating the likelihood that the
researcher’s judgment will be influenced by the secondary interest and the seriousness of the
harm or wrong that is likely to result from such influence or the appearance of undue influence.
RECs can use two tests to assess the implications of actual, perceived, or potential conflicts of
interest:
1) Would an outside person question the ability of the researcher to make a proper decision
despite possible secondary interests (financial, personal, etc.)?
2) Would the public believe that the trust relationship could reasonably be maintained between
relevant parties (e.g., participants and researchers) if they had information on the conflict of
interest?
RECs can help to manage conflicts of interest by:

• raising awareness,
• requiring disclosure of interests to all affected parties,
• prohibiting the secondary interest, and/or
• using continuing ethics review process. (For example, when significant conflicts of interest are
brought to the REC’s attention, it should require that the researcher disclose these conflicts to
prospective participants during the informed consent process.)
However, some conflicts of interest compromise the primary interests of researchers or public trust

to such an extent that they are considered unacceptable. For example, the payment of finders’
fees to physicians for the recruitment of research participants is considered an unacceptable
conflict of interest. Similarly, a contractual clause that unreasonably limits a researcher’s freedom
to publish the research results is also considered unacceptable. In such situations, RECs may
require the researcher to abandon one or all of the secondary interests.
Thompson D., 1993.

Glass K.C., Lemmens T., 1999.

Question 21
(Based WHO case study 53)
An Asian pharmaceutical company has developed a promising new antipsychotic medication for
the treatment of schizophrenia. Sales analysts predict the drug could earn the company a
significant profit within 4 years. The study drug has already been tested on several thousand
volunteers in Asia. During this testing, however, some study participants developed cardiac
arrhythmias. Consequently, the regulatory agency responsible issued a “not approvable” letter,
which requires the drug company to do more tests of the drug on human beings before it can be
considered for approval again.
In response, the company contracts a state hospital in eastern Europe to complete the needed
tests. The hospital is a long-term facility for mentally ill patients; it is overcrowded, and most
patients have been in the facility for many years with no hope of being discharged. Often they have
to wait for several months before they get an opportunity to see a doctor. Many patients do not
have any next of kin or relatives who visit them regularly or at all.
Facility doctors determine whether a patient is competent to enter a study before obtaining
informed consent for their participation. They are paid a fee for each patient who is recruited. The
information sheet given to patients states that the drug “has been tested in thousands of patients
and the results of these studies are being reviewed by authorities in Asia, Europe, and the United
States of America”. It also notes that the drug “appeared to slightly affect the electrical activity of
the heart in some people”. It contains no other mention of cardiac problems or arrhythmias. The
company did not inform the country’s regulators of the Asian regulatory agency’s action; the laws
of this country do not require such reporting and thus the company contends that it “adheres to the
laws of each country in which research is conducted”.
This study raises a number of ethical issues. Amongst other things, you are concerned about the
payment of “finder’s fees” to facility doctors for each patient recruited. Which of the following
statements is TRUE?
The payment of a finder’s fee is a significant conflict of interest that cannot be managed in
any way. As such this aspect of the project is unacceptable.
The payment of finders’ fees to those who recruit patients into clinical trials is a conflict of
interest that can be managed, for example, by ensuring that the amount paid to physicians
is not disproportionate to their usual revenue.
The payment of a fee for the recruitment of patients is not a conflict of interest since it is
normal that physicians should want to receive payment for work that they do.

3.11. Scientific integrity
In conducting research involving humans, researchers have important privileges and freedoms.
They also have responsibilities associated with these privileges and freedoms. Researchers are
expected to meet high levels of scientific integrity that include accurate collecting and reporting of
data generated during the research and appropriate use of research funds. Researchers are also
expected to publish their research findings and have freedom from censorship.
However, integrity (i.e., the quality of being honest) is not always achieved. Misconduct may
include the reporting of unsubstantiated or falsified data, plagiarism, failure to acknowledge
substantive contributions from other persons, the selective reporting of favourable data, the
trimming of inconsistent data. Such misconduct may result in disciplinary actions against
researchers.
Are researcher responsibilities during the conduct of a trial made clear?
When the REC approves protocols, researchers should be reminded of, and commit to, their
responsibilities during the conduct of the trial. These responsibilities include:
Following the protocol and the inclusion and exclusion criteria. Integrity requires that
researchers adhere to inclusion and exclusion criteria, as these are designed to ensure
scientific validity and to ensure protection of participants. Any deviation from
inclusion/exclusion criteria to ensure enrolment for a project can harm participants and
invalidate the results of the research.
Supervising the research team
Reporting serious (unexpected) adverse events to the REC, the sponsor, and any other
agencies that required such information
Submitting protocol amendments to the REC for review and approval before they are
implemented (unless immediate changes are required to avoid harm to participants).
Record keeping according to applicable regulations and national or institutional
requirements
Communicating results: if research results are not made public, research has no value.
Researchers have a duty to disseminate results to those who served as research
participants, to other researchers, and to anyone else who could make use of the results.

WHO, Operational Guidelines for Ethics Committees, 2000, Sec 6.2.1.8.
ICH-GCP, 1996, Sec. 2.6, 2.10, 4.5, 4.9.

Question 22
Which of the following statements is TRUE?
Researchers who, in writing up publications, hide negative results of a clinical trial commit
scientific misconduct.
Since they are often the heads of departments, it is acceptable for primary investigators to
ask their staff to write up journal articles reporting research results and to only list
themselves as authors.
When a physician-investigator considers that one of his patients could benefit from
participating in a trial, then it is acceptable for him to include that patient even if she does
not meet the inclusion criteria.

3.12. Ongoing respect for research participants and collaborating
communities
Research involving humans must be based on a trust relationship if individuals are to continue to
volunteer to participate. Continuing to demonstrate respect for participants and their communities
after the project has ended is essential to maintaining the trust relationship. Ongoing respect to
research participants and collaborating communities is demonstrated by the following actions.
Informing participants of the results of the study
Persons entered into the study are entitled to be informed about the outcome of the study in a
format appropriate to the recipients, and to share any benefits that result from it. Plans to inform
participants of research results should be presented as part of the research protocol.
Providing proper insurance and compensation for damages
Participants who are injured as a result of their participation in a trial must be offered medical
treatment and compensation for damages. The REC should ensure that the protocol provides for
insurance coverage for such eventualities.
Should the protocol provide access to drugs once the trial is finished?
For some drug trials, participants may benefit from receiving the experimental drug. For example, if
a new formulation of an already approved drug is being tested in a developing country that cannot
afford the drug, then it is quite likely that participants will benefit. Sometimes, when new molecules
are tested, Phase III trials will demonstrate benefits for patients. When it reviews protocols, the
REC should consider whether participants should continue to have access to the trial drug after the
trial is completed. These aspects must be discussed before a project starts.

Question 23
You are an HIV researcher from Uganda. You completed your graduate studies in the United
States and then returned to your home town to head up an HIV clinic. A major commercial sponsor
has contacted you to act as an investigator for a forthcoming HIV-1 vaccine trial. The sponsor is
hoping that the fact that you are a local researcher will encourage eligible persons to join the trial.
You have reviewed the protocol and find the design interesting, However, you have concerns
about the protocol since it does not address what will happen to persons who are ineligible
because they test positive for HIV on the screening test. Nor does the protocol address what will
happen to participants who become infected during the trial, whether on the vaccine or the
placebo. When you raise these elements with the sponsor, your concerns are downplayed
because they are not relevant to the scientific design of the protocol that is in fact of high quality.
The sponsor considers that your concerns relate to post-trial issues that are not relevant the actual
protocol.
Is the sponsor correct?
Yes
No

Part 4. Documents to be reviewed
The nature of research projects varies from one project to the next. Ethics evaluation practices also
evolve over time. Hence, it is difficult to establish a definitive list of documents that the REC needs
to conduct a full evaluation. Given the nature of ethics evaluation, the REC may ask to be provided
with any document it considers important.
Certain documents are commonly required by the REC for evaluation. These include:
The completed REC application form, signed and dated by the investigator
The updated full protocol
Investigator brochure (if applicable, but compulsory for clinical trials unless the relevant
information is already incorporated into the protocol)
Information sheets and informed consent documents (including any documents that will be
provided to participants)
Documents on the investigator’s qualifications (e.g. CV and licences)
Financial arrangements for the site (e.g. any compensation for participants and funding
source for the study)
Any questionnaires
Any material to be used for recruitment
Examples of other documents that may be required by the REC for evaluation include:
Any other REC decisions, both positive and negative (in case of multi-centre studies)
Full study site budget
Relevant contracts/agreements (e.g. study site agreement/investigator’s agreement)
When the project involves an experimental drug, vaccine or device, the investigator should also
submit any government authorizations and registrations that are required.
When the research is funded by private industry, the REC should be provided with any contractual
clauses that may have an impact on the ethical acceptability of the project. These include any
clauses that:
are relevant to any indemnity in case of injury

are relevant to the insurance coverage for research participants
affect publication of results
The ICH-GCP provides specific guidance on the content of protocols for clinical drug trials (see
GCP section 6). To ensure it receives information on precise aspects of projects it evaluates, the
REC may want to request specific information in their submission forms. For example, a
submission form may ask for:
a summary of the protocol in non-technical language

a summary of potential benefits
a description of the ethical considerations,
a description of the recruitment process and of the consent process
precisions that may be required by national law

WHO, Operational Guidelines for Ethics Committees, 2000, Sec 5.3.
ICH-GCP, 1996, Sec. 3.1.2.

Subjects, 2002, Appendix 1.
Biomedicine, concerning Biomedical Research, 2005, Art. 11, Appendix 1.

Question 24
The REC has asked a researcher to provide a copy of the contract between herself and the
sponsor of her proposed research project in order for the REC to verify if there are any restrictions
on the publication of research results. Understandably, the researcher hesitates because the
sponsor has specified that the content of the contract is confidential.
True or false? Given the contractual obligation on the researcher, she should not share any of the
content until the contract is finalized, not even with the REC. Once the contract is signed, the REC
is entitled to see the entire contract, which should be included with the researcher’s ethics
submission.
True
False
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Module 2.

Last modified by Thlologelo Masalesa on Friday, 20 September 2019, 2:47 PM

© TRREE, 2009-2021 1 http://elearning.trree.org/

© TRREE, 2009-2021 2 http://elearning.trree.org/

© TRREE, 2009-2021 3 http://elearning.trree.org/

The ethics evaluation and approval of protocols before they commence

Emanuel E.J., Lemmens T., Elliot C., 2006.

© TRREE, 2009-2021 4 http://elearning.trree.org/

© TRREE, 2009-2021 5 http://elearning.trree.org/

A common example of a potential conflict of interest is when an international institution wishes to

WHO, Operational Guidelines, Glossary

CIOMS, International Ethical Guidelines 2002, commentary on Guideline 20. On potential

© TRREE, 2009-2021 6 http://elearning.trree.org/

WMA, Declaration of Helsinki, 2013, Para. 23.

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Why did this raise concerns? Choose the BEST answer.

All of the above.

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WMA, Declaration of Helsinki, 2013, Para. 23.

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Minimally, the following elements of any REC should be clearly established:

the authority which established the REC (Terms of Reference)

WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 4.

© TRREE, 2009-2021 11 http://elearning.trree.org/

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Decision-making involves two distinct phases:

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Listening and openness

Glazer J.W., 1989.

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Making decisions by vote, as opposed to consensus, should be restricted to exceptional

Dissenting and abstaining

Caws P., 1991.

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WHO, Operational Guidelines for Ethics Committees, 2000, Sec. 7, 8, 10.

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All of the statements above are false.

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a. any protocol amendment;

The goal of continuing ethics review

REC decisions during continuing review

If any of the above is deemed unacceptable, the REC might:

WMA, Declaration of Helsinki, 2013, Para. 18, 23.

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(adapted from WHO, case 24))

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WMA, Declaration of Helsinki, 2013, Para. 35.

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© TRREE, 2009-2021 23 http://elearning.trree.org/

© TRREE, 2009-2021 24 http://elearning.trree.org/

WMA, Declaration of Helsinki, 2013, Para. 1, 23.

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“Research” is a systematic investigation conducted in order to establish and communicate facts,

Medication error reporting: Is it research?

Should the director submit a research plan to the REC?

© TRREE, 2009-2021 26 http://elearning.trree.org/