Context The conduct of medical research led by Northern countries in developing countries raises ethical questions. The assessment of research protocols has to be twofold, with a first reading in the country of origin and a second one in the country where the research takes place. This reading should benefit from an independent local ethical review of protocols. Consequently, ethics committees for medical research are evolving in Africa.
Objective To investigate the process of establishing ethics committees and their independence.
Method Descriptive study of 25 African countries and two North American countries. Data were recorded by questionnaire and interviews. Two visits of ethics committee meetings were conducted on the ground: over a period of 3 months in Kigali (Rwanda) and 2 months in Washington DC (USA).
Results 22 countries participated in this study, 20 from Africa and two from North America. The response rate was 80%. 75% of local African committees developed into national ethics committees. During the last 5 years, these national committees have grown on a structural level. The circumstances of creation and the general context of underdevelopment remain the major challenges in Africa. Their independence could not be ensured without continuous training and efficient funding mechanisms. Institutional ethics committees are well established in USA and in Canada, whereas ethics committees in North America are weakened by the institutional affiliation of their members.
Conclusion The process of establishing ethics committees could affect their functioning and compromise their independence in some African countries and in North America.
- Ethics Committees
- North America
- Ethics Committees/Consultation
- Policy Guidelines/Inst. Review Boards/review Cttes
Statistics from Altmetric.com
- Ethics Committees
- North America
- Ethics Committees/Consultation
- Policy Guidelines/Inst. Review Boards/review Cttes
Biomedical research involving human subjects has been conducted in Africa for more than half a century. According to international guidelines,1 2 and several national laws,3 4 research with humans requires an evaluation by ethics committees. Few studies touched on the creation of ethics committees in Africa. The purpose of this work is to describe the establishment of ethics committees for biomedical research in Africa and make a comparison with ethics committees in North America in order to assess their respective degree of independence.
The first ethics committee was created after the Nuremberg trial to supervise human experiments carried out on prisoners during wartime in the USA.5 Appointed by the Governor of Illinois (USA), this ethics committee was mandated to determine whether ethical conditions were satisfied during experiments conducted at the Statesville prison.6 It was the forerunner of the independent committees, to which the Declaration of Helsinki assigned a role in analysing the ethics of research on human subjects.7 From 1980 onwards, due to the increasing involvement of human subjects in industrialised countries, the legislation regarding clinical trials began to incorporate similar structures, for example: Institutional Review Board (IRB) in the USA, Committee for the Protection of Persons in France, and ethics committees elsewhere. In early 2000, ethics committees started to appear in Africa.8
Their way of functioning does not always satisfy the best ways of protecting human participants in biomedical research. If the common use of international textsi is followed during the composition of these committees, the independence, assent and real protection of the participants they hire can be suboptimal.9 The intercultural aspects and the socioeconomic contexts (access to care and to medicines, poverty) can also curb the review of biomedical protocols in developing countries.
In our study, we describe the creation process of ethics committees in some African countries and provide a descriptive analysis of theses committees according to the reference texts on which they were based. The independence of ethics committee is a recommendation pursuant to Article 15 of the Declaration of Helsinki, “The research protocol must be submitted to a research ethics committee before the study begins. This committee must be independent of the researcher, the sponsor and any other undue influence.”
The second objective of this survey is to evaluate how an ethics committee in Africa can be independent and make a comparison with the independence of the ethics committees in North America.
This was a regional descriptive study on research ethics committees of African targeted countries in comparison with two North American committees. Firstly, a pilot study was launched in Rwanda where we worked on the establishment and the functioning of the National Ethics Committee of Rwanda during 3 months in 2006. Data were collected from reports of meetings and from approved protocols of research projects in public health. Additional information was provided by interviewing committee members. We attended meetings as observers to see how the examination of protocols was handled. We also interviewed two different main investigators who had received an approval from the National Ethics Committee of Rwanda for multicentre research in Rwanda. The independence of the National Ethics Committee of Rwanda appeared as the biggest challenge.
Secondly, in order to conduct a regional feasibility study, we questioned the database of the WHO and Unesco. With the help of the personnel of these two international agencies, we identified, among 53 African countries, the national leaders from 25 countries involved in research ethics in Africa. A survey based on the creation process of ethics committees and their independence was submitted to the targeted leaders in these 25 countries. The questionnaire was sent in early 2008, and the potential participants provided a tacit consent by filling out and returning the questionnaire. Respondents answered promptly but most of the responses were incomplete. We then made an initial contact with these individuals and they, in turn, suggested the names of ethics committees' representatives operating in their country. In order to complete data, numerous emails were exchanged with the participants and we collected the questionnaires in May 2009. We completed these data by online bibliographic research.
In order to assess the independence of these ethics committees that review protocols for international studies, we compared the collected data to that of North America ethics committees because the USA and Canada initiate a large number of clinical trials in Africa. Over 2 months, we recorded relevant information on research ethics from experienced people and specialists at the Kennedy Institute of Ethics of Georgetown University, Washington, DC. We anonymously interviewed ethicists from the department of bioethics at the clinical centre of the National Institutes of Health (NIH) and its Office for Human Subjects Protection. Two IRB members from the Georgetown University Hospital were also interviewed. In order to ensure the privacy of respondents, the questionnaire did not collect any personal identifiers. All the respondents in Georgetown University Hospital and NIH were PhD fellows without any conflict of interest and were free from any pressure.
The meetings of IRBs at the NIH and Georgetown University Hospital that we attended gave an overview of the actual process of IRB approval in the USA. Our experience in Rwanda allowed us to see how committees worked in Africa. Data from Canada were recorded through the same questionnaire. We also discussed these issues with a member of the ethics committee of the faculty of medicine, Montreal University, also member of the Canadian national ethics committee.
In addition, the National Reference Center for Bioethics Literature, at the Kennedy Institute, provided us with a broad range of information. It represents the world's largest collection related to ethical issues in medicine and biomedical research. We consulted books, journals, regulations, government publications and other relevant documents related to issues of biomedical and professional research. A comparative analysis was done focusing on two main points: (1) What was the creation process of each committee? (2) What was its degree of independence?
After a year and a half, we recorded data from 20 African countries among 25, producing a response rate of 80%. We received the most information from Western and Central Africa. The National Ethics Committee of Rwanda was the only one we visited in Africa. While in North America, we visited two IRBs in the USA: twice at one of the National Institutes of Health IRBs and once, at the Georgetown University Hospital. IRB Data from the ‘Conseil National d'Ethique en Recherche’ and the Research Ethics Committee of the Montreal School of Medicine were collected as well.
Ethics committee for research in Africa: a local evaluation
The oldest ethics committee was created in 1967 in South Africa. Unfortunately, as in many developing countries, there was a gap between the year of creation and the actual year of full functioning of each recorded ethics committee (table 1). Several regional organisations and workshops have been held in Africa in the last 10 years in order to perform ethical reviews of research projects. The most important ones are listed in table 2.
All local committees (IRB, ethics committees) were created with the main objective of participating in international research due to the need of a double reading of protocols: one in the sponsor's country and the second in the country where the trial is conducted. Before 2002, committee members were fulltime employees of the institution, except in South Africa. Members were 90 % male, scientists, and/or lawyers. In all, 75% of local committees have been extended to national committees. The average number of committee members was 10 and all of them were appointed by the head of institutions in the case of local committees. In 80% of national committees, the ministry of health appointed the members. Almost half of them had recently received a short training (average duration: 12 h) on the ethics review process.
Most of the local committees have spent several years without a meeting and issued no reports. Only 44% of the national committees had a secretariat by 2005. Less then 30% had reference texts of regulations, or standard operational procedures. Approved protocols are incompletely recorded in most committees. None of the committees make any follow-up of the research during the clinical trial, but each committee requires an annual report from the principal investigator. No committee has rejected a research protocol. There exist two particularities: first, in Cameroon, where an institutional committee manages ethical issues at the national and international level instead of the official national committee appointed by the ministry of health; and second, in Gambia where the ethics committee, Gov/MRC, is composed of foreign members who give scientific approval before sending protocols for local ethics approval.
In 2007, the Universal and International Declaration on Bioethics and Human Rights Advocates, Unesco developed the Assisting Bioethics Committees programme for establishing ethics and bioethics committees at all levels as a first step for States to create platforms and bodies for ethical debate, analysis and policy development. The current focus of Assisting Bioethics Committees activities has continued to be the establishment of national bioethics committees (table 3).
Ethics committees in North America: a long experience
The NIH, the biggest centre of health research in the USA, currently has 12 IRBs. Its first IRB was created in 1966 to review research projects applying for US government funds. During the following 8 years, several research projects (involving prisoners and black males) were carried out in questionable ethical conditions.
In 1974, the US Congress created the National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research which produced the Belmont report. During the last decade, the President's Council in Bioethics worked 8 years advising the President on ethical issues related to advances in biomedical science and technology. In the USA, a national commission was appointed to raise main ethics issues for IRBs working within a research institution or university hospital, and for-profit boards. The Office for Human Research Protections (OHRP) supported by the US Department of Health and Human Services (DHHS) manages an OHRP-approved assurance of compliance with DHHS regulations for the protection of human subjects.
An example of an IRB would be the NIH's IRB collaborating with its department of bioethics created in 1996. Twelve IRBs are recorded for the 27 institutions of the NIH. Each IRB includes at least one ethicist from the Department of Bioethics among its minimum of five or more members. The latter are recommended by the director of the research institution and then, appointed by the Deputy Director of NIH. A permanent administrative personnel is in charge of the secretariat, which means the archive system is well managed. All IRB members work for the institution, except one who represents the interests of the community. Most IRB members received a short training on the ethics review process. The 2000 patients who are currently involved as subjects of a biomedical research project at the NIH clinical centre are aware that the objective of this centre is research. It provides healthcare services free of charge for all the research participants.
In Canada, the ethics review includes the use of national and international standards by the research ethic committees (RECs) which are local, independent and multidisciplinary. They are mandated to evaluate the ethical validity of the research projects led within their institutions.
In keeping with the obligation of the Council of Medical Research, and in order to obtain an approval from an ethics committee as a prerequisite for any subsidy, RECs proliferated in Canada from 1995 on. The National Council of Ethics Research was created by the Ministry of Health. Since 1989, the Tri-Council Policy Statement on Ethical Conduct for Research Involving Humans has required that investigators submit all research protocol involving human subjects to an ethics committee. The main role of this council has consisted in facilitating discussion and collaboration in the context of the respect of ethical standards by research institutions. The council describes the policies of the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council of Canada regarding the ethical conduct of research with humans. Researchers and institutions funded by these entities certify that they will comply with this national institution. There are institutional and independent RECs existing in Canada.
The REC of the Montreal Faculty of Medicine is one of the four ethics committees created at the University of Montreal which assures the evaluation of research protocols involving human subjects conducted by the faculty under the supervision of the University Ethic Council. As others with Canadian RECs, the Montreal Faculty of Medicine's REC is composed of 6 to 12 members, of whom at least three should be professors or researchers working on the campus. It also includes one ethicist, one lawyer, one representative of the community and one clinical physician. Although there is an efficient secretariat and the archives are well kept, there is no available follow-up of the approved projects. However, an annual report is required from the principal investigator.
Before the last decade, there were no effective national ethics committees in sub-Saharan Africa.10 The creation of RECs in these 20 countries shows awareness of the stakes surrounding the conduct of biomedical research in emerging countries. The North American model of establishment and functioning of the Institutional Review Boards (IRB) found in the US and Canada differ. Both however, ensure the protection of human subjects involved in biomedical research.
The absence of structures dedicated to the ethical review of clinical trials in certain African countries, as well as the requirements of Western governments' agencies before funding any research involving human subjects were responsible for the creation of the first local committees in Africa. The collection of our data took longer but the response rate of 80% was comparable to what Nyika et al11 found in 2008. The high response rate could be attributed to repeated emails to our personal contacts and personal visits in Kigali and in Washington, DC. As a consequence of the requirements of Western governments' agencies before funding any research involving human subjects, the first local committees in Africa were created in the last decade.
The older local committees come from English speaking countries, which account for half of the countries studied. Nancy et al12 demonstrated that half of the research ethic committees analysed in her study had a Federal Wide Assurance from the US Government, an indication that the institution had received US research funds or collaborated with US institutions. The gap in table 1 between the creation and the real establishment of ethic committees could be explained by the overall context of developing countries, including poor environment of research, inadequate manpower, inadequate infrastructures and lack of funds.
All the RECs were created according to international guidelines.1 2 However, our experience of national ethic committees in Rwanda, or even on IRBs at the US National Institutions of Health and at the Georgetown University Hospital showed a variance in the scope and emphasis of the international instruments involved in the ethics of medical research. The need to reflect on the moral dimension of advances in science and technology, as well as the desire to improve the public's health in many areas of the world, have led to the establishment of national bioethics committees. The number of members on the national committee ranged from seven to 32 with an average of 10. This average membership in our study is similar to what Kirigia MJ et al found in the study carried out by the WHO national offices in 28 African countries.13 The higher number of members was usually found in committees in which the decision makers needed to follow international guidelines. In such cases, only a small part of the committee is really deciding on behalf of the committee itself. Those additional members seem to be on the committee for reasons other than to fulfil the committee mandate.
While the functionality of an ethics committee hinges on an efficient secretariat that serves as the clearing house for protocols, some of the IRBs do not have a working secretariat with dedicated staff. More than half of the committees analysed in this study did not have any secretariat. Each of these committees did keep some documents of the reviewed research proposals and communications with the investigators, but none of them had a specified time period for keeping the documents.
Before the Universal Declaration on Bioethics and Human Rights (Unesco statement), the members of the Africa ethics committees were 90% male and scientists. This could be attributed to the fact that the first appointed members for new ethics committees were researchers who were more comfortable with research methodologies and ethical issues than other people. In 2007, Ikingura JK et al showed that this situation had not evolved enough. He conducted a study of six research centres in Tanzania, in which female representation in the committees remained low (15.2%). The largest proportion of the committee members were biomedical scientists (71.2%) including medical doctors.14 A tendency towards institutional or scientific interests may result from a preponderance of institutional and scientist members. This could be an intimidating atmosphere for community members and other minority members.
Six members of national committees were well familiarised with international guidelines. Indeed, the majority were scientists affiliated with national universities or had recently been trained in research ethics through regional workshops and seminars held by Unesco and WHO programmes, as well as by African organisations such as the Pan-African Bioethics Initiative. Other challenges in the operating of ethics committees include: poor mechanisms of research monitoring, financial constraints, poor data archival systems, a lack of standard operational procedures and guidelines for submission and evaluation of protocols. If all committees do not have a health research policy or a functional national health research system, they are expected, at least, to monitor the current conduct of research so as to ensure justice in the distribution of costs and benefits. We concur with Benatar15 that the “lack of attention to how research is actually being conducted is a serious shortcoming, requiring critical attention in an era of expanding research, growing links with industry and commercial organisations, documented inadequacies in the protection of research subjects and with growing recognition of the need to avoid exploitation”. In short, it is vitally important for ethics committees to competently implement all the guidelines stipulated by the Council for International Organisations of Medical Sciences (CIOMS).2
International support and collaboration with the health research authority
Through the Assisting Bioethics Committees programme, Unesco has supported the establishment of ethics and bioethics committees from the existing local committees. Thus, 15 local ethics committees were extended to the national level; these committees are still making the basic mandate of ethics committees and trying to ensure ethical debates, analysis and policy development. While members of initial local committees were appointed by the institution director, those belonging to national committees were almost all named by the Ministry of Health. One of the objectives was to meet international standards with the purpose of coordinating all the ethic research issues in the country.
The Gambian government/Medical Research Council, Gov/MRC, is an institutional review board which was extended to the national ethics committee of Gambia. The committee members are divided in two parts: one from the UK which is in charge of scientific evaluation of protocols and a second local part which discusses ethic issues. The functioning of this sort of ethics committee revealed a serious problem of establishment. It revealed the danger of dependence on the committee when the foreign component of this Gambia ethics committee considered that “conducting research in a developing country is a civic duty and serves to improve treatments and vaccines where the disease occurs”.16 We agree with Francois Lemaire, that even if patients should be included in a research protocol, the lack of information and the lack of real informed consent is morally reprehensible.17 International guidelines for the establishment of RECs should be followed by the health research authority.
IRBs and RECs are well established in North America. This is thanks to strong national bodies who built a functional national health research system with a policy, a strategic plan and laws relating to health research. There also exist national councils advising on ethical issues related to advances in biomedical science and technology.
In the USA, the DHHS and Food and Drug Administration have established regulations and requirements for the functioning and operation of IRBs. Each research institution requires its IRB to comply with all these regulations in order to get government funds for its research.18 Nevertheless, a private research institution could legally undertake research involving human subjects without any approval from IRB provider if it doesn't apply for public funds. This could bring serious risks to participants in a country where not everyone has health insurance.
The drug industry usually plays a major role in conducting research in the private sector. Relationships between IRB members and industry are common, and members sometimes participate in decisions about protocols sponsored by companies with which they have a financial collaboration. Campbell EG et al reported, in a study carried out in 100 academic institutions,19 that at least one protocol came before their IRB during the previous year, which was sponsored either by a company with which they collaborated or by a competitor of that company, both of which could be considered conflicts of interest. They also found that 36% of 893 IRB members had collaborated at least once with industry in the past year. A lack of national body or regional committees which could manage all the IRBs (institutional and non-institutional) represents a weakness of the system in the protection of human subjects participating in biomedical research in the USA.
In the NIH, each institution director participates in the appointment of his IRB members. He is also allowed to attend the IRB meeting as an observer. The presence of the director may create a pressure that limits careful discussion of protocols. As a result, protocols may not be explored as thoroughly as they would be if the director were not present. Furthermore, research subjects may be exposed to risks. The functioning of these kinds of IRBs is not independent. The US IRB system is designed to make committees as independent as possible from industrial sponsors of research. It entirely ignores the committee commitment to promote research as well as the loyalties IRB members have to their colleagues and to the institution that employs them. In testimony, the chairman of the Department of Bioethics at the NIH's clinical centre, Ezekiel Emanuel said before the President's Council for Bioethics:
One of the problems of having your IRB be institution-bound is that the IRB is actually regulating research within the institution that is paying the IRB. That is the inherent conflict of interest. I, myself, have twice experienced some of the pressures that can be brought to bear by review research done at the institution and people, powerful people, in the institution having some interest in getting that research going.20
Besides, IRBs are mandated to include “at least one member whose primary concerns are in non-scientific areas” and “at least one member who is not otherwise affiliated with the institution”.21 Except the community representative, all the IRB members are usually affiliated with the institution and could face conflicts of interest. We agree with EE Anderson that a single individual often serves both of these roles simultaneously. An approval from this IRB made by the scientist affiliated members would be in conflict of interest.
Avoiding conflicts of interests or even the appearance of conflicts of interests is important for maintaining the independence and integrity of the IRB review process. However, this goal requires all the IRB and staff administrative members to have a shared understanding of what interests are problematic for the protection of human subjects involved in research projects. Some IRB policies explicitly allow members with a conflict of interest to participate in protocol review contrary to regulatory requirements or OHRP guidance.22 This thus allows the member to serve as reviewer, to remain in the room during IRB deliberations and to vote on protocols. His participation could bias the discussion on a protocol or the IRBs decision.
It is important to know that none of the international guidelines require the committee that reviews ethical aspects of research to be independent of the institution in which research is carried out. Instead, they mainly address the independence of IRB/REC members from the investigator or research project under review. Can a typical US IRB be considered ‘independent’? The very name invented for such committee, and their location within academic medical centres and hospitals that conduct research, call for analysis of what constitutes independence. But there are non-institutional IRBs and known independent RECs which operate for profit and are unattached to any research institution, such as the Western Institutional Review Board and the Biomedical Research Alliance of New York IRB. Among prestigious research centres, the John Hopkins University and the Columbia University hire the service of Western Institutional Review Board while they continue to use their own IRBs.23
Canada has no central REB registry. Norton and Wilson have recorded 187 RECs across Canada through their study.24 RECs and independent committees work almost in the same way as in the USA.
North and South: which establishment, which independence for research ethics committees
The creation of ethics committees as a result of the emergence of new drugs and biomedical technologies brought better protection of research participants. While the system of human subject protection has been well established in developed countries for over a quarter of a century, several challenges remain in emerging countries.
According to our study, the main reason for the functional difficulties of ethics committees in Africa could be the general context of underdeveloped societies and its consequences. In the last decade, the African scientist leaders have tried to create regional forums and networking with support from Unesco and WHO in order to strengthen existing ethics committees. However, socio-economic challenges make sustainability and improvement of these committees difficult. More training addressed to committee members and the use of independent funds to assist them would help ethics committee face these challenges.
Additionally, fault may lie in the peculiarity of the origin of these committees. The establishment of the first African ethics committees is connected to the need of conducting Western research projects in developing countries. While African scientists are managing to conduct local research in order to solve some endemic or tropical diseases in the region, ethics committees are still working with the dependences of Western agencies. Committees are not independent enough, according to the history of their creation and the socio-economic context; Gov/MRC, the Gambia ethics committee, is the best example of dependence. In addition, ethics committees in developing countries are required to adhere to standards that might impose practices that conflict with local culture and interpretations of ethics.25 African countries should introduce a framework for research governance based on international guidelines and local cultural, medical and legal realities. These regulations could provide guidance on forming local REC informed consent procedures.26
Besides, if the local ethical committees are well established in North America, they should be truly independent. These local committees are often dealing with conflicts of interest within the institution they serve. For-profit ethics committees seem possibly more independent but they have their weaknesses. IRBs could remain institutional and be required to have a significant number of members from outside the institution. This would be a ‘mixed’ system—something between an institutional and a regional committee.27
This study possesses several limitations. The period of data collection has been extended so as to complete information. The selection of 25 countries according to available contacts constitutes the main methodological weakness because it would have been preferable to launch the survey on the entire African continent even if we preferred this feasibility study. We cannot be certain of the involvement and preciseness of those who responded. In these situations, we cannot totally exclude the possibility of selection and information bias from Africa, except Rwanda. It would be interesting to have better validity and reliability of participants. Much more discussion could be brought on contrasted differences in ethical standards and norms across cultures, socio-economic and traditional aspects. While expressing the establishment of ethics committees in Africa, only the Rwanda committee was visited. In order to compare, we visited two IRBs in USA. The selected criteria of independence were used more for US IRBs but the establishment criteria were used at the same level for African countries and for North America.
People in developing countries are increasingly becoming subjects of studies originating in developed countries; such international research brings greater ethical responsibilities. The establishment of ethics committees has been strengthened these last few years in Africa in order to manage research regulations on human subjects before a review and approval of a proposed study.
This descriptive study compared the mechanism of creation of research ethic committees in 20 African countries and North American countries. Two major points have been evaluated: the history of establishment and the independence of committees. The national ethics committee of Rwanda, one of the NIH's IRBs and one IRB of Georgetown university hospital were visited in USA. Other data were obtained by questionnaire.
Most of the emerging countries in Africa created their research ethics committees 15 years ago, but they have really become functional over the last 5 years. These committees are not independent enough because of their history of establishment, the socio-cultural challenges of managing multicentre studies through international regulations, local realities and the general context of underdevelopment. The well established RECs in North America are still facing indirect conflicts of interest which keep them under the dependence of their own institutions and colleagues. There is a clear need for training and funding mechanisms for RECs in Africa. The RECs and IRBs in North America should try to involve more non-affiliated members in order to become truly independent and create a system of regional boards which would coordinate all the biomedical research applying or not to the government fund.
Having applied these recommendations, a further study could estimate their real impact through a representative sample and allow their validation for better protections of the participants to biomedical research.
We thank Professor Edmund D. Pellegrino from Georgetown University, Washington DC, for reviewing this manuscript, The IIREB for the scholarship in Georgetown and the Paul Sabatier University for the training period in Montreal. We also thank all the participants who provided information for this research.
Funding International Institute of Research in Ethics and Biomedicine, Montreal University, Canada.
Competing interests None.
Provenance and peer review Not commissioned; not externally peer reviewed.
↵i Nuremberg Code, recent versions of the Statement of Helsinki, Oviedo European Council, International Conference of Harmonisation.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.