Governance of Research Involving Human Subjects

Chapter 13
Governance of Research Involving Human Subjects

Simisola Akintola and Remigius N. Nwabueze

Introduction

Most African countries lack clear regulatory structures and frameworks for the conduct of biomedical research involving human subjects in their territories. Thus, research involving human subjects in such countries does not undergo the process of ethics review. In international collaborative research in developing countries, however, foreign sponsors often insist on the ethical appraisal of research protocols in the relevant developing country in order to comply with the funding policy and ethics guideline of the sponsor’s country. This means that, for locally funded and local investigator-led research in most developing countries, there is no legal requirement or compelling need to go through ethics review of a research protocol. Thus, the low levels of research regulation in Africa and other developing countries potentially lead to the exploitation of research subjects, already impoverished by poverty, illiteracy and a heavy burden of both communicable and non-communicable diseases. The exploitation is exacerbated by the recent increase in research and programmatic interventions to combat diseases that are prevalent in developing countries, as a result of which an increasing number of people are enrolled as research subjects.¹ Unsurprisingly, therefore, research scandals have characterized both local and international collaborative research involving human subjects in Africa and other developing countries, of which Pfizer’s clinical trial of Trovan in Nigeria in 1996 is the most paradigmatic.² Such scandals highlight poignantly the low regulatory climate of research governance in most African countries.

However, the occurrence of research scandals should not undermine the potential of an ethically defensible research to help a developing country confront a public health problem and, thus, contribute to its health system, and social and economic development.³ In the past, for instance, international collaborative research between the US, the UK and developing countries’ researchers have helped to combat diseases that rarely occur in developed countries such as malaria, dengue fever and tuberculosis.⁴ The International Haplotype Map Project (HAP MAP) is a significant contemporary example of a potentially altruistic research intervention in a resource-poor setting like Nigeria. The HAP MAP project is an international consortium involving, among others, Nigeria, Canada, Japan, China and the United States, which was launched with a budget of about US$100 million. The HAP MAP project aims to map the human genome according to haplotypes and the blocks of DNA that contain genetic variation. The HAP MAP project is intended to increase the understanding of human genome diversity and improve human health. The HAP MAP project, however, highlights some of the ethical, social, political and governance issues that might arise in genetic research, and biomedical research generally.

For instance, the involvement of Nigeria and Nigerian research subjects in the HAP MAP project raises some potential ethical difficulties. With about one 150 million people, Nigeria is the most populous country in Africa and home to one of every four Africans.5 Should a research endeavour like the HAP MAP project find that the Nigerian population or a significant part of it suffers from a particular genetic disease, the research finding might lead to unjustifiable discrimination and stigmatization of Nigerians, especially Nigerians in the diaspora. Furthermore, the research results of such population-wide studies might challenge established religious, social and political beliefs.⁶ This underscores the need for rigorous ethical oversight of research involving human subjects in developing countries.

Thus, this chapter explores the legal frameworks and regulatory structures for the governance of biomedical research involving human subjects in Nigeria. The section following this introduction traces the history of biomedical research in Nigeria from the colonial era to the year 2000. The section after that examines the sources of Nigerian law relevant to the oversight of biomedical research involving human subjects in Nigeria. The penultimate section examines the provisions of the National Code for Health Research Ethics (the Code) promulgated by the National Health Research Ethics Committee (NHREC), as well as the National Health Act, 2011 which gave the Code a statutory underpinning. The final section concludes.

History of Biomedical Research in Nigeria

Governance is about guidance; it denotes the structures and process (as well as their interactions) that govern the conduct of biomedical research in Africa.⁷ Thus, research governance indicates the processes by which human organizations, whether private or public, steer and regulate themselves.⁸ The study of governance involves:

• examining the distribution of rights, obligations and power that underpin organizations;

• understanding the patterns of coordination that support an organization’s diverse activities and that sustain its coherence.

Governance of research therefore entails setting standards, defining legal mechanisms to deliver standards, monitoring and assessing arrangements, improving research quality, promoting good practice, reducing adverse incidents, ensuring that lessons are learned and preventing poor performance and misconduct.9

The focus on research governance or the regulation of research involving human subjects was catalysed in Nigeria by the controversial and unethical clinical trial of Pfizer’s experimental treatment for epidemic meningitis, better known as Trovan. Out of the 200 Nigerian children that participated in the trial, 11 of them died, five on the experimental arm and six on the control arm of the trial.¹⁰ Following the Trovan clinical trial, which involved litigation both in Nigeria and the US, there were increased calls for greater scrutiny of research involving human subjects in Nigeria. In response to such calls, the federal government of Nigeria, as highlighted below, took steps to establish a comprehensive system of research ethics review in Nigeria, as well as other regulatory structures and infrastructures for research governance in the country.¹¹ However, the regulatory system was not always the way it is today.

Before Nigeria was formally colonized by Britain in the nineteenth-century, it consisted of politically independent nationalities with various systems of political organization. In that historical period, medical care was provided by means of the therapeutic armamentarium of traditional medicine, and medical research, as we know it today, was either non-existent or essentially rudimentary.¹² After the colonization of Nigeria, the colonial administrators introduced Western medical practice into Nigeria, but colonial health policy was focused on the treatment of diseases rather than research, on the colonial administrators and their personnel rather than the generality of Nigerians, and in the cities and urban centres rather than villages and rural areas.¹³ Medical treatment was extended to the generality of Nigerians, including the rural areas, only when that was necessary to control the spread of infectious diseases. After political independence in 1960, however, Nigeria continued the colonial pattern of care delivery and policy.¹⁴ Available records show that some rudimentary biomedical research activities were carried out in Nigeria during the colonial era. The first of such research could be traced back to 1841, when 48 out of 135 Europeans on expedition along the River Niger died of malaria. At that time, the connection between malaria and the mosquito had not been understood. Malaria was then thought to be caused by decaying vegetable matter until Ronald Ross made his discovery of the malaria parasite in 1898.

However, in another expedition along the River Niger organized by Macgregor Laird in 1854, Dr Blake, an army medical officer, discovered that none of the 12 Europeans involved in the expedition, and who took quinine, died of malaria infection. In 1920, the Rockefeller Foundation initiated a colonial research enterprise in the West Coast of Africa known as the ‘Rockefeller Foundation Yellow Fever Commission to the West Coast of Africa’.¹⁵ In 1925, the Yellow Fever Commission, as it was generally called, built a research unit in Yaba, Lagos.¹⁶ Few details, however, are known about any clinical trial or other activities by the Yellow Fever Commission; but, considering that ethics review was developed in the 1960s,17 yellow fever research would probably have raised only issues of informed consent.¹⁸ In 1954, the British colonial government established the West African Council for Medical Research for its West African territories of Nigeria, Ghana, Gambia and Sierra Leone under the West African Council for Medical Research Ordinance.¹⁹ The main function of the Council was to arrange for the conduct of medical research in these West African territories and to provide medical research information concerning West Africa to the British government. Legislation establishing the Council was not specific on the type of medical research to be conducted or sponsored by the Council, nor did it contain any provision relating to the ethics review of research protocols conducted under the auspices of the Council.

In 1952, the colonial government established the University College Hospital, Ibadan (UCH).²⁰ UCH was established as a teaching hospital of the University of Ibadan (then University College, Ibadan). Part of the mandate of the UCH was to carry out clinical research or other medical experimentation, though no research guideline was specifically mentioned.²¹ Following the UCH research mandate, subsequent teaching hospitals established in Nigeria were given the same clinical research jurisdiction.²² In 1972, the then Nigerian military government established the Medical Research Council of Nigeria (MRC).²³ The federal agency was responsible for the conduct of medical research in Nigeria. However, in 1977, the National Science and Technology Development Agency²⁴ (NSTDA) was statutorily established in Nigeria to advise the federal government on matters relating to scientific research and development. The NSTDA Decree repealed the Medical Research Council of Nigeria Decree of 1972. Pursuant to the NSTDA Decree, the Research Institute’s Order of 1977²⁵ established the National Institute of Medical Research in Yaba, Lagos (NIMR). The assets and rights of the MRC were transferred to the NIMR.²⁶ The NIMR is authorized to conduct medical research related to health problems in Nigeria and to cooperate with Nigerian medical schools and universities to provide the necessary facilities for training medical researchers in Nigeria. Though the NIMR is a major Nigerian institute concerned with human medicine and research in Nigeria, it has not promulgated any formal guideline for the conduct of research involving human subjects. The Nigerian Institute of Medical Research (NIMR) in Yaba, Lagos, Nigeria is the apex medical research institute in Nigeria. Until the establishment of the National Institute for Pharmaceutical Research and Development (NIPRID) in Abuja, it was the only institute in the country specifically dedicated to medical research. The institute has five research divisions, three support divisions and other essential units.

Although there was an attempt to establish a formal ethical regulatory framework and infrastructure for research in Nigeria in 1980, the system established was largely moribund until it was reconstituted by the federal government of Nigeria around 2006 through the establishment of the National Health Research Ethics Committee (NHREC).27 The NHREC is now the apex regulatory institution for research involving human subjects in Nigeria, and the NHREC also functions as the national ethics committee, alongside institutional ethics committees. In 2007, the NHREC produced the National Code for Health Research Ethics or research guidelines for Nigeria; both the Code and the existence and functions of the NHREC are statutorily underpinned by the National Health Act, 2011. This marks the origin of systematic research governance in Nigeria.²⁸ The following section thus examines aspects of Nigerian law that are relevant to the governance or regulation of research involving human subjects in Nigeria.

Nigerian Legal System and the Regulation of Biomedical Research

The Nigerian legal system is a mixture of the received common law of England and Wales, statutory law (including the Constitution), customary international law and domesticated international conventions, judicial decisions, and systems of customary laws in force in Nigeria. The English common law applies in Nigeria as part of its colonial heritage; it was statutorily received into the colony of Lagos in 1863 and later extended to the rest of the country in 1900.²⁹ A paradigmatic reception clause is section 45(1) of the Interpretation Act, which provides that ‘the common law of England and the doctrines of equity and the statutes of general application which were in force in England on 1st January, 1900 are applicable in Nigeria, only in so far as local jurisdiction and circumstances shall permit’.³⁰

Through the reception clause therefore, the English common law doctrines relevant to biomedical research such as confidentiality, consent, duty of care and, arguably, ethical and moral principles, such as autonomy, non-maleficence, beneficence and justice, have been received into Nigerian law, of course subject to any relevant local circumstances or applicable legislation. This suggests that until the promulgation of the National Code for Health Research Ethics (Nigerian research guidelines) in 2007, and the National Health Act 2011, which put the conduct of research involving human subjects in Nigeria on a statutory basis, biomedical research in Nigeria was regulated under the principles of common law and certain international ethical guidance documents, such as the Declaration of Helsinki, and Council of International Organization of Medical Sciences.³¹ As highlighted below, however, some local legislation has been relevant in the regulation of biomedical research in Nigeria.

Nigeria operates a federal constitution (1999), that is, a constitution which provides for the division of powers among the constituent elements of the federation,32 particularly between the federal and the state governments. The Nigerian Constitution is supreme to all other laws in Nigeria.³³ While there are no express and direct provisions in the Nigerian Constitution relating to the conduct of biomedical research, the fundamental human rights provisions in Chapter IV of the Constitution might be relevant.³⁴ In addition, Chapter II of the Constitution provides for economic, social and cultural rights, characterized as the Fundamental Objectives and Directive Principles of State Policy; the rights under Chapter II of the Constitution are non-justiciable in contrast to civil and political rights under Chapter IV.³⁵ Interestingly, Chapter II of the Constitution contains significant state objectives, and policies for their implementation, that are relevant to the conduct of biomedical research in Nigeria. For instance, section 14(2)(b) states that ‘the security and welfare of the people shall be the primary purpose of the government’. Similarly, section 17(2) is committed to a social order in which ‘(b) the sanctity of the human person shall be recognized and human dignity shall be maintained and enhanced; … (d) exploitation of human or natural resources in any form whatsoever for reasons, other than the good of the community, shall be prevented’. In the same vein, section 17(3)(d) enjoins the state to ensure that ‘there are adequate medical and health facilities for all persons’. Although these and other rights in Chapter II are not directly enforceable,³⁶ they serve interpretive functions, in that they could be deployed to expound the provisions of other laws in Nigeria, especially Chapter IV of the Constitution.³⁷

Furthermore, Nigeria has domesticated the provisions of the African Charter on Human and Peoples’ Rights, whose human rights provisions are now directly enforceable in Nigeria.³⁸ The African Charter adopts an integrated approach to human rights protection, rather than the bifurcation under the Nigerian Constitution into civil and political rights, on the one hand, and socioeconomic and cultural rights, on the other hand. However, the African Charter does not contain specific provisions for the protection of research subjects. This contrasts with Article 7 of the International Covenant on Civil and Political Rights, which provides that ‘No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment. In particular, no one shall be subjected without his free consent to medical or scientific experimentation.’³⁹ However, some provisions of the African Charter, particularly Article 16, might be relevant to the protection of research subjects. According to Article 16:

Although the provisions of the African Charter have been criticized for being only progressively realizable, on account of the inadequate resources available for their implementation,40 Article 16 above is arguably prone to immediate enjoyment, at least to the extent that it affects the conduct of biomedical research. Thus, in view of the provisions of the African Charter and Chapters II and IV of the Nigerian Constitution, the conduct of research involving human subjects in Nigeria might attract constitutional protections relating to the dignity of the human person, life and privacy. Note that the suggestion above assumes that the Nigerian Constitution has a horizontal application, an interesting but controversial issue analysed in detail elsewhere by one of us.⁴¹

The right to dignity