Ethical international research on human subjects research in the absence of local institutional review boards

Abstract

International health‐related research on human subjects entails unique ethical responsibilities and difficulties. Often, these difficulties are augmented by the lack of a local ethical review infrastructure. In a recent cross‐national study conducted by us, three critical components of ethical regulation were identified—external oversight, local oversight and subject involvement—and integrated into the study design. These three concepts are outlined and established as an important aspect of ensuring ethical coherence in the local context, particularly when reviews by the local institutional review boards cannot practically be obtained. The three levels of ethical oversight identified are suggested to be the framework within which future field studies on human subjects are developed and a standard for maintaining ethical rigorousness in research on humans.

People in the developing countries are increasingly becoming the focus of studies originating in developed countries; such international research brings greater ethical responsibilities. Institutional review boards (IRBs) play an important part in the regulation of research on human subjects, and prior review and approval of a proposed study by an independent review board or ethics committee is an internationally accepted ethical standard.¹,² As varying cultural and social circumstances are encountered by international projects, reviews by both the IRBs of the sponsoring institutions and a local IRB are important in helping to ensure that ethical issues are considered in the local context.³ The ethical review infrastructure in developing nations, may, however, be ineffective or non‐existent;⁴ in such situations, particular care must be taken to ensure the ethical coherence of the study.

We recently faced such a challenge with a proposal for an independent, non‐experimental health status study in an isolated tribal village in Karnataka, India. The study included a sociological and anthropological survey of each family in the village, evaluating family medical history, examining each person for symptoms of current acute or chronic illnesses, and collecting morphological statistics, but involved no invasive techniques. Participation was completely voluntary, with no incentives or compensation provided. Indian policy on biomedical clinical trials originating outside the country, although not necessarily effective in practice,⁵ is fairly well defined, and in theory comparable with the systems in developed nations. Although suggested guidelines exist,⁶ there is a limited formal ethical review infrastructure in place for non‐invasive research on human subjects. In the effort to have our proposal reviewed by an IRB in Karnataka, we discovered that many Indian research institutions that conduct research on human subjects had no functioning IRB system. Meetings of existing IRBs were sporadic, and most were unwilling to review independent international research proposals; some indicated that they would be unable to convene unless financial support was provided, which would have resulted in a major conflict of interest. Moreover, from an international perspective, information on the options for ethical review in India was acutely scarce. Obtaining an effective approval from the local IRB in this case seemed improbable.

Nevertheless, the study was designed in anticipation of such shortcomings. To ensure that the proposed research was ethically coherent with regard to established standards in the US and in the local context, three fundamental principles were explicitly identified a priori to the delineation of study details, and were taken into account in planning.

External oversight

A research proposal on human subjects should be created in accordance with ethical guidelines of a high standard and be reviewed and approved by at least one effective IRB. Our study proposal was designed in accordance with both US and international ethical guidelines,¹,²,⁶,⁷ and was reviewed and approved by the IRB at Princeton University, New Jersey, USA. Though a local IRB review could not be obtained, the American IRB was made cognisant of potential local concerns by us, and was requested to be critical of the proposal in light of its international context.

In the specific situation of our sample population, one of the authors was well qualified to bring potential concerns to light; this may not always be ideal, however, as researcher bias may exist in some cases. In future studies of this kind, we suggest that a third‐party academic “expert” on the culture of the study population is consulted by the foreign IRB, independent of the influence of the researchers; as with obtaining IRB approval, it would be the responsibility of the researchers to ensure that this is done.

Local oversight

Research on humans should be designed and conducted in conjunction with a subject advocate, preferably one who is knowledgeable of the culture and customs of the participants, and with the scientific basis and methods associated with the study. Our study was carried out with a doctor (one of the authors) who has played an integral part in the gradual betterment of the village for the past three decades, and with the support and continued involvement of a local tribal welfare non‐governmental organisation that works within the village. We believed this combination to be appropriate in our case, as the selected sources of local oversight are the foremost proponents of the villager's rights. Doctors, however, hold considerable power over study populations because of the very nature of the doctor–patient relationship, and reliance on local doctors for oversight may not always result in protecting the interests of the subjects. In future studies, we would suggest that researchers carefully draw local oversight from more objective subject advocates with restricted influence on the study population, such as local non‐government organisations or social activist groups.

Involvement of subjects

Ideally, subjects should not be limited to serving as the source of data but should also participate in voicing issues that need to be considered in study design and in gauging the importance of the results to the study population; representatives from the sample population should be presented with the study proposal for their input before the start of data collection. Our study was designed with the input of villagers, and the proposal was presented to and approved by village representatives before data collection. Furthermore, representatives of the sample population worked closely with and guided researchers during data collection on site.

In retrospect, we are confident that our study was completed in an ethically sound manner and was highly sensitive to potential local issues. The three identified aspects with which the study was carried out were consistent with the rigour expected from a review by a local IRB. Support from the village before, during and after the study was strong; the general sentiment towards the study by participants was positive. The scientific results may contribute to the universal understanding of the interaction between poverty, nutrition and health (to be submitted for publication), but, most importantly, they were recognised by participants to be specifically useful to the village and to have shaped the village's plans for future self‐development.

Ethical review by a local IRB remains an important aspect of international research projects on human subjects, and obtaining a dual review in cross‐national proposals is of utmost concern to researchers. We emphasise our recommendation that systemic support should be provided to establish an infrastructure for ethical review in developing nations;⁸ however, this may take some time and, particularly for non‐clinical health‐related studies, obtaining a review by a local IRB may not always be practically possible. Our experience suggests that all studies on human subjects, regardless of whether approval by a local IRB is obtained, should be structured within the framework of the three identified principles of regulation. Establishing external oversight, local oversight and the involvement of subjects are important components of a study that will help in ensuring that research on human subjects is carried out in an ethically appropriate manner. Adherence to these principles in our study was facilitated by access to, familiarity with and cooperation from the research population, and although in other circumstances these conditions may be more difficult to uphold, they none the less should be an indispensable part of research on human subjects. Such an approach is especially important in projects that cross cultural boundaries or entail marginalised populations, where considering ethical issues in the local context is absolutely critical. We hope that our experience will serve as a positive example of the ethical standards with which international research on human subjects should be conducted and will help highlight the importance of ethical considerations in such studies.

Abbreviations

IRB - institutional review board