Undue Inducement in
Internationally Sponsored Research

Paul Ndebele

In terms of their potential for research, developing countries appear to be especially attractive places for scientists. Yet scientific research in developing countries brings with it many challenges for the application of the standard ethical principles involving respect for persons, beneficence, nonmalificence, and justice. What is now emerging is the fact that there are different issues both about the societies and about related ethical questions and dilemmas that people conducting research in developing countries must understand. The goal of this paper is to highlight some of the problems ethics committees in developing countries face in trying to operationalize the use of incentives in human research in a fair and noncoercive way. The subject of incentives has received a lot of attention from bioethicists because of fear that if not handled appropriately, incentives may degenerate into other problems. I approach this topic from an African perspective and, in the end, recommend operationalizing incentives as a way of mitigating some of the ethical dilemmas of international research.

I begin by acknowledging that incentives are not inherently bad. In fact, since research participation can be considered a form of sacrifice, incentives can often be seen as an appropriate gesture of appreciation. More than being dichotomously good or bad, incentives are necessary as a way of encouraging individuals to agree to participate in a trial and to remain in it until the end. The phrases—“money enables participation” and “time is money”—accurately reflect the necessity of paying research participants in order to secure their participation. The need to pay research participants raises the following question: What is the value of time for the person in the study? Incentives become problematic if this question is not appropriately addressed. Specifically, incentives become bad when they sway decisionmaking capacities of individuals by forcing them to ignore risks involved in the trial and to instead only consider the attractive cash amount or gift being offered.

Before continuing my discussion of incentives, it is important to distinguish incentives from compensation and reimbursements. Compensation in research is simply reimbursement for costs incurred while participating in a study. Some types of compensation are more straightforward and thus easier to address than others, including reimbursements for meals, babysitting, and bus fare to and from the research site. Compensation for time spent at the research facility, in contrast, is more difficult to calculate since it has to do with the individual value of one’s time. The value of a person’s time depends on a variety of factors such as local economic conditions as well as individual personalities. In similar circumstances, due inducement varies among people: for example, the circumstances may be due inducement for one person, but not another. Two other types of compensation that are difficult to calculate for similar reasons are payments for pain and inconvenience. Such payments are typically based on a participant’s cooperation in a scientific program, but may also be based on the sale price of the participant’s blood sample, bodily tissues, or bodily fluid. Much literature already exists on these two additional subjects, and so I do not pursue them here. Importantly, incentives also need to be differentiated from reimbursements which give back to trial participants any of their own money or resources that they used in order to participate in a trial.

When compared to both reimbursements and compensation, the use of incentives presents a greater challenge to investigators and ethics committees since incentives require deciding not only what form the incentive should take, but also how much of the chosen form is given. To clarify, when using the term incentive, I am not referring to reasonable payments made to subjects for their participation in research or for the costs they incur as part of the trial. Rather, I am using this term to highlight the use of special incentives or bonuses provided to research participants as a mechanism for encouraging them to join or to remain in a study. Incentives, as I have just defined them here, are used to ensure that clinical research studies gather sufficient sample size necessary to maintain statistical power. If not used appropriately, incentives can have undesirable adverse effects for participants, such as eroding the informed consent process. In contrast, reimbursements and compensation do not typically lead to such problems. A reason for this differential experience is that payments for participation to research participants are not considered a benefit, whereas incentives usually are. For example, financial incentives are often used when health or other benefits to participants are remote or nonexistent.

While a large literature exists on the issues of compensation and incentives for participating in research, little has been written on compensation and incentives specifically within international research contexts, especially on research sponsored by developed countries that is conducted in developing countries (only) or alternatively is conducted in both types of countries. Justice and fairness are central concepts for discussion of compensation and incentives, and the centrality of such concepts are even more compelling in the case of international research. Of particular concern here is potential exploitation of a weaker party by a stronger party. With the expanded practice of developed countries sponsoring international research in developing countries, developing country ethics committees increasingly fear unwarranted exploitation of their populations. As compared to individuals from developed countries, individuals in developing countries are more easily compensated and incentivized. As such, developing country committees grow increasingly concerned that their populations will be used as cheap sources of data in research not intended for internal benefit, but instead to benefit developed countries.

I turn now to address issues of fairness in compensating and incentivizing research participants in international research specifically from the viewpoint of developing country ethics committees. I argue that because trial participants from developed countries and developing countries share equally in the burdens of research, we must have just and fair decisions regarding compensation and incentivization of developing country research participants.

Incentives can be examined from two levels: the micro level in which research participants actively participate in the research and the macro level in which communities or countries participate in research. At the micro level, incentives work either to encourage people to join a study or to persuade them to remain in a study so as to serve the aforementioned need to retain a statistically significant and valid number of participants. Risky research or research that is not of direct and immediate benefit to the individual can apply at both levels mentioned. There are strategies that investigators may use to incentivize potential participants to join or stay in trials including bonuses, raffles for prizes, grocery vouchers, cash, T-shirts, caps, food, drinks, gifts, and gift cards. It is important to note that in developing country settings such incentives may easily be viewed as undue inducements. Whereas developed country researchers might consider a T-shirt a simple gift, poverty-stricken community members may alternatively view it as a once in a lifetime treasure not to be passed over.

Returning to the issue of compensation, the notion that participants should be paid for inconveniences, such as time spent and reimbursement for expenses is uncontroversial. What is instead up for debate, and is in fact often overlooked, is the importance of ensuring that payments are realistic relative to the local economy. Indeed, it is crucial that payments are not so large so as to induce prospective subjects to consent to participate in research against their better judgment. Potential trial participants need to be provided with information about the research, including its attendant risks and benefits, sufficient to reach an informed decision regarding their voluntary participation. Researchers must ascertain if the payment levels or chosen material goods have unintended consequences, such as being coercive or resulting in undue inducement. Unfortunately in a developing country setting all such precautionary measures ultimately may not achieve their set goal. Too often, researchers in developing countries are faced with poor, hungry, and unemployed community members who, as a consequence of such impoverished circumstances, might instead view participation in a clinical trial as a way of earning quick money for survival.

The root cause of problems associated with the use of incentives in developing countries is poverty. The degree of poverty is especially high among those communities typically approached to participate in research and the perplexing problem of undue inducements is a direct consequence of such impoverishment. Potential participants are by circumstance forced to consider the benefits and ignore the risks associated with a study. Amounts offered to participants as compensation might appear reasonably noncoercive to sponsors and participants in developed countries, but prove irresistible in developing countries. For example, consider a $150 incentive. That amount may be regarded as appropriate, noncoercive, and noninducive in a developed country setting. However, that same amount represents up to a year’s earnings in a developing country. Advertising for clinical trials in developing countries is not openly posted on notice boards and in local newspapers. Successful recruitment is instead based more on power differentials between investigators and ordinary community members, trust of the authoritative medical profession, as well as the notion found in some cultures that declining an invitation is simply rude and unfriendly.

In general more participants are successfully recruited from developing country sites than from developed country sites. The two main reasons for this both stem from poverty. First, as already discussed, there are large numbers of potential participants in developing countries who are willing to join to make some quick cash (as well as for other reasons). Second, because the cost of compensation and incentives is less expensive per person in developing countries than developed countries, researchers can compensate and incentivize many more people in the developing world with a given amount of money and material goods than they could in the developed world. Let’s consider a realistic example: 300 developed country participants and 1500 developing country participants are being paid $300 and $40 respectively as compensation for time and inconvenience and as incentives to remain in the study. This large pay difference between developing world participants and developed world participants is simply too obvious and unfair at both the individual and community/country level. Since research pragmatically contributes to development and international relations, sponsoring countries and researchers should be cognizant of current and historical exploitation of developing countries by developed countries. By participating in the global processes of income redistribution, current health research should ideally play a part in redressing imbalances.

I support a practice whereby resources are channeled through research grants into community development efforts. This channeling would provide an ethical way of dealing with the 10/90 gap, as it represents an effective form of income redistribution from developed countries to developing countries without having to expose individual participants to undue inducement. That is to say, in the interest of protecting individuals in developing countries from undue inducement, some of the benefits of internationally sponsored trials should, if possible, be converted into community benefits, such as supporting local clinics or engaging in other community projects that promote good health; resultant benefits can then be enjoyed by all individuals within that community. Health research is about a few individuals sacrificing for the benefit of humankind. In that same vein, the self-sacrifice of the few individuals who participate in trials can result in the common good of those communities.

In addition to locally sponsored research, some African countries have internationally-known research centers sponsored by agencies from developed countries. Those research “centers of excellence” are situated largely in poor rural areas but with stable populations; all major studies within those countries are then conducted in such centers and their surrounding areas. Notably, due both to currency weakness in developing countries and to the limited resources set aside for health research, locally sponsored studies do not often offer incentives equal to those made available through internationally sponsored research. There have been reports of individuals who refuse participation in locally sponsored research because they feel that such research is poorly incentivized. They have grown accustomed to receiving cash incentives and other attractive gifts for participation in internationally sponsored trials. As individuals favor the better paying internationally funded trials, this disparity has then led to deterioration in the quality of locally sponsored research.

In the interest of protecting locally funded research, I think certain benefits from internationally sponsored research should be converted into community benefits; this might include supporting clinics, wiring community centers and schools with electricity, installing boreholes or piped water, and engaging in other community projects that promote good health. Funds from research grants could also be used in training and adequately remunerating personnel from developing countries as well as in technology transfer to those countries. Such strategies might then reduce the current brain drain to developed countries and could also reduce the exportation of specimens to developed countries “for further analysis.” Moreover, such recommendations might then further the ultimate aim of improving developing countries’ capacity to conduct research that directly addresses their own needs. One way of ensuring that locally funded research trials do not suffer at the hands of internationally funded research is to set strict, regulated levels of incentives to be adhered to by both locally funded and internationally funded trials. A percentage of the budget for internationally funded trials might then be diverted to other health promotion activities or to programs for those communities participating in such trials.

In this paper I put forward a view that at both the micro and macro level, compensation and incentivization for participation in research is the most fair and just procedure. Compensation and incentives should not only be monetary, but could also take the form of technology transfer (e.g., scientific, technical, and medical training, and installation and ongoing maintenance of infrastructure of laboratories, clinics, libraries, and other facilities). I end with one additional suggestion. Research ethics committees in developing countries need to be sufficiently strengthened so that they have the capacity to make informed decisions on negotiating compensation, individual incentives, and community benefits for their communities. The ethics committees should review advertisements, recruitment, and payment incentives associated with all studies to ensure that they are consistent with prohibitions on coercion and undue influence and so that internationally funded trials do not unduly affect individuals’ willingness to participate in locally funded research. In order to achieve this end, research ethics committees must critically examine the population of the potential participants, the incentives, the conditions under which offers will be made, and the incentives offered for participation by other trials conducted in their area. Lastly, ethics committees should encourage investigators to consider community benefits and other associated ways of ensuring that communities and institutions realize greater benefit from participation in international research.