The Ethics of Outsourcing

There has been a growing trend for drug companies to outsource clinical trials; the human studies that determine the safety and efficacy of medicines.

Now, as reported in the New York Times, an article about the globalization of clinical trials is raising questions about the ethics and the science of increasingly conducting studies outside the US, when the studies are meant to gather evidence for new drugs to gain approval in this country.

The article, “Ethical and Scientific Implications of the Globalization of Clinical Research,” by several Duke University researchers, suggests an ethical quagmire when drugs intended for wealthy nations are tested on people in developing countries. The authors suggest that human volunteers in foreign countries may be unduly influenced by the promise of financial compensation or free medical care to participate in clinical trials.

The report also asks whether drug research conducted in developing countries is relevant to the treatment of American patients. The authors write that drug research in developing countries, where certain populations may metabolize medications differently because of environmental factors or genetic mutations, might not be relevant for American patients.

Some critics say the authors used overly simplistic data mining to raise an alarm, without presenting hard evidence of widespread ethical or scientific problems. I also have a few observations of my own; some in agreement and some in disagreement with the Duke authors' statements.

The Duke authors are warranted in their worries about volunteers from developing nations being unduly influenced by financial compensation and free medical care. Many of these nations are poor, and the volunteers may be viewed as particularly vulnerable. However, the Declaration of Helsinki, recognizes the need for special protection in vulnerable populations; this protection comes in the source of the clinical trial protocol.

The protocol must include, among other things, information regarding potential conflicts of interest, incentives for volunteers, and provisions for treating and/or compensating volunteers who are harmed as a consequence of participation in the research study. This protocol must be reviewed and approved by an independent research ethics committee before the study can even begin. If the volunteers' health and rights would be subjected to malbeneficience or injustice in any way, then the protocol would be rejected.

Protocol reviewers must take into account the risks involved with the study and weigh those risks against the benefits. If the only benefits for the volunteer are monetary, then researchers are conducting an unethical trial. Participation in risky trials warrants a greater monetary compensation, and volunteers outside the US may be vulnerable because they will accept less money than an American would expect; however, how can one put a monetary value on someone's life?

Medical research involving a disadvantaged or vulnerable population is only justified if the research is responsive to the health needs and priorities of this population and if there is a reasonable likelihood that this population stands to benefit from the results of the research.

I also agree that volunteers may be unduly influenced by free medical treatment. It may be enticing to participate if the volunteer is offered free medical treatment; especially for patients who would never have received treatment at all. However, do the risks of the trial outweigh the benefits of a check up or treatment?

Duke authors also brought up the topic of relevance. Relevance may be a factor when studying safety and efficacy in different age groups, but I feel that, in many instances, relevance is a non-factor because we are all humans. However, populations that are underrepresented in medical research should be provided appropriate access to participation in research.

For example, in many clinical studies based in the US, the majority of participants are Caucasian. However, aren't there many other races/ethnicities represented in the US population? What if the Duke authors are correct, and a drug may have a different effect on African Americans because of mutations such as Sickle Cell Anemia? Wouldn't it prove to be beneficial to go outside the US and enroll subjects of that race/ethnicity?

The authors also questioned the relevance of testing outside the US because they feel that certain populations may metabolize medications differently because of environmental factors. If we are to believe this statement, then should we perform separate clinical trials within the US for Americans in Hawaii (tropical rainforest climate) as well as for Americans in Alaska (subarctic/tundra climate)? Where does it end?

The authors also seem to treat all foreign countries alike. Research conducted in some places outside the United States, like Canada and Sweden, might be perfectly relevant to American patients. For example, a clinical trial of the Merck drug Gardasil, a vaccine against the human papilloma virus, was conducted in Costa Rica, where there is a high incidence of the disease.

Whatever the interpretations, the use of offshore clinical trials is growing, and physicians must be conscious of the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards; and no national or international ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects.