Physicians in Clinical Research and Physicians in Clinical Care
Research physicians dedicated to finding the cause, prevention, and treatment of diseases may find themselves in a position of conflict of interest when conducting research in income poor countries. As new and exciting treatment discoveries proliferate and are coupled with dramatic increases in funds for clinical research, an unprecedented demand for clinical research studies has occurred precipitating an intensified search for thousands of research subjects.
All physicians, whether engaged in clinical research or clinical care have an ethical responsibility to act in the best interest of their patients, providing them with the best standard of care and protecting them from harm. While there are some differences in conducting clinical research and in providing care for patients, the ethics of research and medicine uniformly demand that the interests of the patients be primary. They cannot be secondary to scientific, economic or national agendas. Conflicts arise when physicians participate in research that is either of no direct benefit or is harmful to the research subjects.
The circumstances can be best understood by contrasting the treatment of HIV infected individuals in an income rich country by a research physician and the treatment of an individual in a clinical research study with the same disease by the same physician in an income poor country. Ethically they should be treated in same manner as the obligation to provide the best treatment available extends beyond geographic and economic boundaries. (It cannot be argued that lesser treatment is adequate because the drugs for proving standard of care are not available in the income poor country as it is the funding organization’s responsibility to provide the necessary treatment.) But let us suppose that the same physician is now responsible for conducting a clinical research study in an income poor country and in order to achieve a statistically significant research result in evaluating a new treatment, instead of comparing it to standard of care, a comparative study of placebo vs the experimental drug is conducted. 50% of the research subjects would receive placebo and would be followed until they either progressed from HIV to AIDS, or if a prevention study, until they became HIV infected. The research physician would be deliberately withholding known effective treatment from half of the research study participants knowing that HIV infected individuals would progress to AIDS, or if uninfected, would become HIV infected. In contrast, there would be no justification for withholding treatment in either an income rich or income poor setting by the clinical physician as the objective would be to prevent progression to AIDS or prevent HIV infection.
An obvious conflict of interest exists. The clinical researcher wants the new treatment to be effective and so comparing it to a placebo makes it more likely that a difference will be found. The clinician on the other hand wants to be certain that treatment prevents progression of disease and prevention of infection and so offers the best treatment available to all individuals. As improbable as it seems, a research physician is engaged in deliberately denying effective treatment to 50% of the research population under evaluation to facilitate research study results. In contrast a clinical physician is desirous that all of the patients remain well and HIV uninfected.
Oddly, the discovery of the effectiveness of highly active antiretroviral therapy (HAART) in the late 1990s and the proliferation of new discoveries for treatment precipitated a crisis in clinical research study design. More drugs needed to be studied and more research subjects were needed to test a drug’s effectiveness. Further, if HAART were capable of preventing the progression of HIV to AIDS and preventing more than 90% of new HIV infections it would be a formidable obstacle to determine whether a new experimental treatment was superior to HAART without either reverting to placebo-controlled studies or comparing the a new treatment to a previous, but now inferior, treatment. This is precisely what happened in the US research community requiring a revisionist approach to the ethical conduct of research in vulnerable individuals in income poor countries.
The rationalization for developing two standards of care for clinical research, one for income rich countries and one for income poor countries, was that many of the treatments that had been approved for HIV were unavailable in income poor countries and therefore clinical researchers were justified in offering placebo or inferior treatment to individuals in poor countries. There are many ethical difficulties with this argument.
1) Ethical guidelines require that research be of benefit to individuals and that placebo only be used when no other proven treatment is available.
2) The deliberate selection of individuals for research from income poor countries results in exploitation of vulnerable research subjects.
3) Even though certain treatments are not available in the country where research is conducted, the funders of the clinical research study should provide standard of care.
4) Informed consents are deceptively modified to suggest that the standard of care for HIV is different in an income poor country perverting the definition of standard of care.
5) Physicians from the US engaged in clinical research in income poor countries put aside US-based ethical standards in order to participate in research which utilizes placebo or inferior treatment.
6) Physicians who argue that because a treatment is not available in an income poor country and therefore an inferior standard of care can be employed are complicit in supporting the policies of failed states where the provision of healthcare is secondary to other political agendas.
A final argument used by clinical researchers to justify research of no benefit to the volunteers or for evaluating drugs that would not be available to them after the research study is completed, but readily available to individuals in income rich countries, is that they are participating in research that would be of potential “benefit to mankind.” This argument is nothing short of disingenuous. Why would an individual from a setting of poverty and limited health-care access participate in a study that might be of risk to them but not have any direct benefit, but have benefit for those in income rich countries who never participated in the risks of research? And what of the career and economic benefits accrued to the clinical research investigators and their institutions? It is doubtful that individuals experiencing severe cultural, social, political, and economic disparities understand the concept of “benefit to mankind”.
No matter what ethical or scientific rationalizations are devised for conducting studies of placebo or inferior treatment in income poor countries, a physician should not be able to, on the one hand, provide the best standard of care for patients at risk for HIV disease progression in a research study in a wealthy country, but simultaneous deny the same treatment to individuals just because they are poor or vulnerable.