An Ethical Principle to Prevent Exploitation of Vulnerable Research Subjects.

In 1865 Arthur Charles Ducat writing in “The Practice of Fire Underwriting” articulated the concept of moral hazard applying it to the risk insurance companies undergo proceeding from destruction of property by fires. After observing suspicious fires on insured properties he suggested that some policyholders might be “saturated with immoral character” because they committed arson for the purpose of collecting insurance settlements by means of fraud. 

The economist Paul Krugman defined moral hazard as “…any situation in which one person makes the decision about how much risk to take, while someone else bears the cost if things go badly.” In the field of economics an example would be financial bailouts of leading institutions by government funding (AIG, Citibank, Chrysler). The term “too big to fail” reflects the concept of moral hazard when protection is given to the large and powerful while failing to protect the small and weak.

Medical history is replete with examples of the use of slaves, poor women, women of color, children, orphans, prisoners, mentally impaired persons, and soldiers for experiments, frequently without permission or informed consent. Based on the concepts articulated in more recent definitions of moral hazard, individuals in these categories would be considered disadvantaged and captive. Further they represent examples of asymmetry in two important additional principles related to moral hazard — asymmetry in information and power and asymmetry in benefit versus risk.

Following the public disclosure of the egregious experiments conducted by physicians in Nazi Germany and equally unethical studies on black men with syphilis in Tuskegee, Alabama, and captive populations in Guatemala that withheld treatment, two major documents were developed to protect human subjects from research abuses — the declaration of Helsinki and in the US Belmont report. However, dramatic increases in new treatment discoveries and the complex science involved, coupled with distinct political, ethical, social, economic, and cultural differences when research in resource poor countries has brought into question the ability of IRBs to fulfil their fiduciary responsibilities.

Vast differences in education and power occur when US researchers have more information about their actions and intentions than research subjects. The researchers may receive significant benefits from conducting the research but are able to protect themselves from the consequences of failure while the vulnerable and less informed research subjects assume the burden of failure. Thus, if the interests of the researcher and the research subjects are not aligned, the researches may have an incentive to act inappropriately (unethically). Two US sponsored clinical research studies in resource poor countries have mimicked the Tuskegee study by withholding treatment from captive populations that are vulnerable to exploitation. The South African study, called Children with HIV Early Antiretroviral Randomized Trial (CHER), delayed antiretroviral treatment in HIV-infected infants until they progressed to advanced disease and or death. The VRC01 (an acronym for an experimental highly neutralizing monoclonal antibody to HIV) withheld treatment from infants at high risk of acquiring HIV from their infected mothers until the experimental product, of no known benefit in humans, could be evaluated.;

Both of the studies were approved as ethical by the National Institutes of Health and the IRBs of the academic institutions to which the research investigators belonged. The individuals and organizations that determine the ethics and scientific merit of clinical research studies (IRBs) benefit financially and professionally from the research but are not at risk for any harm. It is apparent that they do not take into consideration principles of moral hazard — the vast asymmetry in power and information and benefits held by the US researchers versus the research subjects in developing countries.

Reinterpretation of fundamental ethical principles and guidelines has resulted in approval of US clinical research studies that violate the autonomy and dignity of research subjects. Current guidelines and rules as interpreted by US researchers, IRBs, and government agencies have not prevented unethical research studies from being conducted in resource poor countries.  The application of the principle of moral hazard to identify circumstances of asymmetry of power and information and benefit vs risk between researchers and research subjects is a necessary additional consideration to prevent exploitation of vulnerable individuals.