Although human challenge studies in infectious disease are not considered unethical, they should be subject to especially rigorous oversight because of their risky nature compared with other types of studies conducted in healthy individuals. Researchers examined the ethics of human challenge studies in an opinion piece published in Public Health Ethics.
The history of medical testing is fraught with examples of unethical experimentation conducted by the Nazis during World War II. Yet when conducted ethically, such research is invaluable for advancing medical science — particularly for fast tracking the development of vaccines.
Ben Bambery, MD, of the Faculty of Medicine, Nursing and Health Sciences at Monash University in Victoria, Australia, and colleagues delved into the ethical issues associated with infection of healthy volunteers for scientific research. They note that infectious diseases still cause more than 13 million deaths annually and stress the importance of continued research to prevent such deaths.
Barriers to challenge studies include ethical guidelines indicating that the generation of scientific knowledge should never supersede the rights and interests of research subjects. Dr Bambery and colleagues argue that it is permissible to expose subjects to necessary risks for scientific purposes only if those risks are reasonable, if there is adequate compensation for any harm incurred, and if the subjects are able to consent voluntarily to participating in the research.
The authors believe challenge studies must be subject to evaluation by an ethics review committee and should involve equitable selection of study participants as well as have an acceptable balance of benefits and harms. They also argue that these studies must have a publicly available rationale for research and measures to protect the public from the spread of infection beyond the research setting.
In their article, Dr Bambery and colleagues review 2 cases involving human challenge studies and the issues involved in each. The first case examined the inoculation of 8-year-old James Phipps with both cowpox and smallpox by Edward Jenner in 1796. Ethical problems here include issues of valid consent and risk, as the procedure could have resulted in the child’s death. However, because Phipps lived in an area with a high rate of smallpox infection, vaccination may have prevented his death. Furthermore, Jenner’s challenge model led to the development of a vaccine — and ultimately the eradication of smallpox — saving millions of lives.
The second case involves current malaria vaccine challenge studies. Vaccinated, healthy adult volunteers are exposed to malaria-causing parasites and monitored for signs of infection, then treated with a curative regimen of antimalarial drugs if malaria develops. The researchers can evaluate the safety and ability of the vaccine to prevent malaria, as well as the immune response to the vaccine. Risks to volunteers include the development of malaria and adverse reactions to the vaccine. The researchers note that in contrast to the Jennings case, where challenge participation may have prevented the contraction of smallpox, healthy volunteers in the United States, United Kingdom, and The Netherlands may not otherwise be exposed to malaria, therefore limiting the medical benefit they receive.
The authors conclude by noting that the challenge model remains one of medicine’s greatest weapons against infectious disease.
Bambery B, Selgelid M, Weijer C, Savulescu J, Pollard AJ. Ethical criteria for human challenge studies in infectious diseases. Public Health Ethics. 2016;9(1):92-103.