Shaping Policy for Human Challenge Trials
Recent outbreaks of Ebola and Zika virus have exposed the dangers posed by emerging infectious diseases and the need for epidemic preparedness for potential future threats. Lawyer and bioethics faculty Seema Shah, along with bioethics faculty Stephanie Kraft and bioethics staff member Devan Duenas, are studying the ethics of research on emerging infectious diseases, and has worked on issues related to the recent Ebola and Zika virus epidemics. In the Ebola epidemic, many questions arose about whether or not unproven interventions should be used outside of research, given the relatively high mortality for people infected with Ebola and the limited treatment and prevention options. Some high profile cases of treatment with experimental interventions led to claims of injustice.
Based on lessons from previous outbreaks, organizations such as the World Health Organization (WHO) and the National Institutes of Health (NIH) recognize an urgent need for research to develop effective interventions for emerging infectious diseases. There are several ethical issues that arise, including:
- When can novel and controversial research designs be used ethically?
- When should experimental medications be made available to individuals who are not enrolled in the research?
- How should we protect and respect participants given the limited time and capacity to conduct and review research?
- How should we engage communities?
Shah believes that although patients may have good reason to try unproven interventions when there are few alternatives, there are many reasons not to offer these interventions, including limited time, resources and concerns about doing more harm than good.
Shah served as chair of a group of experts from various disciplines and federal agencies who provided recommendations on the ethics of Zika virus human challenge trials. In these trials, researchers deliberately expose healthy volunteers to infectious diseases. There is a long history of successful challenge trials, which can be powerful tools to efficiently study new vaccines and treatments. In a famous example from 1796, Edward Jenner’s research ultimately led to the smallpox vaccine. Although researchers have proposed conducting Zika human challenge trials, these types of trials are ethically complex and understudied. Systematic ethical analysis of challenge trials is relatively recent and has been limited in scope and application.
The committee’s report, Ethical Considerations for Zika Virus Human Challenge Trials, stated that while Zika human challenge trials could be ethically justified, their final recommendation was that it would be premature to proceed with at present given the unknowns about the Zika virus.
The committee encountered some questions that they did not have time to fully explore. For instance, are volunteers in these challenge trials vulnerable, or do they understand the risks and have good reasons to participate? Shah plans to build on the committee’s ethical analysis by empirically studying the motivations of volunteers in challenge trials.
Additionally, the committee did not have time to develop a comprehensive framework to determine when and how these trials are ethically acceptable. With funding from The Greenwall Foundation, she is working with stakeholders, researchers and ethicists in collaboration with the WHO, NIH and the nonprofit organization PATH to develop such a framework for the use of human challenge trials in emerging infectious diseases. This framework will address unresolved questions from her work on the Zika report, such as:
- Is it better to conduct a Zika virus human challenge trial in a region that doesn’t face the threat of a Zika virus epidemic and the risks involved, or one that does?
- If there is a risk that a disease studied in a challenge trial might spread to some members of the community, what level of risk is acceptable, and how can that risk be ethically justified?
“This work has the potential to advance key issues in research ethics, develop ethical preparedness for future outbreaks of emerging infectious diseases, and strike the delicate balance necessary between protecting and respecting human subjects and communities while also conducting valuable research.”
This project aims to develop a comprehensive ethical framework for conducting human challenge trials on emerging infectious diseases.
- Ricardo Palacios, Butantan Institute, Colombia
- Annette Rid, King’s College London
- Abha Saxena, World Health Organization
- The Greenwall Foundation
- Bioethics Research Incubator Program, Treuman Katz Center for Pediatric Bioethics