Shah 220x180

Seema Shah, JD

Recent outbreaks of Ebola and Zika viruses have exposed the dangers posed by emerging infectious diseases and the need for epidemic preparedness for potential future threats. Treuman Katz Center faculty member and lawyer-bioethicist Seema Shah studies the ethics of research on emerging infectious diseases, and has worked on issues related to the recent Ebola and Zika virus epidemics.

How do we weigh the value of this research to help future patients, such as children who might suffer from microcephaly and other neurological complications, against the risks to the healthy research volunteers—when we don’t know what all the risks might be?

– Seema Shah

Lessons Learned From Ebola Outbreaks

In the Ebola epidemic, questions arose about whether or not unproven interventions should be used outside of research, given the relatively high mortality for people infected with Ebola virus disease and the limited treatment and prevention options. Some high-profile cases of treatment with experimental interventions led to claims of injustice. This experience made clear that there are many reasons for engaging communities, including developing trust, fostering transparency, allowing the community to evaluate the benefits of research, enabling the community to protect themselves from potential harms, and obtaining buy-in and support for ongoing research in the locations from which participants are drawn.

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, however, including:

  • How should we protect and respect participants given the limited time and capacity to conduct and review research?
  • How should we engage communities?
  • 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?

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.

NIH Ethics Consultation on Zika Virus Research

Shah serves as chair of a group of experts from various disciplines and federal agencies that has provided recommendations on the ethics of human challenge trials on Zika virus. 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 a relatively recent endeavor and has been limited in scope and application.

The committee’s report, Ethical Considerations for Zika Virus Human Challenge Trials (PDF), stated that while Zika human challenge trials could be ethically justified, their final recommendation was that it would be premature to proceed with these at present, given the many unknowns about the Zika virus.

The panel weighed the public health urgency against the risk to human research subjects (and those to whom they might pass the virus), and considered the risk too great. They understood the need for a vaccine, the importance of the research. They provided a path forward. But they also told the researchers: Not quite, not yet.

– Paul McLean, bioethicist, Boston Children’s Hospital, in a March 2017 commentary about the panel’s report

Future Research on the Ethics of Challenge Trials

The committee encountered some questions that they did not have time to fully explore. For instance, are volunteers 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. Additionally, she will work with stakeholders, researchers and ethicists in collaboration with the WHO, NIH and PATH to develop a comprehensive framework to determine when and how human challenge trials in emerging infectious diseases are ethically acceptable. This framework will address unresolved questions from her work on the Zika report, such as:

  • Is it better to conduct a Zika virus challenge trial in a region that doesn’t face the threat of a Zika 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 framework may also be developed into guidelines for the WHO. Further down the line, Shah plans to empirically evaluate whether the framework is useful for review committees and acceptable to communities, or if the framework needs further refinement and adaptation. This work is supported by funding from the Greenwall Foundation.

Shah’s 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, and also conducting valuable research.

Learn more about how Seattle Children's bioethicists are involved in Zika research.