An ad hoc committee of the IOM will review and conduct an analysis of the clinical trials conducted during the 2014-2015 Ebola virus disease (EVD) outbreak in West Africa. The final deliverable from this committee will be a consensus report that explores and analyzes the scientific and ethical issues related to clinical trial design, conduct, and reporting. Particular emphasis will be given to clinical trials for vaccine and therapeutic candidates for EVD conducted by the international community in settings where there is limited healthcare and research infrastructure.

The IOM committee will achieve its objectives by organizing and conducting meetings, interviews, and discussions with key informants in the international research community and in affected countries, including perspectives from government agencies, non-governmental entities, and others. The final report of the committee will be based on the information gathered at these meetings and key informant interviews, and review of the literature and other relevant documentation and communications.

In summary the report will:

• Assess the scientific value of the different EVD vaccine and therapeutic clinical trials conducted in Liberia, Sierra Leone, and Guinea and the data derived from them.

o Describe the specific context (such as disease pathogenicity, high case fatality, political and health system context, and public opinion) and the ethical and scientific practices and considerations related to the design and conduct of each EVD clinical trial.

o To the extent possible, characterize how these considerations have been addressed in similar contexts previously, drawing on case studies of clinical trials conducted during prior disasters to identify transferable best practices.

o Compare pragmatic, ethical, and scientific practices and considerations made in the context of each EVD clinical trial against existing best practices to identify additional best practices and make recommendations on opportunities for improving future clinical research conducted during public health emergencies.

• Make recommendations for how, in the context of an international emerging or re-emerging infectious disease event, clinical trials can best be prioritized and conducted to (1) speed data collection; (2) inform clinical management of patients; (3) assess the safety, efficacy, and effectiveness of therapeutics and vaccines; and/or (4) improve/augment outbreak control efforts.

o Where possible, identify scientific and ethical principles and practical guidance for clinical trial practices and protocols that balance the rapid need for new, useful information with ethical considerations and scientific rigor amid an emerging and rapidly evolving infectious disease event.

o Where possible, identify new ideas for innovative approaches to research in emergency contexts and to alternative methods to evaluate treatments and vaccines.

o Such guidance should include options that facilitate a more flexible and accelerated approach.

• Address whether adjustments to scientific or ethical standards are appropriate in the conduct of research in outbreak settings, and if so, under what circumstances. If such adjustments are found to be appropriate, specify:

o How those adjustments should be decided and implemented; and

o Current and/or future consequences of any such adjustments to patients themselves, or to prevention and treatment strategies.

• Identify opportunities for collaborative investment to achieve long-term ethical and scientific gains from clinical trials conducted during emerging infectious disease events.