Research involving potential pandemic pathogens (PPPs) is essential to protecting global health and security. However, there are biosafety and biosecurity risks associated with undertaking such research that should be adequately considered and appropriately mitigated in order to safely realize the potential benefits. The 2017 Department of Health and Human Services (HHS) Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO Framework) is intended to guide HHS funding decisions on proposed research that is reasonably anticipated to create, transfer, or use PPPs resulting from the enhancement of a pathogen’s transmissibility or virulence in humans (enhanced PPPs). Enhanced PPP do not include naturally occurring pathogens that are circulating in or have been recovered from nature, regardless of their pandemic potential. This framework describes a robust multidisciplinary, pre-funding review process that considers the potential scientific and public health benefits, biosafety and biosecurity risks, and appropriate risk mitigation strategies to help inform agency decisions.
This framework is responsive to, and in accordance with, the Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight issued by the White House Office of Science and Technology Policy on January 9, 2017 and supersedes the previous Framework for Guiding Department of Health and Human Services Funding Decisions about Research Proposals with the Potential for Generating Highly Pathogenic Avian Influenza H5N1 Viruses that are Transmissible among Mammals by Respiratory Droplets. Adoption of this framework lifted the research funding pause on HHS research that was set forth by the U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses.
All proposed research that is being considered for funding by a HHS funding agency, is deemed to be scientifically meritorious by an independent internal or external review process, and has been determined by the funding agency to be reasonably anticipated to create, transfer, or use enhanced PPPs must be referred for additional HHS department-level review.
The HHS P3CO Review Group includes experts in scientific research, biosafety, biosecurity, medical countermeasures, law, ethics, public health preparedness and response, biodefense, select agent regulations, and public health policy. The multidisciplinary review involves critical evaluation of the proposed research, including consideration of a risk/benefit analysis, risk mitigation plan, and additional relevant factors.
Department-level review of proposed research reasonably anticipated to create, transfer, or use enhanced PPPs will be based on the following criteria:
- The research has been evaluated by an independent expert review process (whether internal or external) and has been determined to be scientifically sound;
- The pathogen that is anticipated to be created, transferred, or used by the research must be reasonably judged to be a credible source of a potential future human pandemic;
- An assessment of the overall potential risks and benefits associated with the research determines that the potential risks as compared to the potential benefits to society are justified;
- There are no feasible, equally efficacious alternative methods to address the same question in a manner that poses less risk than does the proposed approach;
- The investigator and the institution where the research would be carried out have the demonstrated capacity and commitment to conduct it safely and securely, and have the ability to respond rapidly, mitigate potential risks and take corrective actions in response to laboratory accidents, lapses in protocol and procedures, and potential security breaches;
- The research’s results are anticipated to be responsibly communicated, in compliance with applicable laws, regulations, and policies, and any terms and conditions of funding, in order to realize their potential benefit;
- The research will be supported through funding mechanisms that allow for appropriate management of risks and ongoing Federal and institutional oversight of all aspects of the research throughout the course of the research; and
- The research is ethically justifiable. Non-maleficence, beneficence, justice, respect for persons, scientific freedom, and responsible stewardship are among the ethical values that should be considered by a multidisciplinary review process in making decisions about whether to fund research involving PPPs.
The department-level review results in recommendations to the funding agency on whether the proposed research is acceptable for HHS funding and if acceptable, whether certain experiments should be modified or certain risk mitigation measures be employed.
Reviews
Three research projects have been reviewed in accordance with the HHS P3CO Framework since its adoption. All three projects were evaluated through the NIH peer review process and found to be scientifically meritorious prior to referral for HHS P3CO review.
Two of the projects underwent peer review in 2013, were found to be scientifically meritorious, and were funded via mechanisms that allow for the addition of specialized terms and conditions of funding and management of risk. Both projects were subsequently determined to be subject to the funding pause on certain gain-of-function (GoF) experiments, announced in October 2014, resulting in the funds being redirected within the awards to support other non-GoF research. In 2018, the Funding Agency referred the two projects, with corresponding risk-benefit analyses and risk mitigation plans, to HHS for review under the new HHS P3CO Framework. The HHS P3CO Review Group determined that, in the case of the two projects, the research was acceptable for HHS funding with recommended changes to increase the potential benefits while decreasing risks; suggested changes were included as terms and conditions of the awards. Further, it was determined that there were no feasible, equally efficacious alternative methods to address the same question in a manner that poses less risk than the proposed approaches. In 2019, the National Institute of Allergy and Infectious Diseases (NIAID) approved the release of funds to support both projects. NIAID support for both of these projects has since ended.
In 2019, a third project, with corresponding risk-benefit analysis and risk mitigation plan, was referred to HHS for review under the HHS P3CO Framework. The HHS P3CO Review Group determined that a subset of the proposed research involving enhanced PPPs was acceptable for funding with the implementation of additional risk mitigation measures. However, NIAID ultimately decided to redirect all funds under the award to support alternative approaches that do not involve enhanced PPP research.
Information about these NIH-funded research projects is available on NIH Reporter, an electronic tool that allows users to search a repository of NIH-funded research projects and access publications and patents resulting from NIH funding, and other publicly available sites. Information can be found at:
