Evaluating human trials: FDA's role.

Abstract

![Figure][1] A Bangkok city worker fumigates to kill Zika-carrying mosquitoes. The search for a Zika vaccine continues. PHOTO: LILLIAN SUWANRUMPHA/AFP/GETTY IMAGES In their Policy Forum “Bystander risk, social value, and ethics of human research” (13 April, p. [158][2]), S. K. Shah et al. discuss the difficulty of determining the risk to bystanders and the benefit to society inherent in human challenge trials (HCTs) in which healthy people are infected with a virus such as Zika. They recommend forming ad hoc Comprehensive Ethics Review Committees, which they assert could address potential risks better than a standard institutional review board. We agree that third-party risks and social value are important considerations in clinical trial evaluation but point out that the U.S. Food and Drug Administration (FDA) is already authorized and well equipped to address these issues. Objective expert reviewers routinely formally evaluate the scientific, clinical, and ethical aspects of all clinical studies performed under the FDA's Investigational New Drug (IND) process ([ 1 ][3]). An IND application is required for challenge studies in which live organisms are administered to subjects to assess vaccine effectiveness or to study disease pathogenesis or the host response to the organism. The FDA has considerable experience in addressing risk to human subjects enrolled into clinical trials as well as evaluating risks to bystanders and in assessing the social value of HCTs. The FDA's review process combines the necessary scientific and regulatory expertise to appropriately evaluate risks and apply rational risk minimization strategies. The FDA is authorized to require studies with potential third-party risks, such as those potentially associated with live-attenuated vaccines and with human challenge trials, to be performed under appropriate containment with explicit consideration for these risks (including potential sexual and environmental transmission). The FDA also evaluates manufacturing and safety testing of challenge strains. If risks are deemed unreasonable or are inadequately described in the Investigator Brochure, the FDA can place a study on “clinical hold.” The FDA can also convene its Vaccines and Related Biological Products Advisory Committee ([ 2 ][4]) to provide public expert discussion and recommendations regarding relevant scientific and human subject protection issues, as occurred in the evaluation of the benefit and risks of HCTs to assess the effectiveness of cholera vaccines. 1. [↵][5]U.S. FDA, Investigational New Drug (IND) application (2017); [www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm][6]. 2. [↵][7]U.S. FDA, Vaccines and Related Biological Products Advisory Committee (2018); [www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/][8]. [1]: pending:yes [2]: /lookup/doi/10.1126/science.aaq0917 [3]: #ref-1 [4]: #ref-2 [5]: #xref-ref-1-1 View reference 1 in text [6]: http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm [7]: #xref-ref-2-1 View reference 2 in text [8]: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/