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Nonbinding Recommendations 5 discontinuations due to COVID-19). This information, summarized in the clinical study report, will be helpful to the sponsor and FDA. • If scheduled visits at clinical sites will be significantly impacted, certain investigational products, such as those that are typically distributed for selfadministration, may be amenable to alternative secure delivery methods. For other investigational products that are normally administered in a health care setting, consulting FDA review divisions on plans for alternative administration (e.g., home nursing or alternative sites by trained but non-study personnel) is recommended. In all cases, existing regulatory requirements for maintaining investigational product accountability remain and should be addressed and documented. • With respect to efficacy assessments, FDA recommends consultation with the appropriate review division regarding protocol modifications for the collection of efficacy endpoints, such as use of virtual assessments, delays in assessments, and alternative collection of research-specific specimens, if feasible. For individual instances where efficacy endpoints are not collected, the reasons for failing to obtain the efficacy assessment should be documented (e.g., identifying the specific limitation imposed by COVID-19 leading to the inability to perform the protocol-specified assessment). • If changes in the protocol will lead to amending data management and/or statistical analysis plans, the sponsor should consider doing so in consultation with the applicable FDA review division. Prior to locking the database, sponsors should address in the statistical analysis plan how protocol deviations related to COVID-19 will be handled for the prespecified analyses. • If planned on-site monitoring visits are no longer possible, sponsors should consider optimizing use of central and remote monitoring programs to maintain oversight of clinical sites. B. In general, and if policies and procedures are not already in place for applicable trials: • Sponsors, clinical investigators, and IRBs should consider establishing and implementing policy and procedures, or revise existing policy and procedures, to describe approaches to be used to protect trial participants and manage study conduct during possible disruption of the study as a result of COVID-19 control measures at study sites. Changes to policy and procedures could address, but not be limited to, impact on the informed consent process, study visits and procedures, data collection, study monitoring, adverse event reporting, and changes in investigator(s), site staff, and/or monitor(s) secondary to travel restrictions, quarantine measures, or COVID-19 illness itself. Policy and procedures should be compliant with applicable (regional or national) policy for the management and control of COVID-19. Depending upon the nature of the Contains Nonbinding Recommendations 6 changes described above, a protocol amendment may be required under the applicable regulations. 6 C. For all trials that are impacted by the COVID-19 public health emergency: Sponsors should describe in appropriate sections of the clinical study report (or in a separate study-specific document): 1. Contingency measures implemented to manage study conduct during disruption of the study as a result of COVID-19 control measures. 2. A listing of all participants affected by the COVID-19 related study disruption by unique trial participant number identifier and by investigational site, and a description of how the individual’s participation was altered. 3. Analyses and corresponding discussions that address the impact of implemented contingency measures (e.g., trial participant discontinuation from investigational product and/or study, alternative procedures used to collect critical safety and/or efficacy data) on the safety and efficacy results reported for the study. Robust efforts by sponsors, investigators, and IRBs/IECs to maintain the safety of trial participants and study data integrity are expected, and such efforts should be documented. As stated above, FDA recognizes that protocol modifications may be required, including unavoidable protocol deviations due to COVID-19 illness and/or COVID-19 control measures. Efforts to minimize impacts on trial integrity, and to document the reasons for protocol deviations, will be important. IV. Additional Resources For further questions on clinical trial conduct during the COVID-19 public health emergency, please email Clinicaltrialconduct-COVID19@fda.hhs.gov. Contact information for FDA’s review divisions is as follows: CDER: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-newdrugs. CBER: https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/contactscenter-biologics-evaluation-research-cber#indcont. CDRH: https://www.fda.gov/about-fda/cdrh-offices/cdrh-management-directory-organization. 6 See 21 CFR 312.30(b) and 812.35(a). Under applicable Federal regulations, investigators must engage with the Drug Enforcement Administration when amending protocols for research involving Schedule I substances under the Controlled Substances Act by requesting a modification to a site-specific investigator registration (see 21 CFR 1301.18). Contains Nonbinding Recommendations 7 Appendix: Questions and Answers Q1. Deciding 

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