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whether to suspend, continue, or initiate trials Re-monitoring after pandemic-related restrictions are lifted Contains Nonbinding Recommendations 8 Q1. What are some of the key factors that a sponsor should consider when deciding whether to suspend or continue an ongoing study or to initiate a new study during the COVID-19 public health emergency? Central to any decision should be ensuring that the safety of clinical trial participants can be maintained. Sponsors, in consultation with clinical investigators and Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs), should assess whether the protection of a participant’s safety, welfare, and rights is best served by continuing a study participant in the trial as per the protocol or by discontinuing the administration or use of the investigational product or even participation in the trial. Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring, the potential impact on the investigational product supply chain, and the nature of the disease under study in the trial. As part of this assessment, sponsors should carefully consider the following aspects of clinical trial conduct when deciding how or whether to proceed with a clinical trial: • Assessing whether the limitations imposed by the COVID-19 public health emergency on protocol implementation pose new safety risks to trial participants, and whether it is feasible to mitigate these risks by amending study processes and/or procedures. • Assessing the continued availability of the clinical investigator/sub-investigators to provide oversight of the trial and properly assess and manage safety issues that may emerge. • Assessing whether there will be sufficient clinical trial support staff given the evolving COVID-19 situation and its impact on staff availability. Are there appropriately trained staff that could be available to handle the expected tasks? Is there adequate equipment and materials for clinical trial support staff? • Assessing whether clinical investigator sites will remain open to trial participants for required in-person assessments or whether the clinical investigator has the ability to provide required in-person assessments at an acceptable alternate location(s), or whether such protocol-specified, in-person assessments can instead be conducted virtually. • Assessing the continued availability of clinical trial supplies and continued operations of vendors, especially related to supply of the investigational product and/or to clinical trial supplies that are essential to maintaining appropriate safety monitoring or other key trial procedures. This should include consideration of product stability (shelf life) if the treatment schedule is revised, or if the clinical site is unable to properly store the product for the needed duration. • Assessing the continued availability of, and support for, information technology systems and any other technological tools that are needed to support the trial. Are current contingency plans adequate for the types of disruptions that might be Contains Nonbinding Recommendations 9 anticipated? What other plans can be put in place to minimize any potential disruptions? • Assessing whether there will be continued operations of, and adequate communications with, IRB/IEC and Data Monitoring Committee (DMC) staff, if applicable, to support trial needs. • Assessing whether it is feasible to conduct the trial in light of any COVID-19 public health measures implemented by Federal and State authorities to control the virus. Involvement of a study’s DMC, if one has been established, can provide support for the assessments discussed above. Since a primary responsibility of the DMC is assuring the safety of participating trial participants, the DMC’s assessment of the impact of modifications of trial conduct due to COVID-19 on patient safety is important to consider. The risks and benefits of continuing a trial are likely different than a decision to initiate a trial (other than trials intended to evaluate investigational treatments or vaccines for COVID-19). Given the evolving situation, with likely increasing impacts on investigators, staff, and supply chains, sponsors should carefully consider the ability to effectively mitigate risks such that patient safety and trial integrity are assured. In addition, it is important to consider whether initiation of the trial could interfere with public health measures implemented by Federal and State authorities to control the virus. Q2. What key factors should sponsors consider when deciding whether to continue administering or using an investigational product that appears to be providing benefit to the trial participant during the COVID-19 public health emergency? There may be circumstances in which an investigational product (either a drug, biological product, or medical device) appears to be providing benefit to the trial participant. A sponsor deciding whether to continue administering or using such a product during the COVID-19 public health emergency should carefully consider context-dependent issues, including whether a trial participant appears to be benefitting from treatment with the investigational product, whether there are reasonable alternative treatments, the seriousness of the disease or condition being treated, and the risks involved in switching to an alternative treatment 

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