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Additionally, a note in the trial records should be made explaining the circumstances of why informed consent was obtained through an alternative 33 If an investigator wants to record the telephone or video conference call, the investigator/designee should ensure that the recording is done in a manner consistent with applicable State and local laws and that all parties agree to being recorded. Contains Nonbinding Recommendations 20 method. The case history for each trial participant must document that informed consent was obtained prior to participation in the trial.34 This alternative approach must be reviewed and approved by the IRB overseeing the trial as required under FDA regulations. 35 Q14. What factors should sponsors consider when deciding whether to change their clinical trial protocol during the COVID-19 public health emergency to include remote clinical outcome assessments? Some clinical outcome assessments (COAs)36 can be conducted remotely in clinical trials during the COVID-19 public health emergency, including COAs for performance outcome (PerfO), interview-based clinician-reported outcome (ClinRO),37 patient-reported outcome (PRO), and observer-reported outcome (ObsRO). During the COVID-19 public health emergency, sponsors may still be conducting in-person assessments on some trial participants, whereas remote assessments may be necessary for others to protect their safety or to respond to COVID-19- related public health measures implemented by government authorities to control the virus. When deciding whether to change their clinical trial protocols to include remote COAs, sponsors should evaluate the general and specific considerations outlined below. General considerations regarding (1) prioritization of trial participant safety and privacy; (2) maintenance of data quality and integrity, including minimizing missing data; and (3) appropriate training for personnel and trial participants, which are discussed elsewhere in this guidance, are also common to all COAs. Other general considerations that are common to all COAs include attention to (1) the potential for increased variability in trial data; (2) the feasibility of conducting a specific type of COA remotely, depending on the context of use; (3) documentation and audit trails; and (4) availability of technology and technical support required for remote assessment. These considerations are explained in more detail below. Increased Variability in Data: When switching from in-person to remote assessments, sponsors should perform remote assessments in a manner as similar as possible to those done inperson, while protecting trial participant safety and privacy. To the extent feasible, sponsors 34 See 21 CFR 312.62(b) and 812.140(a)(3) 35 See 21 CFR 50.27, 56.103, and 56.108(a). 36 For purposes of this guidance, a COA is an assessment of a clinical outcome (i.e., an outcome that describes or reflects how a patient feels, functions or survives); a ClinRO is a measurement by a trained health care professional after observing a trial participant’s health condition, a PerfO is a measurement based on a standardized task performed by a participant that is administered and evaluated by an appropriately trained individual or is individually completed, a PRO is a measurement based on a report that comes directly from the participant about the status of a patient’s health condition without amendment or interpretation of the participant’s response by a clinician or anyone else, and an ObsRO is a measurement based on a report of observable signs, events, or behaviors related to a participant’s health condition by someone other than the participant or a health professional (e.g., a parent or caregiver). See FDA-NIH Biomarker Working Group BEST (Biomarkers, Endpoints, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016, available at https://www.ncbi.nlm.nih.gov/books/NBK326791/. Co-published by National Institutes of Health (US), Bethesda, (MD). 37 Non-interview-based ClinRO assessments, such as those reliant on diagnostic imaging or physical examination, present a distinct set of challenges and are not addressed in this guidance. Contains Nonbinding Recommendations 21 should ensure that the methods and conduct of remote assessments are consistent across sites, trial participants, and visits to minimize variability in the data. For example, if a sponsor decides that video is their preferred method of remote assessment in a clinical trial, then using different methods to conduct assessments (e.g., both telephone and video in the same trial) may increase variability. Maintaining consistency in assessment methods should be balanced, however, against the need to minimize missing data and the decision to use different methods should be justified in study documentation. Feasibility of the Assessment Method Within the Context of Use: Investigators should assess the feasibility of conducting a specific type of COA remotely, which will depend on corresponding trial goals and needs (e.g., ability to conduct the assessment in a way that captures all the data needed to evaluate the endpoint in the trial), given that not all assessments can provide an accurate assessment when done remotely. Documentation and Audit Trails: Investigators should document, and sponsors should include data on related 

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