The Food and Drug Administration (FDA) once again updated its guidance on clinical trial conduct during the COVID-19 pandemic. In this most recent update, the FDA added content to the question-and-answer appendix covering the additional topics listed below.
Obtaining informed consent from patients unable to travel to clinical trial sites and unable to use electronic informed consent capabilities.
It may still be acceptable for investigators to obtain informed consent if the available methods allow for an adequate exchange of information and documentation and if the signer of the consent form is the person who plans to enroll as the subject. For example, the form can be sent to the subject via fax or email; the consent interview may be conducted over the phone; the subject can sign and date the consent form; and the subject may return the signed form to the investigator via mail, fax or a secure email account.
Factors to consider when deciding whether to implement remote performance outcome (PerfO) assessments or interview-based clinician-reported (ClinRO) assessments.
In deciding whether to conduct these clinical outcome assessments remotely, sponsors should consider whether remote assessments over the phone or by video are appropriate for the clinical data they plan to collect (e.g., if a greater degree of visual input is required, remote assessments may be difficult). Sponsors should also consider whether it is safe and feasible for the subject to participate in the assessment at their location. Remote assessments should be performed as similar as possible to on-site assessments to minimize variability and ensure comparability of assessments, and sponsors should also ensure remote assessments are consistent across sites, subjects, and visits. Plans should be made to provide technical support and to ensure the security and privacy of data.
Sponsors may conduct certain aspects of site monitoring visits remotely.
If technically feasible, remote site monitoring should focus on reviewing critical study site documentation, source data, and trial activities that are essential to the safety of trial participants and/or data reliability. Remote monitoring activities should be documented with the same level of detail as on-site monitoring activities.
Commercial sponsors of INDs may qualify for a short-term waiver from electronic common technical document (eCTD) requirements during the COVID-19 pandemic.
Because the public health emergency posed by the COVID-19 pandemic may impact computer operations, some commercial sponsors may be unable to meet eCTD requirements. Companies experiencing technical difficulties with the transmission of their electronic submissions should consult FDA electronic submissions staff for technical assistance rather than submitting a waiver request. Information on waivers can be found in the Q&A of the updated COVID-19 guidance or the FDA’s eCTD guidance.
When local healthcare providers administering investigational product infusions are considered to be sub-investigators.
The COVID-19 pandemic may affect the ability to administer investigational product infusions at a clinical trial site. Alternative infusion sites should have appropriately trained personnel and oversight by a qualified physician. Any changes in protocol to permit alternative site administration must be approved by the IRB. Local providers administering the drugs in a manner consistent with their normal clinical practices would not need to be listed as sub-investigators on Form FDA 1572 but should be listed in site records. If the local provider will be performing study-specific procedures or assessments that contribute to clinical data, the provider would need to be listed as a sub-investigator on Form FDA 1572
Local sourcing of an investigational drug may be acceptable during the COVID-19 pandemic.
If patients are unable to receive an investigational drug from the trial site, but the drug is FDA-approved for other uses and the study does not require blinding, then local sourcing of the drug is acceptable to the FDA (e.g., by having a local physician write a prescription rather than shipping the product directly to the patient). The FDA advised it would not view the sponsor as charging for the investigational drug (per 21 CFR 312.8) when unable to secure it from the trial site during the COVID-19 public health emergency. Nor would the FDA object if the sponsor reimbursed the patient for any costs incurred to obtain or administer the drug.
Communication with FDA regarding changes to ongoing clinical trials.
The primary point of contact between an IND sponsor and the FDA is the review division regulatory project manager (RPM). Telephone may be more appropriate for time-sensitive matters, but the FDA will prioritize responding to safety-related inquiries over all other inquiries. For urgent issues related to IDEs managed in Center for Devices and Radiological Health, sponsors should contact the lead reviewer. For IDEs managed in Center for Biologics Evaluation and Research, sponsors should contact the RPM.
If you have any questions about the FDA guidance, please reach out to the authors.