On June 3, 2020, the U.S. Food & Drug Administration (“FDA”) again updated its guidance on the “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” with new information on the use of electronic signatures on clinical trial records and a reference to FDA’s COVID MyStudies App as an option for obtaining electronic informed consent. This follows a prior update released by FDA on May 14, 2020, also described below. To learn more about FDA’s guidance in this area, please see our prior alerts on our COVID-19 resource center for health care and life sciences clients here.
FDA’s update of June 3, 2020 added guidance addressing:
- Part 11 compliance for electronic systems used to generate electronic signatures on clinical trial records. FDA reiterates that electronic systems used to generate electronic signatures on clinical trial records, including informed consent documents, must comply with 21 CFR Part 11 (“Part 11”) when applicable. When an electronic system that is Part 11 compliant is not available, regulated entities must obtain required signatures by alternate means (e.g., handwritten wet ink signatures executed on documents, handwritten stylus or finger-drawn signatures executed on electronic documents that are then printed or appropriately witnessed) as discussed in previous questions and answers in FDA’s guidance. FDA does not indicate that any increased flexibility will be afforded to regulated entities with respect to Part 11 compliance due to the COVID-19 public health emergency (“PHE”), but FDA is making its COVID MyStudies App available to investigators to facilitate electronic informed consent during this time (see below).
- FDA’s COVID MyStudies App. In its June 3, 2020 update, FDA presents its COVID MyStudies App as an option for obtaining electronic informed consent. As announced on May 29, 2020, FDA has made its COVID MyStudies App available as a free platform to facilitate secure electronic informed consent when face-to-face interaction is impractical due to the COVID-19 PHE. The COVID MyStudies App is now available through the Apple App and Google Play stores and allows investigators to send informed consent forms electronically to the subject (or his/her legally authorized representative), obtain an electronic signature, and distribute signed copies of the form to the study team and subject. Ongoing technical support for the COVID MyStudies App will be provided by Harvard Pilgrim Health Care Institute and funded by FDA, as resources allow.
- Remote clinical outcome assessments. FDA expands its previous answer on remote clinical outcomes assessments (“COAs”) to include patient-reported outcomes (“PROs”) and observer-reported outcomes (“ObsROs”) and offers suggestions for limiting the potential for missing data and mitigating potential bias that might be introduced by switching from paper or electronic-based PRO and ObsRO assessments completed by the subject independently to assessments administered verbally by another person.
FDA’s update of May 14, 2020 added guidance addressing:
- Use of alternative laboratories and imaging centers for protocol-specified assessments. FDA expressed its support for the use of alternative sites for laboratory tests and imaging assessments that focus on the safety of trial subjects when such tests and assessments are routinely performed in those settings (e.g., routine chemistries, blood counts, chest radiographs). FDA encourages consultation with the applicable FDA review division if (1) the results of tests or assessments are the basis for formal hypothesis testing, including primary or secondary efficacy endpoints and some safety endpoints or (2) the tests or assessments are used to determine trial eligibility, particularly if the results may affect trial integrity (e.g., laboratory tests to identify a tumor biomarker required for inclusion, genetic test to identify a marker that is a critical inclusion criterion). Note that Form FDA 1572 need only be updated if the alternative laboratories or imaging centers will be used by all subjects in the trial. However, documentation of when such facilities were used should be retained and submitted to FDA in, for example, an information amendment or a protocol amendment to the investigational new drug (“IND”).
- Use of video conferencing in lieu of in-person clinical trial visits. FDA notes that it does not endorse any particular “best practices” for the use of telemedicine in FDA regulated clinical trials, but it does highlight the need for appropriate training for study personnel, participant privacy protections, and development of an identity verification plan for investigators and subjects. Additionally, the guidance notes that, like for in-person visits, the date and time of the real-time video interaction, the location of the trial subject, and the location of the personnel conducting the remote visit should be documented in the case report form. Furthermore, FDA confirms that telemedicine visits are considered a “live exchange” of information and, therefore, Part 11 requirements do not apply.
- Inability to meet postmarketing requirement timetables. Applicants (i.e. companies that file marketing applications with FDA) who are required to complete postmarketing clinical trials for drugs or biologic products as part of postmarketing requirements (“PMRs”) or who are required to complete postmarket device trials should inform FDA as soon as possible if there are any COVID-19-related delays that may impact the ability to meet specified milestones and should propose feasible revised milestones. FDA will evaluate the facts and circumstances of the explanation the applicant provides regarding COVID-19’s impact, as well as the conduct of the applicant, in determining compliance. FDA also provides additional information on PMRs under the Pediatric Research Equity Act and Accelerated Approval programs.
- Reporting serious adverse events (“SAEs”) that occur with an approved drug being used in clinical practice for treatment of COVID-19, when the sponsor also has an IND application for the same drug being investigated to treat COVID-19. FDA advises that (1) SAEs that occur in clinical practice must be reported in accordance with applicable postmarketing reporting requirements (see e.g. 21 CFR § 314.80 and § 600.80), (2) SAEs that occur during a clinical trial under an IND for an approved drug or biological product being investigated for a new use must be reported as an IND safety report per 21 CFR § 312.32 if they are unexpected and the sponsor determines that there is a reasonable possibly that the drug caused the SAE, and (3) regardless of its source, if safety information indicates a new serious risk associated with a drug under investigation, the sponsor will need to file an IND safety report with FDA, and updates likely will need to be made to the investigator brochure and/or the informed consent document.
- Reporting of SAEs associated with COVID-19 diagnosis in non-COVID 19 trials. FDA advises that a sponsor must report an SAE that is both unexpected and for which there is a reasonable possibility that the drug caused the SAE. FDA notes that it is possible that an investigational drug might be causally related to a SAE associated with COVID-19 by making subjects in the trial more susceptible to complications from COVID-19 and provides suggestions to evaluate whether a reasonably possible causal relationship exists.
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