Celeste A. Elash, Director, eCOA Sciences
This week, the U.S. Food and Drug Administration issued a guidance for industry, investigators and institutional review boards conducting clinical trials of medical products during the coronavirus (COVID-19) pandemic. In a subsequent statement, the FDA recognized that the pandemic may affect trials by introducing challenges related to quarantines, travel limitations, site closures, limited availability of investigational products and other trial supplies as well as other considerations if trial participants or site personnel become infected with the virus that causes COVID-19. The FDA is aware that protocol deviations may be unavoidable due to COVID-19, and the new guidance outlines considerations to assist trial sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice and minimizing risks to trial integrity. Recommended considerations include, among others, evaluation of alternative methods for assessments, like phone contacts or virtual visits.
The guidance advises that while protocol deviations may be required, the implementation of alternative processes should be consistent with the protocol to the extent possible, and sponsors and clinical investigators should document the reason for any contingency measures implemented. 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 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).”
For ongoing trials with an eCOA component, there are several processes available to facilitate eCOA data collection while ensuring participant and site safety during the current pandemic:
- Telephone contacts: Investigative site personnel may facilitate collection of site-based PRO data by interviewing the trial participants over the telephone and recording the participant’s responses in the site-based eCOA tablet. When interviewer-administered versions of the protocol-required PRO Measures (PROMs) are available, the tablet software can be updated virtually with a software push to include the interview versions. If interviewer versions are not available, sponsors are advised to consult their review divisions and consider the risk to data integrity when deciding whether to use interviews to collect efficacy assessments intended to be self-administered by the patient.
- Updates to in-field handheld software to collect site-based PROMs: Handheld eCOA software that trial participants use to collect in-field data, e.g., daily diaries, can be updated with a virtual software push to add the PROMs that were originally intended to be collected at the investigative site. This virtual update can be done without requiring the participant to visit the investigative site.
- Documentation of Reasons for Missing PRO Data: Site-based tablet software can also be updated to include a feature to allow investigative site staff to document the COVID-19- specific reason for missing PRO data directly in the tablet data stream.
Regulatory acceptance of efficacy data collected by multiple, or mixed, modes of data collection will vary on a case by case basis. YPrime’s eCOA scientific advisors are available for consultation regarding best practices, procedural or software modifications and to support discussions with review divisions regarding eCOA efficacy data collection.