Celeste Elash, eCOA Scientific AdvisorCeleste A. Elash, Director, eCOA Science

On April 10, The Critical Path Institute (C-Path) released their presentation titled “Coronavirus Disease 2019 (COVID-19):  Risk Assessment and Mitigation Strategies for the Collection of Patient-Reported Outcome Data through Clinical Sites”.   This risk mitigation plan was a collaboration among C-Path, the Electronic Patient-Reported Outcome (ePRO) Consortium and the Patient-Reported Outcome (PRO) Consortium.

In March, The U.S. Food and Drug Administration (FDA) issued a guidance for industry, investigators and institutional review boards conducting clinical trials of medical products during the pandemic. In a related statement, the FDA recognized that COVID-19 may affect trials by introducing challenges related to quarantines, travel limitations, clinical site closures, limited availability of investigational products and other trial supplies as well as other considerations if patients or clinical site personnel become infected with the virus that causes COVID-19.  The FDA guidance provides insight into the agency’s flexibility regarding reporting procedural changes introduced in ongoing clinical trials to ensure patient safety during the pandemic.  The document outlines considerations to assist trial sponsors in ensuring patient safety, maintaining compliance with good clinical practice and minimizing risks to trial integrity while working to maintain trial continuity.

A specific challenge trial sponsors face during the pandemic is how to collect data that was originally captured, per protocol, at the clinical site. This includes electronic patient-reported outcome (ePRO) data originally designed to be collected on a tablet during regularly scheduled clinic visits.  The FDA guidance acknowledged sponsors may need to evaluate alternative methods for assessments, like remote data collection, phone contacts or virtual visits.

To assist key industry stakeholders making those evaluations, C-Path released their presentation to “Provide a selection of risk assessment and mitigation strategies for consideration by sponsors and electronic clinical outcome assessment (eCOA) providers to facilitate the continued collection of PRO data in clinical trials.”   The document includes an overview of core principles to keep in mind when considering modifications to trial procedures.  It also outlines recommendations for interacting with FDA review divisions, IRBs and PRO instrument license holders, as well as documenting and reporting the modifications.  A table template is included to provide a mechanism for identifying additional risks and impacts of COVID-19 to current eCOA studies. The primary focus, however, is on providing solutions to the current challenges of capturing ePRO data originally intended to be collected from patients during in-person clinic visits.

The presentation includes a very helpful decision tree that outlines the pros and cons of alternative site-based PRO data collection methods in scenarios both when the patient continues to attend scheduled clinic visits and when clinic visits are not possible.  Alternatives for remote PRO data collection to replace site-based ePRO data collection include remote web-based ePRO data collection, clinical-site personnel interviewing patients via telephone and completing the ePROs on the patients’ behalf, Bring Your Own Device (BYOD) remote data collection and patients completing paper versions of the PROs at home.  Based on C-Path’s pros and cons lists for each option, web-based data collection is the most desirable in in terms of ensuring patient safety and data integrity, while paper-based is the least.

YPrime offers electronic solutions to facilitate the alternatives to site-based eCOA data collection outlined in C-Path’s presentation and some of the regulatory documentation requirements:

Web-based alternative to site-based eCOA data collection: Patients who would typically complete their ePRO assessments on a tablet at the clinical site can access their visit-specific assessments via a web-based tablet emulator using a weblink provided by the clinical site staff.  Similarly, clinical site users who typically conduct ClinRO assessments through a tablet device at the clinical-site personnel can access their assessments on the tablet emulator through their study-specific web-based study portal.

Telephone interviews: Clinical-site personnel may facilitate collection of site-based PRO data by interviewing the patient over the telephone and recording the patient’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.

Use existing field-diaries: Handheld ePRO software that patients 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 clinical site.  This virtual update can be done without requiring the patient to visit the clinical site.

Documentation of Reasons for Missing PRO Data: Site-based tablet software can be updated to include a feature to allow clinical-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 and procedural or software modifications as well as to support discussions with review divisions regarding eCOA efficacy data collection.  Our team is also available to review C-Path’s table template that outlines risks and impacts of COVID-19 to eCOA studies and mitigation strategies for each.