Evaluating the Use of Backup Solutions for ePRO Systems

Despite its established disadvantages^1-3, paper backups to electronic patient-reported outcome (ePRO) systems are still requested and used. Web-based backup is often proposed as a practical solution with significant advantages over paper, yet given the frequency of requests for paper backup in lieu of or in addition to web-based backup, the web-based approach has evidently not sufficiently alleviated concerns. Here, in Part 1 of a two-part series, we offer a retrospective examination of the effectiveness, usability, and challenges with web-based electronic clinical outcome assessment (eCOA) backups. Part 2 will present results from a survey of sponsor organizations evaluating the frequency of adoption, the justifications for selecting specific backup solutions, reasons for the persistence of paper, and how backup data are evaluated.

Web-based backup

The benefits of web-based backup over paper backup for ePRO data collection are well established.⁴ Web-based backup not only aligns with regulatory guidance pertaining to ALCOA+ (attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available) principles⁵, but also incorporates the design benefits of electronic methods like logical branching, forced ordering, and timestamps. Given the prevalence of internet availability, it could be reasonably assumed that web backups present the ideal solution to acquire PRO data in the field that is of superior quality when compared to paper. Web-based backup is not without its challenges.

The solution does require (minimal) additional training for trial participants and sites and may require alternative login information, which is generally unappealing to users. In addition, there may be issues with browser compatibility with personal devices or access to suitable web-enabled devices for both trial participants and site staff. Depending on the eCOA provider, a web-based backup could require additional cost and add operational demands that may impact trial timelines. We hypothesize that these challenges are the principal reasons paper backup persists.

Web-based backup was introduced as one of many solutions to mitigate device loss or failure at home and/or at sites. According to an informal poll of the eCOA provider member firms of the eCOA Consortium, device failure is attributed to less than 1% of devices used in the field. As such, web-based backup historically has been of limited need in clinical trials.

COVID-19 pandemic

While web-based approaches have certainly been used as the primary data capture method in clinical trials, this approach gained significant additional interest and adoption as a result of the COVID-19 pandemic. The pandemic not only disrupted participants’ ability to visit a site, but it also impacted supply chains and associated distribution hubs and pathways for management of provisioned devices and accessories. FDA encouraged clinical trial sponsors to embrace alternative methods of data collection, including remote eCOA data capture.⁶ In response to that guidance, the eCOA Consortium offered web-based eCOA as one of the viable options to mitigate risk and reduce missing data⁷, and some eCOA providers repurposed their web-based backup solutions to provide this alternative primary solution.

The primary differences between web-based backup (pre-pandemic) and web-based eCOA (mid-pandemic) were the removal of managed or limited access to the field-based web system and replacement of site-based tablet ePRO with remote web-based ePRO.

Lasting impact?

The increased use of web-based backup during the pandemic was unanticipated but should lead to reconsideration of backup solutions overall. Given how web-based backup is built to mimic app-based solutions and the compelling amount of data supporting measurement comparability when best practices are implemented, there is sufficient evidence to support a more flexible, device- and location-agnostic approach to ePRO; web-based ePRO is a trusted approach already.

Instead of relegating web-based solutions to backup only, we should consider them as an integral component of a flexible bring your own device (BYOD) model with greater applications to support traditional, hybrid, and fully decentralized clinical trials. We hypothesize that by allowing greater flexibility in the eCOA technology solution we will reduce the need for backups, specifically paper.

Authored on behalf of Critical Path Institute’s eCOA Consortium by Lisa Charlton, Senior Director, eCOA, Science 37; Shelly Steele, Senior Scientific Advisor, eCOA, WCG Clinical Endpoint Solutions; Celeste Elash, Vice President, eCOA Science, YPrime; and Scottie Kern, Executive Director, eCOA Consortium

References

1. Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient non-compliance with paper diaries. BMJ 2002 May 18;324(7347):1193-1194.
2. Shields AL, Shiffman S, Stone A. Patient compliance in an ePRO environment: methods for consistent compliance management, measurement, and reporting. In: Byrom B, Tiplady B, eds. ePRO: Electronic Solutions for Patient-Reported Data. Surrey, England: Gower; 2010:127–142.
3. Ganser AL, Raymond SA, Pearson JD. Data Quality and Power in Clinical Trials: A Comparison of ePRO and paper in a randomized clinical trial. In: Byrom B, Tiplady B, eds. ePRO: Electronic Solutions for Patient-Reported Data. Surrey, England: Gower; 2010:49.
4. Howry C, Elash CA, Crescioni M, Eremenco S, O’Donohoe P, Rothrock T. Best practices for avoiding paper backup when implementing electronic approaches to patient-reported outcome data collection in clinical trials. Therapeutic Innovation & Regulatory Science 2019 Jul; 53(4): 441-445
5. Food and Drug Administration. E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) – Guidance for Industry. March 2018.
6. Food and Drug Administration. Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency Guidance for Industry, Investigators, and Institutional Review Boards. March 2020; updated on August 30 2021.
7. Critical Path Institute’s PRO Consortium and ePRO Consortium. Coronavirus Disease 2019 (COVID-19): Risk Assessment and Mitigation Strategies for the Collection of Patient-Reported Outcome Data through Clinical Sites. https://c-path.org/wp-content/uploads/2020/06/COVID-19_CPath_v3.0_2020JUN5.pdf