Patient- reported reasons for non-participation in a COVID-19 therapeutics clinical trial: Findings from a multi-center investigation.

Background: Early in the pandemic, there were no evidence-based treatments for SARS-CoV-2, creating an urgent need to identify effective therapeutics. However, public participation in medical research is low; trial enrollment in the US is typically 10-20%. Thus, the aim of this study was to identify common themes underpinning patient reasons to decline participation and evaluate the impact of specific contextual factors.

Methods: This sub-study was conducted in five VISN-1 Clinical Trials Network participating facilities from 4/10/2020-2/3/2021. The trial evaluated the addition of the IL-6-inhibitor, Sarilumab, to the current standard of care for inpatients with moderate-to-severe SARS-CoV-2. Consent procedures varied by site and included fully in-person and fully remote processes. Reasons for declining enrollment were collected among eligible patients who declined to participate but agreed to answer a short follow-up question. Qualitative data were analyzed using directed content analysis. Enrollment rates were assessed using simple, descriptive statistics.

Results: N = 417 COVID-19 positive inpatients were screened and 53/162 eligible patients enrolled. Enrollment varied across study sites and by study period. Prior to identification of effective treatment, the enrollment rate was 10/11 (91%) versus 43/144 (30%) during the later period of the study. N = 85/102 patients who did not enroll answered the follow-up question. The most commonly reported responses were: concerns about the study drug and participation in clinical research in general, comorbidity concerns, competing priorities, external factors, and external advice and influence from family members and clinicians.

Conclusions: Identifying reasons behind declining to enroll may help investigators develop strategies to increase research participation.