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खुला एक्सेस

अमूर्त

Patient- Reported Reasons for a COVID-19 Therapeutics Clinical Trial: Findings from a Multi-Center Investigation

Samira Reyes Dassum*, Ryan Ferguson, Patricia Woods, Maura Flynn, Karen Visnaw, Erika Holmberg, Sara Schiller, Colleen Shannon, Mary Brophy, Paul Monach, Sarah Leatherman, Westyn Branch-Elliman

Background: Early in the COVID-19 pandemic, no evidence proven therapeutics were available, and thus participation in a clinical trial was often the only way to access experimental therapeutic options. In the US, participation in medical research is low, and patient stated factors driving non-enrollment decisions are poorly characterized. Thus, the aim of this study was to identify patient and legally-authorized representative reported reasons for declining enrollment in a COVID-19 therapeutics trial identify potential strategies for addressing barriers in future investigations.

Methods: As part of a pragmatic randomized trial during the period from 4/10/20-2/3/21, SARS-CoV-2 positive inpatients with moderate to severe disease were screened for eligibility. If eligible patients declined to participate, they were asked an open-ended question about the reasons behind their decision. Qualitative responses were analyzed using a directed content analysis approach; responses were categorized using previously defined factors that have contributed to decisions not to enroll in other clinical therapeutics trials, primarily conducted in oncology. To evaluate the impact of external factors, such as publication of evidence proven therapeutics options, enrollment rates by time period were assessed using simple descriptive statistics: time period 1 (before June 25, 2020) before any evidence-based treatments were available; time period 2 (June 25 August 26), after dexamethasone was recommended but before tocilizumab was recommended against; and time period 3 (August 27 March 5, the study end date).

Results: N=417 patients were screened, and 162 patients met eligibility criteria. Of these, 53 (32.7%) consented to enroll. A total of 102 (62.9%) patients declined to participate, and 7 were unable to give consent and were excluded. Patient reported reasons for non-enrollment were limited perceived benefit, competing priorities, physician or family influence and presence of comorbidities leading to perception of increased risk of participation. Several patients reported that their decision was influenced by physician or family recommendation to decline, which was reported as physician lack of support for participation due to the presence of comorbidities or physician perceived lack of benefit given clinical improvement prior to study enrollment.

Enrollment varied substantially by study period. During the first time period (prior to dexamethasone), the enrollment rate was 10/11 (91%) and during the period from August 25 until the end of the trial, after some other studies suggested lack of effectiveness of IL-6 receptor inhibition for management of severe COVID-19, the enrollment rate fell to 43/144 (30%) (P-value, <0.0001).

Conclusions: Understanding reasons and attitudes driving decisions to decline enrollment may help investigators address them during the recruitment process and increase participation in clinical trials in the US.