COVID-19 pandemic effects on patient decisions regarding clinical trial participation

Introduction:

The COVID-19 pandemic markedly influenced clinical trials initiation, conduct, enrollment, progress, and patient attitudes towards clinical research participation.^1–5 Investigators responded with revised procedures for recruitment, enrollment, and implementation, including electronic consenting and consent forms, video and virtual procedures, reduced surveys and data collection. The Outpatient Surgery Pain Relief Enhancement trial (OSPREy, NCT03726268) is a single-center, randomized, double-blind, comparative effectiveness trial in adults undergoing moderately painful elective same-day or next-day discharge outpatient surgery. This letter reports patient engagement and enrollment, reflecting patient attitudes towards clinical trials participation, in the OSPREy trial before and after the peak of the COVID-19 pandemic.

Methods:

OSPREy was approved by the Duke University Institutional Review Board and all participants provide written informed consent. Except for opioid assignment, anesthesia and surgery techniques are not changed for study purposes. OSPREy evaluates via electronic surveys daily postoperative pain, opioid use, and recovery in patients randomized to anesthesia with long-duration vs short-duration opioids, assessed for 30 days after surgery. OSPREy began enrollment in December 2018. Our institution suspended all clinical research (March 16, 2020 to May 22, 2020) at the height of the pandemic. When suspended, the trial was already fully virtual, except for consent by electronic signature, which was implemented after the shutdown. We evaluated patient participation in OSPREy before the pandemic and after resumption of clinical research activity. Our institutional process allows “contact” with potential research participants after reviewing the surgical schedule and medical records to assess eligibility. Allowable “contact” is via IRB-approved telephone call or via patient portal (MyChart), to notify patients of a research opportunity. Patients may respond to research staff, who then “approach” patients by IRB-authorized telephone and email scripts, to present the research: purpose, protocol, benefits versus risks, and provide an electronic consent form. Patients may provide verbal intent to participate, and then sign a consent form electronically before or in-person on the day of surgery. Subjects may also not respond to the initial “contact,” or decline after the “approach.” We quantified: (1) eligible patients contacted for participation in the trial, (2) patients who responded and were approached for participation, (3) patients indicating verbal intent to participate, and (4) patients declining either through non-response or verbal decline). Data were analyzed pre-COVID-19 (December 2018-March 2020) and post peak-COVID-19 (May 2020-December 2022).

Results:

From December 2018 to December 2022, 1859 patients were contacted and 1250 agreed to be approached. Figure 1A shows the fraction of patients contacted who indicated verbal intent to participate. The remainder declined: by not responding to contact or declining after approach. Figure 1B shows the fraction and absolute number of patients approached, who indicated verbal intent to participate after discussion. At study initiation, 40%−50% of patients contacted electronically indicated verbal intent to participate, which decreased to 22% following research resumption after the pandemic hiatus (Figure 1A). Over the next 18 months, this increased. At study initiation, about half of the patients who discussed possible participation with research staff indicated a verbal intent to participate, which decreased to 23% following resumption of research (Figure 1B). Over the next 16 months this increased. Although the fraction of patients indicating intent to participate increased, the absolute number decreased due to smaller numbers of patients eligible and approached. The number of patients contacted electronically increased from 372 in the year before the research hiatus to 509 in the year after the hiatus.

Figure 1.

COVID-19 effects on intent to participate in the OSPREy comparative effectiveness trial. (A) Fraction of eligible patients initially contacted electronically for research participation who indicated verbal intent to participate. Not shown is the fraction indicating a desire not to participate (by not responding or declining). (B) Fraction (green) and absolute number (black) of patients with whom the study was presented and discussed, who indicated verbal intent to participate.

Discussion:

Patient engagement and enrollment are among the most critical aspects of clinical trials, and they are essential for trial success. Major factors influencing patient engagement and participation decisions include recruiting operations and patient willingness. Patient participation in OSPREy decreased with the COVID-19 pandemic, and was slow to recover, consistent with previous reports.^{1, 2} This occurred despite research process adaptations and all-electronic remote processes: email and telephone communication, e-consent, electronic data collection, which had already been implemented before the pandemic. Separation of these operational considerations therefore suggests that reduced interest in participation likely reflects patients’ perceptions, preferences and willingness, rather than logistical problems related to COVID-19.⁶ Reduced research enrollment, as exemplified in the OSPRey trial, has major implications for accrual, ability to meet enrollment goals and sample-sizes specified in protocols and grant applications, statistical power, and ability to validly test hypotheses and achieve valid conclusions. Although the peak of COVID-19 disease has passed, COVID-19 effects on clinical research continue.