Shrinking awareness of and growing distrust for clinical research could make it challenging for trials to recruit and retain study participants in the near term, according to preliminary results from an ongoing study by the Center for Information and Study on Clinical Research Participation (CISCRP).

CISCRP compared self-reported data from about 8,800 respondents who have never participated in a trial from June/July 2019 to the same data collected in June/July of this year. Preliminary analysis of results indicates that the number of respondents who reported they would be willing to participate in a clinical trial fell to 49 percent in 2020 from 85 percent in 2019.

“More than a 3-5 percent shift in attitude is unusual,” said Ken Getz, founder of CISCRIP and deputy director of the Tufts Center for the Study of Drug Development (CSDD). “This result is quite dramatic,” considering that the 2019 data was a “fairly normal” response.

The CISCRP study also looked at clinical trial literacy, or the respondents’ understanding of the term “clinical research.” Just 10 percent of respondents in 2019 reported that they understood clinical research “not at all” or “not very well.” In 2020, that figure jumped to 36 percent.

The survey also inquired about respondents’ sense of confidence in their ability to find a clinical trial; the number of respondents who were “not very” or “not at all” confident rose to 41 percent in 2020 from 34 percent in 2019.

This apparent lack of awareness of clinical research seems surprising given the substantial media coverage of the clinical research enterprise, both in terms of COVID-19 treatment and vaccine research and the pandemic’s impact on clinical trial activity for other diseases, Getz said.

Perception of the safety of clinical trials also went down between 2019 and 2020. In 2019, 11 percent of respondents to the CISCRP survey indicated that they perceived clinical trials as “not very safe” or “not safe at all.” In 2020, that figure jumped to 29 percent.

In short, clinical research literacy appears to have worsened during the COVID-19 pandemic while perceptions of clinical risk have risen among the general public in “unprecedented shifts,” Getz said during the Conference Forum’s 7th annual Patients as Partners virtual conference last week.

“Results of this research, which is still under way, are alarming,” Getz said, noting that there are several questions to be answered, including, “Are these shifts short-term or long-lived? What strategies and tactics can we bring to address them?”

FDA Also Focuses on Patient Engagement

The preliminary CISCRP results come amid an environment of increasing focus on patient engagement in clinical research, both within the industry and by regulators.

Also speaking at the virtual conference, Robyn Bent, Center for Drug Evaluation and Research (CDER) patient-focused drug development (PFDD) program director, noted that the FDA has been seeing more protocols submitted with patient involvement; Bent estimated that about 80 percent of submissions to CDER “have some amount of patient engagement.” For instance, patient experience data “is referenced very clearly as foundational information that reviewers found very useful as part of their decision-making” with regard to esketamine, a treatment for major depressive disorder, Bent noted.

Similarly, the Center for Biologics Evaluation and Research (CBER) has been holding listening sessions to include patient input into new biologic research, Karen Jackler, CBER patient engagement program manager, said. These have been particularly important in the areas of gene therapies and personalized medicine, for which the center has seen dramatic increases in investigational new drug (IND) applications, she said. A key takeaway from those listening sessions has been that the definition of success can vary, based on a patient’s stage of life or how well currently available therapy already works.

And Bent said she expects this trend to continue, or even increase. The FDA has been actively working to engage with patients since the early 1990s and kicked off its current push in 2013. Given that it takes time to conduct trials, analyze data and submit new drug applications (NDAs) to the agency for approval, the FDA is only now really seeing the impact of increased emphasis on patient engagement, she said.

The PFDD has largely focused on meetings with patients and patient advocates. Participants in these meetings have indicated that, while they don’t expect the FDA to address all gaps in patient engagement, they do feel the FDA needs to provide more clear guidance to researchers and product sponsors. To that end, Bent said, the FDA has begun work on a series of guidances:

• Collecting Comprehensive and Representative Input: The final draft guidance was issued in June.
• Method to Identify What is Important to Patients: Draft guidance was issued in September 2019.
• Select, Develop or Modify Fit-for-Purpose Clinical Outcome Assessments: A workshop was held in October 2018 and a discussion document published.
• Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision-Making: A workshop was held in December 2019.
• Developing and Submitting Proposed Draft Guidance Relating to Patient Experience Data: A workshop was held in March 2018 and draft guidance issued in December 2018.

Additionally, the agency has established a pilot grant program to encourage coordination in development of clinical outcome assessments and endpoints within a given disease area. The goal is to help industry develop core sets of measures of disease and treatment burden for specific areas; these would be made publicly available at little to no cost, Bent said. In 2019, the agency awarded three grants for a migraine clinical outcome assessment system, acute pain therapies in infants and young children and physical function assessments.

Michelle Tarver, the Center for Devices and Radiological Health (CDRH) director of patient science and engagement, pointed to recent efforts within the center to actively include patients in their COVID-19 response efforts. For instance, to address dialysis patients’ access to necessary equipment and supplies, the center sought input from the American Association of Kidney Patients via a survey to their members. The 300 responses to that survey provided important insight, Tarver said, and improved CDRH’s understanding of how potential device shortages might affect these patients. Similarly, patient input into the design and placement of ear tubes in pediatric patients helped to support approval of that product.

Tarver estimated that CDRH has seen 23 industry-sponsored patient preference studies conducted since 2015; three have occurred in the past month, which seems to indicate that industry sees the value in this approach.