Examining the behaviors of clinical trial stakeholders to better understand challenges in patient participation.
Clinical trial performance has been plummeting in recent years, with as many as 80% of trials terminating due to lack of enrollment. Retention rates in clinical trials are suffering as well, as is the diversity of trial participants. One study found that 81% of participants in genome-wide association studies are of European descent, which means other racial and ethnic groups are severely underrepresented in research. Lackluster clinical trial recruitment and retention have numerous downstream implications for future innovation and clinical outcomes.
To better help sponsors recruit and retain trial participants, the ZS Cognitive team, which applieshealth decision science (HDS) to drive greater impact across organizations, commissioned two waves of research aimed at understanding cognitive factors that influence participation in clinical trials. In 2021, the Studying Underrepresented Patients for Equity in Recruiting (S.U.P.E.R.) study looked at patient willingness to participate in clinical trials. This year we turned our attention to principal investigators (PIs) and clinical research coordinators (CRCs) to examine how their behavior can influence clinical trial success. Our research also draws on concepts from the academic disciplines of health decision science and medical decision-making. We view decision science as a tool that provides foundational insight into health judgment and decision processes in the face of uncertainty.
In our 2022 study, our objective was to identify cognitive factors that—at a conscious and subconscious level—feed into the behavior of PIs and CRCs, who have significant influence over enrollment and retention activities in clinical trials. PIs play a major decision-making role in recruitment, while CRCs are more focused on retention have more frequent day-to-day interactions with enrolled patients.
Our behavioral objective (BO), or “north star,” outlines the desired behavior we’d like to see from our study subjects, in this case PIs and CRCs. Defining BOs allows us to test for cognitive factors, or triggers that can be leveraged to achieve a desired behavior.
Our PI BOs were:
Our CRC BOs were:
To investigate the role of cognitive factors in PIs and CRCs, we first brainstormed with ZS leaders and subject matter experts to identify actionable and relevant cognitive factors, landing on 15for PIs and 17 for CRCs.We hypothesized that some or all these cognitive factors could play a role in eliciting our behavioral objectives from PIs and CRCs. The next phase consisted of qualitative and quantitative research, involving interviews with six PIs and CRCs, and a survey fielded across 362 PIs and CRC respondents in the US, Germany, and Japan.We designed the surveys consistent with ZS’s A/B testing methodology to uncover the impact of specific cognitive triggers on PI and CRC behaviors.
We found six cognitive factors to be statistically significant and active across PIs and CRCs or having an influence on recruitment and retention behaviors.
We found five cognitive factors to be statistically significant and active across US PIs and CRCs.
Our research identified several challenges related to patient recruitment that can lead to suboptimal trial outcomes, as well as several strategies for overcoming those hurdles. According to our research, PIs may not proactively offer clinical trials to all their patients due to preconceived notions about patient compliance. Our research looked beneath the surface at the unconscious factors influencing PI behaviors and identified levers sponsors can pull to change behavior.
For example, we found PIs tend to ignore data around likelihood of trial acceptance in favor of their own experience. According to our surveys, PIs indicate they are 11% less likely to offer a trial to an eligible patient who has missed appointments because they neglect base rates about patient willingness—an assumption that results in patients prematurely being excluded from trials (Figure 1, Base Rate Neglect). To counter these assumptions, sponsors can create PI-facing materials that provide strong anecdotal evidence that contradict personal PI experiences. These materials could include a testimonial such as, “I’m glad my doctor involved me in the trial. I made it a priority to participate and feel much better now.”
Another common recruitment frustration for PIs is strict inclusion and exclusion criteria, which limits who they feel they can offer trials to. PIs indicated they are 14% more likely to educate their patients about clinical trials when they felt more involved in the trial design (Figure 1, IKEA Effect). This is an example of IKEA Effect, which reflects how people place a disproportionately high value on products they partially created. Sponsors can help PIs feel more ownership over trials by involving them in trial design early on, and by creating registries that allow PIs to volunteer themselves or their sites to run trials.
A persistent issue in clinical trial recruitment is the tendency of PIs to make assumptions about patient willingness to participate in clinical trials. We found that these assumptions can be dissolved by facilitating more open HCP-patient conversations about trials. Like most people, PIs exhibit Social Desirability Bias—they want to be liked and are thus influenced by what they believe patients want to hear or prefer. Sponsors can take advantage of this inclination by creating questionnaires that invite patients to share their thoughts and feelings about being in a trial with the PI. PIs indicated they are 5% more likely to educate their next referred patient about clinical trials when they read materials that have statements such as, “Your patients will appreciate if you discuss the following topics” or “Your patient will feel more assured if you explain trial time commitments” (Figure 1, Social Desirability Bias).
According to our research, two of the biggest challenges in clinical trial retention are patient noncompliance and drop off due to CRC administrative burden.
Patient noncompliance and drop off is a big problem for PIs and CRCs. In our research, CRCs reported that they are 17% more regretful about patient drop off when they didn’t take action to follow up with the patient (Figure 2, Action Bias). This surprised us, because we expected the degree of regret due to inaction to be higher given patient drop off is such a critical issue for clinical trials. Despite this, we were encouraged by the finding because it means there’s more that can be done to keep patients in trials.
The good news for sponsors is that there are specific actions they can take to motivate CRCs to be more proactive about reaching out to patients at risk for drop out, thanks toAction Bias. This cognitive factor, which motivates action over inaction, succeeds when people recognize the risk of complacency. Therefore, sponsors should consider reminding CRCs about the risk of patient drop off and how they can combat it through frequent, personable interactions. They could also highlight the sense of regret CRCs might experience when a patient drops out of a trial. Sponsors should also consider creating a “trial recruitment playbook,” or a one-pager of tips and tricks for retention.
In general, our research found that CRCs want what is best for their patients and are open to sustaining certain behaviors and a certain level of effort when they’re informed about its positive impact on patient adherence. This is Outcome Sensitivity at play. For example, CRCs indicated they’re 16% to 39% more likely to continue using a new tool or technology when they are informed about positive outcomes of use (Figure 2, Outcome Sensitivity). Sponsors can elicit this behavior by presenting CRCs with data and anecdotes highlighting how trial adherence improves as a result of staff support.
As CRCs told us, most of them are working on multiple trials at once, and studies that are complex can add to the administrative burden they’re managing. Administrative burden causes CRCs to reduce and deprioritize patient engagement. However, we found that CRCs are 11% more likely to provide additional support to patients when the trial’s protocol is less demanding (Figure 2, Cognitive Effort). Sponsors can leverage Cognitive Effort by doing whatever they can to streamline daily administrative tasks. That could include working with experienced CRCs to identify opportunities to optimize workflows or investing in technologies that can automate tasks such as data entry and appointment reminders.
It’s important to note that while our research looked at cognitive factors that influence PIs and CRC behavior, there are trial design issues—such as strict inclusion and exclusion criteria or a burdensome schedule of assessments—that pose major challenges to trial success. Though addressing cognitive factors alone won’t be sufficient to solve for clinical trial challenges, it is an opportunity to take a meaningful step in the right direction by encouraging desired behaviors.
The clinical landscape—and the individuals that populate it—is diverse. Sponsors, PIs, and CRCs make hundreds of clinical trial-related decisions every day. If we can understand the subconscious, underlying reasons for the most important decisions, then we have a good shot at overcoming some key barriers and driving clinical trial success.
Jacob Braude, Principal, Elaine Lim, Strategy Insights & Planning Manager, Matthew Satterthwaite, Strategy Insights & Planning Consultant, Marta Biase, Strategy Insights & Planning Consultant, Jacqueline Dang, Strategy Insights & Planning Associate Consultant; all with ZS