Experiences of and recommendations on clinical trial design in Alzheimer’s disease from the participant’s point of view: a mixed-methods study in two clinical trial centers in the Netherlands

Abstract

Introduction In the context of the development of pharmaceutical interventions, expectations and experiences of participants are essential. Their insights may be particularly helpful to address the challenges of recruiting and retaining participants for Alzheimer’s disease (AD) clinical trials. We examined clinical trial participants’ experiences to optimize trial design in Alzheimer’s disease (AD). Method In this mixed-methods study, we included adults who participated in sponsor-initiated AD trials at Brain Research Center, a clinical trial organization in the Netherlands. Participants (N = 71, age 69 ± 6.5, 54%F, 19 cognitively normal (CN), 19 mild cognitive impairment (MCI), and 33 AD dementia) first completed an online survey. Diagnostic group differences were investigated using chi-square tests or one-way ANOVAs. Next, a subsample (N = 12; 8 = CN, 4 = MCI) participated in focus groups to gain in-depth insight into their opinions on optimizing trial design from a participants’ point of view. Audio recordings from focus group interviews were transcribed verbatim and analyzed by thematic content analysis by two independent researchers. Results Most reported motives for enrolment included “to benefit future generations” (89%), followed by “for science” (66%) and “better monitoring” (42%). Frequent suggestions for increasing willingness to participate included a smaller chance to receive placebo (n = 38, 54%), shorter travel times (n = 27, 38%), and sharing individual results of different assessments (n = 57, 80%), as well as receiving trial results (n = 52, 73). Highest visual analogue burden scores (0–100) were found for the lumbar puncture (M = 47.2, SD = 38.2) and cognitive assessments (M = 27.2, SD = 25.7). Results did not differ between diagnostic groups, nor between patient and caregiver participants (all p-values>.05). Two additional themes emerged from the focus groups: “trial design,” such as follow-up visit(s) after participating, and “trial center,” including the relevance of a professional and empathic staff. Conclusion Relevant factors include expectation management and careful planning of high-burden assessments, provision of individual feedback, and prioritizing professionalism and empathy throughout conduct of the trial. Our findings provide insight into participants’ priorities to increase willingness to participate and can be used to optimize trial success.

Toward the right treatment at the right time: Modeling the trajectory of cognitive decline to identify the earliest age of change in people with Alzheimer's disease

“…Previous authors have suggested one of the reasons RCTs in AD have been largely unsuccessful is because of poor trial design. 28 There has been substantial work on methods to improve RCT design including research on participants' priorities to increase willingness to participate in RCTs, 29 suggestions to use Bayesian adaptive RCT designs, 30 and using polygenic hazard scores to stratify participants. 31 However, limited consideration has been given to the age of participants when they enter into an RCT and the accepted convention is to enroll partic-ipants over 50, 60, or 65 years to 85 years old depending on the target population, study aims or choice of outcome measure.…”

Estimating attrition in mild‐to‐moderate Alzheimer’s disease and mild cognitive impairment clinical trials

“…For example, a previous study observed an association between the number of retention tactics used at NIHfunded ADRCs and rates of retention at 1 and 2 years [14]. Trials that require longer participation may also benefit from adjusting other study design features like reducing/replacing high-burden assessments (e.g., lumbar puncture) and increasing motivating factors such as returning test results [15] and even financial bonuses for trial completion [16].…”