Experiences of and recommendations on clinical trial design in Alzheimer’s disease from the participant’s point of view

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. Next, a subsample (N = 12; 8 = CN, 4 = MCI) participated in focus groups to gain in-depth insight into their views on optimizing trial design. Audio recordings from focus group interviews were transcribed verbatim and analysed by thematic content analysis by two independent researchers. Results. To benefit future generations was most frequently (34%) reported as a motive for enrolment. The lumbar puncture (40%) and memory assessments (15%) were most often experienced as being of high burden. Structurally receiving individualized test results and smaller chance to get placebo, increased willingness to participate. Two main themes emerged from the focus groups: “trials 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.…”