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Introduction: Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development., Methods: We performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs. no disclosure), remote study partner participation (vs. in person), and increased risk of brain swelling (vs. lower risk). We used a generalized estimating equation to model the utility of factor levels., Results: Returning tau PET results had the highest utility (est: 0.47; 95% confidence interval [CI]: 0.13, 0.81; P = 0.007); remote study partner participation showed a similar trend (est: 0.29; 95% CI: -0.05, 0.63; P = 0.097). Trials with active-controlled design (est: 0.01; 95% CI: -0.33, 0.35; P = 0.956) did not demonstrate utility and higher risk of brain swelling had negative utility (est: -0.64; 95% CI: -0.99, -0.30; P < 0.001)., Discussion: Returning additional biomarker results may increase willingness to enroll in early AD trials., Highlights: We compared mild cognitive impairment participant preferences for four trial design features. Returning tau positron emission tomography results had the highest utility. Remote study partner participation showed a positive, albeit non-significant, trend. No utility was observed for an active aducanumab-control design., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Trialists need a thorough understanding of whether reactions to Alzheimer's disease (AD) biomarker information differ among racial and ethnic groups in preclinical AD trials., Methods: We used data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease Study to analyze cognitively unimpaired participants' responses on the Impact of Event Scale (IES) 24 to 72 hours after amyloid disclosure. We fit a linear regression model to test whether mean IES scores differed among participants from specific racial and ethnic groups. We considered potential effect modification by amyloid status., Results: Reactions to disclosure did not significantly differ among participant groups based on self-reported race and ethnicity. Although the results were not significant when stratified by amyloid status, all racial and ethnic groups except for participants self-reporting Hispanic/Latino ethnicity were observed to have higher mean IES in the elevated amyloid group., Discussion: These results support continued use of current disclosure methods in preclinical AD trials., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Participant retention is a key factor that affects clinical trial integrity. Trial protocols estimate attrition as a function of sample size calculations. Alzheimer's disease (AD) is an area of active treatment development. We aimed to quantify the association between trial duration and completion rates and provide guidance for estimating attrition in AD trial protocols., Methods: Using the Alzforum and ClinicalTrials.gov databases, we analyzed retention data from 125 mild-to-moderate AD and 12 mild cognitive impairment (MCI) clinical trials. We compared the rates of completion between trial arms (active vs. control) and ran regression models to test the hypothesis that trials with longer study duration have lower trial completion using all available data and restricting to placebo data. Our primary outcome was the odds of trial completion for a 6-month increase in trial duration. From the regression model, we estimated the proportion of participants completing 6-, 12-, and 18-month trials., Results: We found that 21 (17%) mild-to-moderate AD trials and 1 (8%) MCI trial demonstrated greater dropout in treatment compared to placebo arms. For every 6-month increase in trial duration, there was a 27% decrease in the odds of trial completion (OR = 0.73; 95% CI 0.66, 0.81; p < 0.001) among participants in mild-to-moderate AD trials and a 55% decrease (OR = 0.45; 95% CI 0.36, 0.57; p < 0.001) among participants in MCI trials. The proportion of participants in the placebo group completing 6-, 12-, and 18-month trials were estimated to be 85.2%, 80.0%, and 73.3% for mild-to-moderate AD trials and 91.9%, 84.2%, and 71.3% for MCI trials, respectively., Conclusions: Longer duration trials may be underpowered to demonstrate estimated treatment effects and may suffer from a greater risk of bias than do shorter trials., (© 2023. The Author(s).)

Background: Timely accrual of a representative sample is a key factor in whether Alzheimer's disease (AD) clinical trials successfully answer the scientific questions under study. Studies in other fields have observed that, over time, recruitment to trials has become increasingly reliant on larger numbers of sites, with declines in the average per-site recruitment rate. Here, we examined the trends in recruitment over a 20-year period of NIH-funded AD clinical trials conducted by the Alzheimer's Disease Cooperative Study (ADCS), a temporally consistent network of sites devoted to interventional research., Methods: We performed retrospective analyses of eleven ADCS randomized clinical trials. To examine the recruitment planning, we calculated the expected number of participants to be enrolled per site for each trial. To examine the actual trial recruitment rates, we quantified the number of participants enrolled per site per month., Results: No effects of time were observed on recruitment planning or overall recruitment rates across trials. No trial achieved an overall recruitment rate greater than one subject per site per month. We observed the fastest recruitment rates in trials with no competition and the slowest in trials that overlapped in time. The highest recruitment rates were consistently seen early within trials and declined over the course of studies., Conclusions: Trial recruitment projections should plan for fewer than one participant randomized per site per month and consider the number of other AD trials being conducted concurrently., (© 2023. The Author(s).)

Background: Best approaches for retaining research participants in Alzheimer's disease cohort studies are understudied., Objective: Using data from the National Alzheimer's Coordinating Center Uniform Data Set, we evaluated the associations of unique strategies with participant retention across Alzheimer's Disease Research Centers and explored potential effect modification by race, ethnicity and diagnostic group., Methods: We examined retention at the first follow-up visit among participants enrolled during 2015-2017. Structured surveys ascertained 95 retention tactics among 12 strategies. Strategy-specific summary scores were created based on the number of implemented tactics for each strategy and grouped into tertiles. Generalized estimating equations were constructed to evaluate associations between strategy scores and the odds of retention, controlling for age, sex, education, study partner type, marital status, visit length, battery length, diagnostic group, race and ethnicity. Separate models were stratified by race, ethnicity and diagnostic group. Effect modification was formally tested with interaction terms., Results: Among 5,715 total participants enrolled, 4,515 were Non-Hispanic White (79%), 335 were Hispanic/Latino (6%), 651 were Non-Hispanic Black (11%), and 214 were Non-Hispanic Asian (4%). Compared to the lowest tertile of scores, the highest tertile of scores involving improvement in study personnel and communication of study requirements and details were associated with 61% higher odds of retention in fully adjusted models (adjusted Odds Ratios [aOR] = 1.61, 95% Confidence Interval [CI] = 1.05-2.47 and aOR = 1.55, 95% CI = 1.03-2.35, respectively). We did not find evidence for effect modification., Conclusion: In the setting of limited resources, specific retention strategies may be more valuable than others.

Background: Clinical trials now test promising therapies in the preclinical stages of Alzheimer's disease (AD). Participant willingness to enroll in different types of preclinical AD trials is understudied and whether the FDA approval of aducanumab affected these attitudes is unknown., Objective: To evaluate preferences toward three preclinical AD trial scenarios and whether the FDA approval of aducanumab changed willingness to participate among potential trial participants., Methods: Through an electronic survey, we asked enrollees in a recruitment registry age 50-79 to rate their willingness (using a 6-point Likert scale) to enroll in three hypothetical preclinical AD trial scenarios: an in-clinic infused monoclonal antibody intervention, a home-infused monoclonal antibody intervention, and an oral BACE inhibitor intervention. We administered the survey before and after the FDA approval of aducanumab. We used a generalized estimating equation model to assess group differences in preference for the trial scenarios. We used a paired t-test to determine if willingness to participate (using total willingness across three scenarios as the outcome) changed after the FDA decision., Results: At baseline, the mean participant willingness was highest in the in-clinic infusion scenario. There was no significant change in willingness to participate, overall, after the FDA decision. Participants who were independently aware of the FDA's decision (prior to the second survey) demonstrated reduced willingness to participate; participants unaware of the FDA decision demonstrated no change., Conclusion: Willingness to participate in preclinical AD trials may have been negatively affected by the FDA's decision to approve aducanumab among those aware of the decision.

Importance: Underrepresentation of many racial/ethnic groups in Alzheimer disease (AD) clinical trials limits generalizability of results and hinders opportunities to examine potential effect modification of candidate treatments., Objective: To examine racial and ethnic differences in recruitment methods and trial eligibility in a multisite preclinical AD trial., Design, Setting, and Participants: This cross-sectional study analyzed screening data from the Anti-Amyloid in Asymptomatic AD study, collected from April 2014 to December 2017. Participants were categorized into 5 mutually exclusive ethnic/racial groups (ie, Hispanic, Black, White, Asian, and other) using participant self-report. Data were analyzed from May through December 2020 and included 5945 cognitively unimpaired older adults between the ages of 65 and 85 years screened at North American study sites., Main Outcomes and Measures: Primary outcomes included recruitment sources, study eligibility, and ineligibility reasons. To assess the probability of trial eligibility, regression analyses were performed for the likelihood of being eligible after the first screening visit involving clinical and cognitive assessments., Results: Screening data were included for 5945 participants at North American sites (mean [SD] age, 71.7 [4.9] years; 3524 women [59.3%]; 5107 White [85.9%], 323 Black [5.4%], 261 Hispanic [4.4%], 112 Asian [1.9%], and 142 [2.4%] who reported race or ethnicity as other). Recruitment sources differed by race and ethnicity. While White participants were recruited through a variety of sources, site local recruitment efforts resulted in the majority of Black (218 [69.2%]), Hispanic (154 [59.7%]), and Asian (61 [55.5%]) participants. Participants from underrepresented groups had lower mean years of education (eg, mean [SD] years: Hispanic participants, 15.5 [3.2] years vs White participants, 16.7 [2.8] years) and more frequently were women (226 [70.0%] Black participants vs 1364 [58.5%] White participants), were unmarried (184 [56.9%] Black participants vs 1364 [26.7%] White participants), and had nonspousal study partners (237 [73.4%] Black participants vs 2147 [42.0%] White participants). They were more frequently excluded for failure to meet cognitive inclusion criteria (eg, screen failures by specific inclusion criteria: 147 [45.5%] Black participants vs 1338 [26.2%] White participants). Compared with White participants, Black (odds ratio [OR], 0.43; 95% CI, 0.34-0.54; P < .001), Hispanic (OR, 0.53; 95% CI, 0.41-0.69; P < .001), and Asian participants (OR, 0.56; 95% CI, 0.38-0.82; P = .003) were less likely to be eligible after screening visit 1., Conclusions and Relevance: Racial/ethnic groups differed in sources of recruitment, reasons for screen failure, and overall probability of eligibility in a preclinical AD trial. These results highlight the need for improved recruitment strategies and careful consideration of eligibility criteria when planning preclinical AD clinical trials.

BackgroundMany cognitively unimpaired older adults are interested in learning their Alzheimer's disease (AD) biomarker status, but little is known about motivations to undergo biomarker testing and result disclosure in the setting of preclinical AD trials.ObjectivesExamine whether motivations to undergo AD biomarker testing and disclosure differ for individuals who have elevated amyloid compared to those with not elevated amyloid, and whether disclosure of amyloid results impacts participants' motivations.Design, setting, participantsWe conducted post-hoc analyses using data from the EARLY study, a preclinical AD trial of the beta-secretase inhibitor atabecestat. As part of the screening process of the trial, participants underwent biomarker testing and disclosure. We analyzed data from n=2241 participants.MeasurementsWe analyzed data from the Views and Perceptions of Amyloid Imaging (VPAI), a 9-item questionnaire assessing how strongly participants agreed with motivating factors for undergoing amyloid testing. The VPAI was administered at the first screening visit and again after amyloid disclosure.ResultsPrior to amyloid disclosure, a greater proportion of participants in the elevated amyloid group responded at the two highest levels of endorsement for the items, "to confirm the feeling that I might already be developing symptoms of AD dementia" (p