Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials.
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ABSTRACT:
SUBMITTER: Langbaum JB
PROVIDER: S-EPMC9911558 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials.
Langbaum Jessica B JB Zissimopoulos Julie J Au Rhoda R Bose Niranjan N Edgar Chris J CJ Ehrenberg Evan E Fillit Howard H Hill Carl V CV Hughes Lynne L Irizarry Michael M Kremen Sarah S Lakdawalla Darius D Lynn Nancy N Malzbender Kristina K Maruyama Tetsuyuki T Massett Holly A HA Patel Deep D Peneva Desi D Reiman Eric M EM Romero Klaus K Routledge Carol C Weiner Michael W MW Weninger Stacie S Aisen Paul S PS
Alzheimer's & dementia : the journal of the Alzheimer's Association 20220810 2
Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, ...[more]
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Project description:Among the key challenges in Alzheimer's disease drug development is the timely completion of clinical trials. Unfortunately, clinical trials often suffer from slow or insufficient enrollment. Successful clinical trial recruitment describes a balance between expeditiously achieving full enrollment and ensuring an appropriate study sample. Investigators face a number of challenges to the successful negotiation of this balance. The failure to address these challenges means that drug development may take more time and money and that trial results may not adequately represent drug efficacy or may not be applicable beyond the study. We review the challenges to recruitment and retention in Alzheimer's disease clinical trials and present a framework to address them.
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Project description:BackgroundTimely 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.MethodsWe 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.ResultsNo 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.ConclusionsTrial 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.
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Project description:PurposePalliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study.Patients and methodsThe PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications.ResultsFrom an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%).ConclusionChallenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.
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Project description:BackgroundAlzheimer's disease (AD) is associated with considerable costs and has a significant impact on health and social care systems.ObjectiveThis study assessed whether baseline comorbidities present in 2,594 patients with AD participating in two semagacestat randomized placebo-controlled trials (RCTs) would significantly impact overall costs.MethodsResource utilization was captured using the Resource Utilization in Dementia Scale-Lite. Comorbidities and concomitant medications were tabulated via patient and caregiver reports. Only baseline data were analyzed. Direct and indirect costs per month were calculated per patient. The relationship between cost and explanatory variables was explored in a regression model.ResultsThe baseline monthly cost of care in this RCT population was £1,147 ± 2,483, with informal care costs accounting for 75% of costs. Gender, age, and functional status were significant predictors of costs (p ≤ 0.0001). The cost ratio was not impacted when the number of comorbidities was added to the model (cost ratio = 0.95; 95% CI 0.91-0.99) or when combined with the number of concomitant medications (cost ratio = 0.97; 95% CI 0.95-1.00). Inconsistent findings related to the impact of individual comorbidities on costs were noted in sensitivity analyses.ConclusionsThe number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because RCTs often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for AD.
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Project description:The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.
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