Diversity in Alzheimer's disease drug trials: The importance of eligibility criteria

Franzen, Sanne; Smith, Jade Emily; Berg, Esther van den; Mindt, Monica Rivera; Bruchem-Visser, Rozemarijn L van; Abner, Erin L.; Schneider, Lon S.; Prins, Niels D.; Babulal, Ganesh M.; Papma, Janne M.

doi:10.1002/alz.12433

Cited by 63 publications

(83 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite these milestones, we observed no improvements over time in the racial or ethnic diversity of these trial populations. This result is consistent with a previous systematic review of 101 AD trials of candidate disease-modifying therapies, which showed no improvement (or worsening) in enrollment of participants from minoritized racial and ethnic groups over time between 2001 to 2019 [ 39 ]. Nearly 25% of older Americans are from a racial or ethnic minority group [ 40 ] and certain groups may be overburdened by AD [ 41 ].…”

Section: Discussionsupporting

confidence: 92%

Recruitment across two decades of NIH-funded Alzheimer’s disease clinical trials

Ritchie

Gillen²,

Grill³

2023

Alz Res Therapy

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Recruitment across two decades of NIH-funded Alzheimer’s disease clinical trials

Ritchie

Gillen²,

Grill³

2023

Alz Res Therapy

View full text Add to dashboard Cite

show abstract

“…This finding suggests that overall interest in dementia prevention research participation may be consistent across different sexes, racial and ethnic backgrounds, and socioeconomic statuses. On the other hand, structural and logistical components of AD prevention clinical trials, such as recruitment methods, eligibility criteria, and access to trial sites, pose significant barriers to participation and disproportionately impact communities of color ( 13 ). Previous research on recruitment of under-represented groups to AD clinical trials suggests community outreach may be the most effective tool to address these disparities.…”

Section: Discussionmentioning

confidence: 99%

“…Inadequate and slow recruitment of volunteer participants to dementia prevention clinical trials, however, is delaying progress and requires urgent intervention ( 4 – 9 ). Critically, under-representation of racial and ethnic groups in prevention trials limits the generalizability of results to sub-populations at greatest risk for AD ( 6 , 10 – 13 ). Black and Hispanic adults are at 2 and 1.5 times greater risk to develop AD compared to their Non-Hispanic White counterparts, respectively, but make up just 10% of AD research participants ( 10 , 11 ) compared to 32% of the general population ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…By design, these trials are burdensome on participants and their family members, often requiring large screening efforts to meet stringent eligibility criteria, testing of new drugs with potential side effects, and performing procedures to assess biomarker and genetic risk information. A recent systematic analysis found that eligibility criteria, specifically, may lead to disproportionate exclusion of racially and ethnically diverse individuals in AD clinical trials ( 13 ). Additionally, previous research on barriers to recruitment to dementia prevention clinical trials suggests that logistical constraints (e.g., time commitment, lack of transportation), concerns related to medications and procedures, and general lack of interest in participation are important challenges for enrollment and may vary by sociodemographic factors ( 16 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

US Adults’ Likelihood to Participate in Dementia Prevention Drug Trials: Results from the National Poll on Healthy Aging

et al. 2022

View full text Add to dashboard Cite

Background Recruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. A better understanding of the general public’s interest in dementia prevention research participation is needed to inform future recruitment strategies. Objective To examine US adults’ characteristics associated with self-reported likelihood to participate in dementia prevention clinical trials. Design We conducted a cross-sectional survey using the October 2018 wave of the University of Michigan National Poll on Healthy Aging. Setting The National Poll on Healthy Aging is a nationally representative survey of adults using KnowledgePanel (Ipsos Public Affairs LLC), a probability-based panel of the civilian, noninstitutionalized US population. Participants We analyzed data from 1,028 respondents, ages 50 to 64 years, who completed a web survey module on brain health. Measurements We used logistic regression models to examine associations between sociodemographic and dementia-related factors (e.g., family history) and self-reported likelihood to participate in a dementia prevention clinical trial of a new medicine (“very” or “somewhat likely” vs. “not likely” survey responses). Among respondents not likely to participate, we examined frequency of reasons endorsed for this decision, stratified by age, sex, and race and ethnicity. Results Of the 1,028 respondents, half were female, 68% Non-Hispanic White, 13% Hispanic, and 12% Non-Hispanic Black. Twelve percent of respondents reported being very likely to participate in a dementia prevention trial, 32% somewhat likely, and 56% not likely. Factors associated with higher likelihood to participate were higher perceived risk of dementia [OR, 2.17 (95% CI, 1.61, 2.93)], a positive family history of dementia [OR, 1.75 (95% CI, 1.27, 2.43)], and having discussed dementia prevention with a doctor [OR, 2.20 (95% CI, 1.10, 4.42)]. There were no differences in likelihood to participate by sociodemographic characteristics. Among 570 respondents not likely to participate, 39% said they did not want to be a guinea pig, 23% thought dementia would not affect them, 22% thought there would be too high a chance for harm, 15% indicated study participation would take too much time, and 5% reported fear of learning information about oneself. There were no differences across age, sex, and racial and ethnic groups. Conclusions In this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race and ethnicity were not. Findings suggest that recruitment interventions focused on increasing knowledge of dementia risk and prevention trials and involving healthcare providers may b...

show abstract

“…While the exact cause of AD has not been elucidated, studies have found that AD is the result of a combination of genes, lifestyle, and environmental factors, caused in part by specific genetic changes [ 6 – 9 ]. A combination of drug therapy, non-drug therapy, and careful nursing can reduce symptoms and delay the progression of the disease [ 10 – 12 ], but there is no specific drug that can cure AD or effectively reverse the progression of the disease. The course of Alzheimer's disease is about 5–10 years, and a few patients can survive for more than 10 years.…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Wang

2021

Journal of Healthcare Engineering

View full text Add to dashboard Cite

The purpose of this study was to identify hub genes closely correlated with Alzheimer's disease (AD) and their association with immune cell infiltration. In this work, 119 overlapping differentially expressed genes (DEGs) were obtained from GSE5281 and GSE122063 datasets through differential expression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 119 DEGs, revealing some important biological functions and key pathways. AD immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the AD group and the control group. Finally, correlation analysis between target hub genes and immune cells indicated that GFAP had a positive or negative correlation with some specific immune cells. Our results provided useful clues, which will help to explain the molecular mechanism of AD and search for precise prognostic markers and potential therapeutic targets.

show abstract

Diversity in Alzheimer's disease drug trials: The importance of eligibility criteria

Cited by 63 publications

References 70 publications

Recruitment across two decades of NIH-funded Alzheimer’s disease clinical trials

Recruitment across two decades of NIH-funded Alzheimer’s disease clinical trials

US Adults’ Likelihood to Participate in Dementia Prevention Drug Trials: Results from the National Poll on Healthy Aging

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Contact Info

Product

Resources

About