Authors: Grill, Joshua D. | Zhou, Yan | Karlawish, Jason | Elashoff, David
Article Type: Research Article
Abstract: Most patients with Alzheimer's disease (AD) do not have a spouse. Despite this, the majority of AD research participants enroll with a spouse study partner. It remains unclear if differences between AD patients who do and do not have a spouse may bias study results. In this study, we examined whether AD patients with different study partner types (spouse versus adult child) demonstrate different rates of disease progression over two years on three outcome measures commonly used in AD research, including clinical trials. We used data from the National Alzheimer's Coordinating Center Uniform Data Set to examine disease progression in …participants age 55–90 with probable AD dementia. We examined disease progression as measured by the Clinical Dementia Rating Scale-Sum of the Boxes score, the Mini Mental Status Examination, and the Functional Assessment Questionnaire. Analyses were performed on data for all available eligible participants from the NACC UDS and after performing a propensity-matching model to better account for inherent differences between the populations of interest. Propensity matching was successful only when models did not include age and gender. For both propensity-matched analyses and those of all available data, we did not observe any differences between the study partner populations for any outcome measure. These results suggest that if investigators can improve in recruiting AD patients with adult child caregivers to research, the implications to study results may be minimal. Show more
Keywords: Adult children, Alzheimer's disease, caregivers, clinical trial, disease progression, spouses
DOI: 10.3233/JAD-131052
Citation: Journal of Alzheimer's Disease, vol. 38, no. 3, pp. 507-514, 2014
Authors: Lu, Thuy V. | Grill, Joshua D. | Gillen, Daniel L.
Article Type: Research Article
Abstract: Background: In randomized clinical trials (RCTs), monitoring adverse events (AEs) and serious AEs (SAEs) is critical. All Alzheimer’s disease (AD) RCTs require participants to enroll with a study partner. Objective: We examined AE reporting rates in mild-to-moderate AD trials and their associations with study partner type. Methods: We estimated AE reporting rates using placebo data from seven independent RCTs conducted by the Alzheimer’s Disease Cooperative Study. We assessed the heterogeneity of reporting rates as a function of visits using generalized estimating equations. In the primary analysis, we tested the hypotheses that the rates of reporting differed by study partner type …and time they spent with the participant weekly using Poisson regression with robust variance estimation. In all regression models, log-transformed total patient years was included. Results: The estimated reporting rates were 2.83 (95% CI: 2.66, 3.02), 1.18 (95% CI: 1.09, 1.28), 0.23 (95% CI: 0.19, 0.27), and 0.28 (95% CI: 0.24, 0.33) events per participant year for grade 1–3 AEs and SAEs, respectively. We estimated that greater number of visits per year was associated with increased reporting for grade 1–2 AEs and SAEs. We did not find evidence to suggest that AE reporting differed by study partner type or by time the study partner spent with the participant. Conclusions: Study partner type and time the study partner spent with the participant did not appear to impact AE reporting. Estimated reporting rates may be useful to evaluate safety in future studies, particularly those with no control arm and similar visit frequencies. Show more
Keywords: Adverse event, Alzheimer’s disease, clinical trials, study partner
DOI: 10.3233/JAD-231283
Citation: Journal of Alzheimer's Disease, vol. 98, no. 2, pp. 729-738, 2024
Authors: Grill, Joshua D. | Holbrook, Andrew | Pierce, Aimee | Hoang, Dan | Gillen, Daniel L.
Article Type: Research Article
Abstract: Difficult participant recruitment is a consistent barrier to successful medical research. Potential participant registries represent an increasingly common intervention to overcome this barrier. A variety of models for registries exist, but few data are available to instruct their design and implementation. To provide such data, we surveyed 110 cognitively normal research participants enrolled in a longitudinal study of aging and dementia. Seventy-four (67%) individuals participated in the study. Most (78%, CI: 0.67, 0.87) participants were likely to enroll in a registry. Willingness to participate was reduced for registries that required enrollment through the Internet using a password (26%, CI: 0.16, …0.36) or through email (38%, CI: 0.27, 0.49). Respondents acknowledged their expectations that researchers share information about their health and risk for disease and their concerns that their data could be shared with for-profit companies. We found no difference in respondent preferences for registries that shared contact information with researchers, compared to honest broker models that take extra precautions to protect registrant confidentiality (28% versus 30%; p = 0.46). Compared to those preferring a shared information model, respondents who preferred the honest broker model or who lacked model preference voiced increased concerns about sharing registrant data, especially with for-profit organizations. These results suggest that the design of potential participant registries may impact the population enrolled, and hence the population that will eventually be enrolled in clinical studies. Investigators operating registries may need to offer particular assurances about data security to maximize registry enrollment but also must carefully manage participant expectations. Show more
Keywords: Clinical trial, recruitment, registries
DOI: 10.3233/JAD-160873
Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 939-946, 2017
Authors: Galasko, Douglas R. | Grill, Joshua D. | Lingler, Jennifer H. | Heidebrink, Judith L.
Article Type: Article Commentary
Abstract: A blood test for Alzheimer’s disease is now available for clinical use in persons with cognitive impairment. This is an extraordinary milestone, though the amyloid-based PrecivityAD™ test is not without limitations. Pre and post-test counseling are essential. Phosphorylated tau blood tests are likely to follow soon. When used in conjunction with an appropriate clinical evaluation, blood tests provide the opportunity for an early, accurate, and accessible diagnosis of Alzheimer’s disease. Standalone use, however, carries a significant risk of misinterpretation and is strongly discouraged. Now is the time to develop appropriate use criteria to guide the use of these promising assays.
Keywords: Alzheimer’s disease, biomarker, blood test, diagnosis
DOI: 10.3233/JAD-215490
Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 963-966, 2022
Authors: Salazar, Christian R. | Ritchie, Marina | Gillen, Daniel L. | Grill, Joshua D.
Article Type: Research Article
Abstract: 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. Show more
Keywords: Alzheimer’s disease, diagnostic-related group, ethnicity, patient dropouts, patient participation, race
DOI: 10.3233/JAD-215537
Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1557-1566, 2022
Authors: Ritchie, Marina | Witbracht, Megan | Nuño, Michelle M. | Hoang, Dan | Gillen, Daniel L. | Grill, Joshua D.
Article Type: Research Article
Abstract: 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. Show more
Keywords: Aducanumab, Alzheimer’s disease, clinical trial, earned media, recruitment, secondary prevention
DOI: 10.3233/JAD-220801
Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1291-1300, 2022
Authors: Largent, Emily A. | Bhardwaj, Twisha | Clapp, Justin T. | Sykes, Olivia Saúl | Harkins, Kristin | Grill, Joshua D.
Article Type: Research Article
Abstract: Background: Participants in Alzheimer’s disease (AD) prevention studies are generally required to enroll with a study partner; this requirement constitutes a barrier to enrollment for some otherwise interested individuals. Analysis of dyads enrolled in actual AD trials suggests that the study partner requirement shapes the population under study. Objective: To understand if individuals can identify someone to serve as their study partner and whether they would be willing to ask that individual. Methods: We conducted semi-structured interviews with cognitively unimpaired, English-speaking older adults who had previously expressed interest in AD research by signing up for a research registry. We also …interviewed their likely study partners. Audio-recorded interviews were transcribed and coded in an iterative, team-based process guided by a content analysis approach. Results: We interviewed 60 potential research participants and 17 likely study partners. Most potential participants identified one or two individuals they would be willing to ask to serve as their study partner. Interviewees saw value in the study partner role but also understood it to entail burdens that could make participation as a study partner difficult. The role was seen as relatively more burdensome for individuals still in the workforce or with family responsibilities. Calls from the researcher to discuss the importance of the role and the possibility of virtual visits were identified as potential strategies for increasing study partner availability. Conclusion: Efforts to increase recruitment, particularly representative recruitment, of participants for AD prevention studies should reduce barriers to participation by thoughtfully designing the study partner role. Show more
Keywords: Alzheimer’s disease, ethics, registries, research, research design
DOI: 10.3233/JAD-220061
Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1021-1033, 2022
Authors: Grill, Joshua D. | Hoang, Dan | Gillen, Daniel L. | Cox, Chelsea G. | Gombosev, Adrijana | Klein, Kirsten | O’Leary, Steve | Witbracht, Megan | Pierce, Aimee
Article Type: Research Article
Abstract: Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer’s disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical …data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries. Show more
Keywords: Clinical trial, preclinical Alzheimer’s disease, recruitment, registries
DOI: 10.3233/JAD-180069
Citation: Journal of Alzheimer's Disease, vol. 63, no. 3, pp. 1055-1063, 2018
Authors: Gabel, Matthew | Bollinger, Rebecca M. | Coble, Dean W. | Grill, Joshua D. | Edwards, Dorothy F. | Lingler, Jennifer H. | Chin, Erin | Stark, Susan L.
Article Type: Research Article
Abstract: Background: Retention of study participants is essential to advancing Alzheimer’s disease (AD) research and developing therapeutic interventions. However, recent multi-year AD studies have lost 10% to 54% of participants. Objective: We surveyed a random sample of 443 participants (Clinical Dementia Rating [CDR]≤1) at four Alzheimer Disease Research Centers to elucidate perceived facilitators and barriers to continued participation in longitudinal AD research. Methods: Reasons for participation were characterized with factor analysis. Effects of perceived fulfillment of one’s own goals and complaints on attendance and likelihood of dropout were estimated with logistic regression models. Open-ended responses suggesting study improvements were analyzed with …a Latent Dirichlet Allocation topic model. Results: Factor analyses revealed two categories, personal benefit and altruism, as drivers of continued participation. Participants with cognitive impairment (CDR > 0) emphasized personal benefits more than societal benefits. Participants with higher trust in medical researchers were more likely to emphasize broader social benefits. A minority endorsed any complaints. Higher perceived fulfillment of one’s own goals and fewer complaints were related to higher attendance and lower likelihood of dropout. Facilitators included access to medical center support and/or future treatment, learning about AD and memory concerns, and enjoying time with staff. Participants’ suggestions emphasized more feedback about individual test results and AD research. Conclusion: The results confirmed previously identified facilitators and barriers. Two new areas, improved communication about individual test results and greater feedback about AD research, emerged as the primary factors to improve participation. Show more
Keywords: Alzheimer’s disease, barriers, facilitators, retention
DOI: 10.3233/JAD-215710
Citation: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 945-955, 2022
Authors: Bollinger, Rebecca M. | Gabel, Matthew | Coble, Dean W. | Chen, Szu-Wei | Keleman, Audrey A. | Doralus, Jeff | Chin, Erin | Lingler, Jennifer H. | Grill, Joshua D. | Stark, Susan L. | Edwards, Dorothy F.
Article Type: Research Article
Abstract: Background: Study partners are required for all participants at Alzheimer’s Disease Research Centers (ADRCs). Study partners’ attitudes and beliefs may contribute to missed visits and negatively impact retention of participants in longitudinal AD studies. Objective: Study partners (N = 212) of participants (Clinical Dementia Rating® [CDR]≤2) at four ADRCs were randomly surveyed to examine their facilitators and barriers to continued participation in AD studies. Methods: Reasons for participation were analyzed with factor analysis and regression analysis. Effects of complaints and goal fulfillment on attendance were estimated with fractional logistic models. Open-ended responses were characterized with a Latent Dirichlet Allocation topic model. Results: …Study partners participated for personal benefit and altruism. They emphasized personal benefits more when their participants had a CDR > 0 than when they had a CDR = 0. This difference declined with participant age. The majority of study partners rated their ADRC participation as positive and meeting their goals. Although half reported at least one complaint, very few regretted participating. Those who reported that ADRC participation fulfilled their goals or had fewer complaints were more likely to have perfect attendance. Study partners requested more feedback about test results and better management of study visits. Conclusion: Study partners are motivated by both personal and altruistic goals. The salience of each goal depends on their trust in researchers and the participant’s cognitive status and age. Retention may improve with perceived goal fulfillment and fewer complaints. Potential areas for improving retention are providing more information about the participant’s test results and better management of study visits. Show more
Keywords: Adult children, Alzheimer’s disease, barriers, facilitators, spouse
DOI: 10.3233/JAD-230079
Citation: Journal of Alzheimer's Disease, vol. 94, no. 1, pp. 189-199, 2023