Mikaela K. Nishida, Michelle M. Nuño, Joshua D. Grill, Daniel L. Gillen
{"title":"两项行业赞助的阿尔茨海默病临床试验中信息提供者替代的影响","authors":"Mikaela K. Nishida, Michelle M. Nuño, Joshua D. Grill, Daniel L. Gillen","doi":"10.1002/trc2.70009","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid-trial informant replacement impacts study data in industry-sponsored trials.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We conducted a retrospective analysis of two industry-sponsored AD clinical trials testing semagacestat in mild-to-moderate AD dementia. We assessed the relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores. Using generalized estimating equations, we assessed bias and variability using mean (bias) and mean absolute (variance) change in ADCS-ADL between successive visits as outcomes. Both models adjusted for a priori–specified potential confounding variables including participant sex, age, informant type, trial, time, previous ADCS-ADL score, and region. To analyze the impact on end-of-study change-from-baseline results, we used an analysis of covariance model to estimate the association between replacement and end-of-study change-from-baseline in ADCS-ADL, in which we adjusted for participant sex, age, informant type, trial, baseline measurement, and region. We conducted an <i>F</i>-test to compare the variances of this change.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Among <i>N</i> = 2637 randomized participants, 69 participants (2.6%) experienced 78 occurrences of replacement. For visits standardized to be 3 months apart, the difference in mean between-visit change in ADCS-ADL was approximately −1.61 points (95% confidence interval [CI]: −3.79, 0.57; <i>P</i> = 0.147), comparing participants who experienced replacement to similar participants who had stable informants. The difference in the mean between-visit absolute change was approximately 2.02 points (95% CI: 0.34, 3.70; <i>P</i> = 0.019). We did not estimate a statistically significant difference in end-of-study change-from-baseline (Est. = −0.70 points; 95% CI: −5.88, 4.48; <i>P</i> = 0.790) or a significant ratio of variances (Est. = 1.13; 95% CI: 0.67, 2.28; <i>P</i> = 0.600) for participants with replacement compared to those with stable informants.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Informant replacement was associated with increased between-visit variability but had limited impact on overall trial outcomes.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Informant replacement occurred in 2.6% of participants in these industry trials.</li>\n \n <li>Informant replacement was associated with increased variance in acute Alzheimer's Disease Cooperative Study Activities of Daily Living reporting.</li>\n \n <li>Informant replacement had a limited impact on overall change-from-baseline outcomes.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70009","citationCount":"0","resultStr":"{\"title\":\"Impacts of informant replacement in two industry-sponsored Alzheimer's disease clinical trials\",\"authors\":\"Mikaela K. 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Both models adjusted for a priori–specified potential confounding variables including participant sex, age, informant type, trial, time, previous ADCS-ADL score, and region. To analyze the impact on end-of-study change-from-baseline results, we used an analysis of covariance model to estimate the association between replacement and end-of-study change-from-baseline in ADCS-ADL, in which we adjusted for participant sex, age, informant type, trial, baseline measurement, and region. We conducted an <i>F</i>-test to compare the variances of this change.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>Among <i>N</i> = 2637 randomized participants, 69 participants (2.6%) experienced 78 occurrences of replacement. For visits standardized to be 3 months apart, the difference in mean between-visit change in ADCS-ADL was approximately −1.61 points (95% confidence interval [CI]: −3.79, 0.57; <i>P</i> = 0.147), comparing participants who experienced replacement to similar participants who had stable informants. The difference in the mean between-visit absolute change was approximately 2.02 points (95% CI: 0.34, 3.70; <i>P</i> = 0.019). 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Impacts of informant replacement in two industry-sponsored Alzheimer's disease clinical trials
INTRODUCTION
In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid-trial informant replacement impacts study data in industry-sponsored trials.
METHODS
We conducted a retrospective analysis of two industry-sponsored AD clinical trials testing semagacestat in mild-to-moderate AD dementia. We assessed the relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores. Using generalized estimating equations, we assessed bias and variability using mean (bias) and mean absolute (variance) change in ADCS-ADL between successive visits as outcomes. Both models adjusted for a priori–specified potential confounding variables including participant sex, age, informant type, trial, time, previous ADCS-ADL score, and region. To analyze the impact on end-of-study change-from-baseline results, we used an analysis of covariance model to estimate the association between replacement and end-of-study change-from-baseline in ADCS-ADL, in which we adjusted for participant sex, age, informant type, trial, baseline measurement, and region. We conducted an F-test to compare the variances of this change.
RESULTS
Among N = 2637 randomized participants, 69 participants (2.6%) experienced 78 occurrences of replacement. For visits standardized to be 3 months apart, the difference in mean between-visit change in ADCS-ADL was approximately −1.61 points (95% confidence interval [CI]: −3.79, 0.57; P = 0.147), comparing participants who experienced replacement to similar participants who had stable informants. The difference in the mean between-visit absolute change was approximately 2.02 points (95% CI: 0.34, 3.70; P = 0.019). We did not estimate a statistically significant difference in end-of-study change-from-baseline (Est. = −0.70 points; 95% CI: −5.88, 4.48; P = 0.790) or a significant ratio of variances (Est. = 1.13; 95% CI: 0.67, 2.28; P = 0.600) for participants with replacement compared to those with stable informants.
DISCUSSION
Informant replacement was associated with increased between-visit variability but had limited impact on overall trial outcomes.
Highlights
Informant replacement occurred in 2.6% of participants in these industry trials.
Informant replacement was associated with increased variance in acute Alzheimer's Disease Cooperative Study Activities of Daily Living reporting.
Informant replacement had a limited impact on overall change-from-baseline outcomes.
期刊介绍：
Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.
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