Impact of study partner replacement in a mild cognitive impairment clinical trial

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-02-27 DOI:10.1002/trc2.70063

Lucy A. Dolmadjian, Mary Ryan Baumann, Joshua D. Grill, Daniel L. Gillen

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Abstract

BACKGROUND

In Alzheimer's disease (AD) clinical trials, including trials enrolling patients with mild cognitive impairment (MCI), participants must enroll with a study partner (SP). SPs ensure compliance and are a source of study data, including assessments of the participant's cognition and function. Consistency in SP reporting is essential to trial data integrity.

METHODS

We quantified SP replacement and its impact on bias and variance of SP-reported AD Cooperative Study Activities of Daily Living for MCI (ADCS-ADL-MCI) in the ADCS Vitamin E/Donepezil MCI Trial. We used logistic regression to estimate the association between SP type (spouse or non-spouse) and the odds of experiencing SP change. We used generalized estimating equations to longitudinally model the differences in consecutively recorded ADCS-ADL-MCI scores as a function of whether SP change occurred. We used a similar model to quantify end-of-study change from baseline in ADCS-ADL-MCI scores.

RESULTS

Among 768 participants, 40 (5%) experienced at least one SP change. We estimated that the odds of experiencing a SP change were 65% lower for spousal dyads when compared to non-spousal dyads (odds ratio [OR] = 0.35; 95% confidence interval [CI]: [0.18–0.67]). Compared to those with a consistent SP, participants who experienced a SP change had, on average, a consecutive visit absolute score difference that was 1.60 points greater in magnitude (95% CI: [0.62–2.57]), suggesting greater volatility. ADCS-ADL-MCI scores were neither systematically higher nor lower when SP change occurred, on average (-0.23; 95% CI: [-1.60, 1.14]), suggesting minimal bias. The estimated difference in variance for end-of-study change from baseline ADCS-ADL-MCI was observed to be higher for those with SP change compared to those without, but the difference was not statistically significant (1.29; 95% CI: [0.47–1.17]).

CONCLUSION

SP replacement occurred for a meaningful number of participants but did not result in systematic bias on a functional outcome in this trial, but it did increase variability.

Highlights

Among participants in a mild cognitive impairment trial, approximately 5% experienced at least one study partner replacement.
The estimated odds of replacement were 60% lower for participants with a spousal study partner at baseline, compared to those with a non-spouse partner.
We observed increased variance, but not bias, in the mean within-participant change in consecutive ADCS-ADL-MCI scores among participants experiencing study partner replacement.
We observed greater variance for end-of-study change from baseline ADCS-ADL-MCI for those who experienced a study partner replacement, compared to those who did not.

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

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.