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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在轻度认知障碍临床试验中研究伴侣替代的影响

在阿尔茨海默病（AD）临床试验中，包括纳入轻度认知障碍（MCI）患者的试验，参与者必须与研究伙伴（SP）一起注册。SPs确保依从性，并且是研究数据的来源，包括对参与者认知和功能的评估。SP报告的一致性对试验数据的完整性至关重要。在ADCS维生素E/多奈哌齐MCI试验中，我们量化SP替代及其对SP报告的MCI AD日常生活合作研究活动（ADCS- adl -MCI）的偏倚和方差的影响。我们使用逻辑回归来估计SP类型（配偶或非配偶）与经历SP变化的几率之间的关系。我们使用广义估计方程对连续记录的ADCS-ADL-MCI评分的差异作为SP是否发生变化的函数进行纵向建模。我们使用了类似的模型来量化研究结束时ADCS-ADL-MCI评分与基线的变化。结果在768名参与者中，40名（5%）经历了至少一次SP改变。我们估计，夫妻二人组经历SP变化的几率比无配偶二人组低65%(比值比[OR] = 0.35；95%置信区间[CI]:[0.18-0.67])。与具有一致SP的参与者相比，经历SP变化的参与者平均连续访问的绝对得分差异在幅度上高出1.60分（95% CI:[0.62-2.57]），表明更大的波动性。当SP发生变化时，ADCS-ADL-MCI评分既没有系统地升高，也没有系统地降低，平均(-0.23；95% CI:[-1.60, 1.14])，表明偏差最小。研究结束时ADCS-ADL-MCI基线变化的估计方差差异观察到SP改变的患者比未改变的患者更高，但差异无统计学意义(1.29；95% ci:[0.47-1.17])。结论：在本试验中，SP替代在相当数量的参与者中发生，但并未导致功能结果的系统偏倚，但确实增加了可变性。在轻度认知障碍试验的参与者中，大约5%的人至少更换了一个研究伙伴。与没有配偶的参与者相比，有配偶研究对象的参与者在基线时更换的估计几率低60%。我们观察到，在经历研究伴侣更换的参与者中，连续ADCS-ADL-MCI评分的参与者内平均变化增加了方差，但没有偏倚。我们观察到，与那些没有更换研究伴侣的人相比，那些经历过研究伴侣更换的人在研究结束时ADCS-ADL-MCI基线变化的差异更大。

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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.