Dolmadjian Lucy A, Baumann Mary Ryan, Grill Joshua D, Gillen Daniel L
Department of Statistics Donald Bren School of Information and Computer Sciences University of California Irvine California USA.
Department of Population Health Sciences University of Wisconsin-Madison Madison Wisconsin USA.
Alzheimers Dement (N Y). 2025 Feb 27;11(1):e70063. doi: 10.1002/trc2.70063. eCollection 2025 Jan-Mar.
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.
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.
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]).
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. 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.
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）一起入组。研究伙伴确保依从性，并且是研究数据的一个来源，包括对参与者认知和功能的评估。研究伙伴报告的一致性对于试验数据的完整性至关重要。
我们在ADCS维生素E/多奈哌齐MCI试验中，对研究伙伴更换情况及其对研究伙伴报告的MCI的AD协作研究日常生活活动（ADCS-ADL-MCI）偏差和方差的影响进行了量化。我们使用逻辑回归来估计研究伙伴类型（配偶或非配偶）与研究伙伴更换几率之间的关联。我们使用广义估计方程对连续记录的ADCS-ADL-MCI分数的差异进行纵向建模，将其作为研究伙伴更换是否发生的函数。我们使用类似的模型来量化研究结束时ADCS-ADL-MCI分数相对于基线的变化。
在768名参与者中，40名（5%）经历了至少一次研究伙伴更换。我们估计，与非配偶二元组相比，配偶二元组经历研究伙伴更换的几率低65%（优势比[OR]=0.35；95%置信区间[CI]：[0.18 - 0.67]）。与研究伙伴一致的参与者相比，经历研究伙伴更换的参与者，其连续访视的绝对分数差异平均大1.60分（95%CI：[0.62 - 2.57]），表明波动性更大。当发生研究伙伴更换时，ADCS-ADL-MCI分数平均既没有系统性地更高也没有更低（-0.23；95%CI：[-1.60, 1.14]），表明偏差最小。与未经历研究伙伴更换的参与者相比，经历研究伙伴更换的参与者在研究结束时相对于基线ADCS-ADL-MCI变化的方差估计差异更高，但差异无统计学意义（1.29；95%CI：[0.47 - 1.17]）。
相当数量的参与者发生了研究伙伴更换，但在本试验中这并未导致功能结局出现系统性偏差，但确实增加了变异性。在轻度认知障碍试验的参与者中，约5%经历了至少一次研究伙伴更换。与基线时有非配偶研究伙伴的参与者相比，基线时有配偶研究伙伴的参与者更换的估计几率低60%。我们观察到，在经历研究伙伴更换的参与者中，连续ADCS-ADL-MCI分数的参与者内平均变化的方差增加，但无偏差。与未经历研究伙伴更换的参与者相比，经历研究伙伴更换的参与者在研究结束时相对于基线ADCS-ADL-MCI变化的方差更大。
