在帕金森病改良疗法试验中采用数字化措施对研究设计的影响。

IF 3.2 Q1 HEALTH CARE SCIENCES & SERVICES
Frontiers in digital health Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.3389/fdgth.2024.1430994
Jennie S Lavine, Anthony D Scotina, Seth Haney, Jessie P Bakker, Elena S Izmailova, Larsson Omberg
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引用次数: 0

摘要

导言:帕金森病影响着 850 多万人,目前还没有获准用于治疗该病的药物。由于缺乏足够灵敏的检测治疗效果的方法,疾病调整疗法(DMT)的临床试验受到了阻碍。方法:在此,我们对从 44 名参与者(其中 21 人确诊为帕金森病)收集的原始三轴加速度数据中得出的一整套居家运动测量方法的测试-重复可靠性进行了估算,并将估算结果用于模拟 DMT 试验中的数字测量方法。我们考虑了三种评估时间表,并对模拟数据拟合了线性混合模型,以确定是否能检测出治疗效果:结果:我们发现居家测量的可靠性各不相同;许多测量的 ICC 与 MDS-UPDRS 第三部分总分一样高或更高。与每季度一次的门诊评估相比,频繁的居家评估可将检测疾病进展减少 30% 所需的样本量从每个研究臂超过 300 个减少到 150 个,而连续居家评估和均匀居家评估所需的样本量则分别少于 100 个。放宽对疾病进展反应性和进展率变异性的假设,也能稳健地得出居家评估在检测随时间变化的优越性方面的结果:总的来说,在DMT试验中,居家评估具有良好的可靠性,可以灵敏地检测治疗效果。未来的工作需要更好地了解帕金森病进展变异的原因,并确定最合适的效果检测统计方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impacts on study design when implementing digital measures in Parkinson's disease-modifying therapy trials.

Introduction: Parkinson's Disease affects over 8.5 million people and there are currently no medications approved to treat underlying disease. Clinical trials for disease modifying therapies (DMT) are hampered by a lack of sufficiently sensitive measures to detect treatment effect. Reliable digital assessments of motor function allow for frequent at-home measurements that may be able to sensitively detect disease progression.

Methods: Here, we estimate the test-retest reliability of a suite of at-home motor measures derived from raw triaxial accelerometry data collected from 44 participants (21 with confirmed PD) and use the estimates to simulate digital measures in DMT trials. We consider three schedules of assessments and fit linear mixed models to the simulated data to determine whether a treatment effect can be detected.

Results: We find at-home measures vary in reliability; many have ICCs as high as or higher than MDS-UPDRS part III total score. Compared with quarterly in-clinic assessments, frequent at-home measures reduce the sample size needed to detect a 30% reduction in disease progression from over 300 per study arm to 150 or less than 100 for bursts and evenly spaced at-home assessments, respectively. The results regarding superiority of at-home assessments for detecting change over time are robust to relaxing assumptions regarding the responsiveness to disease progression and variability in progression rates.

Discussion: Overall, at-home measures have a favorable reliability profile for sensitive detection of treatment effects in DMT trials. Future work is needed to better understand the causes of variability in PD progression and identify the most appropriate statistical methods for effect detection.

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来源期刊
CiteScore
4.20
自引率
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审稿时长
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