Holm Sven P, Wolfer Arnaud M, Pointeau Grégoire H S, Lipsmeier Florian, Lindemann Michael
Roche Pharma Research and Early Development, pRED Informatics, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Heliyon. 2022 Aug 17;8(8):e10259. doi: 10.1016/j.heliyon.2022.e10259. eCollection 2022 Aug.
In this systematic review we sought to characterize practice effects on traditional in-clinic or digital performance outcome measures commonly used in one of four neurologic disease areas (multiple sclerosis; Huntington's disease; Parkinson's disease; and Alzheimer's disease, mild cognitive impairment and other forms of dementia), describe mitigation strategies to minimize their impact on data interpretation and identify gaps to be addressed in future work.
Fifty-eight original articles (49 from Embase and an additional 4 from PubMed and 5 from additional sources; cut-off date January 13, 2021) describing practice effects or their mitigation strategies were included.
Practice effects observed in healthy volunteers do not always translate to patients living with neurologic disorders. Mitigation strategies include reliable changes indices that account for practice effects or a run-in period. While the former requires data from a reference sample showing similar practice effects, the latter requires a sufficient number of tests in the run-in period to reach steady-state performance. However, many studies only included 2 or 3 test administrations, which is insufficient to define the number of tests needed in a run-in period.
Several gaps have been identified. In particular the assessment of practice effects on an individual patient level as well as the temporal dynamics of practice effects are largely unaddressed. Here, digital tests, which allow much higher testing frequency over prolonged periods of time, can be used in future work to gain a deeper understanding of practice effects and to develop new metrics for assessing and accounting for practice effects in clinical research and clinical trials.
在本系统评价中，我们试图描述练习效应在四种神经系统疾病领域（多发性硬化症、亨廷顿舞蹈病、帕金森病以及阿尔茨海默病、轻度认知障碍和其他形式的痴呆症）中常用的传统门诊或数字性能结局测量指标上的表现，描述减轻其对数据解释影响的缓解策略，并确定未来工作中需要解决的差距。
纳入了58篇描述练习效应或其缓解策略的原创文章（49篇来自Embase，另外4篇来自PubMed，5篇来自其他来源；截止日期为2021年1月13日）。
在健康志愿者中观察到的练习效应并不总是适用于患有神经系统疾病的患者。缓解策略包括考虑练习效应的可靠变化指数或预试验期。虽然前者需要来自显示类似练习效应的参考样本的数据，但后者需要在预试验期进行足够数量的测试以达到稳定状态表现。然而，许多研究仅包括2或3次测试管理，这不足以确定预试验期所需的测试次数。
已确定了几个差距。特别是，在个体患者层面上对练习效应的评估以及练习效应的时间动态在很大程度上未得到解决。在此，数字测试允许在较长时间内进行更高频率的测试，可在未来工作中用于更深入地了解练习效应，并开发新的指标以评估和考虑临床研究和临床试验中的练习效应。
