Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.
Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.
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DOI：
10.3389/fnagi.2022.883131
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
证明认知能力下降速度减慢是阿尔茨海默病（AD）临床试验中的一项常见结果指标。认知终点的选择通常包括在许多丰富的表型观察性队列研究中对候选结果指标进行建模。选择认知终点的一个重要部分是考虑由于重复认知测试（称为“实践效应”）而导致的性能改善。由于初级和二级AD预防试验主要由认知未受损的参与者组成，因此实践效果可能很大，并且可能对检测认知变化产生相当大的影响。AD预防试验中的实践效果与观察性研究中的实践效果相似的程度以及这些潜在差异如何影响试验尚不清楚。在本研究中，我们分析了最近完成的DIAN-TU-001临床试验（TU）和相关的DIAN观察性（OBS）研究的数据。结果表明，TU中的无症状突变携带者在整个试验期间对几个关键结局表现出持续的实践影响。重要的是，这些实践相关的改善在TU的某些测试中相对于来自OBS研究的匹配参与者更大。我们的研究结果表明，实践效果的大小可能无法通过模拟观察性研究中的潜在终点来捕获，这些研究中的评估通常不太频繁，并且不存在药物预期效应。使用替代工具形式（在我们的研究中由计算机化任务表示）可能会部分减轻临床试验中的实践效果，但将实践效果作为结果也可能是可行的。因此，研究者在设计认知终点AD预防试验时，必须仔细考虑实践效果（通过最小化或直接建模），使用具有相似评估频率的试验数据。
Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer’s disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed “practice effects”). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies.
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影响因子：
7.2
作者：
Duff, Kevin;Lyketsos, Constantine G.;McCaffrey, Robert J.
通讯作者：
McCaffrey, Robert J.
影响因子：
9.9
作者：
McDade, Eric;Wang, Guoqiao;Bateman, Randall J.
通讯作者：
Bateman, Randall J.
DOI：
10.1002/trc2.12050
发表时间：
2020-01-01
影响因子：
4.8
作者：
Cummings, Jeffrey;Lee, Garam;Zhong, Kate
通讯作者：
Zhong, Kate
影响因子：
2.6
作者：
Beglinger, LJ;Gaydos, B;Siemers, ER
通讯作者：
Siemers, ER
DOI：
10.1177/1533317511411907
发表时间：
2011-06
期刊：
American journal of Alzheimer's disease and other dementias
影响因子：
--
作者：
Hammers D;Spurgeon E;Ryan K;Persad C;Heidebrink J;Barbas N;Albin R;Frey K;Darby D;Giordani B
通讯作者：
Giordani B