Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
Department of Biostatistics, University of Iowa, Iowa City, IA, USA.
Mov Disord. 2024 Oct;39(10):1809-1816. doi: 10.1002/mds.29963. Epub 2024 Aug 5.
Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington's Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes.
Investigate time to the event of functional decline (HD-ISS Stage 3) as an endpoint for trials in HD and present sample size estimates after enrichment.
We classified individuals from observational studies according to the HD-ISS. We assessed the ability of the prognostic index normed (PIN) and its components to predict time to HD-ISS Stage 3. For enrichment, we formed groups from deciles of the baseline PIN distribution for HD-ISS Stage 2 participants. We selected enrichment subgroups closer to Stage 3 transition and estimated sample sizes, using delay in the transition time as the effect size.
In predicting time to HD-ISS Stage 3, PIN outperforms its components. Survival curves for each PIN decile show that groups with PIN from 1.48 to 2.74 have median time to Stage 3 of approximately 2 years and these are combined to create enrichment subgroups. Sample size estimates are presented by enrichment subgroup.
PIN is predictive of functional decline. A delay of 9 months or more in the transition to Stage 3 for an enriched sample yields feasible sample size estimates, demonstrating that this approach can aid in planning future trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
可以使用观察性研究的数据来模拟临床试验场景，为真实世界试验的设计提供关键信息。亨廷顿病综合分期系统（HD-ISS）描述了个体一生中疾病的进展情况，并允许试验设计具有灵活性，旨在延缓进展。富集方法可应用于 HD-ISS，以确定需要更小估计样本量的亚组。
将功能下降（HD-ISS 阶段 3）的时间作为 HD 试验的终点，并提出富集后的样本量估计。
我们根据 HD-ISS 对观察性研究中的个体进行分类。我们评估了预后指数归一化（PIN）及其组成部分预测 HD-ISS 阶段 3 时间的能力。为了富集，我们根据 HD-ISS 阶段 2 参与者的基线 PIN 分布的十分位数形成组。我们选择更接近阶段 3 过渡的富集亚组，并使用过渡时间延迟作为效应量来估计样本量。
在预测 HD-ISS 阶段 3 的时间方面，PIN 优于其组成部分。每个 PIN 十分位数的生存曲线表明，PIN 值在 1.48 至 2.74 之间的组中位时间到第 3 阶段约为 2 年，这些组被组合在一起形成富集亚组。按富集亚组呈现样本量估计。
PIN 可预测功能下降。富集样本中过渡到第 3 阶段的延迟 9 个月或更长时间可得出可行的样本量估计，表明这种方法可以帮助规划未来的试验。© 2024 作者。运动障碍由 Wiley 期刊代表国际帕金森病和运动障碍协会出版。
