Department of Medicine (Division of Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada.
Freelance C/O GSK, Wavre, Belgium.
Clin Interv Aging. 2022 Aug 19;17:1261-1274. doi: 10.2147/CIA.S364997. eCollection 2022.
Despite being among those most in need of protection, frail older adults are often not well represented in clinical trials. Although frailty likely influences responses to treatments and vaccines, frailty may not be explicitly considered in trials even when frail participants are enrolled due to the perception that frailty is difficult to measure effectively and efficiently without adding to participant or data collection burden. We developed an easy-to-implement frailty index, the Clinical Trial-Frailty Index (CT-FI), based on baseline medical history and standard patient-reported outcomes using data from clinical trials of recombinant Zoster vaccine (the ZOE-50 and ZOE-70 studies). Our objective was to demonstrate that the CT-FI is a robust measure that may be used retrospectively or prospectively in clinical trials where sufficient patient data have been collected.
The CT-FI was based on baseline medical history and Quality of Life questionnaires (SF-36 and EQ-5D). Items meeting criteria for inclusion were scored from 0 to 1, then summed for each participant and divided by the total number of deficits considered. Validation analyses included descriptive verification of distribution and age- and sex-associations in relation to usual patterns of the frailty index, regressions in relation to outcomes hypothesized to be related to frailty, and resampling methods within the index.
The CT-FI distribution was well represented by a gamma distribution with a range of 0-0.70. Deficit accumulation increased with chronological age and was higher for females. Multivariate Cox regression survival analysis showed that the CT-FI, age, and sex were significant predictors of mortality. Jackknife and Bootstrap resampling methods highlighted the robustness of the CT-FI, which was not sensitive to inclusion/exclusion of specific individual or groups of variables.
We have developed a reliable, robust and easy-to-implement CT-FI with potential retrospective or prospective application in other clinical trials.
尽管脆弱的老年人是最需要保护的人群之一，但他们在临床试验中往往代表性不足。尽管虚弱可能会影响治疗和疫苗的反应，但即使招募了虚弱的参与者，由于认为在不增加参与者或数据收集负担的情况下，虚弱难以有效和高效地衡量，试验中也可能没有明确考虑虚弱。我们基于临床试验中使用的数据，使用基线病史和标准患者报告结果，开发了一种易于实施的虚弱指数，即临床试验虚弱指数（CT-FI），用于重组带状疱疹疫苗（ZOE-50 和 ZOE-70 研究）的临床试验。我们的目的是证明 CT-FI 是一种强大的衡量标准，可以在已经收集了足够患者数据的临床试验中回顾性或前瞻性使用。
CT-FI 基于基线病史和生活质量问卷（SF-36 和 EQ-5D）。符合纳入标准的项目得分为 0 到 1，然后对每个参与者进行评分，并除以考虑的总缺陷数。验证分析包括描述性验证分布以及与虚弱指数通常模式相关的年龄和性别关联、与假设与虚弱相关的结果的回归以及指数内的重采样方法。
CT-FI 的分布通过伽马分布很好地表示，范围为 0 到 0.70。缺陷积累随着年龄的增长而增加，女性更高。多元 Cox 回归生存分析表明，CT-FI、年龄和性别是死亡率的显著预测因素。Jackknife 和 Bootstrap 重采样方法突出了 CT-FI 的稳健性，它对包含/排除特定个体或变量组不敏感。
我们开发了一种可靠、强大且易于实施的 CT-FI，具有在其他临床试验中回顾性或前瞻性应用的潜力。
