Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: We have developed a reliable, robust and easy-to-implement CT-FI with potential retrospective or prospective application in other clinical trials.

Keywords: frailty, frail elderly, older adults, herpes zoster, quality of life, vaccine, clinical trial

中文翻译：

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基于缺陷累积的易于实施的临床试验虚弱指数：带状疱疹疫苗临床试验的验证

目的：尽管是最需要保护的人群之一，但体弱的老年人在临床试验中往往没有得到很好的体现。尽管虚弱可能会影响对治疗和疫苗的反应，但即使在招募虚弱的参与者时，也可能不会在试验中明确考虑虚弱，因为人们认为在不增加参与者或数据收集负担的情况下很难有效地衡量虚弱。我们使用重组带状疱疹疫苗（ZOE-50 和 ZOE -70 项研究）。
方法： 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从 0 到 1 进行评分，然后将每个参与者的总和除以所考虑的缺陷总数。验证分析包括与衰弱指数的通常模式相关的分布和年龄和性别关联的描述性验证，与假设与衰弱相关的结果相关的回归，以及指数内的重新抽样方法。
结果：CT-FI 分布由 0-0.70 范围内的伽马分布很好地表示。赤字积累随着实际年龄的增长而增加，女性更高。多变量 Cox 回归生存分析表明，CT-FI、年龄和性别是死亡率的重要预测因子。Jackknife 和 Bootstrap 重采样方法突出了 CT-FI 的稳健性，它对特定个体或变量组的包含/排除不敏感。
结论：我们开发了一种可靠、稳健且易于实施的 CT-FI，在其他临床试验中具有潜在的回顾性或前瞻性应用。

关键词：体弱，体弱的老年人，老年人，带状疱疹，生活质量，疫苗，临床试验