An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Vaccine Clinical Trials

Melissa K Andrew; Sean Matthews; Joon Hyung Kim; Megan E Riley; Desmond Curran

doi:10.2147/CIA.S364997

An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Vaccine Clinical Trials

Clin Interv Aging. 2022 Aug 19:17:1261-1274. doi: 10.2147/CIA.S364997. eCollection 2022.

Authors

Melissa K Andrew¹, Sean Matthews², Joon Hyung Kim³, Megan E Riley³, Desmond Curran⁴

Affiliations

¹ Department of Medicine (Division of Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada.
² Freelance C/O GSK, Wavre, Belgium.
³ GSK, Rockville, MD, USA.
⁴ GSK, Wavre, Belgium.

Abstract

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: clinical trial; frail elderly; frailty; herpes zoster; older adults; quality of life; vaccine.

Publication types

Clinical Trial

MeSH terms

Aged
Female
Frail Elderly
Frailty*
Geriatric Assessment / methods
Herpes Zoster Vaccine*
Humans
Quality of Life
Retrospective Studies

Substances

Herpes Zoster Vaccine

Grants and funding

This work was sponsored by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA was involved in all stages of the study conduct and analysis, and took responsibility for all costs associated with the development and publishing of the present manuscript. GlaxoSmithKline Biologicals SA does not veto ongoing publications or control the decision about what journal to submit to, with ultimate decision on the target journal made by the coauthors. The lead and corresponding author MKA received no payment related to any aspect of this study.