Validating Restricted Mean Survival Time Estimates From Reconstructed Kaplan-Meier Data Against Original Trial Individual Patient Data From Trials Conducted by the Canadian Cancer Trials Group

Louis Everest; Scott Blommaert; Dongsheng Tu; Joseph L Pater; Annette Hay; Matthew C Cheung; Kelvin K W Chan

doi:10.1016/j.jval.2021.12.004

Validating Restricted Mean Survival Time Estimates From Reconstructed Kaplan-Meier Data Against Original Trial Individual Patient Data From Trials Conducted by the Canadian Cancer Trials Group

Value Health. 2022 Jul;25(7):1157-1164. doi: 10.1016/j.jval.2021.12.004. Epub 2022 Jan 29.

Authors

Louis Everest¹, Scott Blommaert¹, Dongsheng Tu², Joseph L Pater², Annette Hay², Matthew C Cheung³, Kelvin K W Chan⁴

Affiliations

¹ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
² Department of Public Health Sciences, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
³ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada.
⁴ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Cancer Care Ontario, Toronto, ON, Canada. Electronic address: kelvin.chan@sunnybrook.ca.

PMID: 35779942
DOI: 10.1016/j.jval.2021.12.004

Abstract

Objectives: The development of novel cancer therapies, including immuno-oncology agents, has increased interest in reconstructed individual patient data (IPD) based restricted mean survival time (RMST) analyses. Additionally, reconstructed IPD-based RMST is recommended in cost-effectiveness analyses when original trial IPD are not available. Nevertheless, recently concerns regarding potential bias of reconstructed-IPD RMST have been presented, because reconstructed-IPD RMSTs have not been validated and previous validation endpoints may not capture the entire Kaplan-Meier (KM) curve, especially the "tail." Our study aims to validate the recommended method of IPD reconstruction by comparing reconstructed IPD- and original trial IPD-based RMST.

Methods: Canadian Cancer Trials Group trials from 1990 to 2017 were included. Overall survival and progression-free survival IPD were reconstructed based on published KM curves using the Guyot method. Analysts were blinded to original trial IPD. RMST was calculated at 1 year and over the entire KM curve. Reconstructed-IPD and original trial-IPD (gold-standard) RMSTs were compared for accuracy and predictive error via mean deviation, mean absolute error (MAE), mean percentage bias, and Bland-Altman plots and across KM curve quality (vector traced or bitmapped).

Results: We identified 39 trials. The mean deviation, MAE, and mean percentage bias of RMST between the reconstructed IPD and original trial IPD were small. In particular, the mean deviation was -0.01 months and -0.04 months, MAE was 0.19 months and 0.24 months, and mean percentage bias was 0.82% and 0.84% in overall survival KM curves in control and experimental arms, respectively. Accuracy was generally not associated with KM curve quality.

Conclusions: RMST derived from reconstructed IPD displayed excellent accuracy and predictive error compared with the gold standard. Reconstructed IPD could be used to calculate RMST in lieu of original trial IPD, to facilitate decision making for clinicians, researchers, and policy makers.

Keywords: reconstructed individual patient data; restricted mean survival time; validation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bias
Canada
Humans
Medical Oncology
Neoplasms* / therapy
Survival Rate