Interpretability of Cancer Clinical Trial Results Using Restricted Mean Survival Time as an Alternative to the Hazard Ratio

Pak, Kyongsun; Uno, Hajime; Kim, Dae Hyun; Tian, Lü; Kane, Robert C.; Takeuchi, Masahiro; Fu, Haoda; Claggett, Brian; Wei, Lee‐Jen

doi:10.1001/jamaoncol.2017.2797

Cited by 202 publications

(211 citation statements)

References 16 publications

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“…To identify more precisely the perceived value, the design and analysis of a conventional cancer clinical trial can be improved by adopting a robust statistical procedure that enables clinically meaningful interpretations of the treatment effect. The RMST‐based quantitative method may be used as a primary tool for future cancer trials or to help us to better understand the clinical interpretation of the HR .…”

Section: Discussionmentioning

confidence: 99%

“…RMST—the difference in RMST is the area between the curves within a specific time window . We calculated this measure based on the follow‐up period of the clinical trials used for the FDA approvals.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the area between the curves within a specific time window is a reasonable summary to quantify the survival benefit. This alternative measure is the restricted mean survival time (RMST), where the measurement is restricted only to the follow‐up period of the clinical study .…”

Section: Introductionmentioning

confidence: 99%

“…In a comparative clinical study with progression‐free survival (PFS) or OS as the endpoint, the HR is routinely used to report the survival results of the study. The clinical interpretation of the HR may not be straightforward, whereas a quantitative method that is based on the RMST may be used as a primary tool to better understand the clinical interpretation of the HR .…”

Section: Introductionmentioning

confidence: 99%

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Median Survival or Mean Survival: Which Measure Is the Most Appropriate for Patients, Physicians, and Policymakers?

et al. 2019

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Introduction Understanding the efficacy of treatments is crucial for patients, physicians, and policymakers. Median survival, the most common measure used in the outcome reporting of oncology clinical trials, is easy to understand; however, it describes only a single time point. The interpretation of the hazard ratio is difficult, and its underlying statistical assumptions are not always met. The objective of this study was to evaluate alternative measures based on the mean benefit of novel oncology treatments. Materials and Methods We reviewed all U.S. Food and Drug Administration (FDA) approvals for oncology agents between 2013 and 2017. We digitized survival curves as reported in the clinical trials used for the FDA approvals and implemented statistical transformations to calculate for each trial the restricted mean survival time (RMST), as well as the mean survival using Weibull distribution. We compared the mean survival with the median survival benefit in each clinical trial. Results The FDA approved 83 solid tumor indications for oncology agents between 2013 and 2017, of which 27 approvals based on response rates, whereas 49 approvals were based on survival endpoints (progression‐free survival and overall survival). The average improvement in median overall survival or progression‐free survival was 4.6 months versus 3.6 months improvement in the average RMST and 6.1 months improvement in mean survival using Weibull distribution. Conclusion Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of prospective clinical trials. Implications for Practice Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Median Survival or Mean Survival: Which Measure Is the Most Appropriate for Patients, Physicians, and Policymakers?

et al. 2019

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“…Cox proportional hazards models were used to calculate the hazard ratio (HR) of each factor for DFS and OS in the multivariate analysis. Restricted mean survival time (RMST) 14 was also calculated as an alternative estimand for the analysis of time-to-event data. Restricted mean survival time to time to event was determined by integrating the Kaplan-Meier survival curve to 5 or 10 years of follow-up.…”

Section: Discussionmentioning

confidence: 99%