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The restricted mean survival time (RMST) is the mean survival time in the study population followed up to a specific time point, and is simply the area under the survival curve up to the specific time point. The difference between two RMSTs…

Methodology · Statistics 2025-09-18 Peter Zhang , Brent Logan , Michael Martens

A common feature of many recent trials evaluating the effects of immunotherapy on survival is that non-proportional hazards can be anticipated at the design stage. This raises the possibility to use a statistical method tailored towards…

Applications · Statistics 2021-08-27 Dominic Magirr , José L. Jiménez

Delayed separation of survival curves is a common occurrence in confirmatory studies in immuno-oncology. Many novel statistical methods that aim to efficiently capture potential long-term survival improvements have been proposed in recent…

Methodology · Statistics 2022-01-26 Dominic Magirr , José L. Jiménez

The one-sample log-rank test is the method of choice for single-arm Phase II trials with time-to-event endpoint. It allows to compare the survival of the patients to a reference survival curve that typically represents the expected survival…

Methodology · Statistics 2026-03-02 Jannik Feld , Moritz Fabian Danzer , Andreas Faldum , Rene Schmidt

Non-proportional hazards (NPH) are often observed in clinical trials with time-to-event endpoints. A common example is a long-term clinical trial with a delayed treatment effect in immunotherapy for cancer. When designing clinical trials…

Methodology · Statistics 2025-09-18 Yujie Zhao , Yilong Zhang , Larry Leon , Keaven M. Anderson

The restricted mean survival time (RMST) difference offers an interpretable causal contrast to estimate the treatment effect for time-to-event outcomes, yet a wide range of available estimators leaves limited guidance for practice. We…

Methodology · Statistics 2026-03-02 Charlotte Voinot , Clément Berenfeld , Imke Mayer , Bernard Sebastien , Julie Josse

Randomized Controlled Trials (RCT) are the current gold standards to empirically measure the effect of a new drug. However, they may be of limited size and resorting to complementary non-randomized data, referred to as observational, is…

Methodology · Statistics 2025-06-11 Ahmed Boughdiri , Julie Josse , Erwan Scornet

Nonparametric covariate adjustment is considered for log-rank type tests of treatment effect with right-censored time-to-event data from clinical trials applying covariate-adaptive randomization. Our proposed covariate-adjusted log-rank…

Methodology · Statistics 2023-01-23 Ting Ye , Jun Shao , Yanyao Yi

In confirmatory clinical trials, survival outcomes are frequently studied and interim analyses for efficacy and/or futility are often desirable. Methods such as the log rank test and Cox regression model are commonly used to compare…

Methodology · Statistics 2024-03-27 Peter Zhang , Brent Logan , Michael Martens

In clinical or epidemiological follow-up studies, methods based on time scale indicators such as the restricted mean survival time (RMST) have been developed to some extent. Compared with traditional hazard rate indicator system methods,…

Methodology · Statistics 2022-05-26 Chengfeng Zhang , Hongji Wu , Baoyi Huang , Hao Yuan , Yawen Hou , Zheng Chen

We propose a restricted win probability estimand for comparing treatments in a randomized trial with a time-to-event outcome. We also propose Bayesian estimators for this summary measure as well as the unrestricted win probability. Bayesian…

Methodology · Statistics 2024-11-06 Michelle Leeberg , Xianghua Luo , Thomas A. Murray

Time-to-event endpoints show an increasing popularity in phase II cancer trials. The standard statistical tool for such one-armed survival trials is the one-sample log-rank test. Its distributional properties are commonly derived in the…

Methodology · Statistics 2026-03-02 Moritz Fabian Danzer , Andreas Faldum , Rene Schmidt

Randomized controlled trials (RCTs) with binary primary endpoints introduce novel challenges for inferring the causal effects of treatments. The most significant challenge is non-collapsibility, in which the conditional odds ratio estimand…

Methodology · Statistics 2024-03-01 Yunfan Li , Arman Sabbaghi , Jonathan R. Walsh , Charles K. Fisher

In clinical follow-up studies with a time-to-event end point, the difference in the restricted mean survival time (RMST) is a suitable substitute for the hazard ratio (HR). However, the RMST only measures the survival of patients over a…

Methodology · Statistics 2023-06-27 Zijing Yang , Chengfeng Zhang , Yawen Hou , Zheng Chen

The difference in restricted mean survival time (RMST) is a clinically meaningful measure to quantify treatment effect in randomized controlled trials, especially when the proportional hazards assumption does not hold. Several frequentist…

Competing risks data are common in medical studies, and the sub-distribution hazard (SDH) ratio is considered an appropriate measure. However, because the limitations of hazard itself are not easy to interpret clinically and because the SDH…

Applications · Statistics 2021-10-19 Jingjing Lyu , Yawen Hou , Zheng Chen

The Cox regression model and its associated hazard ratio (HR) are frequently used for summarizing the effect of treatments on time to event outcomes. However, the HR's interpretation strongly depends on the assumed underlying survival…

Methodology · Statistics 2021-08-10 Pablo Martinez-Camblor , Todd A. MacKenzie , A. James O'Malley

Desirability Of Outcome Ranking (DOOR) methodology accounts for problems that conventional benefit:risk analyses in clinical trials ignore, such as competing risks and the trade-off relationship between efficacy and toxicity. DOOR levels…

Methodology · Statistics 2025-05-19 Shiyu Shu , Guoqing Diao , Toshimitsu Hamasaki , Scott Evans

Covariate balance is crucial in obtaining unbiased estimates of treatment effects in observational studies. Methods based on inverse probability weights have been widely used to estimate treatment effects with observational data. Machine…

Methodology · Statistics 2021-04-08 Michele Santacatterina

The hazard ratio from the Cox proportional hazards model is a ubiquitous summary of treatment effect. However, when hazards are non-proportional, the hazard ratio can lose a stable causal interpretation and become study-dependent because it…

Methodology · Statistics 2026-02-17 Xiang Meng , Lu Tian , Kenneth Kehl , Hajime Uno