Related papers: Quantifying treatment differences in confirmatory …
What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has…
While well-established methods for time-to-event data are available when the proportional hazards assumption holds, there is no consensus on the best inferential approach under non-proportional hazards (NPH). However, a wide range of…
Studies to compare the survival of two or more groups using time-to-event data are of high importance in medical research. The gold standard is the log-rank test, which is optimal under proportional hazards. As the latter is no simple…
A fundamental concept in two-arm non-parametric survival analysis is the comparison of observed versus expected numbers of events on one of the treatment arms (the choice of which arm is arbitrary), where the expectation is taken assuming…
Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change…
We conducted a systematic comparison of statistical methods used for the analysis of time-to-event outcomes under various proportional and nonproportional hazard (NPH) scenarios. Our study used data from recently published oncology trials…
Background: For RCTs with time-to-event endpoints, proportional hazard (PH) models are typically used to estimate treatment effects and logrank tests are commonly used for hypothesis testing. There is growing support for replacing this…
The log-rank test and the Cox proportional hazards model are commonly used to compare time-to-event data in clinical trials, as they are most powerful under proportional hazards. But there is a loss of power if this assumption is violated,…
Non-proportional hazards (NPH) have been observed in confirmatory clinical trials with time to event outcomes. Under NPH, the hazard ratio does not stay constant over time and the log-rank test is no longer the most powerful test. The…
The log-rank test is most powerful under proportional hazards (PH). In practice, non-PH patterns are often observed in clinical trials, such as in immuno-oncology; therefore, alternative methods are needed to restore the efficiency of…
The introduction of checkpoint inhibitors in immuno-oncology has raised questions about the suitability of the log-rank test as the default primary analysis method in confirmatory studies, particularly when survival curves exhibit…
In oncology, conduct well-powered time-to-event randomized clinical trials may be challenging due to limited patietns number. Many designs for single-arm trials (SATs) have recently emerged as an alternative to overcome this issue. They…
Loss of power and clear description of treatment differences are key issues in designing and analyzing a clinical trial where non-proportional hazard is a possibility. A log-rank test may be very inefficient and interpretation of the hazard…
When planning a clinical trial for a time-to-event endpoint, we require an estimated effect size and need to consider the type of effect. Usually, an effect of proportional hazards is assumed with the hazard ratio as the corresponding…
The classical approach to analyze time-to-event data, e.g. in clinical trials, is to fit Kaplan-Meier curves yielding the treatment effect as the hazard ratio between treatment groups. Afterwards commonly a log-rank test is performed in…
In practice, the logrank test is the most widely used method for testing the equality of survival distributions. It is the optimal method under the proportional hazard assumption. However, since non-proportional hazards are often…
Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…
In confirmatory cancer clinical trials, overall survival (OS) is normally a primary endpoint in the intention-to-treat (ITT) analysis under regulatory standards. After the tumor progresses, it is common that patients allocated to the…
We propose a new class of weighted logrank tests (WLRT) that control the risk of concluding that a new drug is more efficacious than standard of care, when, in fact, it is uniformly inferior. Perhaps surprisingly, this risk is not…
Restricted mean survival time (RMST) offers a compelling nonparametric alternative to hazard ratios for right-censored time-to-event data, particularly when the proportional hazards assumption is violated. By capturing the total event-free…