Related papers: Exhausting the type I error level in event-driven …
When planning an oncology clinical trial, the usual approach is to assume proportional hazards and even an exponential distribution for time-to-event endpoints. Often, besides the gold-standard endpoint overall survival (OS),…
The progression-free survival ratio (PFSr) is a widely used measure in personalized oncology trials. It evaluates the effectiveness of treatment by comparing two consecutive event times - one under standard therapy and one under an…
Classic adaptive designs for time-to-event trials are based on the log-rank statistic and its increments. Thereby, only information from the time-to-event endpoint on which the selected log-rank statistic is based may be used for…
Adjustment of statistical significance levels for repeated analysis in group sequential trials has been understood for some time. Similarly, methods for adjustment accounting for testing multiple hypotheses are common. There is limited…
We analyze control of the familywise error rate (FWER) in a multiple testing scenario with a great many null hypotheses about the distribution of a high-dimensional random variable among which only a very small fraction are false, or…
The analysis of multiple time-to-event outcomes in a randomised controlled clinical trial can be accomplished with exisiting methods. However, depending on the characteristics of the disease under investigation and the circumstances in…
Correlated observations are ubiquitous phenomena in a plethora of scientific avenues. Tackling this dependence among test statistics has been one of the pertinent problems in simultaneous inference. However, very little literature exists…
The development of targeted therapies, which benefit only a subgroup of patients treated for a given type of cancer, has been extremely attractive to many investigators. Adaptive seamless phase II/III designs in oncology clinical trials…
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…
We consider clinical trials with multiple, overlapping patient populations, that test multiple treatment policies specifically tailored to these populations. Such designs may lead to multiplicity issues, as false statements will affect…
In confirmatory clinical trials with small sample sizes, hypothesis tests based on asymptotic distributions are often not valid and exact non-parametric procedures are applied instead. However, the latter are based on discrete test…
The closure principle is a standard tool for achieving strong family-wise error rate (FWER) control in multiple testing problems. We develop an e-value-based closed testing framework that inherits nice properties of e-values, which are…
Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally…
This paper addresses the following general scenario: A scientist wishes to perform a battery of experiments, each generating a sequential stream of data, to investigate some phenomenon. The scientist would like to control the overall error…
We argue that Bonferroni correction is a better choice for online experimentation than it is commonly given credit for. The case rests on four considerations. First, it is the simplest broadly implementable FWER-controlling method that…
We describe group sequential tests which efficiently incorporate information from multiple endpoints allowing for early stopping at pre-planned interim analyses. We formulate a testing procedure where several outcomes are examined, and…
Group sequential design (GSD) is widely used in clinical trials in which correlated tests of multiple hypotheses are used. Multiple primary objectives resulting in tests with known correlations include evaluating 1) multiple experimental…
The $\gamma$-FDP and $k$-FWER multiple testing error metrics, which are tail probabilities of the respective error statistics, have become popular recently as less-stringent alternatives to the FDR and FWER. We propose general and flexible…
The topic of multiple hypotheses testing now has a potpourri of novel theories and ubiquitous applications in diverse scientific fields. However, the universal utility of this field often hinders the possibility of having a generalized…
Structured multiple-testing problems (gatekeeping trials, dose-finding, multi-tissue eQTL mapping, bundled-challenger A/B experiments) organize hypotheses into design-imposed blocks and demand strong family-wise error rate (FWER) control…