Related papers: Statistical Design and Planning of an Adaptive Tri…
Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…
Covariate adjustment aims to improve the statistical efficiency of randomized trials by incorporating information from baseline covariates. Popular methods for covariate adjustment include analysis of covariance for continuous endpoints and…
This paper shows that sequential statistical analysis techniques can be generalised to the problem of selecting between alternative forecasting methods using scoring rules. A return to basic principles is necessary in order to show that…
To increase statistical efficiency in a randomized experiment, researchers often use stratification (i.e., blocking) in the design stage. However, conventional practices of stratification fail to exploit valuable information about the…
Adapting the final sample size of a trial to the evidence accruing during the trial is a natural way to address planning uncertainty. Designs with adaptive sample size need to account for their optional stopping to guarantee strict type-I…
Response-adaptive designs allow the randomization probabilities to change during the course of a trial based on cumulated response data, so that a greater proportion of patients can be allocated to the better performing treatments. A major…
Response-adaptive clinical trial designs allow targeting a given objective by skewing the allocation of participants to treatments based on observed outcomes. Response-adaptive designs face greater regulatory scrutiny due to potential type…
We propose an adaptive sequential framework for testing two simple hypotheses that analytically ensures finite exposure to the less effective treatment. Our proposed procedure employs a likelihood ratio-driven adaptive allocation rule,…
Composite endpoints are commonly used with an anticipation that clinically relevant endpoints as a whole would yield meaningful treatment benefits. The win ratio is a rank-based statistic to summarize composite endpoints, allowing…
Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…
In large observational studies, the case-cohort design is commonly used to reduce the cost associated with covariate measurement. For survival outcomes, literature has suggested that the restricted mean survival time (RMST) be a more…
Informative interim adaptations lead to random sample sizes. The random sample size becomes a component of the sufficient statistic and estimation based solely on observed samples or on the likelihood function does not use all available…
Composite endpoints that combine multiple outcomes on different scales are common in clinical trials, particularly in chronic conditions. In many of these cases, patients will have to cross a predefined responder threshold in each of the…
Likelihood methods for measuring statistical evidence obey the likelihood principle while maintaining bounded and well-controlled frequency properties. These methods lend themselves to sequential study designs because they measure the…
Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of…
Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. Many trials which measure a long-term time-to-event endpoint often also routinely collect repeated…
Clinicians and researchers alike are increasingly interested in how best to personalize interventions. A dynamic treatment regimen (DTR) is a sequence of pre-specified decision rules which can be used to guide the delivery of a sequence of…
Sequential, multiple assignment randomized trials (SMARTs), which assist in the optimization of adaptive interventions, are growing in popularity in education and behavioral sciences. This is unsurprising, as adaptive interventions reflect…
The graph based approach to multiple testing is an intuitive method that enables a study team to represent clearly, through a directed graph, its priorities for hierarchical testing of multiple hypotheses, and for propagating the available…
Composite endpoints are frequently used as primary or secondary analyses in cardiovascular clinical trials to increase clinical relevance and statistical efficiency. Alternatively, the Win Ratio (WR) and other Win Statistics (WS) analyses…