Related papers: Two-stage single-arm trials are rarely reported ad…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more…
In a clinical trial with a survival outcome, an interim analysis is often performed to allow for early stopping for efficacy. If the interim analysis is early in the trial, one might conclude that a new treatment is more effective (compared…
The e-value is gaining traction as a robust alternative to p-values and Bayes factors for quantifying statistical evidence. e-values are a promising method for adaptive clinical trials due to their anytime-validity: e-values ensure type I…
While randomized trials may be the gold standard for evaluating the effectiveness of the treatment intervention, in some special circumstances, single-arm clinical trials utilizing external control may be considered. The causal treatment…
Matching in causal inference from observational data aims to construct treatment and control groups with similar distributions of covariates, thereby reducing confounding and ensuring an unbiased estimation of treatment effects. This…
Practical employment of Bayesian trial designs is still rare. Even if accepted in principle, the regulators have commonly required that such designs be calibrated according to an upper bound for the frequentist type I error rate. This…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
Regulatory guidance notes the need for caution in the interpretation of confidence intervals (CIs) constructed during and after an adaptive clinical trial. Conventional CIs of the treatment effects are prone to undercoverage (as well as…
Multi-arm designs provide an effective means of evaluating several treatments within the same clinical trial. Given the large number of treatments now available for testing in many disease areas, it has been argued that their utilisation…
Modern clinical trials and cohort studies gather low-cost data on all participants but may have limited resources to assess expensive exposures such as biomarkers or genomic data. When interest lies in associations involving expensive…
In meta-analytic modeling, the functional relationship between a primary and surrogate endpoint is estimated using summary data from a set of completed clinical trials. Parameters in the meta-analytic model are used to assess the quality of…
The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…
In recent years new cancer treatments improved survival in multiple histologies. Some of these therapeutics, and in particular treatment combinations, are often associated with severe treatment-related adverse events (AEs). It is therefore…
Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…
Much evidence in comparative effectiveness research is based on observational studies. Researchers who conduct observational studies typically assume that there are no unobservable differences between the treated and control groups.…
Adaptive designs(AD) are a broad class of trial designs that allow preplanned modifications based on patient data providing improved efficiency and flexibility. However, a delay in observing the primary outcome variable can harm this added…
When considering the effect a treatment will cause in a population of interest, we often look to evidence from randomized controlled trials. In settings where multiple trials on a treatment are available, we may wish to synthesize the…