Related papers: Two-stage single-arm trials are rarely reported ad…
Randomized controlled trials (RCTs) in oncology often allow control group participants to crossover to experimental treatments, a practice that, while often ethically necessary, complicates the accurate estimation of long-term treatment…
Background. The DURATIONS design has been recently proposed as a practical alternative to a standard two-arm non-inferiority design when the goal is to optimise some continuous aspect of treatment administration, e.g. duration or frequency,…
Sequential multiple assignment randomized trials mimic the actual treatment processes experienced by physicians and patients in clinical settings and inform the comparative effectiveness of dynamic treatment regimes. In such trials,…
Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…
Over time, clinical trials have increasingly incorporated complex design and analysis elements such as interim analyses, adaptations, multiple endpoints, and sophisticated multiplicity schemes for multiple endpoints and/or treatment arms…
Robins and Richardson (2010) reformulated mediation analysis by decomposing treatments into multiple components and examining separable effects of each component. While this approach is increasingly popular, existing work has analyzed…
This paper studies inference in two-stage randomized experiments under covariate-adaptive randomization. In the initial stage of this experimental design, clusters (e.g., households, schools, or graph partitions) are stratified and randomly…
In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…
Multi-arm multi-stage trial designs can bring notable gains in efficiency to the drug development process. However, for normally distributed endpoints, the determination of a design typically depends on the assumption that the patient…
Efforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. Six antibodies acting on programmed death ligand 1 or programmed death 1 pathways were approved in 75 cancer indications between 2015 and…
Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…
Under two-phase designs, the outcome and several covariates and confounders are measured in the first phase, and a new predictor of interest, which may be costly to collect, can be measured on a subsample in the second phase, without…
Performance uncertainty quantification is essential for reliable validation and eventual clinical translation of medical imaging artificial intelligence (AI). Confidence intervals (CIs) play a central role in this process by indicating how…
Because of the high cost of commercial genotyping chip technologies, many investigations have used a two-stage design for genome-wide association studies, using part of the sample for an initial discovery of ``promising'' SNPs at a less…
Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…
Primarily motivated by the drug development process, several publications have now presented methodology for the design of multi-arm multi-stage experiments with normally distributed outcome variables of known variance. Here, we extend…
In many phase II trials in solid tumours, patients are assessed using endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST) scale. Often, analyses are based on the response rate. This is the proportion of patients…
Sequential trial design is an important statistical approach to increase the efficiency of clinical trials. Bayesian sequential trial design relies primarily on conducting a Monte Carlo simulation under the hypotheses of interest and…