Related papers: Two-stage single-arm trials are rarely reported ad…
In small sample studies with binary outcome data, use of a normal approximation for hypothesis testing can lead to substantial inflation of the type-I error-rate. Consequently, exact statistical methods are necessitated, and accordingly,…
Multi-arm trials are gaining interest in practice given the statistical and logistical advantages they can offer. The standard approach uses a fixed allocation ratio, but there is a call for making it adaptive and skewing the allocation of…
2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…
Though platform trials have been touted for their flexibility and streamlined use of trial resources, their statistical efficiency is not well understood. We fill this gap by establishing their greater efficiency for comparing the relative…
The sequential multiple assignment randomized trial (SMART) is the gold standard trial design to generate data for the evaluation of multi-stage treatment regimes. As with conventional (single-stage) randomized clinical trials, interim…
Background: trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, TB and Hepatitis--C. However, standard non-inferiority designs have several limitations,…
The question of selecting the "best" amongst different choices is a common problem in statistics. In drug development, our motivating setting, the question becomes, for example: what is the dose that gives me a pre-specified risk of…
In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…
PURPOSE Providing rapid answers and early acces to patients to innovative treatments without randomized clinical trial (RCT) is growing, with benefit estimated from single-arm trials. This has become common in oncology, impacting the…
For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints are widely chosen as the primary endpoint. Despite being commonly used, composite endpoints entail…
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 clinical trials, an experimental treatment is sometimes added on to a standard of care or control therapy in multiple treatment phases (e.g., concomitant and maintenance phases) to improve patient outcomes. When the new regimen provides…
The analysis of screening experiments is often done in two stages, starting with factor selection via an analysis under a main effects model. The success of this first stage is influenced by three components: (1) main effect estimators'…
Anchored covariate-adjusted indirect comparisons inform reimbursement decisions where there are no head-to-head trials between the treatments of interest, there is a common comparator arm shared by the studies, and there are patient-level…
In the first stage of a two-stage study, the researcher uses a statistical model to impute the unobserved exposures. In the second stage, imputed exposures serve as covariates in epidemiological models. Imputation error in the first stage…
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…
Clinical trials involving novel immuno-oncology (IO) therapies frequently exhibit survival profiles which violate the proportional hazards assumption due to a delay in treatment effect, and in such settings, the survival curves in the two…
Clinical trial design ensures that primary analysis outcomes have strong statistical properties. However, mainstream methodology for randomised study design does not establish a formal link between statistical and clinical significance.…
Medical imaging is spearheading the AI transformation of healthcare. Performance reporting is key to determine which methods should be translated into clinical practice. Frequently, broad conclusions are simply derived from mean performance…
Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of, stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of…