Related papers: Re-thinking non-inferiority: a practical trial des…
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…
Shared controls in platform trials comprise concurrent and non-concurrent controls. For a given experimental arm, non-concurrent controls refer to data from patients allocated to the control arm before the arm enters the trial. The use of…
Randomization is a common technique used in clinical trials to eliminate potential bias and confounders in a patient population. Equal allocation to treatment groups is the standard due to its optimal efficiency in many cases. However, in…
Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review…
This article proposes different tests for treatment effect heterogeneity when the outcome of interest, typically a duration variable, may be right-censored. The proposed tests study whether a policy 1) has zero distributional (average)…
The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…
Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of…
An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…
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…
Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…
Utilizing non-concurrent control data (NCC) in the analysis of late-entering arms in platform trials has recently received considerable attention. While incorporating NCC can lead to increased power and lower sample sizes, it might…
Platform trials evaluate multiple experimental treatments against a common control group (and/or against each other), which often reduces the trial duration and sample size. Bayesian platform designs offer several practical advantages,…
Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…
In clinical trials, response-adaptive randomization (RAR) has the appealing ability to assign more subjects to better-performing treatments based on interim results. The traditional RAR strategy alters the randomization ratio on a…
Purpose: Two-stage single-arm trial designs are commonly used in phase II oncology to infer treatment effects for a binary primary outcome (e.g., tumour response). It is imperative that such studies be designed, analysed, and reported…
Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs can be categorized into several overarching design groups, including adaptive designs…
Applied researchers in biomedicine and related fields are often interested in estimating the causal effect of a treatment or intervention. Although randomized clinical trials are considered the gold standard for establishing causal effects,…
Network meta-analysis (NMA) is widely used in healthcare decision-making, where estimates of the effect of multiple treatments on outcomes are required. For time-to-event outcomes such as survival or disease progression the most common…
Suppose an online platform wants to compare a treatment and control policy, e.g., two different matching algorithms in a ridesharing system, or two different inventory management algorithms in an online retail site. Standard randomized…
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…