Related papers: A burn-in(g) question: How long should an initial …
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…
Covariate-adaptive randomization (CAR) procedures are frequently used in comparative studies to increase the covariate balance across treatment groups. However, because randomization inevitably uses the covariate information when forming…
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…
The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…
Random forests (RFs) utilize bootstrap sampling to generate individual training sets for each component tree by sampling with replacement, with the sample size typically equal to that of the original training set ($N$). Previous research…
Unblinded sample size re-estimation (SSR) is often planned in a clinical trial when there is large uncertainty about the true treatment effect. For Proof-of Concept (PoC) in a Phase II dose finding study, contrast test can be adopted to…
Continual test-time domain adaptation (CTTA) aims to adjust models so that they can perform well over time across non-stationary environments. While previous methods have made considerable efforts to optimize the adaptation process, a…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
There is currently a dearth of appropriate methods to estimate the causal effects of multiple treatments when the outcome is binary. For such settings, we propose the use of nonparametric Bayesian modeling, Bayesian Additive Regression…
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…
Bayesian clinical trials can benefit of available historical information through the elicitation of informative prior distributions. Concerns are however often raised about the potential for prior-data conflict and the impact of Bayes test…
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…
Investigating the causal relationship between exposure and the time-to-event outcome is an important topic in biomedical research. Previous literature has discussed the potential issues of using the hazard ratio as a marginal causal effect…
Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…
The difference in restricted mean survival time (RMST) is a clinically meaningful measure to quantify treatment effect in randomized controlled trials, especially when the proportional hazards assumption does not hold. Several frequentist…
Optimal designs minimize the number of experimental runs (samples) needed to accurately estimate model parameters, resulting in algorithms that, for instance, efficiently minimize parameter estimate variance. Governed by knowledge of past…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
The advantages of adaptive experiments have led to their rapid adoption in economics, other fields, as well as among practitioners. However, adaptive experiments pose challenges for causal inference. This note suggests a BOLS (batched…
The I-SPY2 phase 2 clinical trial is a long-running platform trial that evaluates neoadjuvant treatments for locally advanced breast cancer, assigning subjects to novel agents using response-adaptive randomization. Recently, I-SPY2 was…
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…