相关论文: Backfilling Cohorts in Phase I Dose-Escalation Stu…
Safety evaluation is an essential component of clinical trials. To protect study participants, these studies often implement safety stopping rules that will halt the trial if an excessive number of toxicity events occur. Existing safety…
We consider clinical trials in which an experimental treatment is compared with a control in pre-specified patient subpopulations. In such settings, adaptive enrichment designs allow the enrolled population to be modified at an interim…
We examine nonparametric dose-finding designs that use toxicity estimates based on all available data at each dose allocation decision. We prove that one such design family, called here "interval design", converges almost surely to the…
We developed a study design for rare disease clinical trials (RDTs) that efficiently evaluate treatments, promotes access to new treatments during treatment development, and optimizes healthcare resource utilization for future treatment…
Estimating causal effects under interference is pertinent to many real-world settings. Recent work with low-order potential outcomes models uses a rollout design to obtain unbiased estimators that require no interference network…
Background -- In phase I clinical trials, historical data may be available through multi-regional programs, reformulation of the same drug, or previous trials for a drug under the same class. Statistical designs that borrow information from…
The ICH E9(R1) Addendum (International Council for Harmonization 2019) suggests treatment-policy as one of several strategies for addressing intercurrent events such as treatment withdrawal when defining an estimand. This strategy requires…
In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…
Two-phase sampling offers a cost-effective way to validate error-prone covariate measurements in biomedical databases. Inexpensive or easy-to-obtain information is collected for the entire study in Phase I. Then, a subset of patients…
Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. Many trials which measure a long-term time-to-event endpoint often also routinely collect repeated…
Identifying subgroups, which respond differently to a treatment, both in terms of efficacy and safety, is an important part of drug development. A well-known challenge in exploratory subgroup analyses is the small sample size in the…
We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…
A new simple method for the first order phase transition kinetics is suggested. The metastable phase consumption can be imagined in frames of the modisperse approximation for the distribution of the droplets sizes. In all situations of the…
We consider planning longitudinal covariate measurements in follow-up studies where covariates are time-varying. We assume that the entire cohort cannot be selected for longitudinal measurements due to financial limitations and study how a…
Reasoning reinforcement learning (RL) has recently revealed a new scaling effect: test-time scaling. Thinking models such as R1 and o1 improve their reasoning accuracy at test time as the length of the reasoning context increases. However,…
In the era of precision medicine, more and more clinical trials are now driven or guided by biomarkers, which are patient characteristics objectively measured and evaluated as indicators of normal biological processes, pathogenic processes,…
Vaccine mandates featuring a deadline, i.e. time-limited, can raise uptake either by pulling forward vaccinations that would have occurred later or by inducing additional vaccinations that would not have occurred absent the mandate. This…
State-of-the-art automated machine learning systems for tabular data often employ cross-validation; ensuring that measured performances generalize to unseen data, or that subsequent ensembling does not overfit. However, using k-fold…
Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls…
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…