Related papers: Assurance Methods for designing a clinical trial w…
We propose a novel adaptive design for clinical trials with time-to-event outcomes and covariates (which may consist of or include biomarkers). Our method is based on the expected entropy of the posterior distribution of a proportional…
Treatment effect estimation in continuous time is crucial for personalized medicine. However, existing methods for this task are limited to point estimates of the potential outcomes, whereas uncertainty estimates have been ignored. Needless…
Sample size reestimation can be a powerful tool to ensure that a clinical trial meets its prespecified power requirements when uncertainty regarding a design parameter exists at the planning stage. However, long term primary endpoints can…
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…
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…
There are several steps to confirming the safety and efficacy of a new medicine. A sequence of trials, each with its own objectives, is usually required. Quantitative risk metrics can be useful for informing decisions about whether a…
The counterfactual distribution models the effect of the treatment in the untreated group. While most of the work focuses on the expected values of the treatment effect, one may be interested in the whole counterfactual distribution or…
In this paper, a Bayesian approach is developed for simultaneously comparing multiple experimental treatments with a common control treatment in an exploratory clinical trial. The sample size is set to ensure that, at the end of the study,…
The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…
Bayesian inference and the use of posterior or posterior predictive probabilities for decision making have become increasingly popular in clinical trials. The current practice in Bayesian clinical trials relies on a hybrid…
If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they…
Survival analysis is a statistical technique used to estimate the time until an event occurs. Although it is applied across a wide range of fields, adjusting for reporting delays under practical constraints remains a significant challenge…
In most nonrandomized observational studies, differences between treatment groups may arise not only due to the treatment but also because of the effect of confounders. Therefore, causal inference regarding the treatment effect is not as…
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…
Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general…
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…
In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the…
An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…
A treatment regime is a deterministic function that dictates personalized treatment based on patients' individual prognostic information. There is a fast-growing interest in finding optimal treatment regimes to maximize expected long-term…
With medical tests becoming increasingly available, concerns about over-testing and over-treatment dramatically increase. Hence, it is important to understand the influence of testing on treatment selection in general practice. Most…