Related papers: Optimal designs for dose response curves with comm…
We consider repeated measurement designs when a residual or carry-over effect may be present in at most one later period. Since assuming an additive model may be unrealistic for some applications and leads to biased estimation of treatment…
An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…
In randomized dose-finding trials, although drug exposure data form a part of key information for dose selection, the evaluation of the dose-response (DR) relationship often mainly uses DR data. We examine the benefit of…
The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…
It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…
Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…
In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…
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…
Triple difference designs have become increasingly popular in empirical economics. The advantage of a triple difference design is that, within a treatment group, it allows for another subgroup of the population -- potentially less impacted…
Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining…
Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…
Treatment effects can be estimated from observational data as the difference in potential outcomes. In this paper, we address the challenge of estimating the potential outcome when treatment-dose levels can vary continuously over time.…
Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…
We consider the problem of how to assign treatment in a randomized experiment, in which the correlation among the outcomes is informed by a network available pre-intervention. Working within the potential outcome causal framework, we…
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…
Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…
We consider maximin and Bayesian $D$-optimal designs for nonlinear regression models. The maximin criterion requires the specification of a region for the nonlinear parameters in the model, while the Bayesian optimality criterion assumes…
We consider optimal designs for the Kiefer cirteria, which include the E-criterion as a particular case, and the G-criterion in random coefficients regression (RCR) models. We obtain general the Kiefer criteria for approximate designs and…
Cumulative link models have been widely used for ordered categorical responses. Uniform allocation of experimental units is commonly used in practice, but often suffers from a lack of efficiency. We consider D-optimal designs with ordered…
Copula modelling has in the past decade become a standard tool in many areas of applied statistics. However, a largely neglected aspect concerns the design of related experiments. Particularly the issue of whether the estimation of copula…