Related papers: Multiplicity for a Group Sequential Trial with Bio…
During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker-mixed populations, later trials are more likely to enrol…
We introduce a new multiple type I error criterion for clinical trials with multiple populations. Such trials are of interest in precision medicine where the goal is to develop treatments that are targeted to specific sub-populations…
In cancer biomarker development, a key objective is to evaluate whether a new biomarker, when combined with an established one, improves early cancer detection compared to using the established biomarker alone. Incremental value is often…
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…
To generalize inferences from a randomized trial to the target population of all trial-eligible individuals, investigators can use nested trial designs, where the randomized individuals are nested within a cohort of trial-eligible…
We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such sub-populations could be defined by a biomarker or risk factor measured at…
Randomization tests are a popular method for testing causal effects in clinical trials with finite-sample validity. In the presence of heterogeneous treatment effects, it is often of interest to select a subgroup that benefits from the…
Background: When planning a cluster randomized trial, evaluators often have access to an enumerated cohort representing the target population of clusters. Practicalities of conducting the trial, such as the need to oversample clusters with…
Biomarker measurements can be relatively easy and quick to obtain and they are useful to investigate whether a compound works as intended on a mechanistic, pharmacological level. In some situations, it is realistic to assume that patients,…
The increasing interest in subpopulation analysis has led to the development of various new trial designs and analysis methods in the fields of personalized medicine and targeted therapies. In this paper, subpopulations are defined in terms…
Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…
Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have…
Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…
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…
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…
Targeted therapies on the basis of genomic aberrations analysis of the tumor have shown promising results in cancer prognosis and treatment. Regardless of tumor type, trials that match patients to targeted therapies for their particular…
Developing targeted therapies based on patients' baseline characteristics and genomic profiles such as biomarkers has gained growing interests in recent years. Depending on patients' clinical characteristics, the expression of specific…
In complex clinical trials, multiple research objectives are often grouped into sets of objectives based on their inherent hierarchical relationships. Consequently, the hypotheses formulated to address these objectives are grouped into…
Biomarker discovery is vital in advancing personalized medicine, offering insights into disease diagnosis, prognosis, and therapeutic efficacy. Traditionally, the identification and validation of biomarkers heavily depend on extensive…
As a future trend of healthcare, personalized medicine tailors medical treatments to individual patients. It requires to identify a subset of patients with the best response to treatment. The subset can be defined by a biomarker (e.g.…