Related papers: Optimal Bayesian predictive probability for delaye…
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…
In early-phase cancer clinical trials, the limited availability of data presents significant challenges in developing a framework to efficiently quantify treatment effectiveness. To address this, we propose a novel utility-based Bayesian…
Multi-arm trials are gaining interest in practice given the statistical and logistical advantages they can offer. The standard approach uses a fixed allocation ratio, but there is a call for making it adaptive and skewing the allocation of…
Clinical trials often evaluate multiple outcome variables to form a comprehensive picture of the effects of a new treatment. The resulting multidimensional insight contributes to clinically relevant and efficient decision-making about…
The conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically…
Determining the extent to which a patient is benefiting from cancer therapy is challenging. Criteria for quantifying the extent of "tumor response" observed within a few cycles of treatment have been established for various types of solid…
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…
Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…
For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints are widely chosen as the primary endpoint. Despite being commonly used, composite endpoints entail…
An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study.…
Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a…
An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage…
The development of oncology drugs progresses through multiple phases, where after each phase a decision is made about whether to move a molecule forward. Early phase efficacy decisions are often made on the basis of single arm studies based…
Most Bayesian response-adaptive designs unbalance randomization rates towards the most promising arms with the goal of increasing the number of positive treatment outcomes during the study, even though the primary aim of the trial is…
Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of…
Immunotherapy has transformed cancer treatment, yet its delayed therapeutic effects often lead to non-proportional hazards, rendering many conventional phase II designs underpowered and prone to type I error inflation. To address this…
The analysis of multiple time-to-event outcomes in a randomised controlled clinical trial can be accomplished with exisiting methods. However, depending on the characteristics of the disease under investigation and the circumstances in…
Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…
Bayesian response adaptive clinical trials are currently evaluating experimental therapies for several diseases. Adaptive decisions, such as pre-planned variations of the randomization probabilities, attempt to accelerate the development of…
Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…