Related papers: Interim decision-making strategies in adaptive des…
Classic adaptive designs for time-to-event trials are based on the log-rank statistic and its increments. Thereby, only information from the time-to-event endpoint on which the selected log-rank statistic is based may be used for…
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…
Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…
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…
In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental drug or treatment regimen (experimental group) is often unobservable if some patients in the control group switch to drugs in the…
Clinical trials often collect data on multiple outcomes, such as overall survival (OS), progression-free survival (PFS), and response to treatment (RT). In most cases, however, study designs only use primary outcome data for interim and…
Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…
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…
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…
Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally…
Overall survival (OS) is the gold standard for assessing patient benefit and cost-effectiveness of new cancer drugs. However, it is often difficult to use OS as the primary endpoint in randomized clinical trials (RCTs) for patients with…
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…
When planning an oncology clinical trial, the usual approach is to assume proportional hazards and even an exponential distribution for time-to-event endpoints. Often, besides the gold-standard endpoint overall survival (OS),…
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…
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…
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more…
Progression free survival (PFS) and tumour response (TR) have been investigated as surrogate endpoints for overall survival (OS) in advanced colorectal cancer (aCRC), however their validity has been shown to be suboptimal. In recent years,…
Hierarchical composite endpoints, such as those analyzed using the Finkelstein-Schoenfeld (FS) statistic, are increasingly used in clinical trials for their ability to incorporate clinically prioritized outcomes. However, adaptive design…
In oncological clinical trials, overall survival (OS) is the gold-standard endpoint, but long follow-up and treatment switching can delay or dilute detectable effects. Progression-free survival (PFS) often provides earlier evidence and is…
Tumor response, a binary variable, has historically been the main measure of antitumor activity for many cancer phase II single-arm trials. Simon two-stage designs are often used. Sargent et al. proposed a three-outcome trial design in this…