Related papers: A time-to-event three-outcome design for randomize…
Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…
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 conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
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…
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…
In clinical trials, multiple outcomes of different priorities commonly occur as the patient's response may not be adequately characterized by a single outcome. Win statistics are appealing summary measures for between-group difference at…
In this paper, a mixed-effect modeling scheme is proposed to construct a predictor for different features of cancer tumor. For this purpose, a set of features is extracted from two groups of patients with the same type of cancer but with…
In oncology clinical trials, tumor burden (TB) stands as a crucial longitudinal biomarker, reflecting the toll a tumor takes on a patient's prognosis. With certain treatments, the disease's natural progression shows the tumor burden…
Background: Well-designed phase II trials must have acceptable error rates relative to a pre-specified success criterion, usually a statistically significant p-value. Such standard designs may not always suffice from a clinical perspective…
Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…
It is a common practice in randomized clinical trials with the standard survival outcome to follow patients until a prespecified number of events have been observed, a type of trial known as the event-driven trial. The event-driven design…
The question of selecting the "best" amongst different choices is a common problem in statistics. In drug development, our motivating setting, the question becomes, for example: what is the dose that gives me a pre-specified risk of…
We conducted a systematic comparison of statistical methods used for the analysis of time-to-event outcomes under various proportional and nonproportional hazard (NPH) scenarios. Our study used data from recently published oncology trials…
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…
A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend…
The analysis of screening experiments is often done in two stages, starting with factor selection via an analysis under a main effects model. The success of this first stage is influenced by three components: (1) main effect estimators'…
Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early-stage clinical studies in oncology when efficacy is assessed by the best overall response (BOR) and presented as the overall…
Over the last decade, the number of randomized trials of programs to reduce intimate partner violence (IPV) has grown precipitously. However, most trials continue to measure and code violence using standards originally designed for global…
Safety evaluation is an essential component of clinical trials. To protect study participants, these studies often implement safety stopping rules that will halt the trial if an excessive number of toxicity events occur. Existing safety…