Related papers: Adaptive treatment allocation and selection in mul…
Background: Adaptive interventions provide a guide for using ongoing information about individuals to decide whether and how to modify the type, amount, delivery modality, or timing of treatment, to improve intervention effectiveness while…
In conventional randomized controlled trials, adjustment for baseline values of covariates known to be at least moderately associated with the outcome increases the power of the trial. Recent work has shown particular benefit for more…
Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…
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…
Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient by reducing the cost and the…
Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID-19 pandemic, the need to establish evidence for the effectiveness of vaccines,…
Various adaptive randomization procedures (adaptive designs) have been proposed to clinical trials. This paper discusses several broad families of procedures, such as the play-the-winner rule and Markov chain model, randomized…
This article proposes a novel adaptive design algorithm that can be used to find optimal treatment allocations in N-of-1 clinical trials. This new methodology uses two Laplace approximations to provide a computationally efficient estimate…
It is generally appreciated that a frequentist analysis of a group sequential trial must in order to avoid inflating type I error account for the fact that one or more interim analyses were performed. It is also to a lesser extent realised…
The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…
The principle of allocating an equal number of patients to each arm in a randomized controlled trial remains widely believed to be optimal for maximising statistical power. However, this long-held belief only holds true if the treatment…
In recent years new cancer treatments improved survival in multiple histologies. Some of these therapeutics, and in particular treatment combinations, are often associated with severe treatment-related adverse events (AEs). It is therefore…
Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…
Primarily motivated by the drug development process, several publications have now presented methodology for the design of multi-arm multi-stage experiments with normally distributed outcome variables of known variance. Here, we extend…
Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions.…
In a sequential multiple-assignment randomized trial (SMART), a sequence of treatments is given to a patient over multiple stages. In each stage, randomization may be done to allocate patients to different treatment groups. Even though…
In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…
Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…
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…
The present paper deals with the problem of allocating patients to two competing treatments in the presence of covariates or prognostic factors in order to achieve a good trade-off among ethical concerns, inferential precision and…