Related papers: Bayesian adaptive randomization in the I-SPY2 sequ…
One of the main goals of sequential, multiple assignment, randomized trials (SMART) is to find the most efficacious design embedded dynamic treatment regimes. The analysis method known as multiple comparisons with the best (MCB) allows…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
Rationale and Objectives: Early prediction of pathological complete response (pCR) can facilitate personalized treatment for breast cancer patients. To improve prediction accuracy at the early time point of neoadjuvant chemotherapy, we…
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…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
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…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
In most clinical trials, patients are randomized with equal probability among treatments to obtain an unbiased estimate of the treatment effect. Response-adaptive randomization (RAR) has been proposed for ethical reasons, where the…
One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose (MTD), followed by a randomization stage where patients are assigned to two or more doses to…
Targeted therapies based on biomarker profiling are becoming a mainstream direction of cancer research and treatment. Depending on the expression of specific prognostic biomarkers, targeted therapies assign different cancer drugs to…
Sequential multiple assignment randomized trials (SMARTs) have grown in popularity in recent years, and many of their study protocols propose conducting a cost effectiveness analysis of the adaptive strategies embedded within them. The cost…
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…
In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…
In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…
Clinical trials are complex and usually involve multiple objectives such as controlling type I error rate, increasing power to detect treatment difference, assigning more patients to better treatment, and more. In literature, both…
Multistage design has been used in a wide range of scientific fields. By allocating sensing resources adaptively, one can effectively eliminate null locations and localize signals with a smaller study budget. We formulate a…
Personalized intervention strategies, in particular those that modify treatment based on a participant's own response, are a core component of precision medicine approaches. Sequential Multiple Assignment Randomized Trials (SMARTs) are…
Individualized treatment rules (ITR) can improve health outcomes by recognizing that patients may respond differently to treatment and assigning therapy with the most desirable predicted outcome for each individual. Flexible and efficient…
Response-adaptive randomization (RAR) methods can be used to adapt randomization probabilities based on accumulating data, aiming to increase the probability of allocating patients to effective treatments. A popular RAR method is Thompson…
We propose an adaptive sequential framework for testing two simple hypotheses that analytically ensures finite exposure to the less effective treatment. Our proposed procedure employs a likelihood ratio-driven adaptive allocation rule,…