Related papers: Design of phase III trials with long-term survival…
In neoadjuvant trials on early-stage breast cancer, patients are usually randomized into a control group and a treatment group with an additional target therapy. Early efficacy of the new regimen is assessed via the binary pathological…
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…
For a trial with primary endpoint overall survival for a molecule with curative potential, statistical methods that rely on the proportional hazards assumption may underestimate the power and the time to final analysis. We show how a cure…
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),…
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…
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…
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…
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.…
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…
In many phase II trials in solid tumours, patients are assessed using endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST) scale. Often, analyses are based on the response rate. This is the proportion of patients…
Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…
Objectives: To evaluate the association between pretreatment MRI descriptors and breast cancer (BC) pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Materials \& Methods: Patients with BC treated by NAC with a breast…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
Effective therapy decisions require models that predict the individual response to treatment. This is challenging since the progression of disease and response to treatment vary substantially across patients. Here, we propose to learn a…
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…
Pathological complete response (pCR) is a key prognostic factor in breast cancer patients undergoing neoadjuvant therapy, strongly associated with long-term survival and treatment personalization. However, accurate pre-treatment pCR…
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…
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…
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…
Background: trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, TB and Hepatitis--C. However, standard non-inferiority designs have several limitations,…