Related papers: Optimal predictive probability designs for randomi…
We study the design of multi-armed parallel group clinical trials to estimate personalized treatment rules that identify the best treatment for a given patient with given covariates. Assuming that the outcomes in each treatment arm are…
Prediction of survival for cancer patients is an open area of research. However, many of these studies focus on datasets with a large number of patients. We present a novel method that is specifically designed to address the challenge of…
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…
Precision oncology aims to prescribe the optimal cancer treatment to the right patients, maximizing therapeutic benefits. However, identifying patient subgroups that may benefit more from experimental cancer treatments based on randomized…
The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…
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…
In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…
We develop a methodology to create data-driven predictive digital twins for optimal risk-aware clinical decision-making. We illustrate the methodology as an enabler for an anticipatory personalized treatment that accounts for uncertainties…
Geometric uncertainty can degrade treatment quality in radiation therapy. While margins and robust optimization mitigate these effects, they provide only implicit control over clinical goal fulfillment probability. We therefore develop a…
Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…
Active surveillance (AS), where biopsies are conducted to detect cancer progression, has been acknowledged as an efficient way to reduce the overtreatment of prostate cancer. Most AS cohorts use fixed biopsy schedules for all patients.…
Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer…
The development of molecular diagnostic tools to achieve individualized medicine requires identifying predictive biomarkers associated with subgroups of individuals who might receive beneficial or harmful effects from different available…
We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such sub-populations could be defined by a biomarker or risk factor measured at…
A treatment regime is a deterministic function that dictates personalized treatment based on patients' individual prognostic information. There is a fast-growing interest in finding optimal treatment regimes to maximize expected long-term…
Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…
Purpose: Two-stage single-arm trial designs are commonly used in phase II oncology to infer treatment effects for a binary primary outcome (e.g., tumour response). It is imperative that such studies be designed, analysed, and reported…
In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…
The U.S. Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach…
Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…