Related papers: Estimands in Hematologic Oncology Trials
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…
For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some…
Prediction models are used amongst others to inform medical decisions on interventions. Typically, individuals with high risks of adverse outcomes are advised to undergo an intervention while those at low risk are advised to refrain from…
Lymphoid infiltration at tumor margins is a key prognostic marker in solid tumors, playing a crucial role in guiding immunotherapy decisions. Current assessment methods, heavily reliant on immunohistochemistry (IHC), face challenges in…
In oncology phase I trials, model-assisted designs have been increasingly adopted because they enable adaptive yet operationally simple dose adjustment based on accumulating safety data, leading to a paradigm shift in dose-escalation…
Estimating the causal effect of a treatment or health policy with observational data can be challenging due to an imbalance of and a lack of overlap between treated and control covariate distributions. In the presence of limited overlap,…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
In healthcare, clinical risks are crucial for treatment decisions, yet the analysis of their associations is often overlooked. This gap is particularly significant when balancing risks that are weighed against each other, as in the case of…
Causal inference is the goal of randomized trials and many observational studies. The first step in a formal causal inference framework is to define the causal estimand, and in both types of study this can be intuitively defined as the…
Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…
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…
This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…
Clinical trial amendments frequently introduce delays, increased costs, and administrative burden, with eligibility criteria being the most commonly amended component. We introduce \textit{eligibility criteria amendment prediction}, a novel…
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…
With the advancement of high-throughput biotechnologies, we increasingly accumulate biomedical data about diseases, especially cancer. There is a need for computational models and methods to sift through, integrate, and extract new…
In clinical trials, an experimental treatment is sometimes added on to a standard of care or control therapy in multiple treatment phases (e.g., concomitant and maintenance phases) to improve patient outcomes. When the new regimen provides…
The best evidence concerning comparative treatment effectiveness comes from clinical trials, the results of which are reported in unstructured articles. Medical experts must manually extract information from articles to inform…
Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient…
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) Addendum provides a framework for defining estimands in clinical trials. Treatment policy strategy is the mostly used…
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…