Related papers: Data-Dependent Early Completion of Dose Finding Tr…
Summary points: - This article considers the combination of two binary or two time-to-event endpoints to form the primary composite endpoint for leading a trial. - It discusses the relative efficiency of choosing a composite endpoint over…
Increasingly high-dimensional data sets require that estimation methods do not only satisfy statistical guarantees but also remain computationally feasible. In this context, we consider $ L^{2} $-boosting via orthogonal matching pursuit in…
Biomarker measurements can be relatively easy and quick to obtain and they are useful to investigate whether a compound works as intended on a mechanistic, pharmacological level. In some situations, it is realistic to assume that patients,…
Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting…
There has been significant attention given to developing data-driven methods for tailoring patient care based on individual patient characteristics. Dynamic treatment regimes formalize this through a sequence of decision rules that map…
Code completion is widely used by software developers to provide coding suggestions given a partially written code snippet. Apart from the traditional code completion methods, which only support single token completion at minimal positions,…
Medication adherence is a major problem for patients with chronic diseases that require long term pharmacotherapy. Many unanswered questions surround adherence, including how adherence rates translate into treatment efficacy and how missed…
Combining experimental and observational follow-up datasets has received a lot of attention lately. In a time-to-event setting, recent work has used medicare claims to extend the follow-up period for participants in a prostate cancer…
The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerable dose (MTD) to determining the optimal…
Missing data is a major challenge in clinical research. In electronic medical records, often a large fraction of the values in laboratory tests and vital signs are missing. The missingness can lead to biased estimates and limit our ability…
Data from both a randomized trial and an observational study are sometimes simultaneously available for evaluating the effect of an intervention. The randomized data typically allows for reliable estimation of average treatment effects but…
Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…
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…
Drug discovery remains a slow and expensive process that involves many steps, from detecting the target structure to obtaining approval from the Food and Drug Administration (FDA), and is often riddled with safety concerns. Accurate…
Randomized controlled trials generate experimental variation that can credibly identify causal effects, but often suffer from limited scale, while observational datasets are large, but often violate desired identification assumptions. To…
The systematic discovery of effective drug combinations is a challenging problem in modern pharmacology, driven by the combinatorial growth of potential pairings and dosage configurations. Network medicine, modeling diseases and drugs as…
Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…
Predictive biomarkers are playing an essential role in precision medicine. Identifying an optimal cutoff to select patient subsets with greater benefit from treatment is critical and more challenging for predictive biomarkers measured with…
Motivated by a clinical trial conducted by Janssen Pharmaceuticals in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have…
The ICH E9(R1) Addendum (International Council for Harmonization 2019) suggests treatment-policy as one of several strategies for addressing intercurrent events such as treatment withdrawal when defining an estimand. This strategy requires…