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Bridging the gap between internal and external validity is crucial for heterogeneous treatment effect estimation. Randomised controlled trials (RCTs), favoured for their internal validity due to randomisation, often encounter challenges in…

Mixed Models for Repeated Measures (MMRMs) are ubiquitous when analyzing outcomes of clinical trials. However, the linearity of the fixed-effect structure in these models largely restrict their use to estimating treatment effects that are…

Methodology · Statistics 2023-01-23 Lars Lau Raket

The call for patient-focused drug development is loud and clear, as expressed in the 21st Century Cures Act and in recent guidelines and initiatives of regulatory agencies. Among the factors contributing to modernized drug development and…

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…

Statistics Theory · Mathematics 2020-05-28 Andrea Arfé , Brian Alexander , Lorenzo Trippa

An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage…

Applications · Statistics 2021-01-08 Linda Z. Sun , Cai , Wu , Xiaoyun , Li , Cong Chen , Emmett V. Schmidt

Hypotension in critically ill ICU patients is common and life-threatening. Escalation to catecholamine therapy marks a key management step, with both undertreatment and overtreatment posing risks. Most machine learning (ML) models predict…

Signal Processing · Electrical Eng. & Systems 2025-10-29 Richard Koebe , Noah Saibel , Juan Miguel Lopez Alcaraz , Simon Schäfer , Nils Strodthoff

In epidemiological studies of time-to-event data, a quantity of interest to the clinician and the patient is the risk of an event given a covariate profile. However, methods relying on time matching or risk-set sampling (including Cox…

Methodology · Statistics 2020-09-23 Sahir Rai Bhatnagar , Maxime Turgeon , Jesse Islam , James A. Hanley , Olli Saarela

We propose a flexible joint longitudinal-survival framework to examine the association between longitudinally collected biomarkers and a time-to-event endpoint. More specifically, we use our method for analyzing the survival outcome of…

Applications · Statistics 2018-07-09 Sepehr Akhavan Masouleh , Tracy Holsclaw , Babak Shahbaba , Daniel L. Gillen

In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…

In order to estimate the proportion of `immune' or `cured' subjects who will never experience failure, a sufficiently long follow-up period is required. Several statistical tests have been proposed in the literature for assessing the…

Methodology · Statistics 2026-01-12 Tsz Pang Yuen , Eni Musta

In comparative effectiveness research, treated and control patients might have a different start of follow-up as treatment is often started later in the disease trajectory. This typically occurs when data from treated and controls are not…

Methodology · Statistics 2024-06-10 Rik van Eekelen , Patrick M. M. Bossuyt , Nan van Geloven

In large observational studies, the case-cohort design is commonly used to reduce the cost associated with covariate measurement. For survival outcomes, literature has suggested that the restricted mean survival time (RMST) be a more…

Methodology · Statistics 2026-05-08 Andy Ni , Wei-En Lu , Bo Lu

Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…

Methodology · Statistics 2025-09-10 James Salsbury , Jeremy Oakley , Steven Julious , Lisa Hampson

Heterogeneous treatment effect estimation is critical in oncology, particularly in multi-arm trials with overlapping therapeutic components and long-term survivors. These shared mechanisms pose a central challenge to identifying causal…

Methodology · Statistics 2025-10-29 Peter Chang , John Kairalla , Arkaprava Roy

This study proposes a novel framework based on the RuleFit method to estimate Heterogeneous Treatment Effect (HTE) in a randomized clinical trial. To achieve this, we adopted S-learner of the metaalgorithm for our proposed framework. The…

Methodology · Statistics 2023-07-28 Mayu Hiraishi , Ke Wan , Kensuke Tanioka , Hiroshi Yadohisa , Toshio Shimokawa

Interval identification of parameters such as average treatment effects, average partial effects and welfare is particularly common when using observational data and experimental data with imperfect compliance due to the endogeneity of…

Econometrics · Economics 2025-04-09 Sukjin Han , Adam McCloskey

Randomized trials are considered the gold standard for making informed decisions in medicine, yet they often lack generalizability to the patient populations in clinical practice. Observational studies, on the other hand, cover a broader…

Methodology · Statistics 2026-04-14 Piersilvio De Bartolomeis , Javier Abad , Konstantin Donhauser , Fanny Yang

Conventional methods for analyzing composite endpoints in clinical trials often only focus on the time to the first occurrence of all events in the composite. Therefore, they have inherent limitations because the individual patients' first…

Methodology · Statistics 2022-11-29 Jialu Wang , Yeh-Fong Chen , Thomas Gwise

Phase I dose-escalation trials constitute the first step in investigating the safety of potentially promising drugs in humans. Conventional methods for phase I dose-escalation trials are based on a single treatment schedule only. More…

Applications · Statistics 2021-03-04 Burak Kürsad Günhan , Sebastian Weber , Abdelkader Seroutou , Tim Friede

One of the most significant barriers to medication treatment is patients' non-adherence to a prescribed medication regimen. The extent of the impact of poor adherence on resulting health measures is often unknown, and typical analyses…

Applications · Statistics 2018-12-04 Luis F. Campos , Mark E. Glickman , Kristen B. Hunter