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The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…

Applications · Statistics 2023-04-14 Zhenghao Jiang , Gu Mi , Ji Lin , Christelle Lorenzato , Yuan Ji

While the gold standard for clinical trials is to blind all parties -- participants, researchers, and evaluators -- to treatment assignment, this is not always a possibility. When some or all of the above individuals know the treatment…

Methodology · Statistics 2020-12-22 E. J. Greene , P. Peduzzi , J. Dziura , C. Meng , M. E. Miller , T. G. Travison , D. Esserman

Although not without controversy, readmission is entrenched as a hospital quality metric, with statistical analyses generally based on fitting a logistic-Normal generalized linear mixed model. Such analyses, however, ignore death as a…

We present a phase-space analysis of a mathematical model of tumor growth with an immune responses. We consider mathematical analysis of the model equations with multipoint initial condition regarding to dissipativity, boundedness of…

Dynamical Systems · Mathematics 2019-02-28 Veli Shakhmurov , Rishad Shahmurov

Phase III randomized clinical trials play a monumentally critical role in the evaluation of new medical products. Because of the intrinsic nature of uncertainty embedded in our capability in assessing the efficacy of a medical product,…

Methodology · Statistics 2019-02-25 Changyu Shen , Xiaochun Li

We are keenly interested in finding the limiting behaviors of total tumor size when tumor cells are subject to the periodic repetition of therapy and rest periods, called intermittent cyclic therapy. We hypothesize that each tumor cell can…

Tissues and Organs · Quantitative Biology 2023-03-15 Jaewook Joo

Advances in anticancer therapies have significantly contributed to declining death rates in certain disease and clinical settings. However, they have also made it difficult to power a clinical trial in these settings with overall survival…

Methodology · Statistics 2025-12-09 Godwin Yung , Kaspar Rufibach , Marcel Wolbers , Mark Yan , Jue Wang

The efficiency of an experimental design is ultimately measured in terms of time and resources needed for the experiment. Optimal sequential (multi-stage) design is studied in the situation where each stage involves a fixed cost. The…

Statistics Theory · Mathematics 2012-11-08 Juha Karvanen

We consider the following comparative effectiveness scenario. There are two treatments for a particular medical condition: a randomized experiment has demonstrated mediocre effectiveness for the first treatment, while a non-randomized study…

Methodology · Statistics 2024-08-23 Brian Knaeble , Erich Kummerfeld

Time-to-event data with long-term survivors (L-TS), subjects who never experience the event, have been reported in multiple areas of oncology as therapies have improved. Conventional two-sample tests ignore L-TS, but alternatives have been…

Methodology · Statistics 2026-05-06 Yu Bi , Durbadal Ghosh , Subodh Selukar

Two-phase design can reduce the cost of epidemiological studies by limiting the ascertainment of expensive covariates or/and exposures to an efficiently selected subset (phase-II) of a larger (phase-I) study. Efficient analysis of the…

Methodology · Statistics 2019-11-04 Prosenjit Kundu , Nilanjan Chatterjee

Hybrid type 2 studies are gaining popularity for their ability to assess both implementation and health outcomes as co-primary endpoints. Often conducted as cluster-randomized trials (CRTs), five design methods can validly power these…

Methodology · Statistics 2026-05-18 Melody Owen , Fan Li , Ruyi Liu , Donna Spiegelman

Mixed outcome endpoints that combine multiple continuous and discrete components to form co-primary, multiple primary or composite endpoints are often employed as primary outcome measures in clinical trials. There are many advantages to…

Methodology · Statistics 2019-12-12 Martina McMenamin , Jessica K. Barrett , Anna Berglind , James M. S. Wason

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…

Methodology · Statistics 2024-05-13 Abigail Burdon , Thomas Jaki , Xijin Chen , Pavel Mozgunov , Haiyan Zheng , Richard Baird

Leveraging external or historical data to improve the efficiency of randomized clinical trials without introducing bias or inflating the Type I error rate remains challenging. Recent work on externally trained prognostic scores, such as…

Methodology · Statistics 2026-05-28 Junyi Zhou , Qing Liu , May Mo , Amy Xia

In clinical studies, the risk of the primary (terminal) event may be modified by intermediate events, resulting in semicompeting risks. To study the treatment effect on the terminal event mediated by the intermediate event, researchers wish…

Methodology · Statistics 2026-05-26 Yuhao Deng , Rui Wang , Tao Zhang , Xiang Zhan

The sequential multiple assignment randomized trial (SMART) is the gold standard trial design to generate data for the evaluation of multi-stage treatment regimes. As with conventional (single-stage) randomized clinical trials, interim…

Methodology · Statistics 2023-09-13 Cole Manschot , Eric Laber , Marie Davidian

Adaptive designs are commonly used in clinical and drug development studies for optimum utilization of available resources. In this article, we consider the problem of estimating the effect of the selected (better) treatment using a…

Statistics Theory · Mathematics 2023-01-24 Masihuddin , Neeraj Misra

Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…

Applications · Statistics 2025-02-25 Cong Chen , Mo Huang

Measuring treatment efficacy in mixture of subgroups from a randomized clinical trial is a fundamental problem in personalized medicine development, in deciding whether to treat the entire patient population or to target a subgroup. We show…

Methodology · Statistics 2014-09-03 Ying Ding , Hui-Min Lin , Jason C. Hsu