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Monitoring Ongoing Clinical Trials under Fractional Brownian Motion with Drift Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-03-08 Peng Zhang, Weichung Joe Shih, Yong Lin, K.K. Gordon Lan, Tai Xie
The standard Brownian motion (Bm) with a linear drift is a convenient statistical structure for monitoring ongoing clinical trials in practice for more than four decades (Lan and DeMets, 1983). Und...
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An Instrumental Variable Approach to Learning the Causal Exposure-Response Relationship in a Randomized Dose Comparison Trial Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-03-06 Zhiwei Zhang, Jixian Wang, Dong Xi
We consider the problem of estimating the causal effect of drug exposure on clinical response in a randomized dose comparison trial where each group receives a different dose. Because exposure is n...
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Implementation of statistical innovation in a pharmaceutical company Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-03-05 Kaspar Rufibach, Marcel Wolbers, Jenny Devenport, Godwin Yung, Chris Harbron, Alun Bedding, Zhiyue Huang, Ray Lin, Herbert Pang, Daniel SabanésBové, Jianmei Wang
Innovation, defined as the successful implementation at scale of a new invention, is key for continued success of the drug development enterprise. In this paper we focus on statistical innovation i...
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Bayesian and Frequentist Approaches to Rescuing Disrupted Trials: A Report from the NISS Ingram Olkin Forum Series on Unplanned Clinical Trial Disruptions Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-02-05 Cornelia Ursula Kunz, Sergey Tarima, Gary L. Rosner, Richard Emsley, Madeline Bauer, Christopher Jennison, James L. Rosenberger, Nigel Stallard, Sarah Zohar, Nancy Flournoy
The COVID-19 pandemic impacted clinical trials in ways never expected. However, similar challenges should now be expected going forward. These challenges made us aware of statistical problems arisi...
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Optimizing Patient Recruitment in Global Clinical Trials using Nature-Inspired Metaheuristics Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-02-06 Mitchell Aaron Schepps, Weng Kee Wong, Matt Austin, Volodymyr Anisimov
A common problem seen in the ineffective execution of global multicenter trials is the frequent inability to recruit a sufficient number of patients. A myriad of barriers to recruiting enough patie...
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Correction Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-02-01
Published in Statistics in Biopharmaceutical Research (Vol. 16, No. 1, 2024)
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Statistics in Biopharmaceutical Research 2023 Associate Editors Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-02-01
Published in Statistics in Biopharmaceutical Research (Vol. 16, No. 1, 2024)
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A Two-Stage Covariate-Adjusted Response-Adaptive Enrichment Design Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-01-23 Li Yang, Guoqing Diao, William F. Rosenberger
In the precision medicine paradigm, it is of interest to identify subgroups that benefit most from the treatment. However, the subgroup often cannot be identified until after a large-scale clinical...
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Dose Optimization for Novel Oncology Agents: Design Options and Strategies Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-01-23 David Dejardin, Bo Huang, Ying Yuan, Ulrich Beyer, Jane Fridlyand, Jiawen Zhu
Over the past decade, drug development in oncology has shifted from cytotoxic agents to drugs with new mechanisms of action, such as cancer immunotherapies, targeted therapeutics, T-cell engagers a...
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Weighted Hazard Ratio Estimation for Delayed and Diminishing Treatment Effect Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-01-05 Bharati Kumar, Jonathan W. Bartlett
Nonproportional hazards (NPH) have been observed in confirmatory clinical trials with time to event outcomes. Under NPH, the hazard ratio does not stay constant over time and the log rank test is n...
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Effects of Allocation Method and Time Trends on Identification of the Best Arm in Multi-arm Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2024-01-02 Lindsay R Berry, Elizabeth Lorenzi, Nicholas S Berry, Amy M Crawford, Peter Jacko, Kert Viele
Many trial designs, such as dose-finding trials, shared-control designs, or adaptive platform trials, investigate multiple therapies simultaneously. Often these trials seek to identify the best arm...
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Estimands in oncology early clinical development: Assessing the impact of intercurrent events on the dose-toxicity relationship Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-12-18 Francois Mercier, Victoria Homer, Junxian Geng, Hontao Zhang, Stefan Englert, Natalia Kan-Dobrosky, Anja Victor
The R1 addendum to ICH E9 (E9-R1) provides guidance on the definition of estimands in clinical drug development. While the E9-R1 has seen uptake in randomized late-stage clinical trials, its implem...
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Conditional and Unconditional treatment effects in randomized clinical trials: Estimands, Estimation, and Interpretation Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-12-12 Jiawei Wei, Jiajun Xu, Björn Bornkamp, Ray Lin, Hong Tian, Dong Xi, Xin Zhang, Ziqiang Zhao, Satrajit Roychoudhury
ICH E9(R1) specifies the importance of precisely defining the treatment effect for clinical trials – to inform patient choices and facilitate evidence-based decision-making. FDA's guidance on covar...
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Predicting Probability of Success for Phase III Trials via Propensity-Score-Based External Data Borrowing Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-12-12 Jennifer L. Proper, Veronica Bunn, Bradley Hupf, Jianchang Lin
Given the rising costs and time length of confirmatory phase III trials, drug developers have become increasingly reliant on quantitative methods to support critical decisions such as whether drug ...
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DODII: Bayesian Dose Optimization Design for Randomized Phase II Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-12-07 Ziji Yu, Yanzhao Wang, Jianchang Lin
The traditional MTD-based dose selection paradigm commonly used for cytotoxic chemotherapies might not be optimal for targeted therapies because a higher dose does not necessarily result in improve...
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Treatment Comparisons in Adaptive Platform Trials Adjusting for Temporal Drift Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-12-11 Beibei Guo, Li Wang, Ying Yuan
An adaptive platform trial (APT) is a multi-arm trial in the context of a single disease where treatment arms are allowed to enter or leave the trial based on some decision rule. If a treatment ent...
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Joint Analysis of Longitudinal Ordinal Categorical Item Response Data and Survival Times with Cure Fraction Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-11-30 Ming Chi, Xiaogang Wang, Hui Song, Yingwei Peng, Dongsheng Tu
For longitudinal ordinal categorical item response data which may not be observable after a subject develops a terminal event, some statistical models have been proposed for the joint analysis of t...
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Adjusting for time-varying treatment switches in randomized clinical trials: the danger of extrapolation and how to address it Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-11-29 Hege Michiels, An Vandebosch, Stijn Vansteelandt
When choosing estimands and estimators in randomized clinical trials, caution is warranted, as intercurrent events, such as, due to patients who switch treatment after disease progression, are ofte...
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Isotonic Phase I cancer clinical trial design utilizing patient-reported outcomes Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-11-28 Nolan A. Wages, Ruitao Lin
This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determin...
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Selected Articles from the Nonclinical Biostatistics Conference 2021 Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-11-08 John Kolassa, Eve Pickering
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 4, 2023)
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A method for ensuring a consistent dose-response relationship between an entire population and one region in multiregional dose-response studies using MCP-Mod Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-31 Shuhei Kaneko
Multiregional clinical studies are frequently conducted worldwide to accelerate drug approval. Conducting multiregional dose-response studies is useful to determine the effects of important ethnic ...
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Using Randomization Tests to Address Disruptions in Clinical Trials: A Report from the NISS Ingram Olkin Forum Series on Unplanned Clinical Trial Disruptions Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-18 Diane Uschner, Oleksandr Sverdlov, Kerstine Carter, Jonathan Chipman, Olga Kuznetsova, Jone Renteria, Adam Lane, Chris Barker, Nancy Geller, Michael Proschan, Martin Posch, Sergey Tarima, Frank Bretz, William F. Rosenberger
Recent examples for unplanned external events are the global COVID-19 pandemic, the war in Ukraine, or most recently Hurricane Ian in Puerto Rico. Disruptions due to unplanned external events can l...
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A randomization-based theory for preliminary testing of covariate balance in controlled trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-13 Anqi Zhao, Peng Ding
Randomized trials balance all covariates on average and are the gold standard for estimating treatment effects. Chance imbalances nevertheless exist more or less in realized treatment allocations a...
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Covariate-adaptive biased coin randomization for master protocols with multiple interventions and biomarker-stratified allocation Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-09 Tianhao Song, Lisa M. LaVange, Anastasia Ivanova
In a multi-arm trial with predefined subgroups for each intervention to target, it is often desirable to enrich assignment to an intervention by enrolling more biomarker-positive participants to th...
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Generalized Likelihood Ratios for Designing Dose Optimization Studies of Targeted Therapies Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-05 Zhiwei Zhang, Yan Li
Dose optimization studies of new therapeutic agents aim to identify one or more promising doses for further evaluation in subsequent studies. Traditionally, dose optimization has focused on finding...
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Non-concurrent controls in platform trials: can we borrow their concurrent observation data? Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-10-05 Ziren Jiang, Cindy Lu, Jialing Liu, Satrajit Roychoudhury, Daniel Meyer, Bo Huang, Haitao Chu
Adaptive platform trials (APTs) offer an innovative approach to studying multiple therapeutic interventions more efficiently through flexible features such as adding and dropping interventions as e...
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Validity of tests for time-to-event endpoints in studies with the Pocock and Simon covariate-adaptive randomization Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-09-25 Victoria P. Johnson, Michael Gekhtman, Olga M. Kuznetsova
Randomization procedures that enforce balance in prognostic factors, most commonly stratified randomization, are often employed in clinical trials. When the number of factors or factor levels is la...
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Randomization-Based Inference for Clinical Trials with Missing Outcome Data Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-09-27 Nicole Heussen, Ralf-Dieter Hilgers, William F. Rosenberger, Xiao Tan, Diane Uschner
Randomization-based inference is a natural way to analyze data from a clinical trial. But the presence of missing outcome data is problematic: if the data are removed, the randomization distributio...
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Balancing the Objectives of Statistical Efficiency and Allocation Randomness in Randomized Controlled Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-09-20 Oleksandr Sverdlov, Yevgen Ryeznik
Various restricted randomization procedures are available to achieve equal (1:1) allocation in a randomized clinical trial. However, for some procedures, there is a nonnegligible probability of imb...
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Deep Neural Networks Guided Ensemble Learning for Point Estimation Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-09-20 Tianyu Zhan, Haoda Fu, Jian Kang
In modern statistics, interests shift from pursuing the uniformly minimum variance unbiased estimator to reducing mean squared error (MSE) or residual squared error. Shrinkage-based estimation and ...
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Estimands in Real-World Evidence Studies Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-09-18 Jie Chen, Daniel Scharfstein, Hongwei Wang, Binbing Yu, Yang Song, Weili He, John Scott, Xiwu Lin, Hana Lee
A Real-World Evidence (RWE) Scientific Working Group (SWG) of the American Statistical Association Biopharmaceutical Section (ASA BIOP) has been reviewing statistical considerations for the generat...
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A Comparison of Randomization Methods for Multi-Arm Clinical Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-08-29 Ruqayya A. Azher, James M. S. Wason, Michael J. Grayling
Abstract Randomized controlled trials are widely accepted as the best design for evaluating the efficacy of a treatment, due to the advantages of randomization. The objectives of randomization include removing bias in the assignment of treatments, balancing numbers allocated to arms, and balancing observed and unobserved covariates between arms. Different randomization procedures, each with varying
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Statistical inference for vaccine efficacy: a re-randomization procedure to analyse Poisson outcomes under covariate-adaptive randomization. Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-08-24 Leroy Jide Ovbude, Luca Grassano, Brigitte Cheuvart, Francesca Solmi
ABSTRACT Re-randomization inference is used as an alternative approach to more traditional statistical methods. Free from parametric assumptions, its use is particularly suited for studies incorporating covariate-adaptive randomization, and can provide additional evaluation and confirmation of inferences drawn from the original analyses, e.g., as a sensitivity analysis. We discuss methodological and
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Statistical Innovation in Healthcare: Celebrating the Past 40 Years and Looking Toward the Future–Special Issue for the 2021 Regulatory-Industry Statistics Workshop Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-08-02 Bo Huang, Gene Pennello
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 3, 2023)
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Enhancement of Basket Trial Designs with Incorporation of a Bayesian Three-Outcome Decision-Making Framework Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-08-04 Gu Mi, Yue Yang, Zhumengmeng Jin, Ji Lin, Christelle Lorenzato
With recent accelerated approvals of histology-agnostic novel agents, conducting basket trials that evaluate an investigational therapy on different histologies is gaining momentum, thanks to the underlying common biological anti-cancer mechanism of action. Statistical models are proposed to boost statistical efficiency by leveraging information across cohorts to harvest the shared response signal
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A note on stratification errors in the analysis of clinical trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-27 Neal Thomas
Abstract Stratification in both the design and analysis of randomized clinical trials is common. Despite features in automated randomization systems to re-confirm the stratifying variables, incorrect values of these variables may be entered. These errors are often detected during subsequent data collection and verification. Questions remain about whether to use the mis-reported initial stratification
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Modified Robust Meta-Analytic-Predictive Priors for Incorporating Historical Controls in Clinical Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-26 Qiang Zhao, Haijun Ma
Abstract Incorporating historical information in clinical trials has been of much interest recently because of its potential to reduce the size and cost of clinical trials. Data-conflict is one of the biggest challenges in incorporating historical information. In order to address the conflict between historical data and current data, several methods have been proposed including the robust meta-analytic-predictive
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A Case Study of 2-stage Seamless Adaptive Sample Size Re-Estimation Design with Efficacy Interim analysis When Slope is the Primary Endpoint Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-25 Qi Zhang, Yuqian Shen, Hui Quan, Pascal Minini, Lin Wang
Due to highly unmet medical needs in rare disease areas, there is great desire to speed up the drug development process. A two-stage adaptive design option for a placebo-controlled registration study is being evaluated. Stage 1 consists of participants in an ongoing phase 2 study with 1-year double blinded (DB) treatment and Stage 2 includes newly enrolled participants with 2-year DB treatment period
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Experience with Advisory Committee Meeting Preparation and Execution Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-26 Christine Gause, Jing Zhao
Abstract The FDA uses advisory committees and panels to obtain independent expert advice on scientific, technical, and policy matters. Advisory Committee Meetings (ACMs) may be convened if the agency has significant questions or concerns about clinical data submitted for review. Statisticians from both FDA and industry can play a key role in providing insight into the data under review in an ACM. This
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Statistical Considerations in Pediatric Cancer Trials: Report of American Statistical Association Biopharmaceutical Section Open Forum Discussions Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-25 Rajeshwari Sridhara, Olga Marchenko, Qi Jiang, Elizabeth Barksdale, Todd A. Alonzo, Anup Amatya, David Arons, Alex Bliu, Qiuyi Choo, Michael Coory, Martha Donoghue, Lori Ehrlich, Leonardo Fabio Costa Filho, Elizabeth Fox, Boris Freidlin, Nancy Goodman, Douglas S. Hawkins, Dieter A. Häring, Dominik Karres, E. Anders Kolb, Helen Mao, Pallavi S. Mishra Kalyani, Arlene Naranjo, Alberto Pappo, Martin Posch
This article provides a summary of discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forum organized by the ASA BIOP Statistical Methods in Oncology ...
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The Role of Statistical Thinking in Biopharmaceutical Research Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-07-24 Frank Bretz, Joel B. Greenhouse
Abstract The development of new drugs has evolved dramatically over the past decade. Advances in technology enable scientists to generate “big data” faster than ever before. The availability of complex, high-volume data in turn creates demand for innovative quantitative solutions and tools in a rapidly evolving landscape. As a result, the role of the statistical scientist in collaborative research
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A Bayesian Adaptive Umbrella Trial Design with Robust Information Borrowing for Screening Multiple Combination Therapies Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-06-26 Qing Liu, Wenxi Yu, Leiwen Gao, Xun Jiang, Michael Wolf, May Mo
Abstract In immuno-oncology, developing combination therapies to overcome resistance to single agent or induce synergistic effects has become a new focus. To accelerate the screening process to identify promising combinations based on objective response rates, we propose a Bayesian adaptive Umbrella Trial design to simultaneously evaluate combinations of an investigational compound with different backbones
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A Novel Approach for Modeling Biphasic Dose–Response Curves Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-06-30 Ya-Ching M. Hsieh, Leon Chang, Alfred M. Barron
Estimates of EC501 from dose–response data play an important role in comparing drug potencies. When the sampling data of dose–response studies fail to follow a sigmoidal shaped curve, and the data ...
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Which Randomization Methods Are Used Most Frequently in Clinical Trials? Results of a Survey by the Randomization Working Group Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-06-15 Oleksandr Sverdlov, Kerstine Carter, Ralf-Dieter Hilgers, Colin C. Everett, Vance W. Berger, Yuqun Abigail Luo, Jonathan J. Chipman, Yevgen Ryeznik, Jennifer Ross, Ruth Knight, Kazumi Yamada
Abstract Background: Randomization is the foundational element of modern randomized clinical trials (RCTs). The proper choice and implementation of a randomization procedure is essential for obtaining credible trial results. Purpose: To survey current practices, gaps and challenges in the application of randomization in RCTs, and identify opportunities for improvement. Methods: An online survey by
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A propensity-score integrated approach to Bayesian dynamic power prior borrowing Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-06-13 Jixian Wang, Hongtao Zhang, Ram Tiwari
Abstract Use of historical control data to augment a small internal control arm in a randomized control trial (RCT) can lead to significant improvement of the efficiency of the trial. It introduces the risk of potential bias, since the historical control population is often rather different from the RCT. Power prior approaches have been introduced to discount the historical data to mitigate the impact
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Properties of a confirmatory two-stage adaptive procedure for assessing average bioequivalence Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-06-08 Marie Louise Østerdal, Kyle Raymond, Christian Bressen Pipper
Abstract We investigate a confirmatory two stage adaptive procedure for assessing average bioequivalence and provide some insights to its theoretical properties. Effectively, we perform Two One-Sided Tests (TOST) to reach overall decision about each of the two traditional null-hypotheses involved in declaring average bioequivalence. The tests are performed as combination tests separately for each hypothesis
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Comment on “Non-Proportional Hazards – an Evaluation of the MaxCombo Test in Cancer Clinical Trials” by the Cross-Pharma Non-Proportional Hazards Working Group Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Ray S. Lin, Pralay Mukhopadhyay, Satrajit Roychoudhury, Keaven M. Anderson, Tianle Hu, Bo Huang, Larry F. Leon, Jason J. Z. Liao, Ji Lin, Rong Liu, Xiaodong Luo, Yabing Mai, Rui Qin, Kay Tatsuoka, Yang Wang, Jiabu Ye, Jian Zhu, Tai-Tsang Chen, Renee Iacona, Cross-Pharma Non-proportional Hazards Working Group
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 2, 2023)
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Statistics in Biopharmaceutical Research Best Papers Award 2023 Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Toshimitsu Hamasaki, Freda Cooner
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 2, 2023)
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Editor’s Note: Special Section on Estimands, Design and Analysis of Clinical Trials with Time-to-Event Outcomes Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Toshimitsu Hamasaki
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 2, 2023)
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We Need Subject Matter Expertise to Choose and Identify Causal Estimands: Comment on “Estimands for Recurrent Event Endpoints in the Presence of a Terminal Event” Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Matias Janvin, Jessica G. Young, Mats J. Stensrud
Abstract We summarize what we consider to be the two main limitations of the “Estimands for Recurrent Event Endpoints in the Presence of a Terminal Event” (Schmidli et al. Citation2022Schmidli, H., Roger, J. H., and Akacha, M. (2022), “Estimands for Recurrent Event Endpoints in the Presence of a Terminal Event,” Statistics in Biopharmaceutical Research, this issue. DOI: 10.1080/19466315.2021.1895883
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Rejoinder to Commentaries on “Estimands for Recurrent Event Endpoints in the Presence of a Terminal Event” Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Heinz Schmidli, James H. Roger, Mouna Akacha, on behalf of the Recurrent Event Qualification Opinion Consortium
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 2, 2023)
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Rejoinder to Comments on “Non-Proportional Hazards – An Evaluation of the MaxCombo Test in Cancer Clinical Trials” Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-22 Yuan-Li Shen, Sirisha Mushti, Flora Mulkey, Thomas Gwise, Xin Wang, Jiaxi Zhou, Xin Gao, Shenghui Tang, Marc R. Theoret, Richard Pazdur, Rajeshwari Sridhara
Published in Statistics in Biopharmaceutical Research (Vol. 15, No. 2, 2023)
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Vaccine development during a pandemic: General lessons for clinical trial design Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-09 Benjamin Hofner, Elina Asikanius, Wolfgang Jacquet, Theodor Framke, Katrien Oude Rengerink, Lukas Aguirre Dávila, Maria Grünewald, Florian Klinglmüller, Martin Posch, Finbarr P. Leacy, Thomas Lang, Armin Koch, Jörg Zinserling, Kit Roes
The COVID-19 pandemic triggered an unprecedented research effort to develop vaccines and therapeutics. Urgency dictated that development and regulatory assessment were accelerated, while maintaining all standards for quality, safety and efficacy. To speed up evaluation the European Medicines Agency (EMA) implemented “rolling reviews” allowing developers to submit data for assessment as they became
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Coping with Information Loss and the Use of Auxiliary Sources of Data: A Report from the NISS Ingram Olkin Forum Series on Unplanned Clinical Trial Disruptions Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-09 Silvia Calderazzo, Sergey Tarima, Carissa Reid, Nancy Flournoy, Tim Friede, Nancy Geller, James L Rosenberger, Nigel Stallard, Moreno Ursino, Marc Vandemeulebroecke, Kelly Van Lancker, Sarah Zohar
Abstract While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable
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Minimizing Selection Bias Under the Blackwell and Hodges Model with an Equal Allocation Procedure in a Symmetric Allocation Space Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-05-09 Olga M. Kuznetsova
The investigator in a randomized open-label single-center trial knows the treatment assignments of all randomized subjects and thus can introduce a selection bias in the study results by allocating subjects with a better prognosis when he guesses the next allocation is to the experimental group. When the allocation procedure is known to the investigator, Blackwell and Hodges (1957) demonstrated that
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Application of Group Sequential Methods to the 2-in-1 Design and Its Extensions for Interim Monitoring Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-04-18 Xuekui Zhang, Haijun Jia, Li Xing, Cong Chen
The 2-in-1 adaptive design (Chen et al. 2018) allows seamless expansion of an ongoing Phase 2 trial into a Phase 3 trial to expedite a drug development program. Under a mild assumption expected to ...
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Multiply Robust Weighted Generalized Estimating Equations for Incomplete Longitudinal Binary Data Using Empirical Likelihood Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-04-18 Hiroshi Komazaki, Masaaki Doi, Naohiro Yonemoto, Tosiya Sato
In clinical trials, missing data may lead to serious misinterpretation of trial results. To address this issue, it is important to collect post-randomization data (such as efficacy measurement data...
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From Logic-Respecting Efficacy Estimands to Logic-Ensuring Analysis Principle for Time-to-Event Endpoint in Randomized Clinical Trials with Subgroups Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-04-18 Yi Liu, Miao Yang, Siyoen Kil, Jiang Li, Shoubhik Mondal, Yue Shentu, Hong Tian, Liwei Wang, Godwin Yung
Abstract An important goal of precision medicine is to identify biomarkers that are predictive, and tailor the treatment according to the biomarker levels of individual patients. Differentiating prognostic versus predictive biomarkers impacts important decision makings for patients and treating physicians. Using Hazard Ratio (HR) can mistake a purely prognostic biomarker for a predictive one leading
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Some Multiplicity Adjustment Procedures for Clinical Trials with Sequential Design and Multiple Endpoints Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-04-14 Xiaodong Luo, Hui Quan
This article proposes some new multiplicity adjustment procedures for clinical trials with multiple endpoints and multiple interim analyses. The proposed sequential procedures, adapting the popular...
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Copula-Based Model for Incorporating Single-Agent Historical Data into Dual-Agent Phase I Cancer Trials Stat. Biopharm. Res. (IF 1.8) Pub Date : 2023-04-14 Koichi Hashizume, Jun Tsuchida, Takashi Sozu
Phase I clinical trials for testing the combination of anticancer drugs (combination trials) generally start after the tolerability of each drug is evaluated in phase I clinical trials for monother...