A case study in identifying targeted patients population in major depressive disorder by enhanced enrichment design
Summary
Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high‐placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing,...
Source: Pharmaceutical Statistics - November 1, 2017 Category: Statistics Authors: Peter Zhang, Kevin Carroll, Mary Hobart, Carole Augustine, Gary Koch Tags: MAIN PAPER Source Type: research
A dynamic power prior for borrowing historical data in noninferiority trials with binary endpoint
Summary
Traditionally, noninferiority hypotheses have been tested using a frequentist method with a fixed margin. Given that information for the control group is often available from previous studies, it is interesting to consider a Bayesian approach in which information is “borrowed” for the control group to improve efficiency. However, construction of an appropriate informative prior can be challenging. In this paper, we consider a hybrid Bayesian approach for testing noninferiority hypotheses in studies with a binary endpoint. To account for heterogeneity between the historical information and the current trial for ...
Source: Pharmaceutical Statistics - November 1, 2017 Category: Statistics Authors: G. Frank Liu Tags: MAIN PAPER Source Type: research
The plan of enrichment designs for dealing with high placebo response
To deal with high placebo response in clinical trials for psychiatric and other diseases, different enrichment designs, such as the sequential parallel design, two‐way enriched design, and sequential enriched design, have been proposed and implemented recently. Depending on the historical trial information and the trial sponsors' resources, detailed design elements are needed for determining which design to adopt. To assist in making more suitable decisions, we perform evaluations for selecting required design elements in terms of power optimization and sample size planning. We also discuss the implementation of the inte...
Source: Pharmaceutical Statistics - November 1, 2017 Category: Statistics Authors: Xiangmin Zhang, Yeh ‐Fong Chen, Roy Tamura Tags: MAIN PAPER Source Type: research
---
Pharmaceutical Statistics,Volume 17, Issue 1, Page 4-11, January/February 2018. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - September 29, 2017 Category: Statistics Source Type: research
Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - September 20, 2017 Category: Statistics Tags: ISSUE INFORMATION Source Type: research
Equivalence testing for similarity in bioassays using bioequivalence criteria on the relative bioactivity
This article provides a general equivalence approach to evaluate similarity that is directly related to bioequivalence on the relative bioactivity of the standard and test preparations. Bioequivalence on the relative bioactivity can only be guaranteed for positive (only nonblanks) and finite dose intervals. The approach is demonstrated on 4 case studies in which we also show how to calculate a sample size and how to investigate the power of equivalence on similarity. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - September 1, 2017 Category: Statistics Authors: Corine Balj é‐Volkers, Thembile Mzolo, Erik Talens, Pieta IJzerman‐Boon, Edwin Van den Heuvel Tags: MAIN PAPER Source Type: research
Some statistical considerations in the clinical development of cancer immunotherapies
Immuno‐oncology has emerged as an exciting new approach to cancer treatment. Common immunotherapy approaches include cancer vaccine, effector cell therapy, and T‐cell–stimulating antibody. Checkpoint inhibitors such as cytotoxic T lymphocyte–associated antigen 4 and programmed death‐1/L1 antagonists have shown promising results in multiple indications in solid tumors and hematology. However, the mechanisms of action of these novel drugs pose unique statistical challenges in the accurate evaluation of clinical safety and efficacy, including late‐onset toxicity, dose optimization, evaluation of combination agents...
Source: Pharmaceutical Statistics - September 1, 2017 Category: Statistics Authors: Bo Huang Tags: MAIN PAPER Source Type: research
A simple, doubly robust, efficient estimator for survival functions using pseudo observations
Survival functions are often estimated by nonparametric estimators such as the Kaplan‐Meier estimator. For valid estimation, proper adjustment for confounding factors is needed when treatment assignment may depend on confounding factors. Inverse probability weighting is a commonly used approach, especially when there is a large number of potential confounders to adjust for. Direct adjustment may also be used if the relationship between the time‐to‐event and all confounders can be modeled. However, either approach requires a correctly specified model for the relationship between confounders and treatment allocation or...
Source: Pharmaceutical Statistics - September 1, 2017 Category: Statistics Authors: Jixian Wang Tags: MAIN PAPER Source Type: research
A Bayesian sequential design with adaptive randomization for 2 ‐sided hypothesis test
Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2‐arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the prop...
Source: Pharmaceutical Statistics - September 1, 2017 Category: Statistics Authors: Qingzhao Yu, Lin Zhu, Han Zhu Tags: MAIN PAPER Source Type: research
Antibiotics to outpatients in Norway —Assessing effect of latitude and municipality population size using quantile regression in a cross‐sectional study
The objective of this study was to investigate how geographic location (latitude) and municipality population size affect antibiotic consumption in Norway. We analysed all outpatient antibiotic prescriptions (n > 14 000 000) in Norway between 2004 and 2010 using quantile regression. Data were stratified by year, and we aggregated individual data to municipality, county, or latitudinal range. We specified the quantile regression models using directed acyclic graphs and selected the model based on Akaike information criteria. Yearly outpatient antibiotic consumption in Norway varied up to 10‐fold at municipality lev...
Source: Pharmaceutical Statistics - September 1, 2017 Category: Statistics Authors: P ål Haugen, Gunnar Skov Simonsen, Raul Primicerio, Anne‐Sofie Furberg, Lars Småbrekke Tags: MAIN PAPER Source Type: research
Competing risk analysis in a large cardiovascular clinical trial: An APEX substudy
Summary
Competing risk methods are time‐to‐event analyses that account for fatal and/or nonfatal events that may potentially alter or prevent a subject from experiencing the primary endpoint. Competing risk methods may provide a more accurate and less biased estimate of the incidence of an outcome but are rarely applied in cardiology trials. APEX investigated the efficacy of extended‐duration betrixaban versus standard‐duration enoxaparin to prevent a composite of symptomatic deep‐vein thrombosis (proximal or distal), nonfatal pulmonary embolism, or venous thromboembolism (VTE)–related death in acute medically ...
Source: Pharmaceutical Statistics - August 24, 2017 Category: Statistics Authors: Douglas F. Arbetter, Purva Jain, Megan K. Yee, Nathan Michalak, Adrian F. Hernandez, Russell D. Hull, Samuel Z. Goldhaber, Robert A. Harrington, Alex Gold, Alexander T. Cohen, C. Michael Gibson Tags: MAIN PAPER Source Type: research
Issue Information
Abstract
No abstract is available for this article. (Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 12, 2017 Category: Statistics Tags: ISSUE INFORMATION Source Type: research
Adaptive phase I/II clinical trials for drug combination assessment in oncology using the outcomes of each cycle
In this study, we proposed a method that randomizes the next cohort of patients in the phase II part to the dose combination based on the estimated response rate using all the available observed data upon determination of the overall response in the current cohort. We compared the proposed method to the existing method using simulation studies. These demonstrated that the percentage of optimal dose combinations selected in the proposed method is not less than that in the existing method and that the trial duration in the proposed method is shortened compared to that in the existing method. The proposed method meets both et...
Source: Pharmaceutical Statistics - July 1, 2017 Category: Statistics Authors: Shinjo Yada, Chikuma Hamada Tags: MAIN PAPER Source Type: research
Control ‐based imputation for sensitivity analyses in informative censoring for recurrent event data
In clinical trials, missing data commonly arise through nonadherence to the randomized treatment or to study procedure. For trials in which recurrent event endpoints are of interests, conventional analyses using the proportional intensity model or the count model assume that the data are missing at random, which cannot be tested using the observed data alone. Thus, sensitivity analyses are recommended. We implement the control‐based multiple imputation as sensitivity analyses for the recurrent event data. We model the recurrent event using a piecewise exponential proportional intensity model with frailty and sample the p...
Source: Pharmaceutical Statistics - July 1, 2017 Category: Statistics Authors: Fei Gao, Guanghan F. Liu, Donglin Zeng, Lei Xu, Bridget Lin, Guoqing Diao, Gregory Golm, Joseph F. Heyse, Joseph G. Ibrahim Tags: MAIN PAPER Source Type: research
Be a model communicator (and sell your models to anyone) Peter L. Bonate, 2014 ISBN 978 ‐0‐692‐32381‐6; $19.99
(Source: Pharmaceutical Statistics)
Source: Pharmaceutical Statistics - July 1, 2017 Category: Statistics Authors: Andreas Krause Tags: BOOK REVIEW Source Type: research
