Abstract:
:The gold standard for evaluating treatment efficacy of a medical product is a placebo-controlled trial. However, when the use of placebo is considered to be unethical or impractical, a viable alternative for evaluating treatment efficacy is through a noninferiority (NI) study where a test treatment is compared to an active control treatment. The minimal objective of such a study is to determine whether the test treatment is superior to placebo. An assumption is made that if the active control treatment remains efficacious, as was observed when it was compared against placebo, then a test treatment that has comparable efficacy with the active control, within a certain range, must also be superior to placebo. Because of this assumption, the design, implementation, and analysis of NI trials present challenges for sponsors and regulators. In designing and analyzing NI trials, substantial historical data are often required on the active control treatment and placebo. Bayesian approaches provide a natural framework for synthesizing the historical data in the form of prior distributions that can effectively be used in design and analysis of a NI clinical trial. Despite a flurry of recent research activities in the area of Bayesian approaches in medical product development, there are still substantial gaps in recognition and acceptance of Bayesian approaches in NI trial design and analysis. The Bayesian Scientific Working Group of the Drug Information Association provides a coordinated effort to target the education and implementation issues on Bayesian approaches for NI trials. In this article, we provide a review of both frequentist and Bayesian approaches in NI trials, and elaborate on the implementation for two common Bayesian methods including hierarchical prior method and meta-analytic-predictive approach. Simulations are conducted to investigate the properties of the Bayesian methods, and some real clinical trial examples are presented for illustration.
journal_name
J Biopharm Statjournal_title
Journal of biopharmaceutical statisticsauthors
Gamalo-Siebers M,Gao A,Lakshminarayanan M,Liu G,Natanegara F,Railkar R,Schmidli H,Song Gdoi
10.1080/10543406.2015.1074920subject
Has Abstractpub_date
2016-01-01 00:00:00pages
823-41issue
5eissn
1054-3406issn
1520-5711journal_volume
26pub_type
杂志文章,评审abstract::We consider the problem of estimating a biomarker-based subgroup and testing for treatment effect in the overall population and in the subgroup after the trial. We define the best subgroup as the subgroup that maximizes the power for comparing the experimental treatment with the control. In the case of continuous outc...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2019.1633655
更新日期:2019-01-01 00:00:00
abstract::Gene expression profiling has played an important role in cancer risk classification and has shown promising results. Since gene expression profiling often involves determination of a set of top rank genes for analysis, it is important to evaluate how modeling performance varies with the number of selected top ranked ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400802277967
更新日期:2008-01-01 00:00:00
abstract::A framework is proposed for making quality predictions in situations for which only systematically inaccurate data are available. The predictions are based on the systematically inaccurate data, complete data from similar situations, and expert knowledge. The proposed predictive model is well suited to functional data...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.860153
更新日期:2014-01-01 00:00:00
abstract::Pharmaceutical product development culminates in confirmatory trials whose evidence for the product's efficacy and safety supports regulatory approval for marketing. Regulatory agencies in countries whose patients were not included in the confirmatory trials often require confirmation of efficacy and safety in their p...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543406.2012.701579
更新日期:2012-09-01 00:00:00
abstract::The dose-response models for full agonists and for a particular type of partial agonist can be described by sigmoidal curves and bell-shaped curves, respectively. The methods currently used to evaluate the interaction of a full agonist and a partial agonist require a large number of experimental units and base their a...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409808835266
更新日期:1998-11-01 00:00:00
abstract::Sample size calculation formulas for testing equality, noninferiority, superiority, and equivalence based on odds ratio were derived under both parallel and one-arm crossover designs. An example concerning the study of odds ratio between a test compound (treatment) and a standard therapy (control) for prevention of re...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-120016231
更新日期:2002-11-01 00:00:00
abstract::Hypoglycemia is a major safety concern for diabetic patients. Hypoglycemic events can be modeled based on time to recurrent events or count data. In this article, we evaluated a gamma frailty model with variance estimated by the inverse of observed Fisher information matrix, a gamma frailty model with the sandwich var...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2020.1765370
更新日期:2020-05-18 00:00:00
abstract::According to ICH Q6A (1999), a specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. For drug products, specifications usually consist of test methods and acceptance criteria ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543406.2014.972511
更新日期:2015-01-01 00:00:00
abstract::A randomized, active-control clinical trial setting with the objective of testing noninferiority for a continuous response variable is considered. Noninferiority margin is based on the concept of preserving a certain fraction of the active control effect. Noninferiority is established if the ratio of the lower (upper)...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400600609478
更新日期:2006-05-01 00:00:00
abstract::When marketed lots of pharmaceutical products produce a number of out-of-specification (OOS) samples, it can be very disruptive. In some cases such lots must be recalled, at substantial expense. We present a model of the probability of OOS samples and show quantitatively how this probability depends on the underlying ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-120022763
更新日期:2003-08-01 00:00:00
abstract::We study the statistical efficiency for rising-dose designs in the context of first-in-human studies. Specifically, we identify a class of crossover designs that are appealing in terms of both subject safety and statistical efficiency and, for a three-period, two-panel design in such a class, we compare its A-efficien...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.792827
更新日期:2013-01-01 00:00:00
abstract::Although asymptotically, the empirical covariance estimator is consistent and robust with respect to the selection of the working correlation matrix, when the sample size is small, its bias may not be negligible. This article proposes a small sample correction for the empirical covariance estimator in general Gaussian...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2011.557792
更新日期:2012-01-01 00:00:00
abstract::Sample size calculation based on normal approximations is often associated with the loss of statistical power for a single-arm trial with a time-to-event endpoint. Recently, Wu (2015) derived the exact variance for the one-sample log-rank test under the alternative and showed that a single-arm one-stage study based on...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2020.1730869
更新日期:2020-09-02 00:00:00
abstract::In preclinical tumor xenograft experiments, the antitumor activity of the tested agents is often assessed by endpoints such as tumor doubling time, tumor growth delay (TGD), and log10 cell kill (LCK). In tumor xenograft literature, the values of these endpoints are presented without any statistical inference, which ig...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2010.481802
更新日期:2011-05-01 00:00:00
abstract::Predictive probability is particularly useful in aiding a decision-making process related to drug development. This is especially true for decisions occurring as the result of interim analyses of clinical trials. Examples of clinical trial applications of Bayesian predictive probability and the use of the beta-binomia...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-100101000
更新日期:1999-03-01 00:00:00
abstract::ETRANK is a statistical software which uses nonparametric (randomization) technique to analyze incomplete repeated measures data, where the pattern of withdrawal is treatment related. This stand alone program is written in C, presently runs in MS-DOS, and a Windows version is in development. The program has been devel...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543409608835156
更新日期:1996-11-01 00:00:00
abstract::Exact overall significance levels for selected sample sizes and response probabilities are graphically displayed when a dichotomous variable is compared between a placebo and two or more active treatments. A Z-statistic with a pooled variance estimator is used as the test statistic and critical values are based on the...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-120024207
更新日期:2003-11-01 00:00:00
abstract::In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2017.1293081
更新日期:2017-01-01 00:00:00
abstract::The small n, Sequential, Multiple Assignment, Randomized Trial (snSMART) is a two-stage clinical trial design for rare diseases motivated by the comparison of three active treatments for isolated skin vasculitis in the ongoing clinical trial ARAMIS (a randomized multicenter study for isolated skin vasculitis, NCT09239...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2020.1815032
更新日期:2020-09-06 00:00:00
abstract::To confirm results obtained from local evaluation at investigational centers, many oncology studies utilize blinded independent central review (BICR) to make assessments of the primary endpoint, progression-free survival (PFS). The comparison of data often leads to large discordances between these observations, castin...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.813516
更新日期:2013-01-01 00:00:00
abstract::A common question in clinical studies is how to use historical data from earlier studies, leveraging relevant information into the design and analysis of a new study. Bayesian approaches are particularly well-suited to this task, with their natural ability to borrow strength across data sources. In this paper, we prop...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2016.1226324
更新日期:2016-01-01 00:00:00
abstract::This article deals with seven special issues related to the assumptions, applicability, and practical use of formulas for calculating power or sample size, respectively, for comparative clinical trials with time-to-event endpoints, with particular focus on the well-known Freedman and Schoenfeld methods. All problems a...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.1000546
更新日期:2015-01-01 00:00:00
abstract::Four multidose animal carcinogenicity assay trend test procedures based on the chi-square, Hoel-Walburg, log-rank, and Peto procedures are compared under conditions of competing risks. A total of 42 different risk populations are simulated in which a simulated animal can contract one or more of five different tumor ty...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409408835089
更新日期:1994-11-01 00:00:00
abstract::Frequentist design for two-arm randomized Phase II clinical trials with outcomes from the exponential dispersion family was proposed previously, where the total sample sizes are minimized under multiple constraints on the standard errors of the estimated group means and their difference. This design was generalized fr...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2017.1402779
更新日期:2018-01-01 00:00:00
abstract::The adverse events data of randomized clinical trials are often analyzed based on either crude incidence rates or exposure-adjusted incidence rates. These rates do not adequately account for an individual patient's profile of adverse events over the study period when an individual may remain in the trial after experie...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400903105463
更新日期:2009-09-01 00:00:00
abstract::The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually documented by protocol amendments. However, the actual patient popula...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-200062286
更新日期:2005-01-01 00:00:00
abstract::Patient-reported outcomes are important for assessing the effectiveness of treatments in many disease areas. For this reason, many new instruments that capture patient-reported outcomes have been developed over the past several decades. With the development of each new instrument, there is the ensuing question of what...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400903315757
更新日期:2010-09-01 00:00:00
abstract::Historical control trials (HCTs) are frequently conducted to compare an experimental treatment with a control treatment from a previous study, when they are applicable and favored over a randomized clinical trial (RCT) due to feasibility, ethics and cost concerns. Makuch and Simon developed a sample size formula for h...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2015.1052495
更新日期:2016-01-01 00:00:00
abstract::Ratio of means (ROM) and difference of means (DOM) are often used in a superiority, noninferiority (NI), or average bioequivalence (ABE) test to evaluate whether the test mean is superior, NI, or equivalent to the reference (placebo or active control) mean. The literature provides recommendations regarding how to choo...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2016.1265536
更新日期:2017-01-01 00:00:00
abstract::The Food and Drug Administration of the United States issued a draft guidance on adaptive design clinical trials in February 2010. This draft guidance has attracted a lot of attention because of the increasing interest in adaptive trials by the pharmaceutical industry in recent years. In this paper, we report on highl...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2010.514456
更新日期:2010-11-01 00:00:00