Abstract:
:We introduce the idea of a design to detect signals of efficacy in early phase clinical trials. Such a design features three possible decisions: to kill the compound; to continue with staged development; or to continue with accelerated development of the compound. We describe how such studies improve the trade-off between the two errors of killing a compound with good efficacy and committing to a complete full development program for a compound that has no efficacy and describe how they can be designed. We argue that such studies could be used to screen compounds at the proof-of-concept state, reduce late Phase 2 attrition, and speed up the development of highly efficacious drugs.
journal_name
J Biopharm Statjournal_title
Journal of biopharmaceutical statisticsauthors
Brown MJ,Chuang-Stein C,Kirby Sdoi
10.1080/10543406.2011.570466subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1097-108issue
6eissn
1054-3406issn
1520-5711journal_volume
22pub_type
杂志文章,评审abstract::A statistic, W, for measuring change from baseline is developed. Its distribution is found. Simulations using W and analysis of covariance (ANCOVA) are run and the results are compared. W is found to be less powerful than ANCOVA, yet is not seen to suffer some of the ill effects to which ANCOVA can fall prey, namely b...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409708835187
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abstract::Pharmacokinetic studies of drug and metabolite concentrations in the blood are usually conducted as crossover trials, especially in phases I and II. A longitudinal series of measurements is collected on each subject within each period. However, much of the dependence among such observations, within and between periods...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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abstract::Recently, two CPMP Points to Consider, one on adjustment for baseline covariates and the other on multiplicity issues in clinical trials, have included recommendations on the use of subgroup analysis for regulatory purposes. However, despite their regular use and regulatory attention, the validity and nature of subgro...
journal_title:Journal of biopharmaceutical statistics
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abstract::The design of a three-arm trial including the experimental treatment, an active reference treatment, and a placebo is recommended as a useful approach to the assessment of noninferiority of the experimental treatment. The inclusion of the placebo arm enables the assessment of assay sensitivity and internal validation,...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.789893
更新日期:2013-01-01 00:00:00
abstract::In the early stages of traditional drug development, the frequency of dosing (e.g., QD, BID, etc.) is typically determined by the pharmacokinetic properties of a compound. After an appropriate dose frequency is chosen, the magnitude of dose is then evaluated via parallel-group dose-response trials. For some drugs, how...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409608835141
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abstract::As more biologic products are going off patent protection, the development of follow-on biologic products (also known as biosimilars) has gained much attention from both the biotechnology industry and regulatory agencies. Unlike small molecules, the development of biologic products is not only more complicated but als...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.941991
更新日期:2014-01-01 00:00:00
abstract::There is often a need to determine parallelism or linearity between pairs of dose-response data sets for various biological applications. This article describes a technique based on a modification of the well-known extra-sum-of-squares principle of statistical regression. The standard extra-sum-of-squares method uses ...
journal_title:Journal of biopharmaceutical statistics
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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abstract::For approval of generic drugs, the U.S. Food and Drug Administration (FDA) requires the evidence of bioequivalence in average bioavailability be provided. This is based on the Fundmental Bioequivalence Assumption from FDA that if two drug products are shown to be bioequivalent, it is assumed that they are therapeutica...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.941985
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abstract::A main challenge in molecular diagnostic research is to accurately evaluate the performance of a new nucleic acid amplification test when the reference standard is imperfect. Several approaches, such as discrepant analysis, composite reference standard (CRS) method, or latent class analysis (LCA), are commonly applied...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2018.1428613
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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::Randomized controlled clinical trials often use a composite endpoint as a primary endpoint especially when treatment effects or frequency of individual components of the composite are likely to be small and combining them makes clinical sense for the disease under study. An advantage of the composite endpoint is that,...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2011.551327
更新日期:2011-07-01 00:00:00
abstract::In a clinical dose finding study with active control a new drug with several dose levels is compared with an active comparator drug. The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control. This article investigates the finite sample properties of the...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.920343
更新日期:2015-01-01 00:00:00
abstract::The United States Pharmacopeia (USP) content uniformity sampling acceptance plan consisting of a two-stage sampling plan with criteria on sample mean and number of out-of-range tablets is the standard for compendium. It is, however, often used mistakenly for lot quality assurance. In comparison to the Japan Phamacopei...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400601001527
更新日期:2007-01-01 00:00:00
abstract::A test and a reference analytical method are usually compared for agreement based on paired data obtained from several independent subjects. Bias between two methods can be classified as constant and proportional. In this article, we provide an approach for maximum likelihood estimation of total bias between two metho...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-200035450
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/bip-100101202
更新日期:1999-11-01 00:00:00
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract::Multipopulation tailoring trials provide a trial design option that supports the realization of tailored therapeutics or personalized medicine. Several recent publications have focused on statistical and clinical considerations that arise in these trials that are designed to study the overall treatment effect in a pop...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543406.2013.856025
更新日期:2014-01-01 00:00:00
abstract::In method comparison and reliability studies, it is often important to assess agreement between multiple measurements made by different methods, devices, laboratories, observers, or instruments. For continuous data, the concordance correlation coefficient (CCC) is a popular index for assessing agreement between multip...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400701329497
更新日期:2007-01-01 00:00:00
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journal_title:Journal of biopharmaceutical statistics
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doi:10.1080/10543406.2014.972515
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.860153
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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更新日期:2020-09-02 00:00:00
abstract::Using multistage adaptive group sequential test designs, the investigator may perform data-driven changes in the design during the course of the trial without inflation of the Type I error rate. This is possible, for example, through the use of the inverse normal method of combining the p-values from the separate stag...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00
abstract::Recently, a design was proposed for the Simultaneous Global Drug Development Program (SGDDP) to assess the impact of ethnic factors on the effect of a new treatment for a targeted ethnic (TE) population. It used weighted Z tests to combine the information collected from the TE and non-TE (NTE) subgroups in the SGDDP b...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.971166
更新日期:2015-01-01 00:00:00
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.972508
更新日期:2016-01-01 00:00:00
abstract::Dichotomizing a continuous biomarker is a common practice in medical research. Various methods exist in the literature for dichotomizing continuous biomarkers. The most widely adopted minimum p-value approach uses a sequence of test statistics for all possible dichotomizations of a continuous biomarker, and it chooses...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2012.756503
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abstract::Group sequential methods to allow the possibility of early termination of a trial due to sufficiently convincing results are a standard in therapeutic clinical trials but have been little considered in bioequivalence trials. We investigate the statistical properties of one group sequential approach to bioequivalence t...
journal_title:Journal of biopharmaceutical statistics
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journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2017.1321006
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