Abstract:
:Failure to recognize the serious implications of heterogeneous correlations and disregard of the multiple test problem in interpreting the results from repeated measurements ANOVA of any single primary outcome measure can produce false-positive error rates that are more than five times the alpha level that is reported. Alternative analyses that do not depend on the symmetry assumption, together with a Bonferroni correction of the multiple tests of significance that are routinely accomplished by the repeated measurements ANOVA, appropriately control the probability of statistical support for a false-positive claim. The magnitudes of error inflation and appropriate procedures for error control are examined in this article using simulated clinical trials data.
journal_name
J Biopharm Statjournal_title
Journal of biopharmaceutical statisticsauthors
Overall JE,Doyle SRdoi
10.1080/10543409608835123subject
Has Abstractpub_date
1996-03-01 00:00:00pages
69-81issue
1eissn
1054-3406issn
1520-5711journal_volume
6pub_type
杂志文章abstract::The study of drug combinations has become important in drug development due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. The goal is to identify which combinations are additive, synergistic, or antagonistic. Although there exists statistical ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400902964019
更新日期:2009-07-01 00:00:00
abstract::In randomized controlled trials, patients are recruited and randomly allocated to treatments. Patients are never randomly sampled from large population of patients on treatments under study. Therefore, it is important to consider the design and statistical analysis based on the randomization model. In this article, we...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400802527908
更新日期:2009-01-01 00:00:00
abstract::An integral part of routine health checkups involves laboratory measurements on various analytes in the blood. It is then common to compare the value of two consecutive measurements sampled at different times from the same patient. A "significant" change requires an action (additional sample and/or clinical action). T...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-100107656
更新日期:2001-01-01 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::The aim of this work is to quantitatively assess the impact of structural model misspecifications on the estimates of mean and interindividual variability of clearance in the context of population approaches. This assessment is conducted from simulated datasets. Our results show that impact magnitude of model misspeci...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-120028516
更新日期:2004-02-01 00:00:00
abstract::Sample size estimation (SSE) is an important issue in the planning of clinical studies. While larger studies are likely to have sufficient power, it may be unethical to expose more patients than necessary to answer a scientific question. Budget considerations may also cause one to limit the study to an adequate size t...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543406.2015.1092031
更新日期:2016-01-01 00:00:00
abstract::The potency of a batch of drug product needs to meet a release limits at the time of release so that the potency at the end of shelf life remains above the lower registration limit (LRL). This article discusses two methods which determine the release limits such that the chance to fail LRL at the end of shelf life of ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409808835225
更新日期:1998-03-01 00:00:00
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
doi:10.1081/BIP-100101186
更新日期:1999-08-01 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::People exposed to certain diseases are required to be treated with a safe and effective dose level of a drug. In epidemiological studies to find out an effective dose level, different dose levels are applied to the exposed and a certain number of cures is observed. Negative binomial distribution is considered to fit o...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.834916
更新日期:2013-01-01 00:00:00
abstract::The Youden index, a main summary index for the receiver operating characteristic (ROC) curve, is a comprehensive measurement for the effectiveness of a diagnostic test. For a continuous-scale diagnostic test, the optimal cut point for positive disease is the cut point leading to the maximization of the sum of sensitiv...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2011.592234
更新日期:2012-01-01 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
abstract::Statistical methodologies for human abuse potential studies are rarely evaluated. Human abuse potential studies assess whether test drugs produce positive and negative subjective responses on abuse-related measures using volunteers with histories of recreational drug use. These studies typically have a randomized, dou...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2011.616972
更新日期:2013-03-11 00:00:00
abstract::We studied the sensitivity of the number of unique design points and their placement, in Bayesian optimal designs for pharmacokinetic models, with respect to the magnitude of prior uncertainty. We used two and three-parameter pharmacokinetic models with fixed and mixed effects and two Bayesian optimal design criteria,...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400701514007
更新日期:2007-01-01 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
abstract::In analytical similarity assessment of a biosimilar product, key quality attributes of the test and reference products need to be shown statistically similar. When there were multiple references, similarity among the reference products is also required. We proposed a simultaneous confidence approach based on the fiduc...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2019.1657142
更新日期:2019-01-01 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::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::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::Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to "multivariate" multiplicity problems with several components or sources of multiplicity. A ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2017.1399901
更新日期:2018-01-01 00:00:00
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 bet...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543406.2011.570466
更新日期:2012-01-01 00:00:00
abstract::Analyses of multicenter trials consider the estimated treatment effect differences of the individual centers and combine them into an estimate of the overall treatment effect. There has been much debate in the literature concerning the best way to combine these treatment effect differences. We emphasize that first of ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::In cancer drug development, demonstrated efficacy in tumor xenograft models is an important step toward bringing a promising compound to human use. A key outcome variable is tumor volume measured over a period of time, while mice are treated with certain treatment regimens. A constrained parametric model has been prop...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2014.901340
更新日期:2014-01-01 00:00:00
abstract::Highly clustered count data are commonly seen in medical device clinical studies such as cardiac rhythm management. For instance, anti-arrhythmia shocks delivered from an implantable cardioverter-defibrillator (ICD) often occur as "storms", i.e., multiple shocks within a short period of time. There are unique challeng...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400701668241
更新日期:2008-01-01 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
pub_type: 杂志文章
doi:10.1081/BIP-200056532
更新日期:2005-01-01 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::A mathematical model is described for selecting combinations of chemotherapeutic drugs in order to maximize antitumor dose intensity subject to constraints on toxicity to normal organ systems. Determination of which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibi...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543409108835022
更新日期:1991-01-01 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::During a clinical trial, balancing statistical and ethical considerations are important. Response-adaptive randomization methods use the information from past patients to increase the probability of the next patient receiving the better treatment while avoiding the statistical concern of selection bias. We compared th...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2018.1437172
更新日期:2018-01-01 00:00:00
abstract::For the assessment of biosimilarity of biosimilar products, the United States (US) Food and Drug Administration (FDA) proposed a stepwise approach for providing the totality-of-the-evidence of similarity between a proposed biosimilar product and a US-licensed (reference) product. The stepwise approach starts with the ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2016.1265539
更新日期:2017-01-01 00:00:00