Mixture-based gatekeeping procedures in adaptive clinical trials.

abstract：:Receptor occupancy (RO) PET is a non-invasive way to determine drug on target. Given the complexity of procedures, long acquisition times, and high cost, ligand displacement imaging trials often have a limited size and produce sparse RO results over the time course of the blocking drug. To take the best advantage of t...

journal_title：Journal of biopharmaceutical statistics

authors： Vandenhende F,Renard D,Nie Y,Kumar A,Miller J,Tauscher J,Witcher J,Zhou Y,Wong DF

更新日期：2008-01-01 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

authors： Zhu H,Zhang S,Ahn C

更新日期：2016-01-01 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

authors： Fan C,Zhang D,Zhang CH

更新日期：2012-01-01 00:00:00

abstract：:For noninferiority testing with the maximum allowable noninferiority margin being prespecified, one can perform valid statistical testing at the same alpha level for multiple noninferiority hypotheses with margins being smaller than this maximum margin. This is easily comprehensible because only one confidence level i...

journal_title：Journal of biopharmaceutical statistics

authors： Hung HM,Wang SJ

更新日期：2004-05-01 00:00:00

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 a...

journal_title：Journal of biopharmaceutical statistics

authors： Gamalo-Siebers M,Gao A,Lakshminarayanan M,Liu G,Natanegara F,Railkar R,Schmidli H,Song G

更新日期：2016-01-01 00:00:00

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

authors： Fang HB,Tian GL,Li W,Tan M

更新日期：2009-07-01 00:00:00

abstract：:For administrative convenience or cost efficiency, we may often employ a cluster randomized trial (CRT), in which randomized units are clusters of patients rather than individual patients. Furthermore, because of ethical reasons or patient's decision, it is not uncommon to encounter data in which there are patients no...

journal_title：Journal of biopharmaceutical statistics

authors： Lui KJ,Chang KC

更新日期：2011-01-01 00:00:00

abstract：:Sample size adjustment at an interim analysis can mitigate the risk of failing to meet the study objective due to lower-than-expected treatment effect. Without modification to the conventional statistical methods, the type I error rate will be inflated, primarily caused by increasing sample size when the interim obser...

journal_title：Journal of biopharmaceutical statistics

authors： Chen YHJ,Yuan SS,Li X

更新日期：2018-01-01 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

authors： Liu K,Yuan Z,Chen G,Huang Q,Wenrich J

更新日期：2015-01-01 00:00:00

abstract：:In confidence interval estimation of the difference between two proportions with overdispersion due to positive correlations, the usual asymptotic normality-based method generally has lower coverage rates than desired, especially when sample size is moderate. Applying the concept of effective sample size to existing m...

journal_title：Journal of biopharmaceutical statistics

authors： Chen C,Li J,Zhou Z

更新日期：2004-05-01 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

authors： Millen BA,Dmitrienko A,Song G

更新日期：2014-01-01 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

authors： Yan Z,Hosmane B,Locke C

更新日期：2013-01-01 00:00:00

abstract：:The world of medical devices while highly diverse is extremely innovative, and this facilitates the adoption of innovative statistical techniques. Statisticians in the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA) have provided leadership in implementing statistical innova...

journal_title：Journal of biopharmaceutical statistics

authors： Campbell G,Yue LQ

更新日期：2016-01-01 00:00:00

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

authors： Hida E,Tango T

更新日期：2013-01-01 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

authors： Shan G

更新日期：2020-09-02 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

authors： Fang HB,Deng D,Zhang T,Tan M

更新日期：2014-01-01 00:00:00

abstract：:Clinical trials often use a binary "fold increase" endpoint defined according to the ratio of interval-censored measurement at end-of-study to that at baseline. We propose a simple yet principled analytic approach based on the linear mixed-effects model for interval-censored data for the analysis of such paired measur...

journal_title：Journal of biopharmaceutical statistics

authors： Xu Y,Lam KF,Ooi EE,Wilder-Smith A,Paton NI,Lee LS,Cheung YB

更新日期：2015-01-01 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

authors： Fairweather WR

更新日期：2003-08-01 00:00:00

abstract：:After a group sequential test, the naive confidence interval (CI) is usually biased in the sense that it does not cover the true parameter at the correct nominal level. Furthermore, when the stopping time is taken into account, the actual conditional confidence coverage probability can be much less accurate. In this a...

journal_title：Journal of biopharmaceutical statistics

authors： Fan X,DeMets DL

更新日期：2006-01-01 00:00:00

abstract：:This article discusses the design of a clinical trial where a new treatment will be compared to a control. For a specific type of endpoint, there are a wide variety of test statistics that can be used. Also, the investigator must decide how many patients to accrue in each arm as well as the duration of the study. Afte...

journal_title：Journal of biopharmaceutical statistics

authors： Lawrence J

更新日期：2002-05-01 00:00:00

abstract：:Investigating the prevalence of a disease is an important topic in medical studies. Such investigations are usually based on the classification results of a group of subjects according to whether they have the disease. To classify subjects, screening tests that are inexpensive and nonintrusive to the test subjects are...

journal_title：Journal of biopharmaceutical statistics

authors： Tang ML,Qiu SF,Poon WY,Tang NS

更新日期：2012-01-01 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

authors： Piccorelli AV,Fraker SA

更新日期：2018-01-01 00:00:00

abstract：:A new three-arm parallel design was recently proposed to investigate the biosimilarity between a biological product and a reference product by using the relative distance. The purpose of this article is to extend their results to binary endpoints for three popular metrics: the risk difference, the log relative risk, a...

journal_title：Journal of biopharmaceutical statistics

authors： Shin W,Kang SH

更新日期：2016-01-01 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

authors： Simon R,Korn EL

更新日期：1991-01-01 00:00:00

abstract：:The Log-odds ratio for 2 × 2 contingency tables is often approximated by a normal distribution with an approximated variance. Hwang and Biswas (2008) illustrated that the standard expression for the variance should be modified in the presence of correlation. They also provided an adjustment to this variance expression...

journal_title：Journal of biopharmaceutical statistics

authors： Biswas A,Hwang JS

更新日期：2011-01-01 00:00:00

abstract：:All too often in clinical trials the assessment of quality of life is seen as a bolt-on study. Consequently insufficient consideration is often given to its design, collection, analysis and presentation, and its impact on the trial results and on clinical practice is minimal. In many trials quality of life is a key en...

journal_title：Journal of biopharmaceutical statistics

authors： Stephens R

更新日期：2004-02-01 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

authors： Chow SC,Shao J

更新日期：2005-01-01 00:00:00

abstract：:Rubinstein et al. presented a procedure for determining the required duration of accrual for a clinical trial comparing the survival distributions of two treatments using a classical hypothesis testing formulation. Here their testing procedure is modified in two ways. First, the asymptotic variances used in computatio...

journal_title：Journal of biopharmaceutical statistics

authors： Bristol DR

更新日期：1993-09-01 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

authors： Mannino FV,Amit O,Lahiri S

更新日期：2013-01-01 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

authors： Magari RT

更新日期：2004-11-01 00:00:00