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 maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms. Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.
journal_name
J Biopharm Statjournal_title
Journal of biopharmaceutical statisticsauthors
Helms HJ,Benda N,Friede Tdoi
10.1080/10543406.2014.920343subject
Has Abstractpub_date
2015-01-01 00:00:00pages
939-57issue
5eissn
1054-3406issn
1520-5711journal_volume
25pub_type
杂志文章abstract::A method is proposed for the estimation of drug or toxicity potencies using in vitro data. A typical experiment in cancer research is presented where cells from a tumor-derived cell line were deposited as fixed volumes in 12-well cell culture plates. After waiting for 72 hours (for further growth), the wells were expo...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400500265595
更新日期:2005-01-01 00:00:00
abstract::We propose a new adaptive threshold detection and enrichment design in which the biomarker threshold is adaptively estimated and updated by optimizing a trade-off between the size of the biomarker positive population and the magnitude of the treatment effect in that population. Enrichment is based on an enrollment cri...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2020.1832110
更新日期:2020-11-11 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 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
pub_type: 杂志文章,评审
doi:10.1080/10543406.2015.1092037
更新日期:2016-01-01 00:00:00
abstract::Multiple comparisons are commonly seen in clinical trials and many other fields. An example, which is the focus of this paper, is the comparison of several test treatments (possibly different doses of a compound) with placebo (control). It is well known that steps must be taken to control the type I error rate when mu...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409708835193
更新日期:1997-07-01 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::We would like to estimate the parameters of a dose-response function with the greatest precision as possible. For a two-parameter model, this is equivalent to minimizing the area of the confidence ellipsoid, i.e., a D-optimal design. Previous work on this particular model has included minimal designs. These designs ar...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1081/BIP-100101012
更新日期:2000-02-01 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
pub_type: 杂志文章
doi:10.1081/BIP-200062286
更新日期:2005-01-01 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
pub_type: 杂志文章
doi:10.1080/10543406.2013.813516
更新日期:2013-01-01 00:00:00
abstract::The purpose of this paper is to describe, illustrate, and compare a number of different approaches to the analysis of repeated binary and categorical data. These approaches include empirical generalized least squares and generalized estimating equations, as well as traditional log-linear modeling methods. It is shown ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543409208835036
更新日期:1992-01-01 00:00:00
abstract::How long a dementia patient is cared for in the home before admission to a nursing home depends on the state of the patient and the state of the caregiver. Using 5-year follow-up data, the times until entry to nursing home and until death are modeled using a Cox survival model in which patient and caregiver variables ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409408835076
更新日期:1994-03-01 00:00:00
abstract::In this paper I consider a problem of identifying all effective and superior drug combinations. I formulate this problem in terms of a family of hypotheses and propose a two-stage method to solve it. The first stage uses individual p-values obtained via the Min tests, whereas Holm's approach is employed in the second ...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400802622469
更新日期:2009-01-01 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
更新日期:2004-11-01 00:00:00
abstract::Drug-related side effects are one of the leading causes of death and illness in the developed world. Finding genes that modify drug response has the potential to significantly improve drug delivery, by identifying both individuals that can benefit from therapy and those at increased risk of harm. We present a simple a...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543400903572761
更新日期:2010-03-01 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
abstract::Classification measures play essential roles in the assessment and construction of classifiers. Hence, determining how to prevent these measures from being affected by individual observations has become an important problem. In this paper, we propose several indexes based on the influence function and the concept of l...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2017.1377728
更新日期:2018-01-01 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
pub_type: 杂志文章
doi:10.1080/10543406.2015.1052495
更新日期:2016-01-01 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 thorough QT trial is typically designed to test for two set of hypotheses. The primary set of hypotheses is for demonstrating that the test treatment will not prolong QT interval. The second set of hypotheses is to demonstrate the assay sensitivity of the positive control treatment in the study population. The conve...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2013.735762
更新日期:2013-01-01 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::This paper addresses the problem of analyzing multivariate response with the variates having different distributions. We use the generalized estimating equations proposed by Prentice and Zhao (1) to estimate mean and covariance parameters. Wald statistics are used to test hypotheses about the parameters. Data from a t...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409608835129
更新日期:1996-05-01 00:00:00
abstract::Due to the importance of precision medicine, it is essential to identify the right patients for the right treatment. Biomarkers, which have been commonly used in clinical research as well as in clinical practice, can facilitate selection of patients with a good response to the treatment. In this paper, we describe a b...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543406.2018.1434191
更新日期:2018-01-01 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::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
pub_type: 杂志文章
doi:10.1080/10543400500406595
更新日期:2006-01-01 00:00:00
abstract::I review the designs available for Phase I dose-finding studies of chemotherapeutic agents in cancer patients. The designs are based on the assumption that both efficacy and toxicity increase with dose, and thus attempt to minimize the number of patients treated at low doses, and also to minimize the chance that patie...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543400600860295
更新日期:2006-01-01 00:00:00
abstract::A model-based approach is developed to estimate the distribution of time from seroconversion to diagnosis with acquired immunodeficiency syndrome (AIDS) as a function of selected time-dependent covariates. The approach is applied to longitudinal data collected over 4 years of follow-up from 450 men seropositive for th...
journal_title:Journal of biopharmaceutical statistics
pub_type: 临床试验,杂志文章
doi:10.1080/10543409408835078
更新日期:1994-07-01 00:00:00
abstract::Fisher's exact test and Pearson's chi-square with continuity correction are frequently employed in the analysis of epidemiological data involving a 2 x 2 contingency table. This paper reviews the concepts and controversies underlying these procedures and discusses their appropriateness and adequacies in analyzing such...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章,评审
doi:10.1080/10543409508835098
更新日期:1995-03-01 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::Nonparametric methods are presented for the analysis of the two-treatment, two-period crossover design with multivariate response. After forming within-subject sums and differences, the usual tests, including those for carry-over effects and direct treatment effects, can be constructed using a multivariate analysis of...
journal_title:Journal of biopharmaceutical statistics
pub_type: 杂志文章
doi:10.1080/10543409308835045
更新日期:1993-03-01 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