A Bayesian hierarchical nonlinear model for assessing the association between genetic variation and drug cytotoxicity.

Abstract:

:Non-tumor cell-based model systems have recently gained interest in pharmacogenetic research as a hypothesis generating tool. The hypotheses generated from these model systems can be followed up in functional studies, or tested in individuals taking the same investigational agents. The current cellular phenotypes (e.g. cytotoxicity) of interest in these studies are based on the effects of an individual dosage of a drug on the cell lines, or a summary of results at many dosages of a drug (e.g. dose that inhibits 50 per cent of cell growth, GI 50). A more complete analysis of the impact of genetic variation on all aspects of the dose-response curve may lend additional insight into the pharmacogenomics of a particular drug. This paper illustrates the use of a Bayesian hierarchical nonlinear model for the analysis of pharmacogenomic data with cytotoxicity endpoints. The model is illustrated with cytotoxicity and expression data collected on cell lines from a pharmacogenomic study of the drug gemcitabine. By completing an analysis based on the entire dose-response curve, we were able to detect additional genes that affect not only the GI 50, but also the slope of the curve, which reflects the therapeutic index of the drug. Simulation studies also demonstrate that in comparison with the analyses based on the commonly used summary measure GI 50, investigation of the impact of genetic variation on all aspects of the cytotoxicity dose-response curve is more informative, and more powerful with respect to detecting the effect of gene expression on cytotoxicity.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Fridley BL,Jenkins G,Schaid DJ,Wang L

doi

10.1002/sim.3649

subject

Has Abstract

pub_date

2009-09-20 00:00:00

pages

2709-22

issue

21

eissn

0277-6715

issn

1097-0258

journal_volume

28

pub_type

杂志文章
  • Interval censoring in longitudinal data of respiratory symptoms in aluminium potroom workers: a comparison of methods.

    abstract::In a longitudinal study of workers in seven Norwegian aluminium plants, the time to development of asthmatic symptoms could only be determined to lie in the interval between two consecutive health examinations. In a previous paper we analysed the data by survival techniques for interval censored data. In the present p...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780131708

    authors: Samuelsen SO,Kongerud J

    更新日期:1994-09-15 00:00:00

  • Bounding the bias of unmeasured factors with confounding and effect-modifying potentials.

    abstract::Confounding is a major concern in observational studies. To adjust for confounding bias, the potential confounder(s) for a study must first be identified and measured. But this is not always possible. The unmeasured factors may also exhibit effect modification, and this further complicates the situation. In this paper...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4151

    authors: Lee WC

    更新日期:2011-04-30 00:00:00

  • Exact test size and power of a Gaussian error linear model for an internal pilot study.

    abstract::Wittes and Brittain recommended using an 'internal pilot study' to adjust sample size. The approach involves five steps in testing a general linear hypothesis for a general linear univariate model, with Gaussian errors. First, specify the design, hypothesis, desired test size, power, a smallest 'clinically meaningful'...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19990530)18:10<1199::aid-s

    authors: Coffey CS,Muller KE

    更新日期:1999-05-30 00:00:00

  • Bayesian clinical trials in action.

    abstract::Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesi...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sim.5404

    authors: Lee JJ,Chu CT

    更新日期:2012-11-10 00:00:00

  • Marker values at the time of an AIDS diagnosis.

    abstract::In this paper statistical methods are proposed to estimate the distribution of a CD4 T-cell number at the time of a clinical AIDS endpoint from serial measurements of CD4 T-cell values in a cohort study. The statistical formulation of the problem is that of survival analysis with interval censored data, but in which t...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780131915

    authors: Taylor JM,Kim DK

    更新日期:1994-10-15 00:00:00

  • Testing for publication bias in diagnostic meta-analysis: a simulation study.

    abstract::The present study investigates the performance of several statistical tests to detect publication bias in diagnostic meta-analysis by means of simulation. While bivariate models should be used to pool data from primary studies in diagnostic meta-analysis, univariate measures of diagnostic accuracy are preferable for t...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6177

    authors: Bürkner PC,Doebler P

    更新日期:2014-08-15 00:00:00

  • The social contagion hypothesis: comment on 'Social contagion theory: examining dynamic social networks and human behavior'.

    abstract::I reflect on the statistical methods of the Christakis-Fowler studies on network-based contagion of traits by checking the sensitivity of these kinds of results to various alternate specifications and generative mechanisms. Despite the honest efforts of all involved, I remain pessimistic about establishing whether bin...

    journal_title:Statistics in medicine

    pub_type: 评论,杂志文章

    doi:10.1002/sim.5551

    authors: Thomas AC

    更新日期:2013-02-20 00:00:00

  • Seamless phase 2/3 oncology trial design with flexible sample size determination.

    abstract::Conventional seamless phase 2/3 design with fixed sample size determination (SSD) has gained its popularity in oncology drug development due to attractive features such as significantly shortening the development timeline, minimizing sample size, as well as early decision making. However, this design is not immune to ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8543

    authors: Teng Z,Tian Y,Liu Y,Liu G

    更新日期:2020-08-15 00:00:00

  • Multivariate test power approximations for balanced linear mixed models in studies with missing data.

    abstract::Multilevel and longitudinal studies are frequently subject to missing data. For example, biomarker studies for oral cancer may involve multiple assays for each participant. Assays may fail, resulting in missing data values that can be assumed to be missing completely at random. Catellier and Muller proposed a data ana...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6811

    authors: Ringham BM,Kreidler SM,Muller KE,Glueck DH

    更新日期:2016-07-30 00:00:00

  • Assessing the effect of interventions in the context of mixture distributions with detection limits.

    abstract::Many quantitative assay measurements of metabolites of environmental toxicants in clinical investigations are subject to left censoring due to values falling below assay detection limits. Moreover, when observations occur in both unexposed individuals and exposed individuals who reflect a mixture of two distributions ...

    journal_title:Statistics in medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/sim.2079

    authors: Chu H,Kensler TW,Muñoz A

    更新日期:2005-07-15 00:00:00

  • Efficient semiparametric inference for two-phase studies with outcome and covariate measurement errors.

    abstract::In modern observational studies using electronic health records or other routinely collected data, both the outcome and covariates of interest can be error-prone and their errors often correlated. A cost-effective solution is the two-phase design, under which the error-prone outcome and covariates are observed for all...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8799

    authors: Tao R,Lotspeich SC,Amorim G,Shaw PA,Shepherd BE

    更新日期:2021-02-10 00:00:00

  • Comparing and combining data across multiple sources via integration of paired-sample data to correct for measurement error.

    abstract::In biomedical research such as the development of vaccines for infectious diseases or cancer, study outcomes measured by an assay or device are often collected from multiple sources or laboratories. Measurement error that may vary between laboratories needs to be adjusted for when combining samples across data sources...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5446

    authors: Huang Y,Huang Y,Moodie Z,Li S,Self S

    更新日期:2012-12-10 00:00:00

  • Inconsistencies with formulas for the standard error of the standardized mean difference of repeated measures experiments.

    abstract::There are inconsistencies between the formulas for the variance of standardized mean difference (SMD) in the Cochrane Handbook for Systematic Reviews and the variance reported in other sources. Instead of the variance appropriate for the SMD of a crossover experiment, the Cochrane Handbook uses the variance appropriat...

    journal_title:Statistics in medicine

    pub_type: 信件

    doi:10.1002/sim.8669

    authors: Kitchenham B,Madeyski L

    更新日期:2020-11-30 00:00:00

  • Dropouts in the AB/BA crossover design.

    abstract::Missing data arise in crossover trials, as they do in any form of clinical trial. Several papers have addressed the problems that missing data create, although almost all of these assume that the probability that a planned observation is missing does not depend on the value that would have been observed; that is, the ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4497

    authors: Ho WK,Matthews JN,Henderson R,Farewell D,Rodgers LR

    更新日期:2012-07-20 00:00:00

  • Bayesian approach to average power calculations for binary regression models with misclassified outcomes.

    abstract::We develop a simulation-based procedure for determining the required sample size in binomial regression risk assessment studies when response data are subject to misclassification. A Bayesian average power criterion is used to determine a sample size that provides high probability, averaged over the distribution of po...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3505

    authors: Cheng D,Stamey JD,Branscum AJ

    更新日期:2009-02-28 00:00:00

  • A general statistical principle for changing a design any time during the course of a trial.

    abstract::A general method is presented that allows the researcher to change statistical design elements such as the residual sample size during the course of an experiment, to include an interim analysis for early stopping when no formal rule for early stopping was foreseen, to increase or reduce the number of planned interim ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1852

    authors: Müller HH,Schäfer H

    更新日期:2004-08-30 00:00:00

  • Assessing agreement with relative area under the coverage probability curve.

    abstract::There has been substantial statistical literature in the last several decades on assessing agreement, and coverage probability approach was selected as a preferred index for assessing and improving measurement agreement in a core laboratory setting. With this approach, a satisfactory agreement is based on pre-specifie...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6903

    authors: Barnhart HX

    更新日期:2016-08-15 00:00:00

  • A comparison of arm-based and contrast-based models for network meta-analysis.

    abstract::Differences between arm-based (AB) and contrast-based (CB) models for network meta-analysis (NMA) are controversial. We compare the CB model of Lu and Ades (2006), the AB model of Hong et al(2016), and two intermediate models, using hypothetical data and a selected real data set. Differences between models arise prima...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8360

    authors: White IR,Turner RM,Karahalios A,Salanti G

    更新日期:2019-11-30 00:00:00

  • How serious is bias in effect estimation in randomised trials with survival data given risk heterogeneity and informative censoring?

    abstract::It is often assumed that randomisation will prevent bias in estimation of treatment effects from clinical trials, but this is not true of the semiparametric Proportional Hazards model for survival data when there is underlying risk heterogeneity. Here, a new formula is proposed for estimation of this bias, improving o...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7343

    authors: McNamee R

    更新日期:2017-09-20 00:00:00

  • Some considerations in the analysis of rates of change in longitudinal studies.

    abstract::This paper discusses and compares several estimators of mean rate of change in unbalanced longitudinal data based on a model with randomly distributed regression coefficients across individuals. The estimators are unweighted and weighted means of these coefficients. The paper also evaluates commonly used variance esti...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780060509

    authors: Palta M,Cook T

    更新日期:1987-07-01 00:00:00

  • Surveillance of clustering near point sources.

    abstract::Health authorities are often alerted to suspected cancer clusters near the vicinity of potential point sources by members of the public. A surveillance system, where administrative regions around the potential point sources are regularly monitored for high disease rates, would allow for responses which are easier to o...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19960415)15:7/9<727::aid-s

    authors: Le ND,Petkau AJ,Rosychuk R

    更新日期:1996-04-15 00:00:00

  • Bias in methods for deriving standardized morbidity ratio and attributable fraction estimates.

    abstract::This paper examines several methods for deriving standardized morbidity ratios (SMR) and attributable fraction (attributable risk percentage) estimates. We show that some of the proposed methods will, in general, produce biased estimators, although the low variance of certain estimators sometimes compensates for their...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780030206

    authors: Greenland S

    更新日期:1984-04-01 00:00:00

  • Modelling heterogeneity in clustered count data with extra zeros using compound Poisson random effect.

    abstract::In medical and health studies, heterogeneities in clustered count data have been traditionally modeled by positive random effects in Poisson mixed models; however, excessive zeros often occur in clustered medical and health count data. In this paper, we consider a three-level random effects zero-inflated Poisson model...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3619

    authors: Ma R,Hasan MT,Sneddon G

    更新日期:2009-08-15 00:00:00

  • An extension of the continual reassessment methods using a preliminary up-and-down design in a dose finding study in cancer patients, in order to investigate a greater range of doses.

    abstract::In a phase I clinical trial in cancer patients, the drug involved had one known main adverse effect, which also occurs spontaneously in cancer patients with a fairly high frequency. Experiments in rats have shown marked effects of the drug on tumour growth in high doses, but also dose-dependent toxicity. Consequently,...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780140909

    authors: Møller S

    更新日期:1995-05-15 00:00:00

  • The relationship between hot-deck multiple imputation and weighted likelihood.

    abstract::Hot-deck imputation is an intuitively simple and popular method of accommodating incomplete data. Users of the method will often use the usual multiple imputation variance estimator which is not appropriate in this case. However, no variance expression has yet been derived for this easily implemented method applied to...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19970115)16:1<5::aid-sim46

    authors: Reilly M,Pepe M

    更新日期:1997-01-15 00:00:00

  • A simple method for estimating the odds ratio in matched case-control studies with incomplete paired data.

    abstract::Paired data from matched case-control studies are commonly used to estimate the association between the exposure to a risk factor and the occurrence of a disease. The odds ratio is typically used to quantify this association. Difficulties in estimating the true odds ratio with matched pairs arise, however, when the ex...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5355

    authors: Miller KM,Looney SW

    更新日期:2012-11-30 00:00:00

  • Promoting interactions with basic scientists and clinicians: the NIA Alzheimer's Disease Data Coordinating Center.

    abstract::To benefit Alzheimer's disease research, a central data co-ordinating centre (CDCC) is planned that will systematically collect data from 27 Alzheimer's disease centres (ADCs) located nationwide. This CDCC will combine, analyse and disseminate epidemiologic, demographic, clinical and neuropathological data to research...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(20000615/30)19:11/12<1453:

    authors: Cronin-Stubbs D,DeKosky ST,Morris JC,Evans DA

    更新日期:2000-06-15 00:00:00

  • Group sequential designs for clinical trials with bivariate endpoints.

    abstract::Although all clinical trials are designed and monitored using more than one endpoint, methods are needed to assure that decision criteria are chosen to reflect the clinically relevant tradeoffs that assure the trial's scientific integrity. This article presents a framework for the design and monitoring clinical trials...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8696

    authors: Hu J,Blatchford PJ,Goldenberg NA,Kittelson JM

    更新日期:2020-11-20 00:00:00

  • Model selection in logistic joinpoint regression with applications to analyzing cohort mortality patterns.

    abstract::We consider a general model for anomaly detection in a longitudinal cohort mortality pattern based on logistic joinpoint regression with unknown joinpoints. We discuss backward and forward sequential procedures for selecting both the locations and the number of joinpoints. Estimation of the model parameters and the se...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3017

    authors: Czajkowski M,Gill R,Rempala G

    更新日期:2008-04-30 00:00:00

  • An index of disease activity in rheumatoid arthritis.

    abstract::This paper describes the Stoke Index which has been designed to give a global measure of disease activity in rheumatoid arthritis. The index is based on two objective laboratory measurements, one subjective and two semi-objective clinical measurements, chosen from 13 measurements using clinical judgement. Variable sel...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780121206

    authors: Jones PW,Ziade MF,Davis MJ,Dawes PT

    更新日期:1993-06-30 00:00:00