On choosing the number of interim analyses in clinical trials.

Abstract:

:Small but important therapeutic effects of new treatments can be most efficiently detected through the study of large randomized prospective series of patients. Such large scale clinical trials are nowadays commonplace. The alternative is years of polemic and debate surrounding several trials each too small to detect plausible differences with any certainty. Such trials produce equivocal and contradictory results, which could be predicted from power calculations based upon sensible pre-trial estimates of treatment differences. Unfortunately such calculations often lead to sample sizes of several thousands. It is not surprising that investigators tend to be over-optimistic in their estimation of treatment effects (which are necessarily uncertain) especially when the sample size requirements are so stark. In this paper a method is outlined for incorporating into the sample size calculations the uncertainty of the estimate made at the design stage of a clinical trial. In particular a formal scheme is described for deciding how many interim analyses should be performed to satisfy ethical and pragmatic requirements of large clinical trial design. Although the argument will be 'Bayesian', the criteria for assessment and comparison will be strictly of a Neyman-Pearson (i.e. significance testing) kind.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

McPherson K

doi

10.1002/sim.4780010105

subject

Has Abstract

pub_date

1982-01-01 00:00:00

pages

25-36

issue

1

eissn

0277-6715

issn

1097-0258

journal_volume

1

pub_type

杂志文章
  • The many weak instruments problem and Mendelian randomization.

    abstract::Instrumental variable estimates of causal effects can be biased when using many instruments that are only weakly associated with the exposure. We describe several techniques to reduce this bias and estimate corrected standard errors. We present our findings using a simulation study and an empirical application. For th...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6358

    authors: Davies NM,von Hinke Kessler Scholder S,Farbmacher H,Burgess S,Windmeijer F,Smith GD

    更新日期:2015-02-10 00:00:00

  • Exact approaches for testing hypotheses based on the intra-class kappa coefficient.

    abstract::Testing involving the intra-class kappa coefficient is commonly performed in order to assess agreement involving categorical ratings. A number of procedures have been proposed, which make use of the limiting null distribution as the sample size goes to infinity in order to compute the observed significance. As with ma...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6135

    authors: Wilding GE,Consiglio JD,Shan G

    更新日期:2014-07-30 00:00:00

  • Direct effects testing: a two-stage procedure to test for effect size and variable importance for correlated binary predictors and a binary response.

    abstract::In applications such as medical statistics and genetics, we encounter situations where a large number of highly correlated predictors explain a response. For example, the response may be a disease indicator and the predictors may be treatment indicators or single nucleotide polymorphisms (SNPs). Constructing a good pr...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4014

    authors: Sperrin M,Jaki T

    更新日期:2010-10-30 00:00:00

  • Group sequential large sample T2-like chi2 tests for multivariate observations.

    abstract::In many studies, a K degree of freedom large sample chi2 test is used to assess the effect of treatment on a multivariate response, such as an omnibus T2-like test of a difference between two treatment groups in any of K repeated measures. Alternately, a K df chi2 test may be used to test the equality of K+1 groups in...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1637

    authors: Lachin JM,Greenhouse SW,Bautista OM

    更新日期:2003-11-15 00:00:00

  • Covariate adjusted mixture models and disease mapping with the program DismapWin.

    abstract::The analysis and recognition of disease clustering in space and its representation on a map is an important problem in epidemiology. An approach using mixture models to identify spatial heterogeneity in disease risk and map construction within an empirical Bayes framework is described. Once heterogeneity is detected, ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19960415)15:7/9<919::aid-s

    authors: Schlattmann P,Dietz E,Böhning D

    更新日期:1996-04-15 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

  • 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

  • Adaptive prior variance calibration in the Bayesian continual reassessment method.

    abstract::The use of the continual reassessment method (CRM) and other model-based approaches to design Phase I clinical trials has increased owing to the ability of the CRM to identify the maximum tolerated dose better than the 3 + 3 method. However, the CRM can be sensitive to the variance selected for the prior distribution ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5621

    authors: Zhang J,Braun TM,Taylor JM

    更新日期:2013-06-15 00:00:00

  • CoPlot: a tool for visualizing multivariate data in medicine.

    abstract::Many critical questions in medicine require the analysis of complex multivariate data, often from large data sets describing numerous variables for numerous subjects. In this paper, we describe CoPlot, a tool for visualizing multivariate data in medicine. CoPlot is an adaptation of multidimensional scaling (MDS) that ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3078

    authors: Bravata DM,Shojania KG,Olkin I,Raveh A

    更新日期:2008-05-30 00:00:00

  • Marginal versus conditional versus 'structural source' models: a rationale for an alternative to log-linear methods for capture-recapture estimates.

    abstract::Log-linear models for capture-recapture type data are widely used for estimating sizes of populations. Log-linear methods model conditional interactions between the sources. Often, however, the marginal associations are more appropriate and easier for the practitioner to conceptualize. Analyses here of previously publ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19980115)17:1<69::aid-sim7

    authors: Regal RR,Hook EB

    更新日期:1998-01-15 00:00:00

  • Global goodness-of-fit tests for group testing regression models.

    abstract::In a variety of biomedical applications, particularly those involving screening for infectious diseases, testing individuals (e.g. blood/urine samples, etc.) in pools has become a standard method of data collection. This experimental design, known as group testing (or pooled testing), can provide a large reduction in ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3678

    authors: Chen P,Tebbs JM,Bilder CR

    更新日期:2009-10-15 00:00:00

  • Estimating treated prevalence and service utilization rates: assessing disparities in mental health.

    abstract::There is considerable public concern about health disparities among different cultural/racial/ethnic groups. Important process measures that might reflect inequities are treated prevalence and the service utilization rate in a defined period of time. We have previously described a method for estimating N, the distinct...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3904

    authors: Laska EM,Meisner M,Wanderling J,Siegel C

    更新日期:2010-07-20 00:00:00

  • Sample size to test for interaction between a specific exposure and a second risk factor in a pair-matched case-control study.

    abstract::We discuss a sample size calculation for a pair-matched case-control study to test for interaction between a specific exposure and a second risk factor. The second risk factor could be either binary or continuous. An algorithm for the calculation of sample size is suggested which is based on a logistic regression mode...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(20000415)19:7<923::aid-sim

    authors: Qiu P,Moeschberger ML,Cooke GE,Goldschmidt-Clermont PJ

    更新日期:2000-04-15 00:00:00

  • A statistical methodology for postmarketing surveillance of adverse drug reaction reports.

    abstract::This paper presents a statistically optimal exact hypothesis testing procedure for detecting changes in sales adjusted adverse drug reaction (ADR) rates between historical and current periods, with a computer program that implements this test appended. We provide discussions and illustrations on how to monitor ADR rat...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780071004

    authors: Norwood PK,Sampson AR

    更新日期:1988-10-01 00:00:00

  • Discrimination and other statistical intervals for the interpretation of in vivo patient monitoring data.

    abstract::A calibration line is used to define the relationship between a new clinical technique and a standard in vitro laboratory methodology. Discrimination intervals quantify the reliability of inverse estimates obtained from the calibration line. Applied to transcutaneous PCO2 monitoring, a new in vivo measurement, discrim...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780050407

    authors: Kost GJ

    更新日期:1986-07-01 00:00:00

  • A robust method for proportional hazards regression.

    abstract::In this paper we give an informal introduction to a robust method for survival analysis which is based on a modification of the usual partial likelihood estimator (PLE). Large sample results lead us to expect reduced bias for this robust estimator compared with the PLE whenever there are even slight violations of the ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0258(19960530)15:10<1033::AID-S

    authors: Minder CE,Bednarski T

    更新日期:1996-05-30 00:00:00

  • Assessing surrogacy from the joint modelling of multivariate longitudinal data and survival: application to clinical trial data on chronic lymphocytic leukaemia.

    abstract::In clinical research, we are often interested in assessing how a biomarker changes with time, and whether it could be used as a surrogate marker when evaluating the efficacy of a new drug. However, when the longitudinal marker is correlated with survival, linear mixed models for longitudinal data may be inappropriate....

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3142

    authors: Deslandes E,Chevret S

    更新日期:2007-12-30 00:00:00

  • Combining biomarker trajectories to improve diagnostic accuracy in prospective cohort studies with verification bias.

    abstract::In this paper, we develop methods to combine multiple biomarker trajectories into a composite diagnostic marker using functional data analysis (FDA) to achieve better diagnostic accuracy in monitoring disease recurrence in the setting of a prospective cohort study. In such studies, the disease status is usually verifi...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8079

    authors: Li H,Gatsonis C

    更新日期:2019-05-20 00:00:00

  • Competing approaches to analysis of failure times with competing risks.

    abstract::For the analysis of time to event data in contraceptive studies when individuals are subject to competing causes for discontinuation, some authors have recently advocated the use of the cumulative incidence rate as a more appropriate measure to summarize data than the complement of the Kaplan-Meier estimate of discont...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1135

    authors: Farley TM,Ali MM,Slaymaker E

    更新日期:2001-12-15 00:00:00

  • Estimating the stenosis probabilities in arteriosclerosis obliterans using generalized estimating equations.

    abstract::For each of 211 arteriosclerosis obliterans patients, the degree of stenosis of arteries at four sites were examined at Hiroshima University Hospital to analyse the relationship between the degree of stenosis and age, sex and site. The generalized estimating equations using a proportional odds model for the stenosis p...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1363

    authors: Nakashima E,Tsuji S,Fukuoka H,Ohtaki M,Ito K

    更新日期:2003-07-15 00:00:00

  • Group sequential designs for cure rate models with early stopping in favour of the null hypothesis.

    abstract::Ewell and Ibrahim derived the large sample distribution of the logrank statistic under general local alternatives. Their asymptotic results enable us to extend several group sequential designs which allow for early stopping in favour of the null hypothesis to the setting in which the cure rate model is appropriate. In...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/1097-0258(20001130)19:22<3023::aid-sim638>

    authors: Patricia Bernardo MV,Ibrahim JG

    更新日期:2000-11-30 00:00:00

  • A comparison of group sequential methods for binary longitudinal data.

    abstract::Interim analyses are conducted to allow for early termination of the trial, for ethical as well as economical reasons. Here we consider interim analyses in repeated measurements studies where the measurements are binary. Two methods for analysing this kind of data are compared according to their operating characterist...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1361

    authors: Spiessens B,Lesaffre E,Verbeke G

    更新日期:2003-02-28 00:00:00

  • Corrected score estimation in the proportional hazards model with misclassified discrete covariates.

    abstract::We consider Cox proportional hazards regression when the covariate vector includes error-prone discrete covariates along with error-free covariates, which may be discrete or continuous. The misclassification in the discrete error-prone covariates is allowed to be of any specified form. Building on the work of Nakamura...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3159

    authors: Zucker DM,Spiegelman D

    更新日期:2008-05-20 00:00:00

  • Scientific considerations for assessing biosimilar products.

    abstract::The problem for assessing biosimilarity and drug interchangeability of follow-on biologics (biosimilar products) is studied. Unlike the generic products, the development of biosimilar products is much more complicated because of fundamental differences in functional structures and manufacturing processes. As a result,...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5571

    authors: Chow SC,Wang J,Endrenyi L,Lachenbruch PA

    更新日期:2013-02-10 00:00:00

  • Analysis of additive risk model with high-dimensional covariates using partial least squares.

    abstract::In this paper, we construct a partial additive regression (PAR) model to predict the survival times of cancer patients based on microarray gene expression data with right censoring. The area under time-dependent receiver operating characteristic curve is used as a model evaluation criterion. We conduct a simulation st...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3412

    authors: Zhao Y,Zhou Y,Zhao M

    更新日期:2009-01-30 00:00:00

  • Commentary: How the debate about comparative effectiveness research should impact the future of clinical trials.

    abstract::Comparative effectiveness research represents the kind of research that arguably more directly affects clinical practice and policy. It includes observational studies, clinical trials, and systematic syntheses of existing literature. In this commentary, I argue for the ongoing and critical role of randomization in com...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5400

    authors: Lauer MS

    更新日期:2012-11-10 00:00:00

  • Familial associations of lipid profiles: a generalized estimating equations approach.

    abstract::Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influe...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/1097-0258(20001230)19:24<3345::aid-sim829>

    authors: Ziegler A,Kastner C,Brunner D,Blettner M

    更新日期:2000-12-30 00:00:00

  • A copula-based mixed Poisson model for bivariate recurrent events under event-dependent censoring.

    abstract::In many chronic disease processes subjects are at risk of two or more types of events. We describe a bivariate mixed Poisson model in which a copula function is used to model the association between two gamma distributed random effects. The resulting model is a bivariate negative binomial process in which each type of...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3830

    authors: Cook RJ,Lawless JF,Lee KA

    更新日期:2010-03-15 00:00:00

  • A note on the bias of standard errors when orthogonality of mean and variance parameters is not satisfied in the mixed model for repeated measures analysis.

    abstract::The mixed effect models for repeated measures (MMRM) analysis is sometimes used as a primary analysis in longitudinal randomized clinical trials. The SE for the treatment effect in the MMRM analysis is usually estimated by assuming the orthogonality of the fixed effect and variance-covariance parameters, which is the ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8474

    authors: Maruo K,Ishii R,Yamaguchi Y,Doi M,Gosho M

    更新日期:2020-04-30 00:00:00

  • Correcting for the dependent competing risk of treatment using inverse probability of censoring weighting and copulas in the estimation of natural conception chances.

    abstract::When estimating the probability of natural conception from observational data on couples with an unfulfilled child wish, the start of assisted reproductive therapy (ART) is a competing event that cannot be assumed to be independent of natural conception. In clinical practice, interest lies in the probability of natura...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6280

    authors: van Geloven N,Geskus RB,Mol BW,Zwinderman AH

    更新日期:2014-11-20 00:00:00