A simulation-free approach to assessing the performance of the continual reassessment method.

Abstract:

:The continual reassessment method (CRM) is an adaptive design for Phase I trials whose operating characteristics, including appropriate sample size, probability of correctly identifying the maximum tolerated dose, and the expected proportion of participants assigned to each dose, can only be determined via simulation. The actual time to determine a final "best" design can take several hours or days, depending on the number of scenarios that are examined. The computational cost increases as the kernel of the one-parameter CRM design is expanded to other settings, including additional parameters, monitoring of both toxicity and efficacy, and studies of combinations of two agents. For a given vector of true DLT probabilities, we have developed an approach that replaces a simulation study of thousands of hypothetical trials with a single simulation. Our approach, which is founded on the consistency of the CRM, very accurately reflects the results produced by the simulation study, but does so in a fraction of time required by the simulation study. Relative to traditional simulations, we extensively examine how our method is able to assess the operating characteristics of a CRM design for a hypothetical trial whose characteristics are based upon a previously published Phase I trial. We also provide a metric of nonconsistency and demonstrate that although nonconsistency can impact the operating characteristics of our method, the degree of over- or under-estimation is unpredictable. As a solution, we provide an algorithm for maintaining the consistency of a chosen CRM design so that our method is applicable for any trial.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Braun TM

doi

10.1002/sim.8746

subject

Has Abstract

pub_date

2020-09-16 00:00:00

eissn

0277-6715

issn

1097-0258

pub_type

杂志文章
  • Semiparametric Bayesian variable selection for gene-environment interactions.

    abstract::Many complex diseases are known to be affected by the interactions between genetic variants and environmental exposures beyond the main genetic and environmental effects. Study of gene-environment (G×E) interactions is important for elucidating the disease etiology. Existing Bayesian methods for G×E interaction studie...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8434

    authors: Ren J,Zhou F,Li X,Chen Q,Zhang H,Ma S,Jiang Y,Wu C

    更新日期:2020-02-28 00:00:00

  • Internal pilot studies I: type I error rate of the naive t-test.

    abstract::When sample size is recalculated using unblinded interim data, use of the usual t-test at the end of a study may lead to an elevated type I error rate. This paper describes a numerical quadrature investigation to calculate the true probability of rejection as a function of the time of the recalculation, the magnitude ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19991230)18:24<3481::aid-s

    authors: Wittes J,Schabenberger O,Zucker D,Brittain E,Proschan M

    更新日期:1999-12-30 00:00:00

  • Bayesian methods to compare dose levels with placebo in a small n, sequential, multiple assignment, randomized trial.

    abstract::Clinical trials studying treatments for rare diseases are challenging to design and conduct due to the limited number of patients eligible for the trial. One design used to address this challenge is the small n, sequential, multiple assignment, randomized trial (snSMART). We propose a new snSMART design that investiga...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8813

    authors: Fang F,Hochstedler KA,Tamura RN,Braun TM,Kidwell KM

    更新日期:2021-02-20 00:00:00

  • Assessing diagnostic reliability and estimating incidence rates associated with a strictly progressive disease: dental caries.

    abstract::This paper presents a general approach for simultaneously assessing, from serial data, diagnostic consistency, interrater reliability and incidence of a strictly progressive disease. Observed data are viewed as incomplete: diagnostic errors are not distinguished from true diagnoses. We introduce a broad class of model...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780070306

    authors: Espeland MA,Murphy WC,Leverett DH

    更新日期:1988-03-01 00:00:00

  • A random forest approach for competing risks based on pseudo-values.

    abstract::Random forest is a supervised learning method that combines many classification or regression trees for prediction. Here we describe an extension of the random forest method for building event risk prediction models in survival analysis with competing risks. In case of right-censored data, the event status at the pred...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5775

    authors: Mogensen UB,Gerds TA

    更新日期:2013-08-15 00:00:00

  • Likelihood-based analysis of outcome-dependent sampling designs with longitudinal data.

    abstract::The use of outcome-dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters. The motivating scenario is when outcome data exist for all cohort members but key exposure variables will be gathered only on a subset. Inference with outcom...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7633

    authors: Zelnick LR,Schildcrout JS,Heagerty PJ

    更新日期:2018-06-15 00:00:00

  • Ratio of geometric means to analyze continuous outcomes in meta-analysis: comparison to mean differences and ratio of arithmetic means using empiric data and simulation.

    abstract::Meta-analyses pooling continuous outcomes can use mean differences (MD), standardized MD (MD in pooled standard deviation units, SMD), or ratio of arithmetic means (RoM). Recently, ratio of geometric means using ad hoc (RoGM (ad hoc) ) or Taylor series (RoGM (Taylor) ) methods for estimating variances have been propos...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4501

    authors: Friedrich JO,Adhikari NK,Beyene J

    更新日期:2012-07-30 00:00:00

  • Racial/ethnic disparities in vaccination coverage by 19 months of age: an evaluation of the impact of missing data resulting from record scattering.

    abstract::We describe how trends in the vaccination coverage at 19 months of age vary by race/ethnicity; explore the extent to which data required to evaluate a child's up-to-date vaccination status is missing as a result of the scattering of vaccination records among many vaccination providers; evaluate how the prevalence of t...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3223

    authors: Smith PJ,Stevenson J

    更新日期:2008-09-10 00:00:00

  • Nonparametric collective spectral density estimation with an application to clustering the brain signals.

    abstract::In this paper, we develop a method for the simultaneous estimation of spectral density functions (SDFs) for a collection of stationary time series that share some common features. Due to the similarities among the SDFs, the log-SDF can be represented using a common set of basis functions. The basis shared by the colle...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7972

    authors: Maadooliat M,Sun Y,Chen T

    更新日期:2018-12-30 00:00:00

  • Methods for assessing reliability and validity for a measurement tool: a case study and critique using the WHO haemoglobin colour scale.

    abstract::Before introducing a new measurement tool it is necessary to evaluate its performance. Several statistical methods have been developed, or used, to evaluate the reliability and validity of a new assessment method in such circumstances. In this paper we review some commonly used methods. Data from a study that was cond...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1804

    authors: White SA,van den Broek NR

    更新日期:2004-05-30 00:00:00

  • A new proposal to adjust Moran's I for population density.

    abstract::We analyse the effect of using prevalence rates based on populations with different sizes in the power of spatial independence tests. We compare the well known spatial correlation Moran's index to three indexes obtained after adjusting for population density, one proposed by Oden, another proposed by Waldhör, and a th...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19990830)18:16<2147::aid-s

    authors: Assunção RM,Reis EA

    更新日期:1999-08-30 00:00:00

  • A Markov mixed effect regression model for drug compliance.

    abstract::Patient compliance (adherence) with prescribed medication is often erratic, while clinical outcomes are causally linked to actual, rather than nominal medication dosage. We propose here a hierarchical Markov model for patient compliance. At the first stage, conditional upon individual random effects and a set of indiv...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19981030)17:20<2313::aid-s

    authors: Girard P,Blaschke TF,Kastrissios H,Sheiner LB

    更新日期:1998-10-30 00:00:00

  • Weighted estimation for confounded binary outcomes subject to misclassification.

    abstract::In the presence of confounding, the consistency assumption required for identification of causal effects may be violated due to misclassification of the outcome variable. We introduce an inverse probability weighted approach to rebalance covariates across treatment groups while mitigating the influence of differential...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7522

    authors: Gravel CA,Platt RW

    更新日期:2018-02-10 00:00:00

  • Describing time and age variations in the risk of radiation-induced solid tumour incidence in the Japanese atomic bomb survivors using generalized relative and absolute risk models.

    abstract::Generalized relative and absolute risk models, in which various functions of time and age modify the excess relative or absolute risk of radiation-induced cancer, are fitted to the Japanese atomic bomb survivor cancer incidence data set. Among generalized relative risk models, those in which a product of powers of tim...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19990115)18:1<17::aid-sim9

    authors: Little MP,Muirhead CR,Charles MW

    更新日期:1999-01-15 00:00:00

  • Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models.

    abstract::Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynami...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4393

    authors: Rosthøj S,Keiding N,Schmiegelow K

    更新日期:2012-02-28 00:00:00

  • Explaining heterogeneity in meta-analysis: a comparison of methods.

    abstract::Exploring the possible reasons for heterogeneity between studies is an important aspect of conducting a meta-analysis. This paper compares a number of methods which can be used to investigate whether a particular covariate, with a value defined for each study in the meta-analysis, explains any heterogeneity. The main ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19991030)18:20<2693::aid-s

    authors: Thompson SG,Sharp SJ

    更新日期:1999-10-30 00:00:00

  • Doubly robust generalized estimating equations for longitudinal data.

    abstract::A popular method for analysing repeated-measures data is generalized estimating equations (GEE). When response data are missing at random (MAR), two modifications of GEE use inverse-probability weighting and imputation. The weighted GEE (WGEE) method involves weighting observations by their inverse probability of bein...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3520

    authors: Seaman S,Copas A

    更新日期:2009-03-15 00:00:00

  • Correcting for regression in assessing the response to treatment in a selected population.

    abstract::Previous work on the consequences of regression to the mean for the interpretation of responses to treatment is extended to the situation where the response measured is the proportional change in some variable. Methods for correcting for the bias are discussed. ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780060203

    authors: Curnow RN

    更新日期:1987-03-01 00:00:00

  • The detection of adverse reactions to therapeutic drugs.

    abstract::The risk that a drug newly introduced into medical use will occasionally cause adverse reactions is neither negligible nor totally avoidable. Only well organized systems of monitoring can bring early detection and appropriate action. These in turn require either detailed supervision or spontaneous reporting. The paper...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780010208

    authors: Finney DJ

    更新日期:1982-04-01 00:00:00

  • There is no impact of exposure measurement error on latency estimation in linear models.

    abstract::Identification of the latency period for the effect of a time-varying exposure is key when assessing many environmental, nutritional, and behavioral risk factors. A pre-specified exposure metric involving an unknown latency parameter is often used in the statistical model for the exposure-disease relationship. Likelih...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8038

    authors: Peskoe SB,Spiegelman D,Wang M

    更新日期:2019-03-30 00:00:00

  • An application of kappa-type analyses to interobserver variation in classifying chest radiographs for pneumoconiosis.

    abstract::We investigated interobserver variation between three physician readers in the independent classification of chest radiographs from 1771 taconite workers for pneumoconiosis. We analysed variation with a general methodology for the analysis of categorical data, and quantified interobserver agreement in terms of kappa-t...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780030109

    authors: Musch DC,Landis JR,Higgins IT,Gilson JC,Jones RN

    更新日期:1984-01-01 00:00:00

  • Individualizing drug dosage with longitudinal data.

    abstract::We propose a two-step procedure to personalize drug dosage over time under the framework of a log-linear mixed-effect model. We model patients' heterogeneity using subject-specific random effects, which are treated as the realizations of an unspecified stochastic process. We extend the conditional quadratic inference ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7016

    authors: Zhu X,Qu A

    更新日期:2016-10-30 00:00:00

  • Multi-state models for colon cancer recurrence and death with a cured fraction.

    abstract::In cancer clinical trials, patients often experience a recurrence of disease prior to the outcome of interest, overall survival. Additionally, for many cancers, there is a cured fraction of the population who will never experience a recurrence. There is often interest in how different covariates affect the probability...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6056

    authors: Conlon AS,Taylor JM,Sargent DJ

    更新日期:2014-05-10 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

  • Estimating the causal effect of smoking cessation in the presence of confounding factors using a rank preserving structural failure time model.

    abstract::Estimating the causal effect of quitting smoking on time to death or first myocardial infarction requires that one control for the differences in risk factors between individuals who elect to quite at each time t versus those who elect to continue smoking at time t. In this paper we examine the limitations of standard...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1002/sim.4780121707

    authors: Mark SD,Robins JM

    更新日期:1993-09-15 00:00:00

  • Weighted hurdle regression method for joint modeling of cardiovascular events likelihood and rate in the US dialysis population.

    abstract::We propose a new weighted hurdle regression method for modeling count data, with particular interest in modeling cardiovascular events in patients on dialysis. Cardiovascular disease remains one of the leading causes of hospitalization and death in this population. Our aim is to jointly model the relationship/associat...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6232

    authors: Sentürk D,Dalrymple LS,Mu Y,Nguyen DV

    更新日期:2014-11-10 00:00:00

  • The multiple-record systems estimator when registrations refer to different but overlapping populations.

    abstract::In multiple-record systems estimation it is usually assumed that all registration relate to the same population. In this paper, we develop a method which can be used when the registrations relate to different populations, in the sense that they cover, for example, different time periods or regions. We show that under ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1818

    authors: Zwane EN,van der Pal-de Bruin K,van der Heijden PG

    更新日期:2004-07-30 00:00:00

  • What do we mean by validating a prognostic model?

    abstract::Prognostic models are used in medicine for investigating patient outcome in relation to patient and disease characteristics. Such models do not always work well in practice, so it is widely recommended that they need to be validated. The idea of validating a prognostic model is generally taken to mean establishing tha...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(20000229)19:4<453::aid-sim

    authors: Altman DG,Royston P

    更新日期:2000-02-29 00:00:00

  • Long-term survivor mixture model with random effects: application to a multi-centre clinical trial of carcinoma.

    abstract::A mixture model incorporating long-term survivors has been adopted in the field of biostatistics where some individuals may never experience the failure event under study. The surviving fractions may be considered as cured. In most applications, the survival times are assumed to be independent. However, when the survi...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.932

    authors: Yau KK,Ng AS

    更新日期:2001-06-15 00:00:00

  • Random models for margins of a 2 x 2 contingency table and application to pharmacovigilance.

    abstract::The identification of new adverse drug reactions is often tricky. For a given case, the relationship between drug exposure and symptom occurrence is usually questionable. It could be investigated statistically from a series of drug-event association cases with an independence test between the two variables. Analysing ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780100621

    authors: Tubert P,Begaud B

    更新日期:1991-06-01 00:00:00