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 individual-specific nominal daily dose times, we assume that (i) the subject-specific probability of taking zero, one, or more than one dose associated with a given nominal dose time depends on the value of certain covariates, and on the number of doses associated with the immediate previous time, but is independent of any other previous or future dosing events (the Markov hypothesis); and (ii) the set of 'errors' between actual dose times associated with each nominal time is multivariate normally distributed, conditional on covariates and the number of such actual dose times, as in (i). At the second stage, a multivariate normal distribution is assumed for the individual random effects. We fit this model by maximum likelihood to data collected over three months using an electronic system for recording actual dose times in HIV-positive patients assigned to a regimen of zidovudine thrice daily. Beyond its value for describing and quantifying compliance behaviour, as illustrated here, the model may prove useful for explanatory analyses of clinical trials.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Girard P,Blaschke TF,Kastrissios H,Sheiner LBdoi
10.1002/(sici)1097-0258(19981030)17:20<2313::aid-ssubject
Has Abstractpub_date
1998-10-30 00:00:00pages
2313-33issue
20eissn
0277-6715issn
1097-0258pii
10.1002/(SICI)1097-0258(19981030)17:20<2313::AID-Sjournal_volume
17pub_type
杂志文章abstract::Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Although most previous works on adaptive designs and mid-course sample size re-estimation have focused on two-stage or group-sequential designs ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3201
更新日期:2008-05-10 00:00:00
abstract::Incomplete and unbalanced multivariate data often arise in longitudinal studies due to missing or unequally-timed repeated measurements and/or the presence of time-varying covariates. A general approach to analysing such data is through maximum likelihood analysis using a linear model for the expected responses, and s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780070132
更新日期:1988-01-01 00:00:00
abstract::We study the competing risks model and show that the cause j cumulative incidence function integrated from 0 to τ has a natural interpretation as the expected number of life years lost due to cause j before time τ. This is analogous to the τ-restricted mean lifetime, which is the survival function integrated from 0 to...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5903
更新日期:2013-12-30 00:00:00
abstract::This paper presents a procedure for obtaining short-term projections and lower bounds on the size of the acquired immunodeficiency syndrome (AIDS) epidemic. The method is similar to that proposed by Brookmeyer and Gail but adapted to the situation where individual dates of AIDS diagnosis are available. It gives result...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780081210
更新日期:1989-12-01 00:00:00
abstract::This paper introduces a dynamic clustering methodology based on multi-valued descriptors of dermoscopic images. The main idea is to support medical diagnosis to decide if pigmented skin lesions belonging to an uncertain set are nearer to malignant melanoma or to benign nevi. Melanoma is the most deadly skin cancer, an...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4285
更新日期:2011-09-10 00:00:00
abstract::Joint models initially dedicated to a single longitudinal marker and a single time-to-event need to be extended to account for the rich longitudinal data of cohort studies. Multiple causes of clinical progression are indeed usually observed, and multiple longitudinal markers are collected when the true latent trait of...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6731
更新日期:2016-02-10 00:00:00
abstract:BACKGROUND:The need to deliver interventions targeting multiple diseases in a cost-effective manner calls for integrated disease control efforts. Consequently, maps are required that show where the risk of co-infection is particularly high. Co-infection risk is preferably estimated via Bayesian geostatistical multinomi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4243
更新日期:2011-06-30 00:00:00
abstract::We simulated multinomial AIDS incidence counts from 27 'representative' AIDS epidemics that spanned a period corresponding to previous applications of backcalculation (1 January 1977 to 1 July 1987) and assessed mean square error for several back-calculated estimators of HIV prevalence and short-term AIDS projections....
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780100802
更新日期:1991-08-01 00:00:00
abstract::Assessing the calibration of methods for estimating the probability of the occurrence of a binary outcome is an important aspect of validating the performance of risk-prediction algorithms. Calibration commonly refers to the agreement between predicted and observed probabilities of the outcome. Graphical methods are a...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8281
更新日期:2019-09-20 00:00:00
abstract::The use of the last observation carried forward (LOCF) method for imputing missing outcome data in randomized clinical trials has been much criticized and its shortcomings are well understood. However, only recently have published studies widely started using more appropriate imputation methods. Consequently, meta-ana...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8009
更新日期:2019-02-28 00:00:00
abstract::Nutritional exposures are often measured with considerable error in commonly used surrogate instruments such as the food frequency questionnaire (FFQ) (denoted by Q(i) for the ith subject). The error can be both systematic and random. The diet record (DR) denoted by R(i) for the ith subject is considered an alloyed go...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3238
更新日期:2008-08-15 00:00:00
abstract::The use of classification and regression tree (CART) methodology is explored for the diagnosis of patients complaining of anterior chest pain. The results are compared with those previously obtained using correspondence analysis and independent Bayes classification. The technique is shown to be of potential value for ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19970415)16:7<717::aid-sim
更新日期:1997-04-15 00:00:00
abstract::This article deals with determination of a sample size that guarantees the success of a trial. We follow a Bayesian approach and we say an experiment is successful if it yields a large posterior probability that an unknown parameter of interest (an unknown treatment effect or an effects-difference) is greater than a c...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3175
更新日期:2008-06-15 00:00:00
abstract::The design of clinical trials often requires knowledge of quantities such as between- and within subject variances about which only imprecise information exists. To provide assurance that the study has the desired power to detect a minimum clinically meaningful difference between treatment groups. Gould, Gould and Shi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780142007
更新日期:1995-10-30 00:00:00
abstract::Multivariate finite mixture models have been applied to the identification of dietary patterns. These models are known to have many parameters, and consequently large samples are usually required. We present a special case of a multivariate mixture model that reduces the number of parameters to be estimated and seems ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5336
更新日期:2012-08-30 00:00:00
abstract::Increasing numbers of economic evaluations are conducted alongside randomised controlled trials. Such studies include factorial trials, which randomise patients to different levels of two or more factors and can therefore evaluate the effect of multiple treatments alone and in combination. Factorial trials can provide...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7322
更新日期:2017-08-15 00:00:00
abstract::With reference to a real data on cataract surgery, we discuss the problem of zero-inflated circular-circular regression when both covariate and response are circular random variables and a large proportion of the responses are zeros. The regression model is proposed, and the estimation procedure for the parameters is ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7496
更新日期:2018-01-15 00:00:00
abstract::Pearson's chi-squared, the likelihood-ratio, and Fisher-Freeman-Halton's test statistics are often used to test the association of unordered r x c tables. Asymptotical, exact conditional, or exact conditional with mid-p adjustment methods are commonly used to compute the p-value. We have compared test power and signif...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2839
更新日期:2007-10-15 00:00:00
abstract::Clinical trials, especially the randomized clinical trial, have been and will remain the gold standard for the evaluation of new interventions, including pharmaceuticals, biologics, medical devices, procedures, or behavioral modifications. Despite more than five decades of experience, there are still challenges in the...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5405
更新日期:2012-11-10 00:00:00
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
更新日期:2004-08-30 00:00:00
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
更新日期:2005-07-15 00:00:00
abstract::Many split-mouth trials are characterized by the pairing of site-specific outcome and baseline data within each segment of a subject's mouth. However when the response variable of interest is binary, methods of statistical analysis for this design are not well developed. In this paper we present several analytic appro...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2782
更新日期:2007-08-15 00:00:00
abstract::We discuss the use of the trichotomous logistic model to discriminate between patients with gastrointestinal (GI) cancer, patients with benign GI disease and 'normal' subjects, using symptoms and the concentrations of some serum proteins that are potentially indicative of malignancy as covariates. A parsimonious model...
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pub_type: 杂志文章
doi:10.1002/sim.4780040313
更新日期:1985-07-01 00:00:00
abstract::The goal of screening programmes for cancer is early detection and treatment with a consequent reduction in mortality from the disease. Screening programmes need to assess the true benefit of screening, that is, the length of time of extension of survival beyond the time of advancement of diagnosis (lead-time). This p...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780142410
更新日期:1995-12-30 00:00:00
abstract::Meta-analysis to investigate the joint effect of multiple factors in the aetiology of a disease is of increasing importance in epidemiology. This task is often challenging in practice, because studies typically concentrate on studying the effect of only one exposure, sometimes may report the interaction between two ex...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2689
更新日期:2006-12-30 00:00:00
abstract::Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7297
更新日期:2017-07-30 00:00:00
abstract::Observational cohort studies often feature longitudinal data subject to irregular observation. Moreover, the timings of observations may be associated with the underlying disease process and must thus be accounted for when analysing the data. This paper suggests that multiple outputation, which consists of repeatedly ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6829
更新日期:2016-05-20 00:00:00
abstract::Omitted variable bias is discussed in the context of linear models. It is shown that the effect of omitted variables can be controlled in linear models for metric dependent variables by using data from follow-up studies. Two different models for analysing such data are proposed. In the first model the omitted variable...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780110906
更新日期:1992-06-30 00:00:00
abstract::In recent years, there has been an increasing trend in conducting seamless phase 2/3 clinical trials for drug development in the pharmaceutical industry due to the visible advantages compared with traditional approaches for separate phase 2 and 3 development. Innovative study designs have been proposed for seamless ph...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7910
更新日期:2018-12-10 00:00:00
abstract::We extend the shared frailty model of recurrent events and a dependent terminal event to allow for a nonparametric covariate function. We include a Gaussian random effect (frailty) in the intensity functions of both the recurrent and terminal events to capture correlation between the two processes. We employ the penal...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4297
更新日期:2011-09-30 00:00:00