Abstract:
:When the accrual rate is low and the treatment period is long, a long observational period is required before information concerning the primary end point, such as binary response, becomes available in the study. Simon's two-stage designs are often employed in Phase II clinical trials to avoid giving patient an ineffective drug. Thus, if the new drug is ineffective then this design would certainly accelerate the process of drug discovery and development. However, for a promising new drug this design may still require a long observational period. Therefore, when drug safety is not a primary concern, this paper proposes curtailed two-stage designs to shorten the drug development process as soon as the treatment either shows lack of efficacy or is very effective. The proposed design is superior to Simon's two-stage designs in terms of savings in expected sample size and is much easier to implement in practice than stochastically curtailed Simon's designs.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Chi Y,Chen CMdoi
10.1002/sim.3424subject
Has Abstractpub_date
2008-12-20 00:00:00pages
6175-89issue
29eissn
0277-6715issn
1097-0258journal_volume
27pub_type
杂志文章abstract::A mediator acts as a third variable in the causal pathway between a risk factor and an outcome. In this paper, we consider the estimation of the mediation effect when the mediator is a binary variable. We give a precise definition of the mediation effect and examine asymptotic properties of five different estimators o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2730
更新日期:2007-08-15 00:00:00
abstract::The two tailed Fisher's exact P value is extremely sensitive to small perturbations in 2 x 2 contingency tables. An example indicates that a 1 per cent increase in the denominator of one treatment group results in a 32 per cent drop in the exact P value, but a mere 0.1 per cent decrease in the treatment success rate. ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780050610
更新日期:1986-11-01 00:00:00
abstract::Screening and diagnostic tests are important in disease prevention or control. The predictive values of positive and negative (PPV and NPV) test results are two of four operational characteristics of a screening test. We review an existing method based on the generalized estimating equation (GEE) methodology for compa...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2332
更新日期:2006-07-15 00:00:00
abstract::Most statistical methodology for phase III clinical trials focuses on the comparison of a single experimental treatment with a control. An increasing desire to reduce the time before regulatory approval of a new drug is sought has led to development of two-stage or sequential designs for trials that combine the defini...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1362
更新日期:2003-03-15 00:00:00
abstract::We applied a two-stage random effects model to pulmonary function data from 31 sarcoidosis patients to illustrate its usefulness in analysing unbalanced longitudinal data. For the first stage, repeated measurements of percentage of predicted forced vital capacity (FVC%) from an individual were modelled as a function o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780080206
更新日期:1989-02-01 00:00:00
abstract::Writing the variance of the Mantel-Haenszel estimator under the null of homogeneity and inverting the corresponding test, we arrive at an improved confidence interval for the common risk difference in stratified 2 × 2 tables. This interval outperforms a variety of other intervals currently recommended in the literatur...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6122
更新日期:2014-07-30 00:00:00
abstract::Assessment of equivalence or non-inferiority in accuracy between two diagnostic procedures often involves comparisons of paired areas under the receiver operating characteristic (ROC) curves. With some pre-specified clinically meaningful limits, the current approach to evaluating equivalence is to perform the two one-...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2358
更新日期:2006-04-15 00:00:00
abstract::For time-to-event outcomes, a rich literature exists on the bias introduced by covariate measurement error in regression models, such as the Cox model, and methods of analysis to address this bias. By comparison, less attention has been given to understanding the impact or addressing errors in the failure time outcome...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7554
更新日期:2018-04-15 00:00:00
abstract::With the increasing availability of detailed clinical information, there is optimism that treatment choices can be selectively directed to those individuals most likely to benefit. While standard clinical trials can establish whether a treatment appears to be effective on average, subsequent work is needed to determin...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6138
更新日期:2014-07-30 00:00:00
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
更新日期:1994-10-15 00:00:00
abstract::In clinical research, investigators are interested in inferring the average causal effect of a treatment. However, the causal parameter that can be used to derive the average causal effect is not well defined for ordinal outcomes. Although some definitions have been proposed, they are limited in that they are not iden...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7400
更新日期:2017-11-10 00:00:00
abstract::Models for infant growth have usually been based on parametric forms, commonly an exponential or similar model, which have been shown to fit poorly especially during the first year of life. An alternative approach is to use a non-parametric model, based on a shape invariant model (SIM), where a single function is tran...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2718
更新日期:2007-05-30 00:00:00
abstract::Many observational studies adopt what we call retrospective convenience sampling (RCS). With the sample size in each arm prespecified, RCS randomly selects subjects from the treatment-inclined subpopulation into the treatment arm and those from the control-inclined into the control arm. Samples in each arm are represe...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7808
更新日期:2018-05-20 00:00:00
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
更新日期:2014-08-15 00:00:00
abstract::Confounding factors are commonly encountered in observational studies. Several confounder-adjusted tests to compare survival between differently exposed subjects were proposed. However, only few studies have compared their performances regarding type I error rates, and no study exists evaluating their type II error ra...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6777
更新日期:2016-03-30 00:00:00
abstract::Many randomized clinical trials include a data and safety monitoring board (DSMB) that is responsible for reviewing accruing data, monitoring performance of the trial, assuring safety of the participants in the trial, and assessing the efficacy of treatment. The DSMB often makes recommendations about continuation of t...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780120504
更新日期:1993-03-01 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::We construct nonparametric regression estimators of a number of temporal functions in a multistate system based on a continuous univariate baseline covariate. These estimators include state occupation probabilities, state entry, exit, and waiting (sojourn) time distribution functions of a general progressive (e.g., ac...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5703
更新日期:2013-07-30 00:00:00
abstract::In epidemiological studies we often want to learn about the direct effect of an exposure on an outcome, i.e. the effect that is not relayed by a specific intermediate variable. In the literature, there are two common definitions of direct effects; controlled and natural. When the intermediate variable and the outcome ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3493
更新日期:2009-02-15 00:00:00
abstract::It has been increasingly common to analyze simultaneously repeated measures and time to failure data. In this paper we propose a joint model when the repeated measures are semi-continuous, characterized by the presence of a large portion of zero values, as well as right skewness of non zero (positive) values. Examples...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3497
更新日期:2009-03-15 00:00:00
abstract::Meta-analyses of clinical trials are increasingly seeking to go beyond estimating the effect of a treatment and may also aim to investigate the effect of other covariates and how they alter treatment effectiveness. This requires the estimation of treatment-covariate interactions. Meta-regression can be used to estimat...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2768
更新日期:2007-07-10 00:00:00
abstract::Longitudinal biomarker data are often collected in studies, providing important information regarding the probability of an outcome of interest occurring at a future time. With many new and evolving technologies for biomarker discovery, the number of biomarker measurements available for analysis of disease progression...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8687
更新日期:2020-11-20 00:00:00
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
更新日期:2014-07-30 00:00:00
abstract::Health surveillance involves collecting public health data on chronic and infectious diseases to detect changes in disease incidence rates in order to improve public health. Timely detection of disease clusters is essential in prospective public health surveillance. Most existing health surveillance research is based ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3877
更新日期:2011-02-28 00:00:00
abstract::In many epidemiological studies it is common to resort to regression models relating incidence of a disease and its risk factors. The main goal of this paper is to consider inference on such models with error-prone observations and variances of the measurement errors changing across observations. We suppose that the o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3343
更新日期:2008-11-10 00:00:00
abstract::The lifetime risk of a clinical condition is the probability of onset of the condition during one's lifespan. Recent advances in Alzheimer's disease (AD) research have identified screening tests for biomarkers that can identify persons who are in the earliest stages of the AD process but who do not yet have any clinic...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8056
更新日期:2019-04-30 00:00:00
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
更新日期:2019-05-20 00:00:00
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
更新日期:2020-11-20 00:00:00
abstract::It is not uncommon for a continuous outcome variable Y to be dichotomized and analysed using logistic regression. Moser and Coombs (Statist. Med. 2004; 23:1843-1860) provide a method for converting the output from a standard linear regression analysis using the original continuous outcome Y to give much more efficient...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3474
更新日期:2009-01-30 00:00:00
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
更新日期:2017-09-20 00:00:00