Abstract:
:The log-rank test is the most powerful non-parametric test for detecting a proportional hazards alternative and thus is the most commonly used testing procedure for comparing time-to-event distributions between different treatments in clinical trials. When the log-rank test is used for the primary data analysis, the sample size calculation should also be based on the test to ensure the desired power for the study. In some clinical trials, the treatment effect may not manifest itself right after patients receive the treatment. Therefore, the proportional hazards assumption may not hold. Furthermore, patients may discontinue the study treatment prematurely and thus may have diluted treatment effect after treatment discontinuation. If a patient's treatment termination time is independent of his/her time-to-event of interest, the termination time can be treated as a censoring time in the final data analysis. Alternatively, we may keep collecting time-to-event data until study termination from those patients who discontinued the treatment and conduct an intent-to-treat analysis by including them in the original treatment groups. We derive formulas necessary to calculate the asymptotic power of the log-rank test under this non-proportional hazards alternative for the two data analysis strategies. Simulation studies indicate that the formulas provide accurate power for a variety of trial settings. A clinical trial example is used to illustrate the application of the proposed methods.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Zhang D,Quan Hdoi
10.1002/sim.3501subject
Has Abstractpub_date
2009-02-28 00:00:00pages
864-79issue
5eissn
0277-6715issn
1097-0258journal_volume
28pub_type
杂志文章abstract::Selection of dose for cancer patients treated with radiation therapy (RT) must balance the increased efficacy with the increased toxicity associated with higher dose. Historically, a single dose has been selected for a population of patients (e.g., all stage III non-small cell lung cancer). However, the availability o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6285
更新日期:2014-12-30 00:00:00
abstract::In an individually matched case-control study, effects of potential risk factors are ascertained through conditional logistic regression (CLR). Extension of CLR to situations with multiple disease or reference categories has been made through polychotomous CLR and is shown to be more efficient than carrying out separa...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2790
更新日期:2007-07-30 00:00:00
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
更新日期:1996-05-30 00:00:00
abstract::A preference trial is a special form of cross-over trial where clinical conditions determine when patients change treatment, in a prescribed order. This can be modelled using a geometric distribution. The model can be simply fitted using standard logistic regression methodology. The procedure is applied to a trial stu...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19960229)15:4<443::AID-SIM
更新日期:1996-02-28 00:00:00
abstract::Our objective is to develop a model to estimate the relative risk of disease in each area, Ai, i=1, ... , n, of a region and to identify areas of unusually high or low risk. We use a product partition model (PPM) in which we assume that the true relative risks can be partitioned into a number of components or sets of ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3253
更新日期:2008-08-30 00:00:00
abstract::In randomised trials, continuous endpoints are often measured with some degree of error. This study explores the impact of ignoring measurement error and proposes methods to improve statistical inference in the presence of measurement error. Three main types of measurement error in continuous endpoints are considered:...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8359
更新日期:2019-11-30 00:00:00
abstract::In genetic association studies, mixed effects models have been widely used in detecting the pleiotropy effects which occur when one gene affects multiple phenotype traits. In particular, bivariate mixed effects models are useful for describing the association of a gene with a continuous trait and a binary trait. Howev...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8688
更新日期:2020-11-20 00:00:00
abstract::Current methods for statistical analysis of twin studies focus on continuous and dichotomous data, while only limited methodology exists for analysing multinomial data. As a consequence, investigators are often tempted to collapse multinomial data into two categories simply to facilitate the analysis. We address this ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/1097-0258(20010130)20:2<249::aid-sim641>3.
更新日期:2001-01-30 00:00:00
abstract::Sample size planning should reflect the primary objective of a trial. If the primary objective is prediction, the sample size determination should focus on prediction accuracy instead of power. We present formulas for the determination of training set sample size for survival prediction. Sample size is chosen to contr...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5550
更新日期:2013-02-28 00:00:00
abstract::Weak measurement of epidemiologic exposures is an impediment to appreciation of the effects of those exposures. This paper discusses two strategies to assess the true effects of weakly measured exposure. The first is to use external information about the extent of mismeasurement to adjust estimates of the effects of e...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780080904
更新日期:1989-09-01 00:00:00
abstract::New combination regimens evaluated in phase II cancer clinical trials often show promising results compared to the standard therapy for a disease system. Selection of patients with a better prognosis can be a prominent factor for this optimism. For most disease systems, prognostic variables that are related to the out...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.706
更新日期:2001-03-30 00:00:00
abstract::Subjects in randomized controlled trials do not always comply to the treatment condition they have been assigned to. This may cause the estimated effect of the intervention to be biased and also affect efficiency, coverage of confidence intervals, and statistical power. In cluster randomized trials non-compliance may ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8351
更新日期:2019-11-20 00:00:00
abstract::Confidence intervals for a standardized effect are derived after stabilizing the variance of the Welch t-statistic. Simulation studies demonstrate the viability of the resulting intervals for a wide range of parameter values and sample sizes as small as five. The methodology is extended to the combination of results f...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2751
更新日期:2007-06-30 00:00:00
abstract::Several relative risk models for survival time data in drug combination therapy are derived and their properties are discussed. The main intention of this paper is to clarify the differences among the models in order to help to choose the appropriate one in a given situation. The models are motivated by discussing the...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780091216
更新日期:1990-12-01 00:00:00
abstract::Surrogate endpoint validation has been well established by the meta-analytical correlation-based approach as outlined in the seminal work of Buyse et al. (Biostatistics, 2000). Surrogacy can be assumed if strong associations on individual and study levels can be demonstrated. Alternatively, if an effect on a true endp...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6778
更新日期:2016-03-30 00:00:00
abstract::Several large-sample confidence intervals for the ratio of independent binomial proportions are compared in terms of exact coverage probability and width. A non-iterative approximate Bayesian interval is derived and its frequency properties are superior to all of the non-iterative confidence intervals considered. The ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3376
更新日期:2008-11-20 00:00:00
abstract::Variation in heart disease (HD) mortality rates across census tracts is greater than expected given binomial error and available explanatory variables. We extended an extra-binomial variation model for rates standardized by the direct method. The overdispersion parameter accounted for 36 per cent of the observed varia...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780091009
更新日期:1990-10-01 00:00:00
abstract::We analyze data obtained from a study designed to evaluate training effects on the performance of certain motor activities of Parkinson's disease patients. Maximum likelihood methods were used to fit beta-binomial/Poisson regression models tailored to evaluate the effects of training on the numbers of attempted and su...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3303
更新日期:2008-07-30 00:00:00
abstract::Methods for dealing with tied event times in the Cox proportional hazards model are well developed. Also, the partial likelihood provides a natural way to handle covariates that change over time. However, ties between event times and the times that discrete time-varying covariates change have not been systematically s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5683
更新日期:2013-06-30 00:00:00
abstract::With increasingly abundant spatial data in the form of case counts or rates combined over areal regions (eg, ZIP codes, census tracts, or counties), interest turns to formal identification of difference "boundaries," or barriers on the map, in addition to the estimated statistical map itself. "Boundary" refers to a bo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7408
更新日期:2017-11-10 00:00:00
abstract::This paper assesses the coverage probability of commonly used confidence intervals for the standardized mortality ratio (SMR) when death certificates are missing. It also proposes alternative confidence interval approaches with coverage probabilities close to .95. In epidemiology, the SMR is an important measure of ri...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7432
更新日期:2017-11-30 00:00:00
abstract::In the last decade or so, pharmaceutical drug development activities in the area of new antibacterial drugs for treating serious bacterial diseases have declined, and at the same time, there are worries that the increased prevalence of antibiotic-resistant bacterial infections, especially the increase in drug-resistan...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6233
更新日期:2014-11-10 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::The treatment effect sizes that can be detected with sufficient power up to the different interim analyses constitute a clinically meaningful criterion for the selection of a group sequential test for a clinical trial. For any pre-specified sequence of effect sizes, it is possible to construct group sequential boundar...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1751
更新日期:2004-05-15 00:00:00
abstract::In failure time studies involving a chronic disease such as cancer, several competing causes of mortality may be operating. Commonly, the conventional statistical technique of Kaplan-Meier, which is only meaningfully interpreted by assuming independence of failure types and the censoring mechanism, is employed in clin...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/sim.711
更新日期:2001-03-15 00:00:00
abstract::The development of drugs and biologicals whose mechanisms of action may extend beyond their target indications has led to a need to identify unexpected potential toxicities promptly even while blinded clinical trials are under way. One component of recently issued FDA rules regarding safety reporting requirements rais...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7129
更新日期:2017-01-15 00:00:00
abstract::Motivated by a study about prompt coronary angiography in myocardial infarction, we propose a method to estimate the causal effect of a treatment in two-arm experimental studies with possible noncompliance in both treatment and control arms. We base the method on a causal model for repeated binary outcomes (before and...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5856
更新日期:2013-11-10 00:00:00
abstract::In this paper, we consider a full likelihood method to analyze continuous longitudinal responses with non-ignorable non-monotone missing data. We consider a transition probability model for the missingness mechanism. A first-order Markov dependence structure is assumed for both the missingness mechanism and observed d...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5359
更新日期:2012-12-10 00:00:00
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
更新日期:2012-07-30 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