Abstract:
:Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so-called 'responder analysis', which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so-called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Senn S,Julious Sdoi
10.1002/sim.3603subject
Has Abstractpub_date
2009-11-20 00:00:00pages
3189-209issue
26eissn
0277-6715issn
1097-0258journal_volume
28pub_type
杂志文章abstract::We consider the problem of comparing cumulative incidence functions of non-mortality events in the presence of informative coarsening and the competing risk of death. We extend frequentist-based hypothesis tests previously developed for non-informative coarsening and propose a novel Bayesian method based on comparing ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3397
更新日期:2008-12-10 00:00:00
abstract::This paper discusses design considerations and the role of randomization-based inference in randomized community intervention trials. We stress that longitudinal follow-up of cohorts within communities often yields useful information on the effects of intervention on individuals, whereas cross-sectional surveys can us...
journal_title:Statistics in medicine
pub_type: 杂志文章,评审
doi:10.1002/(SICI)1097-0258(19960615)15:11<1069::AID-S
更新日期:1996-06-15 00:00:00
abstract::Funnel plots are widely used to visualize grouped data, for example, in institutional comparison. This paper extends the concept to a multi-level setting, displaying one level at a time, adjusted for the other levels, as well as for covariates at all levels. These level-adjusted funnel plots are based on a Markov chai...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5677
更新日期:2014-09-20 00:00:00
abstract::A method is proposed to infer the randomized treatment effect on survival after an adjustment for a post-randomization variable. The post-randomization variable is made independent of the treatment assignment and is considered a surrogate for baseline prognostic factors. The relationship between the post-randomization...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.968
更新日期:2001-11-30 00:00:00
abstract::This paper, arising out of an event to honour the statistical and scientific contributions of Professor Peter Armitage, is concerned with research strategies and needs for chronic disease prevention. A few highlights from recent intervention trials for the prevention of cancer, cardiovascular disease, fractures and di...
journal_title:Statistics in medicine
pub_type:
doi:10.1002/sim.2045
更新日期:2004-11-30 00:00:00
abstract::The 'at least as good as' criterion, introduced by Laster and Johnson for a continuous response variate, is developed here for applications with dichotomous data. This approach is adaptive in nature, as the margin of non-inferiority is not taken as a fixed difference; it varies as a function of the positive control re...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2476
更新日期:2006-04-15 00:00:00
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
更新日期:2021-02-20 00:00:00
abstract::In many community-based studies on the incidence of dementia, a target population is screened and a subsample is clinically evaluated at baseline and follow-up. Incidence rates are affected by missed cases at both exams and this complicates the estimation of these rates. Recent work proposes a regression-based techniq...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000615/30)19:11/12<1577:
更新日期:2000-06-15 00:00:00
abstract::This paper concerns using modified weighted Schoenfeld residuals to test the proportionality of subdistribution hazards for the Fine-Gray model, similar to the tests proposed by Grambsch and Therneau for independently censored data. We develop a score test for the time-varying coefficients based on the modified Schoen...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5815
更新日期:2013-09-30 00:00:00
abstract::This paper examines several methods for deriving standardized morbidity ratios (SMR) and attributable fraction (attributable risk percentage) estimates. We show that some of the proposed methods will, in general, produce biased estimators, although the low variance of certain estimators sometimes compensates for their...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780030206
更新日期:1984-04-01 00:00:00
abstract::Important differences between explanatory and pragmatic studies were originally argued by Schwartz and Lellouch. Three important differences between the two types of study involve study control, study violators and inclusion criteria. It was originally argued that explanatory studies are highly controlled, and pragmat...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1120
更新日期:2002-05-30 00:00:00
abstract::For the meta-analysis of controlled clinical trials with binary outcome a test statistic for testing an overall treatment effect is proposed, which is based on a refined estimator for the variance of the treatment effect estimator usually used in the random-effects model of meta-analysis. In simulation studies it is s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1009
更新日期:2001-12-30 00:00:00
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>
更新日期:2000-11-30 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::We consider the problem of identifying a subgroup of patients who may have an enhanced treatment effect in a randomized clinical trial, and it is desirable that the subgroup be defined by a limited number of covariates. For this problem, the development of a standard, pre-determined strategy may help to avoid the well...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4322
更新日期:2011-10-30 00:00:00
abstract::Various aspects of portfolio management and project prioritization within the pharmaceutical industry are examined. It is shown that the cost and probability architecture of a project is a crucial aspect of its value. An appropriate simple tool for ranking projects is the Pearson index. Various difficulties are consid...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19961230)15:24<2689::AID-S
更新日期:1996-12-30 00:00:00
abstract::Spatial scan statistics are widely used for count data to detect geographical disease clusters of high or low incidence, mortality or prevalence and to evaluate their statistical significance. Some data are ordinal or continuous in nature, however, so that it is necessary to dichotomize the data to use a traditional s...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2607
更新日期:2007-03-30 00:00:00
abstract::Inference for randomized clinical trials is generally based on the assumption that outcomes are independently and identically distributed under the null hypothesis. In some trials, particularly in infectious disease, outcomes may be correlated. This may be known in advance (e.g. allowing randomization of family member...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2977
更新日期:2008-03-15 00:00:00
abstract::Recent studies have indicated variation in the infectivity beta of HIV among heterosexual couples. We represent this heterogeneity by modelling beta as a random variable. Using data on the number of contacts and seroconversion of couples, we fit the model by maximum-likelihood estimation with a beta distribution and a...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780080110
更新日期:1989-01-01 00:00:00
abstract::When a cancer patient develops a new tumor it is necessary to determine if it is a recurrence (metastasis) of the original cancer, or an entirely new occurrence of the disease. This is accomplished by assessing the histo-pathology of the lesions. However, there are many clinical scenarios in which this pathological di...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3866
更新日期:2010-07-10 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::In the recent two decades, data mining methods for signal detection have been developed for drug safety surveillance, using large post-market safety data. Several of these methods assume that the number of reports for each drug-adverse event combination is a Poisson random variable with mean proportional to the unknow...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6510
更新日期:2015-08-30 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::Laboratory determinations on children aged 6 to 10 years obtained over a 5-year period are analysed by a method described in detail for differentiating between children from exposed and control areas of Seveso, Italy. In the analysis, stratification is employed to distinguish the separate days of laboratory measuremen...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780020221
更新日期:1983-04-01 00:00:00
abstract::Although radical changes in drug regulation are rare (e.g., the Federal Food, Drug and Cosmetic Act of 1938 and the 1962 amendment to the Act creating an effectiveness requirement), regulations and guidance do evolve significantly in the face of new problems and accumulating experience. Recent changes have been driven...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1298
更新日期:2002-10-15 00:00:00
abstract::Binary classification rules based on covariates typically depend on simple loss functions such as zero-one misclassification. Some cases may require more complex loss functions. For example, individual-level monitoring of HIV-infected individuals on antiretroviral therapy requires periodic assessment of treatment fail...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8082
更新日期:2019-05-20 00:00:00
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 ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780010105
更新日期:1982-01-01 00:00:00
abstract::Suppression of premature ventricular contractions (PVCs) is one of the goals of antiarrhythmic therapy. In a clinical trial, however, it may be difficult to distinguish antiarrhythmic drug effect from spontaneous variation in PVCs. We propose the application of linear regression to PVC histories to ascertain drug effe...
journal_title:Statistics in medicine
pub_type: 临床试验,杂志文章
doi:10.1002/sim.4780020305
更新日期:1983-07-01 00:00:00
abstract::We suggest measures to quantify the degrees of necessity and of sufficiency of prognostic factors for dichotomous and for survival outcomes. A cause, represented by certain values of prognostic factors, is considered necessary for an event if, without the cause, the event cannot develop. It is considered sufficient fo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8331
更新日期:2019-10-15 00:00:00
abstract::Prevention studies, as distinguished from studies investigating treatments for established disease, present some distinct challenges. Perhaps the most extensive experience with preventive agents is in the area of infectious diseases; vaccines have been extremely effective in preventing many such diseases. Vaccines hav...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1717
更新日期:2004-01-30 00:00:00