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 in a bivariate outcome space. The framework uses a rectangular hyperbola to define a bivariate null curve that divides outcome space into regions of benefit and lack of benefit. The curve is shown to be a flexible mapping of bivariate space that allows a continuous tradeoff between the two endpoints in a manner that captures many previous bivariate designs. The curve is extended to a distance function in bivariate space that allows different decisions in each of the four quadrants that comprise bivariate space. The distance function forms a statistic ( δ ); the distribution of its estimate is derived and used as a basis for trial design and group sequential monitoring plans in bivariate space. A recursive form of the bivariate group sequential density is used to evaluate and control operating characteristics for the proposed design. The bivariate designs are shown to meet or exceed the usual standards for size and power. The proposed design is illustrated in the ongoing NHLBI-sponsored Kids-DOTT multinational randomized controlled trial comparing shortened versus conventional anticoagulation for the treatment of venous thromboembolism in patients less than 21 years of age. The proposed methods are broadly applicable to a wide range of clinical settings and trial designs.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Hu J,Blatchford PJ,Goldenberg NA,Kittelson JMdoi
10.1002/sim.8696subject
Has Abstractpub_date
2020-11-20 00:00:00pages
3823-3839issue
26eissn
0277-6715issn
1097-0258journal_volume
39pub_type
杂志文章abstract::Timeliness of a public health surveillance system is one of its most important characteristics. The process of predicting the present situation using available incomplete information from surveillance systems has received the term nowcasting and has high public health interest. Generally in Europe, general practitione...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5670
更新日期:2013-07-10 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::When estimating the probability of natural conception from observational data on couples with an unfulfilled child wish, the start of assisted reproductive therapy (ART) is a competing event that cannot be assumed to be independent of natural conception. In clinical practice, interest lies in the probability of natura...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6280
更新日期:2014-11-20 00:00:00
abstract::Service on the Data Monitoring Committee of the CPEP (Calcium for Pre-eclampsia Prevention) has led us to four conclusions about clinical trials which we should like to present to this gathering of biostatisticians for their reactions: (i) meta-analyses of the pertinent published trials of the same therapy should alwa...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0258(19960630)15:12<1263::AID-S
更新日期:1996-06-30 00:00:00
abstract::A considerable number of the clinical reports which are presented to the Dutch Board for the Evaluation of Drugs, have deficiencies and/or shortcomings. A number of these, including loose description of the target population and sampling method, methodological flaws, incorrect treatment of withdrawals, confounding of ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780020209
更新日期:1983-04-01 00:00:00
abstract::Residuals in normal regression are used to assess a model's goodness-of-fit (GOF) and discover directions for improving the model. However, there is a lack of residuals with a characterized reference distribution for censored regression. In this article, we propose to diagnose censored regression with normalized rando...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8852
更新日期:2020-12-13 00:00:00
abstract::Clinical prediction models (CPMs) can inform decision making about treatment initiation, which requires predicted risks assuming no treatment is given. However, this is challenging since CPMs are usually derived using data sets where patients received treatment, often initiated postbaseline as "treatment drop-ins." Th...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7913
更新日期:2018-12-10 00:00:00
abstract::To compare the survival functions based on right-truncated data, Lagakos et al. proposed a weighted logrank test based on a reverse time scale. This is in contrast to Bilker and Wang, who suggested a semi-parametric version of the Mann-Whitney test by assuming that the distribution of truncation times is known or can ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.2556
更新日期:2007-02-20 00:00:00
abstract::The mutation and natural selection phenomenon can and often does cause the failure of antimicrobial, herbicidal, pesticide and cancer treatments selection pressures. This phenomenon operates in a mathematically predictable behavior, which when understood leads to approaches to reduce and prevent the failure of the use...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6307
更新日期:2014-12-20 00:00:00
abstract::The analysis of multivariate time-to-event (TTE) data can become complicated due to the presence of clustering, leading to dependence between multiple event times. For a long time, (conditional) frailty models and (marginal) copula models have been used to analyze clustered TTE data. In this article, we propose a gene...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8506
更新日期:2020-05-30 00:00:00
abstract::For clinical trials with multiple treatment arms or endpoints a variety of sequentially rejective, weighted Bonferroni-type tests have been proposed, such as gatekeeping procedures, fixed sequence tests, and fallback procedures. They allow to map the difference in importance as well as the relationship between the var...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3495
更新日期:2009-02-15 00:00:00
abstract::Although transportation safety has greatly improved over the past 2 decades, motor vehicle crash injuries remain a leading cause of morbidity and mortality, particularly among young drivers. Driver errors and behaviors such as speeding and distraction contribute disproportionately to crashes among inexperienced novice...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.7404
更新日期:2017-10-30 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::Growth trends in children are often based on cross-sectional studies, in which a sample of the population is investigated at one given point in time. Estimating age-related percentiles in such studies involves fitting data distributions, each of which is specific for one age group, and a subsequent smoothing of the pe...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(20000315)19:5<697::aid-sim
更新日期:2000-03-15 00:00:00
abstract::In different fields of applications including, but not limited to, behavioral, environmental, medical sciences, and econometrics, the use of panel data regression models has become increasingly popular as a general framework for making meaningful statistical inferences. However, when the ordinary least squares (OLS) m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8732
更新日期:2020-12-20 00:00:00
abstract::The effective dose (ED) is the pharmaceutical dosage required to produce a therapeutic response in a fixed proportion of the patients. When only one drug is considered, the problem is a univariate one and has been well-studied. However, in the multidimensional setting, that is, in the presence of combinations of agent...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6226
更新日期:2014-10-30 00:00:00
abstract::A method has been developed for simultaneously comparing the usefulness of many treatments of established value for symptomatic medical conditions. Medical assessment of outcome is not employed. Instead patients are required to assess treatments prescribed during the course of ordinary general practice rather than und...
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.4780040104
更新日期:1985-01-01 00:00:00
abstract::Comparative Poisson trials of prophylactic interventions, such as vaccines, can be lengthy and costly. We evaluate two easily implemented approaches to reduce numbers of disease cases and person years of follow up (N(u+t)) for comparative Poisson trials with fixed numbers of cases (T); (i) altering k the portion of N(...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1724
更新日期:2004-04-30 00:00:00
abstract::Technologic advances give rise to new tests for detecting disease in many fields, including cancer and sexually transmitted disease. Before a new disease screening test is approved for public use, its accuracy should be shown to be better than or at least not inferior to an existing test. Standards do not yet exist fo...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1058
更新日期:2002-03-30 00:00:00
abstract::Graphical methods based on the analysis of differences between log cumulative hazard functions are considered for a two-group semi-proportional hazard model which allows for interaction between treatments and covariates. Confidence procedures and test statistics that can be used to test for interaction and for main ef...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780111105
更新日期:1992-08-01 00:00:00
abstract::This paper presents a statistical analysis of treatment effects in 24-hour ambulatory blood pressure recordings. The statistical models account for circadian rhythms, subject effects, and the effects of treatment with drugs or relaxation therapy. In view of the heterogeneity of the subjects, we fit a separate linear m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780070608
更新日期:1988-06-01 00:00:00
abstract::Exposure to a carcinogen is likely to be reflected by temporal clustering of cancer cases among the community members. Detection of such clustering is a complicated task in general and more so in a small workplace community with low turnover rate. In this study we applied the CUSCORE test and the q-interval statistic ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1534
更新日期:2003-10-15 00:00:00
abstract::To study the effect of a mega hydropower dam in southwest Ethiopia on malaria incidence, we have set up a longitudinal study. To gain insight in temporal and spatial aspects, that is, in time (period = year-season combination) and location (village), we need models that account for these effects. The frailty model w...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5752
更新日期:2013-08-15 00:00:00
abstract::It is valuable in many studies to assess both intrarater and interrater agreement. Most measures of intrarater agreement do not adjust for unequal estimates of prevalence between the separate rating occasions for a given rater and measures of interrater agreement typically ignore data from the second set of assessment...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1138
更新日期:2002-06-30 00:00:00
abstract::Population dynamic models, commonly used tools in the study of epidemics and other complex population processes, are implicit non-linear mathematical equations. Inference based on such models can be difficult due to the problems associated with high dimensional parameters that may be non-identified and complex likelih...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1258
更新日期:2002-12-15 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 research often involves continuous outcome measures, such as blood cholesterol, that are amenable to statistical techniques of analysis based on the mean, such as the t-test or multiple linear regression. Clinical interest, however, frequently focuses on the proportion of subjects who fall below or above a cl...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780140303
更新日期:1995-02-15 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::A few large multi-centre male-only heart trials done in the 1970s and 1980s have been seen as ill-conceived because they did not include females. The purpose here is to revisit two of those trials and to consider consequences in terms of cost and power had they been designed to include females. ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19990215)18:3<241::aid-sim
更新日期:1999-02-15 00:00:00
abstract::Equivalence trials aim to show that two treatments have equivalent therapeutic effects. The approach is to define, in advance, a range of equivalence -d to +d for the treatment difference such that any value in the range is clinically unimportant. If the confidence interval for the difference, calculated after the tri...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19980815/30)17:15/16<1691:
更新日期:1998-08-15 00:00:00