Analytical, practical and regulatory issues in prevention studies.

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 have been, and continue to be, studied in other disease areas such as certain cancers, but as yet have not achieved success outside of infectious disease prevention. One obvious and important feature of prevention studies is that they enroll healthy individuals; thus such studies require particularly high standards for the safety of those enrolled (and those who might ultimately receive the product being tested). Prevention studies often need to be quite large, as the types of diseases most important to prevent tend to be uncommon. Large studies usually require simplified approaches; to ensure high quality of data on the key variables it may be necessary to compromise on the amount of data collected, frequency of data collection, and other aspects of trial design. The reliability of randomization and blinding may be especially important in these large studies, as bias could easily overwhelm the small effects that are usually sought. Often, biomarkers thought to indicate developing but as yet subclinical disease, will be important to evaluate; whether such markers can serve as primary endpoints in prevention studies has been a contentious issue in many contexts. Studies in older populations, such as those at risk for Alzheimer's Disease, raise challenges such as accounting for competing risks, and considering potential interactions of preventive agents with multiple medications often used by the elderly.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Ellenberg SS

doi

10.1002/sim.1717

subject

Has Abstract

pub_date

2004-01-30 00:00:00

pages

297-303

issue

2

eissn

0277-6715

issn

1097-0258

journal_volume

23

pub_type

杂志文章
  • A score test for establishing non-inferiority with respect to short-term survival in two-sample comparisons with identical proportions of long-term survivors.

    abstract::In recent years randomized trials designed to establish non-inferiority of a new treatment as compared to a standard one have been more widely used. Two-sample statistics have been proposed for this equivalence testing problem. However, they are not suited to situations where a long-term survivor fraction is expected....

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1453

    authors: Broët P,Tubert-Bitter P,De Rycke Y,Moreau T

    更新日期:2003-03-30 00:00:00

  • Goodman and Kruskal's lambda: a new look at an old measure of association.

    abstract::We examine Goodman and Kruskal's lambda using Efron's approach to regression and analysis of variance (ANOVA) for zero-one outcome data. For a binary response cross-classified by a single nominal predictor, we present a computationally simple ANOVA table in which lambda is analogous to Pearson's R-square. We character...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780080511

    authors: Makuch RW,Rosenberg PS,Scott G

    更新日期:1989-05-01 00:00:00

  • Logistic regression with incompletely observed categorical covariates--investigating the sensitivity against violation of the missing at random assumption.

    abstract::Missing values in the covariates are a widespread complication in the statistical inference of regression models. The maximum likelihood principle requires specification of the distribution of the covariates, at least in part. For categorical covariates, log-linear models can be used. Additionally, the missing at rand...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780141205

    authors: Vach W,Blettner M

    更新日期:1995-06-30 00:00:00

  • Performance assessment for radiologists interpreting screening mammography.

    abstract::When interpreting screening mammograms radiologists decide whether suspicious abnormalities exist that warrant the recall of the patient for further testing. Previous work has found significant differences in interpretation among radiologists; their false-positive and false-negative rates have been shown to vary widel...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.2633

    authors: Woodard DB,Gelfand AE,Barlow WE,Elmore JG

    更新日期:2007-03-30 00:00:00

  • Small clinical trials: are they all bad?

    abstract::Statisticians have long argued that randomized controlled trials should be sufficiently large to achieve their purpose, and for common diseases with major public health implications this has brought many benefits. However, there are many instances where it is unrealistic to expect clinicians to provide the information...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sim.4780140204

    authors: Matthews JN

    更新日期:1995-01-30 00:00:00

  • Extending the c-statistic to nominal polytomous outcomes: the Polytomous Discrimination Index.

    abstract::Diagnostic problems in medicine are sometimes polytomous, meaning that the outcome has more than two distinct categories. For example, ovarian tumors can be benign, borderline, primary invasive, or metastatic. Extending the main measure of binary discrimination, the c-statistic or area under the ROC curve, to nominal ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5321

    authors: Van Calster B,Van Belle V,Vergouwe Y,Timmerman D,Van Huffel S,Steyerberg EW

    更新日期:2012-10-15 00:00:00

  • Pros and cons of permutation tests in clinical trials.

    abstract::Hypothesis testing, in which the null hypothesis specifies no difference between treatment groups, is an important tool in the assessment of new medical interventions. For randomized clinical trials, permutation tests that reflect the actual randomization are design-based analyses for such hypotheses. This means that ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(20000530)19:10<1319::aid-s

    authors: Berger VW

    更新日期:2000-05-30 00:00:00

  • Effects of time-invariant covariates on the estimation of longitudinal trends for transition mixed models.

    abstract::In this paper, we investigate the impact of time-invariant covariates when fitting transition mixed models. This is carried out by emphasizing on the role of baseline responses on the estimation process. Transition models are allowed for two cases of exogenous and endogenous baseline responses. We illustrate these con...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6270

    authors: Rikhtehgaran R,Kazemi I,Verbeke G

    更新日期:2014-11-30 00:00:00

  • Estimating heterogeneous treatment effects for latent subgroups in observational studies.

    abstract::Individuals may vary in their responses to treatment, and identification of subgroups differentially affected by a treatment is an important issue in medical research. The risk of misleading subgroup analyses has become well known, and some exploratory analyses can be helpful in clarifying how covariates potentially i...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7970

    authors: Kim HJ,Lu B,Nehus EJ,Kim MO

    更新日期:2019-02-10 00:00:00

  • Kappa coefficients in medical research.

    abstract::Kappa coefficients are measures of correlation between categorical variables often used as reliability or validity coefficients. We recapitulate development and definitions of the K (categories) by M (ratings) kappas (K x M), discuss what they are well- or ill-designed to do, and summarize where kappas now stand with ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sim.1180

    authors: Chmura Kraemer H,Periyakoil VS,Noda A

    更新日期:2002-07-30 00:00:00

  • The standard error of Cohen's Kappa.

    abstract::This paper gives a standard error for Cohen's Kappa, conditional on the margins of the observed r x r table. An explicit formula is given for the 2 x 2 table, and a procedure for the more general situation. A parsimonious log-linear model is suggested for the general case and an approximate confidence interval for kap...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780100512

    authors: Garner JB

    更新日期:1991-05-01 00:00:00

  • A graphical approach to sequentially rejective multiple test procedures.

    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

    authors: Bretz F,Maurer W,Brannath W,Posch M

    更新日期:2009-02-15 00:00:00

  • Practical modifications to the time-to-event continual reassessment method for phase I cancer trials with fast patient accrual and late-onset toxicities.

    abstract::The goal of phase I cancer trials is to determine the highest dose of a treatment regimen with an acceptable toxicity rate. Traditional designs for phase I trials, such as the Continual Reassessment Method (CRM) and the 3 + 3 design, require each patient or a cohort of patients to be fully evaluated for the dose-limit...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4255

    authors: Polley MY

    更新日期:2011-07-30 00:00:00

  • Model selection and diagnostics for joint modeling of survival and longitudinal data with crossing hazard rate functions.

    abstract::Comparison of two hazard rate functions is important for evaluating treatment effect in studies concerning times to some important events. In practice, it may happen that the two hazard rate functions cross each other at one or more unknown time points, representing temporal changes of the treatment effect. Also, besi...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6259

    authors: Park KY,Qiu P

    更新日期:2014-11-20 00:00:00

  • A cluster model for space-time disease counts.

    abstract::Modelling disease clustering over space and time can be helpful in providing indications of possible exposures and planning corresponding public health practices. Though a considerable number of studies focus on modelling spatio-temporal patterns of disease, most of them do not directly model a spatio-temporal cluster...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.2424

    authors: Yan P,Clayton MK

    更新日期:2006-03-15 00:00:00

  • Sampling design of multiwave studies with an application to the Massachusetts Health Care Panel Study.

    abstract::A technique is presented which provides guidance on the spacing of follow-up waves in a multiwave study. Only information from the baseline wave is needed, as well as rough parameter estimates for the survival distribution. The computations use the expected Fisher information; a new method for its calculation is given...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780101209

    authors: Chappell R

    更新日期:1991-12-01 00:00:00

  • Empirical Bayes versus fully Bayesian analysis of geographical variation in disease risk.

    abstract::This paper reviews methods for mapping geographical variation in disease incidence and mortality. Recent results in Bayesian hierarchical modelling of relative risk are discussed. Two approaches to relative risk estimation, along with the related computational procedures, are described and compared. The first is an em...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780110802

    authors: Bernardinelli L,Montomoli C

    更新日期:1992-06-15 00:00:00

  • A framework establishing clear decision criteria for the assessment of drug efficacy.

    abstract::Much has been published on various aspects of data analysis and reporting from clinical trials within the biopharmaceutical environment. This ranges from regulatory guidelines on the format and content of registration dossiers to recommendations on data presentation and the statistical methodologies that are appropria...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1097-0258(19980815/30)17:15/16<1829:

    authors: Huster WJ,Enas GG

    更新日期:1998-08-15 00:00:00

  • Discriminant analysis when all variables are ordered.

    abstract::Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780110804

    authors: Johnston B,Seshia SS

    更新日期:1992-06-15 00:00:00

  • A maximally selected test of symmetry about zero.

    abstract::The problem of testing symmetry about zero has a long and rich history in the statistical literature. We introduce a new test that sequentially discards observations whose absolute value is below increasing thresholds defined by the data. McNemar's statistic is obtained at each threshold and the largest is used as the...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5384

    authors: Laska E,Meisner M,Wanderling J

    更新日期:2012-11-20 00:00:00

  • Identifying optimal risk windows for self-controlled case series studies of vaccine safety.

    abstract::In vaccine safety studies, subjects are considered at increased risk for adverse events for a period of time after vaccination known as risk window. To our knowledge, risk windows for vaccine safety studies have tended to be pre-defined and not to use information from the current study. Inaccurate specification of the...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4125

    authors: Xu S,Zhang L,Nelson JC,Zeng C,Mullooly J,McClure D,Glanz J

    更新日期:2011-03-30 00:00:00

  • A frailty model for recurrent events during alternating restraint and non-restraint time periods.

    abstract::We consider recurrent events of the same type that occur during alternating restraint and non-restraint time periods. This research is motivated by a study on juvenile recidivism, where the probationers were followed for re-offenses during alternating placement periods and free-time periods. During the placement perio...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7150

    authors: Li X,Chen Y,Li R

    更新日期:2017-02-20 00:00:00

  • Statistical models for longitudinal biomarkers of disease onset.

    abstract::We consider the analysis of serial biomarkers to screen and monitor individuals in a given population for onset of a specific disease of interest. The biomarker readings are subject to error. We survey some of the existing literature and concentrate on two recently proposed models. The first is a fully Bayesian hierar...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(20000229)19:4<617::aid-sim

    authors: Slate EH,Turnbull BW

    更新日期:2000-02-29 00:00:00

  • A semi-Markov model for multistate and interval-censored data with multiple terminal events. Application in renal transplantation.

    abstract::The semi-Markov assumption emphasizes the importance of time spent in a state. In order to compute this type of multistate model, most transition times are always considered to be exactly identified or right censored. However, in the longitudinal analysis of chronic diseases, investigators are often confronted with in...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3100

    authors: Foucher Y,Giral M,Soulillou JP,Daures JP

    更新日期:2007-12-30 00:00:00

  • Mediation effect selection in high-dimensional and compositional microbiome data.

    abstract::The microbiome plays an important role in human health by mediating the path from environmental exposures to health outcomes. The relative abundances of the high-dimensional microbiome data have an unit-sum restriction, rendering standard statistical methods in the Euclidean space invalid. To address this problem, we ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8808

    authors: Zhang H,Chen J,Feng Y,Wang C,Li H,Liu L

    更新日期:2021-02-20 00:00:00

  • Identifiability and estimation of causal mediation effects with missing data.

    abstract::Mediation analysis is a standard approach to understanding how and why an intervention works in social and medical sciences. However, the presence of missing data, especially missing not at random data, poses a great challenge for the applicability of this approach in practice. Current methods for handling such missin...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7413

    authors: Li W,Zhou XH

    更新日期:2017-11-10 00:00:00

  • Comparison of objective Bayes factors for variable selection in parametric regression models for survival analysis.

    abstract::This paper considers the problem of selecting a set of regressors when the response variable is distributed according to a specified parametric model and observations are censored. Under a Bayesian perspective, the most widely used tools are Bayes factors (BFs), which are undefined when improper priors are used. In or...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6249

    authors: Cabras S,Castellanos ME,Perra S

    更新日期:2014-11-20 00:00:00

  • Semiparametric ROC surfaces for continuous diagnostic tests based on two test measurements.

    abstract::We propose a semiparametric method for estimating ROC surfaces for continuous diagnostic tests based on two test measurements. Such a three-class diagnostic problem based on two test measurements arises naturally from some DNA amplification-related diagnostic scenarios. Simulation results show that our proposed semipa...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3625

    authors: Wan S,Zhang B

    更新日期:2009-08-15 00:00:00

  • Comparison of operational characteristics for binary tests with clustered data.

    abstract::Although statistical methodology is well-developed for comparing diagnostic tests in terms of their sensitivity and specificity, comparative inference about predictive values is not. In this paper, we consider the analysis of studies comparing operating characteristics of two diagnostic tests that are measured on all ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6485

    authors: Kwak M,Um SW,Jung SH

    更新日期:2015-07-10 00:00:00

  • Combining mortality and longitudinal measures in clinical trials.

    abstract::Clinical trials often assess therapeutic benefit on the basis of an event such as death or the diagnosis of disease. Usually, there are several additional longitudinal measures of clinical status which are collected to be used in the treatment comparison. This paper proposes a simple non-parametric test which combines...

    journal_title:Statistics in medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/(sici)1097-0258(19990615)18:11<1341::aid-s

    authors: Finkelstein DM,Schoenfeld DA

    更新日期:1999-06-15 00:00:00