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 investigates the response rates of a drug tested at a low and high dose compared with placebo. Patients are randomized to an initial treatment (stage 1). In stage 2, patients are rerandomized, depending on their initial treatment and their response to that treatment in stage 1, to either the same or a different dose of treatment. Data from both stages are used to determine the efficacy of the active treatment. We present a Bayesian approach where information is borrowed between stage 1 and stage 2. We compare our approach to standard methods using only stage 1 data and a log-linear Poisson model that uses data from both stages where parameters are estimated using generalized estimating equations. We observe that the Bayesian method has smaller root-mean-square-error and 95% credible interval widths than standard methods in the tested scenarios. We conclude that it is advantageous to utilize data from both stages for a primary efficacy analysis and that the specific snSMART design shown here can be used in the registration of a drug for the treatment of rare diseases.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Fang F,Hochstedler KA,Tamura RN,Braun TM,Kidwell KMdoi
10.1002/sim.8813subject
Has Abstractpub_date
2021-02-20 00:00:00pages
963-977issue
4eissn
0277-6715issn
1097-0258journal_volume
40pub_type
杂志文章abstract::Clinical studies that involve the recording of two or more distinct and well-defined events on each subject give rise to multiple event data. Treatment comparisons are usually reported in univariate analyses of time to first event or number of events observed. However, this approach may not uncover the 'full story' of...
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/(sici)1097-0258(19970430)16:8<941::aid-sim
更新日期:1997-04-30 00:00:00
abstract::In a long-running longitudinal study using complex machinery to obtain measurements, it is sometimes necessary to replace the machine. This can result in lack of continuity in the measurements that can overwhelm any treatment effect or time trend. We propose a Bayesian procedure implemented using Markov chain Monte Ca...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1868
更新日期:2004-09-30 00:00:00
abstract::A new goodness-of-fit test for the logistic regression model is proposed. It exploits the property of this model that when it is correct, i.e. not misspecified, the parameter estimates are (asymptotically) invariant under reweighting the observations by weights wi that are a function of the binary (0/1) outcomes yi. M...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1997
更新日期:2005-01-15 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::The serial dilution assay (for example, an in vitro antimicrobic susceptibility test or a serum antibody titer assay) is an important technique in biomedical research. The structure of the experiment forces grouping of the threshold concentrations into intervals. Statistical methods to analyse threshold concentrations...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780070410
更新日期:1988-04-01 00:00:00
abstract::This field study sought to measure the effects of dental delivery and school-based, dental health education on use of dental health care by children in grades K-6. We attempted to control for two potential confounding factors by an approximate randomization of children into treatment groups with stratification on grad...
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.4780020107
更新日期:1983-01-01 00:00:00
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
更新日期:1991-12-01 00:00:00
abstract::For each of 211 arteriosclerosis obliterans patients, the degree of stenosis of arteries at four sites were examined at Hiroshima University Hospital to analyse the relationship between the degree of stenosis and age, sex and site. The generalized estimating equations using a proportional odds model for the stenosis p...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1363
更新日期:2003-07-15 00:00:00
abstract::Public health interventions are often designed to target communities defined either geographically (e.g. cities, counties) or socially (e.g. schools or workplaces). The group randomized trial (GRT) is regarded as the gold standard for evaluating these interventions. However, community leaders may object to randomizati...
journal_title:Statistics in medicine
pub_type: 杂志文章,随机对照试验
doi:10.1002/sim.4237
更新日期:2011-07-10 00:00:00
abstract::Pattern-mixture models (PMM) and selection models (SM) are alternative approaches for statistical analysis when faced with incomplete data and a nonignorable missing-data mechanism. Both models make empirically unverifiable assumptions and need additional constraints to identify the parameters. Here, we first introduc...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6302
更新日期:2014-11-30 00:00:00
abstract::We obtained maximum likelihood estimates (MLEs) of the proportion cured pi c and mean log survival time mu t for a sample of 4355 patients with intraocular melanoma whose survival times subsequent to treatment were assumed to follow a log-normal distribution. Following stratification by tumour size, MLEs of pi c and m...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780090814
更新日期:1990-08-01 00:00:00
abstract::The need for resource-intensive laboratory assays to assess exposures in many epidemiologic studies provides ample motivation to consider study designs that incorporate pooled samples. In this paper, we consider the case in which specimens are combined for the purpose of determining the presence or absence of a pool-w...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4426
更新日期:2012-09-28 00:00:00
abstract::While genome-wide association studies (GWASs) have been widely used to uncover associations between diseases and genetic variants, standard SNP-level GWASs often lack the power to identify SNPs that individually have a moderate effect size but jointly contribute to the disease. To overcome this problem, pathway-based ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.8442
更新日期:2020-03-15 00:00:00
abstract::In this paper, we construct a partial additive regression (PAR) model to predict the survival times of cancer patients based on microarray gene expression data with right censoring. The area under time-dependent receiver operating characteristic curve is used as a model evaluation criterion. We conduct a simulation st...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.3412
更新日期:2009-01-30 00:00:00
abstract::When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-p...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6973
更新日期:2016-09-10 00:00:00
abstract::Given N points or events occurring according to some probability distribution in the unit interval (0, 1), the simple scan statistic is defined to be the maximum number of points in any sub-interval of length d. In many areas, as in epidemiology, it is used to test the null hypothesis that the events are random, again...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19960415)15:7/9<845::aid-s
更新日期:1996-04-15 00:00:00
abstract::A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6783
更新日期:2016-04-15 00:00:00
abstract::We investigate a binary partitioning algorithm in the case of a continuous repeated measures outcome. The procedure is based on the use of the likelihood ratio statistic to evaluate the performance of individual splits. The procedure partitions a set of longitudinal data into two mutually exclusive groups based on an ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1266
更新日期:2002-11-30 00:00:00
abstract::A statistical analysis is presented of the intensities of admissions to psychiatric hospitals among women in Denmark who either gave birth to a child in the year 1975 or had an induced abortion in the same year. The models used are time-continuous Markov and semi-Markov processes, and the methods employed include non-...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4780050305
更新日期:1986-05-01 00:00:00
abstract::This paper investigates the design and analysis of dose-finding trials with two agents. The set of doses for each agent is fixed in advance. The goal of the trial is to find the set of dose combinations with probability of toxicity closest to a pre-specified value. For each of the two agents we assume that the probabi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1796
更新日期:2004-06-30 00:00:00
abstract::Instrumental variable estimates of causal effects can be biased when using many instruments that are only weakly associated with the exposure. We describe several techniques to reduce this bias and estimate corrected standard errors. We present our findings using a simulation study and an empirical application. For th...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.6358
更新日期:2015-02-10 00:00:00
abstract::Subjective judgements of complex variables are commonly recorded as ordered categorical data. The rank-invariant properties of such data are well known, and there are various statistical approaches to the analysis and modelling of ordinal data. This paper focuses on the non-additive property of ordered categorical dat...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19981230)17:24<2923::aid-s
更新日期:1998-12-30 00:00:00
abstract::Data monitoring committees (DMCs) have become an increasingly common component of randomized clinical trials in recent years. As experience has accumulated, and more individuals and organizations have become involved in such activities, a variety of approaches to the operation of such committees has inevitably arisen....
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.730
更新日期:2001-09-15 00:00:00
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
更新日期:2007-12-30 00:00:00
abstract::Health authorities are often alerted to suspected cancer clusters near the vicinity of potential point sources by members of the public. A surveillance system, where administrative regions around the potential point sources are regularly monitored for high disease rates, would allow for responses which are easier to o...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19960415)15:7/9<727::aid-s
更新日期:1996-04-15 00:00:00
abstract::In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethi...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.5585
更新日期:2012-12-30 00:00:00
abstract::The recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated increased interest in active-control trials, particularly those intended to show equivalence or non-inferiority to the activ...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.1400
更新日期:2003-01-30 00:00:00
abstract::Sam Greenhouse joined the Census Bureau as a clerk at an interesting time period for the agency. The first use of sampling in the decennial census occurred in 1940. There was a major expansion of the amount of data collected. The organization of the Census Bureau underwent radical changes, including the growth of the ...
journal_title:Statistics in medicine
pub_type: 传,历史文章,杂志文章
doi:10.1002/sim.1627
更新日期:2003-11-15 00:00:00
abstract::Standard approaches to analysis of randomized controlled trials (RCTs) using Markov models make it difficult to generalize treatment effects to new patient groups and synthesize evidence across trials. This paper demonstrates how pair-wise and mixed treatment comparison meta-analysis can be applied to event history da...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/sim.4059
更新日期:2011-01-30 00:00:00
abstract::Between-community variance or community-by-time variance is one of the key factors driving the cost of conducting group randomized trials, which are often very expensive. We investigated empirically whether between-community variance could be reduced by controlling individual- and/or community-level covariates and ide...
journal_title:Statistics in medicine
pub_type: 杂志文章
doi:10.1002/(sici)1097-0258(19990315)18:5<539::aid-sim
更新日期:1999-03-15 00:00:00