Abstract:
:Immunotherapy, gene therapy or adoptive cell therapies, such as the chimeric antigen receptor+ T-cell therapies, have demonstrated promising therapeutic effects in oncology patients. We consider statistical designs for dose-finding adoptive cell therapy trials, in which the monotonic dose-response relationship assumed in traditional oncology trials may not hold. Building upon a previous design called "TEPI", we propose a new dose finding method - Probability Intervals of Toxicity and Efficacy (PRINTE), which utilizes toxicity and efficacy jointly in making dosing decisions, does not require a pre-elicited decision table and at the same time can handle Ockham's razor properly in the statistical inference. We show that optimizing the joint posterior expected utility of toxicity and efficacy under a 0-1 loss is equivalent to maximizing the marginal model posterior probability in the two-dimensional probability space. An extensive simulation study under various scenarios are conducted and results show that PRINTE outperforms existing designs in the literature since it assigns more patients to optimal doses and less to toxic ones, and selects optimal doses with higher percentages. The simple and transparent features together with good operating characteristics make PRINTE an improved design for dose-finding trials in oncology trials.
journal_name
Stat Methods Med Resjournal_title
Statistical methods in medical researchauthors
Lin X,Ji Ydoi
10.1177/0962280220977009subject
Has Abstractpub_date
2020-12-16 00:00:00pages
962280220977009eissn
0962-2802issn
1477-0334pub_type
杂志文章abstract::In the past two decades, it has become increasingly clear that genetic factors contribute to the aetiology of many common diseases including cancers, coronary disease, allergy and psychiatric disorders. While one goal of genetic epidemiological studies is to locate susceptibility genes for these complex diseases, it i...
journal_title:Statistical methods in medical research
pub_type: 杂志文章,评审
doi:10.1177/096228020000900603
更新日期:2000-12-01 00:00:00
abstract::Nonlinear mixed-effects modeling is a popular approach to describe the temporal trajectory of repeated measurements of clinical endpoints collected over time in clinical trials, to distinguish the within-subject and the between-subject variabilities, and to investigate clinically important risk factors (covariates) th...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280218812595
更新日期:2019-12-01 00:00:00
abstract::We propose a semiparametric multi-state frailty model to analyze clustered event-history data subject to interval censoring. The proposed model is motivated by an attempt to study the life course of dental caries at the tooth level, taking into account the multiplicity of caries states and the intra-oral clustering of...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280218788383
更新日期:2019-09-01 00:00:00
abstract::A bivariate generalised linear mixed model is often used for meta-analysis of test accuracy studies. The model is complex and requires five parameters to be estimated. As there is no closed form for the likelihood function for the model, maximum likelihood estimates for the parameters have to be obtained numerically. ...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280219853602
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Dyspepsia diagnoses and treatment decisions are made in situations in which multiple factors must be taken into account. Evolving from neuro-biological insights, artificial neural networks (ANNs) can employ multiple factors in resolving medical prediction, classification, pattern recognition, and pattern com...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280206071839
更新日期:2007-08-01 00:00:00
abstract::Post-therapeutic surveillance is one important component of cancer care. However, there still is no evidence-based strategies to schedule patients' follow-up examinations. Our approach is based on the modeling of the probability of the onset of relapse at an early asymptotic or preclinical stage and its transition to ...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280214524178
更新日期:2016-12-01 00:00:00
abstract::Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible tre...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280216662070
更新日期:2018-05-01 00:00:00
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journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/096228020101000305
更新日期:2001-06-01 00:00:00
abstract::In biomedical research, various longitudinal markers measuring different quantities are often collected over time. For example, repeated measures of psychometric scores are very informative about the degradation process toward dementia. These trajectories are generally nonlinear with an acceleration of the decline a f...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280219898719
更新日期:2020-09-01 00:00:00
abstract::Statistical methods for spatial health data to identify the significant covariates associated with the health outcomes are of critical importance. Most studies have developed variable selection approaches in which the covariates included appear within the spatial domain and their effects are fixed across space. Howeve...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280215627184
更新日期:2018-01-01 00:00:00
abstract::In this paper, we describe a Bayesian hierarchical Poisson model for the prospective analysis of data for infectious diseases. The proposed model consists of two components. The first component describes the behavior of disease during nonepidemic periods and the second component represents the increase in disease coun...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280214527385
更新日期:2014-12-01 00:00:00
abstract::Nonlinear mixed-effects modeling is one of the most popular tools for analyzing repeated measurement data, particularly for applications in the biomedical fields. Multiple integration and nonlinear optimization are the two major challenges for likelihood-based methods in nonlinear mixed-effects modeling. To solve thes...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280220949898
更新日期:2020-08-24 00:00:00
abstract::Evaluation of medical imaging devices often involves clinical studies where multiple readers (MR) read images of multiple cases (MC) for a clinical task, which are often called MRMC studies. In addition to sizing patient cases as is required in most clinical trials, MRMC studies also require sizing readers, since both...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280219869370
更新日期:2020-06-01 00:00:00
abstract::Monte Carlo evaluation of resampling-based tests is often conducted in statistical analysis. However, this procedure is generally computationally intensive. The pooling resampling-based method has been developed to reduce the computational burden but the validity of the method has not been studied before. In this arti...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280216661876
更新日期:2018-05-01 00:00:00
abstract::Count responses are becoming increasingly important in biostatistical analysis because of the development of new biomedical techniques such as next-generation sequencing and digital polymerase chain reaction; a commonly met problem in modeling them with the popular Poisson model is overdispersion. Although it has been...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280215583397
更新日期:2017-06-01 00:00:00
abstract::Clinical trials investigating the efficacy of two or more doses of an experimental treatment compared to a single reference arm are not uncommon. In such situations, if each dose is compared to the reference arm using an un-adjusted significance level, consideration of the Type I familywise error is likely to be requi...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280210378943
更新日期:2011-12-01 00:00:00
abstract::This work presents a brief overview of Markov models in cancer screening evaluation and focuses on two specific models. A three-state model was first proposed to estimate jointly the sensitivity of the screening procedure and the average duration in the preclinical phase, i.e. the period when the cancer is asymptomati...
journal_title:Statistical methods in medical research
pub_type: 杂志文章,评审
doi:10.1177/0962280209359848
更新日期:2010-10-01 00:00:00
abstract::Mixed models are widely used for the analysis of one repeatedly measured outcome. If more than one outcome is present, a mixed model can be used for each one. These separate models can be tied together into a multivariate mixed model by specifying a joint distribution for their random effects. This strategy has been u...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280206075305
更新日期:2007-10-01 00:00:00
abstract::The threat of pandemics has made influenza surveillance systems a priority in epidemiology services around the world. The emergence of A-H1N1 influenza has required accurate surveillance systems in order to undertake specific actions only when and where they are necessary. In that sense, the main goal of this article ...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280210370265
更新日期:2011-04-01 00:00:00
abstract::Tree-based methods are very powerful and popular tools for analysing survival data with right-censoring. The existing methods assume that the true time-to-event and the censoring times are independent given the covariates. We propose different ways to build survival forests when dependent censoring is suspected, by us...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280217727314
更新日期:2019-02-01 00:00:00
abstract::Pediatric cardiac surgery may lead to poor outcomes such as acute kidney injury (AKI) and prolonged hospital length of stay (LOS). Plasma and urine biomarkers may help with early identification and prediction of these adverse clinical outcomes. In a recent multi-center study, 311 children undergoing cardiac surgery we...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280214530608
更新日期:2016-12-01 00:00:00
abstract::In genomic analysis, it is significant though challenging to identify markers associated with cancer outcomes or phenotypes. Based on the biological mechanisms of cancers and the characteristics of datasets, we propose a novel integrative interaction approach under a semiparametric model, in which genetic and environm...
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doi:10.1177/0962280220909969
更新日期:2020-10-01 00:00:00
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journal_title:Statistical methods in medical research
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doi:10.1177/0962280220921912
更新日期:2020-11-01 00:00:00
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journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280220958177
更新日期:2020-09-21 00:00:00
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journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280206074464
更新日期:2007-06-01 00:00:00
abstract::In many experiments and especially in translational and preclinical research, sample sizes are (very) small. In addition, data designs are often high dimensional, i.e. more dependent than independent replications of the trial are observed. The present paper discusses the applicability of max t-test-type statistics (mu...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280220970228
更新日期:2020-11-24 00:00:00
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journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280214526193
更新日期:2016-12-01 00:00:00
abstract::Purpose The prevalence estimates of binary variables in sample surveys are often subject to two systematic errors: measurement error and nonresponse bias. A multiple-bias analysis is essential to adjust for both biases. Methods In this paper, we linked the latent class log-linear and proxy pattern-mixture models to ad...
journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280217690939
更新日期:2018-10-01 00:00:00
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journal_title:Statistical methods in medical research
pub_type: 杂志文章
doi:10.1177/0962280209347953
更新日期:2011-08-01 00:00:00
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