A stochastically curtailed two-arm randomised phase II trial design for binary outcomes

Randomised controlled trials are considered the gold standard in trial design. However, phase II oncology trials with a binary outcome are often single-arm. Although a number of reasons exist for choosing a single-arm trial, the primary reason is that single-arm designs require fewer participants than their randomised equivalents. Therefore, the development of novel methodology that makes randomised designs more efficient is of value to the trials community. This article introduces a randomised two-arm binary outcome trial design that includes stochastic curtailment (SC), allowing for the possibility of stopping a trial before the final conclusions are known with certainty. In addition to SC, the proposed design involves the use of a randomised block design, which allows investigators to control the number of interim analyses. This approach is compared with existing designs that also use early stopping, through the use of a loss function comprised of a weighted sum of design characteristics. Comparisons are also made using an example from a real trial. The comparisons show that for many possible loss functions, the proposed design is superior to existing designs. Further, the proposed design may be more practical, by allowing a flexible number of interim analyses. One existing design produces superior design realisations when the anticipated response rate is low. However, when using this design, the probability of rejecting the null hypothesis is sensitive to misspecification of the null response rate. Therefore, when considering randomised designs in phase II, we recommend the proposed approach be preferred over other sequential designs.     

Individual differences in numerical representations of risk in health decision making: A fuzzy-trace theory approach

Fuzzy-trace theory predicts that decisionmakers process numerical information about risk at multiple levels in parallel: the simplest level, nominal (categorical some-none) gist, and at more fine-grained levels, involving relative comparison (ordinal less-more gist) and exact quantities (verbatim representations). However, little is known about how individual differences in these numerical representations relate to judgments and decisions, especially involving health tradeoffs and relative risks. To investigate these differences, we administered measures of categorical and ordinal gist representations of number, objective numeracy, and intelligence in two studies (Ns = 978 and 956). In both studies, categorical and ordinal gist representations of number predicted risk judgments and decisions beyond objective numeracy and intelligence. Participants with higher scores in categorical gist were more likely to choose options to avoid cancer recurrence risks; those who were higher in ordinal gist of numbers were more likely to discriminate relative risk of skin cancer; and those with higher scores in objective numeracy were more likely to choose options that were numerically superior overall in terms of relative risk of skin cancer and of genetic risks of breast cancer (e.g., lower numerical probability of cancer). Results support parallel-processing models that assume multiple representations of numerical information about risk, which vary in precision, and illustrate how individual differences in numerical representations are relevant to tradeoffs and risk comparisons in health decisions. These representations cannot be reduced to one another and explain psychological variations in risk processing that go beyond low versus high levels of objective numeracy.     

Bayesian age-stratified joinpoint regression model: an application to lung and brain cancer mortality

Joinpoint regression model identifies significant changes in the trends of the incidence, mortality, and survival of a specific disease in a given population. The purpose of the present study is to develop an age-stratified Bayesian joinpoint regression model to describe mortality trend assuming that the observed counts are probabilistically characterized by the Poisson distribution. The proposed model is based on Bayesian model selection criteria with the smallest number of joinpoints that are sufficient to explain the Annual Percentage Change. The prior probability distributions are chosen in such a way that they are automatically derived from the model index contained in the model space. The proposed model and methodology estimates the age-adjusted mortality rates in different epidemiological studies to compare the trends by accounting the confounding effects of age. In developing the subject methods, we use the cancer mortality counts of adult lung and bronchus cancer, and brain and other Central Nervous System cancer patients obtained from the Surveillance Epidemiology and End Results data base of the National Cancer Institute.     

Nonparametric Comparison for Multivariate Panel Count Data

Multivariate panel count data often occur when there exist several related recurrent events or response variables defined by occurrences of related events. For univariate panel count data, several nonparametric treatment comparison procedures have been developed. However, it does not seem to exist a nonparametric procedure for multivariate cases. Based on differences between estimated mean functions, this article proposes a class of nonparametric test procedures for multivariate panel count data. The asymptotic distribution of the new test statistics is established and a simulation study is conducted. Moreover, the new procedures are applied to a skin cancer problem that motivated this study.     

Significance test of clustering under high dimensional setting with applications to cancer data

For high dimensional data, the SigClust is developed for testing the significance of clustering. The cluster index (CI) for SigClust is conducted by the ratio of the within-cluster and total sum of squares. But its empirical size is too conservative to be over controlled. By removing the cumbrous terms in the CI, an improved index (BCI) is proposed in this paper. The coefficient of variation of the BCI can be significantly reduced, implying that the new index BCI is stable. Moreover, the new significance test (NewSig) maintains the size, meanwhile, provides a greater power. Simulation experiments and two real cancer data examples are analysed for illustrating the performance of the new methodology.     

A Bayesian approach for generalized linear models with explanatory biomarker measurement variables subject to detection limit: an application to acute lung injury

Biomarkers have the potential to improve our understanding of disease diagnosis and prognosis. Biomarker levels that fall below the assay detection limits (DLs), however, compromise the application of biomarkers in research and practice. Most existing methods to handle non-detects focus on a scenario in which the response variable is subject to the DL; only a few methods consider explanatory variables when dealing with DLs. We propose a Bayesian approach for generalized linear models with explanatory variables subject to lower, upper, or interval DLs. In simulation studies, we compared the proposed Bayesian approach to four commonly used methods in a logistic regression model with explanatory variable measurements subject to the DL. We also applied the Bayesian approach and other four methods in a real study, in which a panel of cytokine biomarkers was studied for their association with acute lung injury (ALI). We found that IL8 was associated with a moderate increase in risk for ALI in the model based on the proposed Bayesian approach.     

Human papillomavirus vaccine and Pap tests on college campuses: How do historically black colleges and universities (HBCUs) measure up?

ABSTRACT

Objective: The availability of cervical cancer prevention services at college health centers was compared between historically black colleges and universities (HBCUs) and non-HBCUs.

Methods: Four-year, non–primarily distant learning colleges, matching HBCUs with randomly selected non-HBCUs within the same states (N = 136) were examined. Data were collected (2014–2015 academic year) on the availability of human papillomavirus (HPV) vaccine and Pap tests at college health centers. HBCUs were compared with non-HBCUs using conditional logistic regression, and correlates of offering these services were identified. Results: Many institutions did not offer HPV vaccine or Pap tests. Fewer HBCUs offered HPV vaccine (18% vs 53%) and Pap tests (50% vs 76%) compared with non-HBCUs. In multivariable analyses, HBCUs remained less likely than non-HBCUs to offer HPV vaccine (odds ratio [OR] = 0.07, 95% confidence interval [CI]: 0.02–0.26) and Pap tests (OR = 0.19, 95% CI: 0.06–0.61). Conclusions: Greater effort is needed to make cervical cancer prevention services available at colleges, especially at HBCUs.     

Indoor Tanning and Problem Behavior

Objective: The authors examined factors predicting college students' use of tanning beds. Participants and Methods: Undergraduate students (N = 745) at a large Northeastern university participated in the study by answering a survey measuring tanning behavior and other psychosocial variables, including sensation seeking, self-esteem, tanning image beliefs, and friends' tanning bed use. Results: All 3 systems from problem behavior theory predicted past tanning bed use and intention to use tanning beds. The authors observed a positive association between sensation seeking and intention to use tanning beds. Tanning image beliefs were positively associated with both past tanning behavior and intention to use tanning beds. Conclusions: Interventions focusing on friend and acquaintance social network influences may be more effective than health-risk campaigns in reducing tanning bed use.     

培美曲塞联合顺铂治疗晚期乳腺癌36例疗效分析

目的 探讨培美曲塞联合顺铂治疗晚期乳腺癌36例临床疗效.方法 研究对象为2010年6月至2012年6月本院收治的36例晚期乳腺癌患者.静脉滴注培美曲塞二钠500mg/m2,d1;顺铂25mg/m2,d1～d3.21天为1个周期.每个患者至少治疗2个疗程后评价疗效和不良反应.结果 36例患者,CR 0例,PR 7例（19.4％）,SD 17例（47.2％）,PD12例（33.3％）,总有效率为19.4％ （7/36）,临床获益率为66.7％ （24/36）.主要不良反应为骨髓抑制,20例表现为白细胞减少（Ⅰ～Ⅱ级）,占55.6％.其他不良反应还包括疲乏21例,占58.3％;皮疹17例,占47.2％例;恶心、呕吐15例,占41.7％.结论 培美曲塞联合顺铂方案治疗蒽环类和紫杉类化疗失败的转移性乳腺癌有较好的疗效,患者耐受性好,值得临床进一步研究.