A note on calculating asymptotic confidence intervals for the adjusted risk difference and number needed to treat in the Cox regression model

Recently, Laubender and Bender (Stat. Med. 2010; 29: 851–859) applied the average risk difference (RD) approach to estimate adjusted RD and corresponding number needed to treat measures in the Cox proportional hazards model. We calculated standard errors and confidence intervals by using bootstrap techniques. In this paper, we develop asymptotic variance estimates of the adjusted RD measures and corresponding asymptotic confidence intervals within the counting process theory and evaluated them in a simulation study. We illustrate the use of the asymptotic confidence intervals by means of data of the Düsseldorf Obesity Mortality Study. Copyright © 2013 John Wiley & Sons, Ltd.     

按GB／T3359用随机样本检验数据判定医疗器械总体质量水平

计量抽样检验目前在中国医疗器械行业应用较少。本文结合两个国外医疗器械标准的实例对GB／T3359在医疗器械标准中的应用进行了解读,并通过与传统的计数抽样检验进行比较,得出医疗器械检验中采用GB／T3359进行计量抽样的优势所在。     

BECKMAN DxI800全自动化学发光仪甲状腺检测项目的性能验证

目的 评价BECKMAN DxI 800全自动化学发光仪甲状腺检测项目（TT3、TT4、FT3、FT4、TSH）的分析性能.方法参照美国临床实验室标准化协会（CLSI）文件,对BECKMAN DxI 800全自动化学发光仪检测TT3、TT4、FT3、FT4、TSH的精密度、线性范围及生物参考区间等方面进行验证,并与厂商声明的性能标准进行比较.结果 批内和批间精密度即变异系数（CV）均小于厂家声明的CV值,均在允许范围内;线性范围验证结果显示,各检测项目的 斜率（a值）均在（1±0.05）范围内,相关系数（r值）≥0.975,均在仪器要求范围内,并具有良好的线性;生物参考区间与厂商提供的性能指标相符.结论 BECKMAN DxI 800全自动化学发光仪5项甲状腺检测在精密度、线性范围及生物参考区间三个性能指标上,均在相关要求范围内,符合实验室要求,可应用于临床检测.     

Multiple Comparisons and Multiple Contrasts in Randomized Dose-Response Trials—Confidence Interval Oriented Approaches

According to the ICH E9 recommendation, the evaluation of randomized dose-finding trials focuses on the graphical presentation of different kinds of simultaneous confidence intervals: i) superiority of at least one dose vs. placebo with and without the assumption of order restriction, ii) noninferiority of at least one dose vs. active control, iii) identification of the minimum effective dose, iv) identification of the peak dose, v) identification of the maximum safe dose for a safety endpoint, and vi) estimation of simultaneous confidence intervals for “many-to-one-by-condition interaction contrasts.” Moreover, global tests for a monotone trend or a trend with a possible downturn effect are discussed. The basic approach involved obtaining multiple contrasts for different problem-related contrast definitions. For all approaches, definitions of relevance margins for superiority or noninferiority are needed. Because consensus on margins only exists for selected therapeutic areas and the definition of absolute thresholds may be difficult, simultaneous confidence intervals for ratio to placebo were also used. All approaches are demonstrated in an example-based manner using the R-packages multcomp (difference), for hypotheses based on difference, and mratios (ratio), for hypotheses based on ratios.     

Assessing Equivalence of Two Assays Using Sensitivity and Specificity

In medical device clinical studies, including therapeutic device and in vitro test assay method studies, the investigator is frequently interested in demonstrating the equivalence of clinical response, generally in continuous measurements, between a standard assay method and a new assay method over various occasions or times. The new assay method may be less invasive or more convenient or cheaper to use than the standard assay method. In this paper, several statistical approaches are discussed, including various repeated-measure regression models, the simultaneous 95% confidence interval for paired mean differences derived from Hotelling's multivariate T ² analysis for repeated-measure, paired data, repeatability and reproducibility studies, and concordance correlation coefficient.

     

Sharper Confidence Intervals for Hochberg- and Hommel-Related Multiple Tests Based On an Extended Simes Inequality

This article concerns recent developments related to the now classical multiple-testing procedures (MTPs) of Holm, Hochberg, and Hommel based on marginal p-values. For a long time, the derivation of simultaneous confidence intervals (SCIs) corresponding to these MTPs was considered to be a difficult problem, but solutions were published in 2008 for Holm's MTP, and in 2012 for Hochberg's and Hommel's MTPs. These SCIs turned out to be as simple and easily implemented as the MTPs themselves, and to be remarkably similar. However, they also turned out to have the property/limitation, shared with other powerful stepwise MTPs, that no confidence assertions sharper than rejection assertions are possible unless all null hypotheses are rejected. A possibility is then to construct related families of MTPs that do not have this limitation but are somewhat less powerful, so users may choose among various such trade-off MTPs. It is shown in this article how an extended Simes inequality can be used to construct Hochberg- and Hommel-related MTPs of this kind that: (i) are more powerful than corresponding trade-off MTPs proposed previously, and (ii) lead to SCIs that are sharper than the ones proposed previously. Corresponding Holm-related MTPs and SCIs are considered for completeness and comparisons.     

Low Prenatal Weight Gain Among Adult WIC Participants Delivering Term Singleton Infants: Variation by Maternal and Program Participation Characteristics

Objective: To determine the association of maternal and prenatal WIC program participation characteristics with low prenatal weight gain among adult women delivering liveborn, singleton infants at term. Methods: WIC program data for 19,017 Black and White Alabama women delivering in 1994 were linked with birth certificate files to examine the association of anthropometric, demographic, reproductive, hematologic, behavioral and program participation characteristics with low prenatal weight gain. Results: One third (31.0%) had low prenatal weight gain as defined by the Institute of Medicine. The incidence of low weight gain was increased among women who had < 12 years of education, were single, Black, anemic, had low or normal pre-pregnancy body mass index (BMI), increased parity, interpregnancy intervals 24 months, used tobacco or alcohol, or entered prenatal care or WIC programs after the first trimester. After adjusting for selected maternal characteristics, the adjusted odds ratios (AOR) for low weight gain were increased with short interpregnancy intervals (AOR 1.21 to 2.20); tobacco use (AOR 1.16 to 1.40), anemia (AOR 1.20 to 1.25), and second trimester entry into prenatal care (AOR 1.14 to 1.20); the size of the AORs and 95% confidence intervals varied by BMI and racial subgroup. Conclusions: The results of this study suggest that WIC interventions targeting low prenatal weight gain be focused on risk factors present not only during pregnancy, but during the pre- and interconceptional periods as well. Interventions should target low BMI, tobacco use, and anemia, and include attention to nutrition screening and risk reduction among women in postpartum and family planning clinic settings.     

Impact of mercury exposure on blood pressure and cardiac autonomic activity among Cree adults (James Bay, Quebec, Canada)

Aboriginal populations from Quebec (Canada) are exposed to higher mercury levels than southern regions since these populations consume high quantities of fish. Epidemiological evidence suggests a detrimental impact of mercury on cardiovascular risk factors such as heart rate variability (HRV) and blood pressure (BP). The objective of this study was to assess the impact of mercury exposure on BP, resting heart rate (HR) and HRV among Cree adults. Data were collected among 791 adults ≥18 years old living in seven communities of the James Bay. Blood mercury and hair levels were used as biomarkers of recent and long-term exposure. BP was measured through a standardised protocol while HRV was derived from a 2-h Holter monitoring assessment. The relationship between mercury and the outcomes was studied using ANOVA and ANCOVA analysis. Geometric mean of blood mercury and hair mercury concentration was 17.0 nmol/L (95%CI: 6.1–44.0) and 2.36 nmol/g (95%CI: 2.09–2.65); respectively. After adjusting for confounders, blood mercury was associated with HRV parameters such as LF (β=0.21, P=0.0002), HF (β=0.15, P=0.004) and LF/HF (β=0.06, P=0.003). Similar associations were observed with hair mercury. In contrast, no significant association was observed between blood mercury or hair mercury and BP after adjusting for confounders. In conclusion, mercury exposure seems to affect HRV among Cree adults even after considering fish nutrients (n-3 fatty acids and selenium) and other contaminants (lead and polychlorinated biphenyls) that are also present in the traditional diet of this population.