Multiparameter evidence synthesis in epidemiology and medical decision-making: current approaches

Summary.  Alongside the development of meta-analysis as a tool for summarizing research literature, there is renewed interest in broader forms of quantitative synthesis that are aimed at combining evidence from different study designs or evidence on multiple parameters. These have been proposed under various headings: the confidence profile method, cross-design synthesis, hierarchical models and generalized evidence synthesis. Models that are used in health technology assessment are also referred to as representing a synthesis of evidence in a mathematical structure. Here we review alternative approaches to statistical evidence synthesis, and their implications for epidemiology and medical decision-making. The methods include hierarchical models, models informed by evidence on different functions of several parameters and models incorporating both of these features. The need to check for consistency of evidence when using these powerful methods is emphasized. We develop a rationale for evidence synthesis that is based on Bayesian decision modelling and expected value of information theory, which stresses not only the need for a lack of bias in estimates of treatment effects but also a lack of bias in assessments of uncertainty. The increasing reliance of governmental bodies like the UK National Institute for Clinical Excellence on complex evidence synthesis in decision modelling is discussed.     

论电子商务对税收的冲击

针对迅速崛起的电子商务的特点深入分析电子商务对税收各个方面的冲击和影响 ,提出加大对电子商务征税力度的有关建议 ,对完善电子商务征税有积极意义。     

社会民主主义复兴的两种模式比较

20世纪90年代在社会民主主义复兴的过程中,英国和法国由于竞选方式、政策策略等一系列方面存在显著差别,被认为是社会民主主义复兴的两种典型模式,对英国道路与法国道路的相同之处和不同之处进行比较,说明二者存在共同性和差异性的原因。     

Still-births among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant: detailed results and statistical aspects

Summary. This study investigates whether there was evidence of increasing risk of still-birth with increasing paternal exposure to ionizing radiation received during employment at the Sellafield nuclear installation before the child was conceived. A significant positive association is found between the total paternal preconceptional exposure to external ionizing radiation and the risk of still-birth (after adjustment for year of birth, social class, birth order and paternal age, odds ratio at 100 mSv 1.24 (95% confidence interval 1.04–1.45)). A summary of the principal scientific findings of this study has been published in the Lancet . This paper describes in detail the statistical methods that were used in the investigation and presents the results in full.     

Book Reviews

Books reviewed:
M Hollander and D Wolfe, Nonparametric Statistical Methods
T Leonard and J.S.J Hsu, Bayesian Methods     

Simple detection of outlying short time series

Sets of relatively short time series arise in many situations. One aspect of their analysis may be the detection of outlying series. We examine the performance of standard normal outlier tests applied to the means, or to simple functions of the means, of AR(1) series, not necessarily of equal lengths. Although unequal lengths of series implies that the means have unequal variances, that are only known approximately, it is shown that nominal significance levels hold good under most circumstances. Thus a standard outlier test can usefully be applied, avoiding the complication of estimating the time series' parameters. The test's power is affected by unequal lengths, being higher when the slippage occurs in one of the longer series     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Merging information for semiparametric density estimation

Summary.  The density ratio model specifies that the likelihood ratio of m −1 probability density functions with respect to the m th is of known parametric form without reference to any parametric model. We study the semiparametric inference problem that is related to the density ratio model by appealing to the methodology of empirical likelihood. The combined data from all the samples leads to more efficient kernel density estimators for the unknown distributions. We adopt variants of well-established techniques to choose the smoothing parameter for the density estimators proposed.     

Estimation of Hazard, Density and Survivor Functions for Randomly Censored Data

Maximum likelihood estimation and goodness-of-fit techniques are used within a competing risks framework to obtain maximum likelihood estimates of hazard, density, and survivor functions for randomly right-censored variables. Goodness-of- fit techniques are used to fit distributions to the crude lifetimes, which are used to obtain an estimate of the hazard function, which, in turn, is used to construct the survivor and density functions of the net lifetime of the variable of interest. If only one of the crude lifetimes can be adequately characterized by a parametric model, then semi-parametric estimates may be obtained using a maximum likelihood estimate of one crude lifetime and the empirical distribution function of the other. Simulation studies show that the survivor function estimates from crude lifetimes compare favourably with those given by the product-limit estimator when crude lifetimes are chosen correctly. Other advantages are discussed.