Assessing and communicating heterogeneity of treatment effects for patient subpopulations: Keynote and panel discussion on communicating heterogeneous treatment effects across populations

How do we communicate nuanced regulatory information to different audiences, recognizing that the consumer audience is very different from the physician audience? In particular, how do we communicate the heterogeneity of treatment effects - the potential differences in treatment effects based on sex, race, and age? That is a fundamental question at the heart of this panel discussion. Each panelist addressed a specific “challenge question” during their 5-minute presentation, and the list of questions is provided. The presentations were followed by a question and answer session with members of the audience and the panelists.     

Selected problems concerning changes in the population age structure in Czechoslovakia in comparison with those in Poland

A comparative analysis of changes in the characteristics of the populations of Czechoslovakia and Poland by age and sex since 1921 is presented. The emphasis is on changes occurring since 1950.     

双截面数据及其处理思路初探

在研究一组相关总体的数量特征、总体间数量特征关系和总体间的交互作用时,如果从每一总体中抽取一组截面数据,就形成了一种不同于截面数据、时间序列数据和面板数据的特殊数据类型——双截面数据,虽然现有数据处理方法可以为双截面数据提供“面板化”、“平行化”和方程结构耐抗性检验等处理思路,但鉴于双截面数据的特殊性,每种思路都有不完善的地方,充分挖掘双截面数据所隐含信息的针对性处理方法仍需进一步探索。     

Simultaneous prediction intervals for all patrwise differences among several future sample means

Hahn (1977) suggested a procedure for constructing prediction intervals for the difference between the means of two future samples from normal populations having equal variance, based on past samples selected from both populations. In this paper, we extend Hahn's work by constructing simultaneous prediction intervals for all pairwise differences among the means of k ≥ 2 future samples from normal populations with equal variances, using past samples taken from each of the k populations. For K = 2, this generalization reduces to Hahn's special case. These prediction intervals may be used when one has sampled the performance of several products and wishes to simultaneously as- sess the differences in future sample mean performance of these products with a predetermined overall coverage probability. The use of the new procedure is demonstrated with a numerical example.     

Establishing the nadir of the body mass index-mortality relationship: a case study

The relationship between body weight and mortality is examined using U.S. data from the National Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study concerning 13,242 individuals, the emphasis being on identifying the body mass index associated with the lowest levels of mortality. Factors such as smoking status, sex, race, and age are taken into consideration. The results suggest that only the interaction between race and body mass index is significant.     

Combining census and registration data to estimate detailed elderly migration flows in England and Wales

Summary.  A log-linear model is developed to estimate detailed elderly migration flows by combining data from the 2001 UK census and National Health Services patient register. After showing that the census and National Health Service migration flows can be reasonably combined, elderly migration flows between groupings of local authority districts by age, sex and health status for the 2000–2001 and 2003–2004 periods are estimated and then analysed to show how the patterns have changed. By combining registration data with census data, we can provide recent estimates of detailed elderly migration flows, which can be used for improvements in social planning or policy.     

Quality engineering in japan

For controlling quality of products, there are two things we have to consider; how to measure the quality and how to improve it. The former is discussed in section 2 by introducing the difference in quality levels between Japan and USA. After briefly introducing all countermeasures for improving quality of products, an on-line quality control system design is proposed as the one which is more economical than removing defec- tives after manufacturing by conducting inspection. It has been ma?y Japanese companies' policy to keep pro- cess conditions at best in order to produce uniform products as far as possible. This paper discusses the optimum feed-back process control system design by checking either quality characteristics or process pa- rameters after introducing overall quality countermea- sures starting with product design.     

When is a curve an outlier? An account of a tricky problem

ABSTRACT The analysis of a set of data consisting of N short (≤20 observations each) multivariate time series, where the observations are irregularly spaced and where observations for the different components of each multivariate series are observed at different times, is discussed. With the increased use of automatic recording devices in many fields, data such as these, which are of course samples from smooth response curves, are becoming more common. In this application, which was a clinical trial comparing two cements for use in hip replacement surgery, the key to the analysis was in recognizing that the interest lay in the degree to which the five curves representing a patient's vital signs deviated from baseline (i.e., normal for that patient) during surgery. This enabled the statisticians to define appropriate response variables. The analysis included Rosseeuw's (1984) technique for the identification of multivariate outliers and logistic regressions to identify any effects on the process producing the outliers due to treatment or covariates.     

Inference on treatment effects for targeted clinical trials under enrichment design

After completion of a human genome project, the disease targets at molecular level can be identified. As a result, treatment modality for molecular targets can be developed. In practice, targeted clinical trials are usually conducted for evaluation of the possibility and feasibility of the individualized treatment of patients. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Therefore, some of the patients enrolled in targeted clinical trials with a positive result by the diagnostic device might not have the specific molecular targets and hence the treatment effects of the targeted drugs estimated from targeted clinical trials could be biased for the patient population truly with the molecular targets. Under an enrichment design for targeted clinical trials, we propose to use the EM algorithm and bootstrap method for obtaining the inference of the treatment effects of the targeted drugs in the patient population truly with molecular targets. A simulation study was conducted to empirically investigate the bias and variability of the proposed estimator and the size and power of the proposed testing method. Simulation results demonstrate that the proposed estimator is unbiased with adequate precision and the confidence interval can provide satisfactory coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. A practical example illustrates the utility of the proposed method. Copyright © 2009 John Wiley & Sons, Ltd.     

Distributional properties of simpson's index of diversity

Closed expressions for the first four moments of Simpson's index of diversity are derived using techniaues suggested by Haldane (1937). As the samole size increases the behavior of the skewness and kurtosis is studied for several Dopulations with varying degrees of diversity, If the populationproportions decrease accordinq to a geometric progression, graphs of β₁and β₂ indicate that convergence to normality in general is more rapid for populations which are less diverse.     

Multivariate analysis of variance with additional data from an unknown subset of the populations

In this paper we consider the problem of testing the means of k multivariate normal populations with additional data from an unknown subset of the k populations. The purpose of this research is to offer test procedures utilizing all the available data for the multivariate analysis of variance problem because the additional data may contain valuable information about the parameters of the k populations. The standard procedure uses only the data from identified populations. We provide a test using all available data based upon Hotelling' s generalized T²statistic. The power of this test is computed using Betz's approximation of Hotelling' s generalized T²statistic by an F-distribution. A comparison of the power of the test and the standard test procedure is also given.     

Two-Dimensional Warranty Cost Analysis for Second-Hand Products

In spite of the recent steady increase of the volume of the second-hand markets, often customers remain in doubt regarding the quality and durability of the second-hand products. Aiming to reduce and share this uncertainty, dealers offer warranty on their products. Offering warranty for second-hand products is a relatively new marketing strategy employed by dealers of used electronic equipment, furniture, automobiles, etc. Usually, for used products, the dealer's expected warranty cost is a function of product reliability, past age and usage, servicing strategy and conditions and terms of the warranty policy/contract. Sometimes the offered policy is limited by two parameters, typically the product age and usage after the sale. This type of policies is referred to as two-dimensional warranty policies. In this article, we develop statistical models for estimating the dealer's expected warranty cost for second-hand products sold with two-dimensional free repair/replacement warranty.     

Application of an empirically derived classification of ‘non-specific’ low back pain

The ambiguity of low back pain diagnoses presently available proves detrimental to the patient's morale and impedes research into optimal treatment and prevention. This paper shows that the classification of patients into seven empirically derived groups clarifies problems in clinical diagnosis and can reveal differences in treatment responses otherwise undetected. The clinician is provided with sign and symptom patterns for each of the diagnoses and group specific response to treatment is discussed. The results are consistent with those found in clinical practice but further validation in different patient and observer populations is needed before the system can be adopted as a routine aid to clinical practice.     

Bayesian incorporation of repeated measurements in logistic discrimination

A common problem in medical statistics is the discrimination between two groups on the basis of diagnostic information. Information on patient characteristics is used to classify individuals into one of two groups: diseased or disease-free. This classification is often with respect to a particular disease. This discrimination has two probabilistic components: (1) the discrimination is not without error, and (2) in many cases the a priori chance of disease can be estimated. Logistic models (Cox 1970; Anderson 1972) provide methods for incorporating both of these components. The a posteriori probability of disease may be estimated for a patient on the basis of both current measurement of patient characteristics and prior information. The parameters of the logistic model may be estimated on the basis of a calibration trial. In practice, not one but several sets of measurements of one characteristic of the patient may be made on a questionable case. These measurements typically are correlated; they are far from independent. How should these correlated measurements be used? This paper presents a method for incorporating several sets of measurements in the classification of a case.     

Mark-resighting analysis of a California gull population

California gulls ( Larus californicus ) of known age and sex were censused on their breeding colony in 1979, 1980 and 1984 through 1993. Ages of 235 males and 196 females ranged from 4 to 27 years. Age classes used in the analysis were limited to 17, 4 through 19, and 20 or more as a final age category because data on gulls over 20 were sparse. Survival declined with age in a way that was parsimoniously modelled with a quadratic function. Other factors, sex and time, did not explain any variation in survival. Resighting depended on age, sex and time. Younger adults skipped breeding more frequently than did older adults, and females skipped breeding more frequently than did males. There was also good evidence for time dependence in resighting probability, but its inclusion in the model occurred at the expense of interpretability and precision. In a data set such as this, resighting probability may assume more importance than a mere 'nuisance parameter'. In this study, resighting history measured attendance at the breeding ground. In turn, attendance rates may be a manifestation of reproductive strategy, which can also have consequences for survival. In this situation, there may be heterogeneity in both survival and resighting probability that is unexplained by the model. While such complexity may well be a nuisance to deal with, it can also point to important biological questions.     

Estimating Probability Distributions by Observing Betting Practices

A bookmaker takes bets on a two-horse race, attempting to minimize expected loss over all possible outcomes of the race. Profits are controlled by manipulation of customer' betting behavior; in order to do this, we need some information about the probability distribution which describes how the customers will bet. We examine what information initial customer' betting behavior provides about this probability distribution, and consider how to use this to estimate the probability distribution for remaining customers.     

Measuring the Experience-Productivity Relationship: The Case of Major League Baseball

This article develops and estimates a model of the typical major league baseball player's lifetime batting average profile. The batting average profile can be thought of as an experience-productivity relationship. The estimation techniques are those suggested by MaCurdy (1981 a, b) for estimating model parameters when using panel data, including the parameters of the error structure. The method could be used to estimate the relationship between experience and productivity in any situation where a measure of individual output is available. The results include estimates of the peak of a baseball player's career and the rate at which batting averages change with age.     

Saddlepoint <Emphasis Type="Italic">p</Emphasis>-values and confidence intervals for a class of two sample permutation tests for current status and panel count data

The current status and panel count data frequently arise from cancer and tumorigenicity studies when events currently occur. A common and widely used class of two sample tests, for current status and panel count data, is the permutation class. We manipulate the double saddlepoint method to calculate the exact mid-p-values of the underlying permutation distributions of this class of tests. Permutation simulations are replaced by analytical saddlepoint computations which provide extremely accurate mid-p-values that are exact for most practical purposes and almost always more accurate than normal approximations. The method is illustrated using two real tumorigenicity panel count data. To compare the saddlepoint approximation with the normal asymptotic approximation, a simulation study is conducted. The speed and accuracy of the saddlepoint method facilitate the calculation of the confidence interval for the treatment effect. The inversion of the mid-p-values to calculate the confidence interval for the mean rate of development of the recurrent event is discussed.     

行驶里程数对环境、交通和能源的影响——基于外部性视角的省际面板数据研究

近年来,机动车污染日趋成为中国空气污染的重要来源.选取2006-2010年中国30个省、市、自治区的面板数据,运用单位根检验、协整检验和面板数据模型等方法来研究行驶里程数对环境、交通和能源的影响.结论认为公路交通氮氧化物排放量、汽油消耗量、交通事故数与公路里程数之间存在显著的相关关系,为将行驶里程数纳入车险费率改革、开发绿色低碳车险产品提供参考.     

Testing the homogeneity of several two‐parameter populations

The authors extend Fisher's method of combining two independent test statistics to test homogeneity of several two‐parameter populations. They explore two procedures combining asymptotically independent test statistics: the first pools two likelihood ratio statistics and the other, score test statistics. They then give specific results to test homogeneity of several normal, negative binomial or beta‐binomial populations. Their simulations provide evidence that in this context, Fisher's method performs generally well, even when the statistics to be combined are only asymptotically independent. They are led to recommend Fisher's test based on score statistics, since the latter have simple forms, are easy to calculate, and have uniformly good level properties.