Relation Between Benchmark Dose and No-Observed-Adverse-Effect Level in Clinical Research: Effects of Daily Alcohol Intake on Blood Pressure in Japanese Salesmen

The benchmark dose (BMD) is defined as the dose that corresponds to a specific change in an adverse response compared to the response in unexposed subjects, and the lower 95% confidence limit is termed the benchmark dose level (BMDL). In this study, the threshold of daily ethanol intake affecting blood pressure was calculated by both the BMD approach and multiple logistic regression analysis to clarify the relation between the BMDL and no-observed-adverse-effect level (NOAEL). Systolic and diastolic blood pressures (SBP and DBP) and daily ethanol intake were explored in 1,100 Japanese salesmen. The SBP and DBP were positively related to daily ethanol intake (p < 0.001) when adjusting for possible confounders such as age, body mass index, and smoking status. The adjusted risk for hypertension (SBP >or= 140 mmHg or DBP >or= 90 mmHg) increased significantly when daily ethanol intake exceeded 60 g/day, and the categorical dose of interest was 60.1-90 g/day. The BMDL and BMD of ethanol intake for increased SBP and DBP were estimated to be approximately 60 and 75 g/day, respectively. These findings suggest that the BMDL and BMD correspond to the NOAEL and lowest-observed-adverse-effect level, respectively, if the sample number of clinical data is large enough to confirm the dose-response association.     

ESTIMATING A LOGIT MODEL WITH RANDOMIZED DATA: THE CASE OF COCAINE USE

In his influential book, Maddala (1983) suggests combining randomized response survey data with other personal information to estimate logit models predicting immoral, unpopular, or unlawful behaviour. This study is one of the first to implement this technique using real data. Models of college students' recent cocaine use are estimated with academic performance and socio-economic characteristics as determinants. Parameter estimates obtained from randomized response surveys are compared to those obtained using conventional, direct question surveys. The results indicate that randomized response estimates provide useful information on the degree to which inferences regarding the determinants of cocaine use are sensitive to survey type.     

On the curtailment of sampling

We address the problem of the curtailment or continuation of an experiment or trial at some interim point where say N observations are in hand and at least S > N observations had originally been scheduled for a decision. A Bayesian predictive approach is used to determine the probability that if one continued the trial with a further sample of size M where N +M ≥S, one would come to a particular decision regarding a parameter or a future observable. This point of view can also be applied to significance tests if one is willing to admit the calculation as a subjective assessment.     

Analyzing continuous randomized response data with an indifference-zone selection procedure

A review of the randomized response model introduced by Warner (1965) is given, then a randomized response model applicable to continuous data that considers a mixture of two normal distributions is considered. The target here is not to estimate any parameter, but rather to select the population with the best parameter value. This article provides a study on how to choose the best population between k distinct populations using an indifference-zone procedure. Also, this article includes tables for the required sample size needed in order to have a probability of correct selection higher than some specified value in the preference zone for the randomized response model considered.     

A new quasi empirical bayes estimate in randomized response sampling

In this article, a new notion of “quasi-empirical” Bayes estimation is developed for estimating the proportion of a sensitive attribute in a population by making use of both a prior distribution of prevalence of the sensitive attribute in addition to the known prior distribution of an unrelated characteristic. The proposed quasi-empirical Bayes estimate is compared with those of the unrelated question model due to Greenberg et al. by means of a simulation study.     

An evaluation of the trimmed mean approach in clinical trials with dropout

The trimmed mean is a method of dealing with patient dropout in clinical trials that considers early discontinuation of treatment a bad outcome rather than leading to missing data. The present investigation is the first comprehensive assessment of the approach across a broad set of simulated clinical trial scenarios. In the trimmed mean approach, all patients who discontinue treatment prior to the primary endpoint are excluded from analysis by trimming an equal percentage of bad outcomes from each treatment arm. The untrimmed values are used to calculated means or mean changes. An explicit intent of trimming is to favor the group with lower dropout because having more completers is a beneficial effect of the drug, or conversely, higher dropout is a bad effect. In the simulation study, difference between treatments estimated from trimmed means was greater than the corresponding effects estimated from untrimmed means when dropout favored the experimental group, and vice versa. The trimmed mean estimates a unique estimand. Therefore, comparisons with other methods are difficult to interpret and the utility of the trimmed mean hinges on the reasonableness of its assumptions: dropout is an equally bad outcome in all patients, and adherence decisions in the trial are sufficiently similar to clinical practice in order to generalize the results. Trimming might be applicable to other inter‐current events such as switching to or adding rescue medicine. Given the well‐known biases in some methods that estimate effectiveness, such as baseline observation carried forward and non‐responder imputation, the trimmed mean may be a useful alternative when its assumptions are justifiable.     

中外临床医学专业学位研究生培养的同质化之策

医学留学生教育不仅是我国加强医学文化对外交流的需要,也逐渐成为我国医学教育国际化的核心。本文旨在探索中外临床医学专业学位研究生培养同质化的障碍及其对策,对进一步推进留学生的医学教育具有重要的现实意义。     

临床医学专业实践技能培养的有效路径

临床医学专业的实践性很强,临床基本技能是医学专业学生临床能力的重要组成部分。针对目前高职院校临床医学专业学生实践技能薄弱、难以胜任基层医院基本技能操作的现状,从增加实践课时、改革考核方式及科学合理调整相关实习见习安排等,探讨了临床医学专业学生临床实践技能水平提升的有效路径和相关举措。