Incremental net benefit in randomized clinical trials

There are three approaches to health economic evaluation for comparing two therapies. These are (i) cost minimization, in which one assumes or observes no difference in effectiveness, (ii) incremental cost-effectiveness, and (iii) incremental net benefit. The latter can be expressed either in units of effectiveness or costs. When analysing data from a clinical trial, expressing incremental net benefit in units of cost allows the investigator to examine all three approaches in a single graph, complete with the corresponding statistical inferences. Furthermore, if costs and effectiveness are not censored, this can be achieved using common two-sample statistical procedures. The above will be illustrated using two examples, one with censoring and one without.     

The benefit of stratification in clinical trials revisited

Stratification is common in clinical trials because it can reduce the variance of the estimated treatment effect. The traditional demonstration of variance reduction relies on the assumption of stratum sizes being fixed quantities. However, in practice, to speed up enrollment, and to obtain a study population with a similar distribution as the overall population, the stratum sizes are allowed to vary. Under the condition that the total sample size is fixed and that the stratum sizes have a multinomial distribution, the criterion changes for achieving a reduction in variance. The relationship between the stratified and unstratified variances is established and shown to be approximately the same for prestratified and post-stratified trials. It is demonstrated why stratification may actually increase the variance compared with no stratification even when the mean square error is reduced on account of stratification. Data from a real clinical trial will be used for illustration. The benefit attributed to stratification needs to be re-examined in light of the findings presented, particularly given its widespread use.     

让烟草化害为利

2003年2月17日，世界卫生组织总干事布伦特兰在日内瓦召开的政府间谈判机构《烟草控制框架公约》会议上说，在中国，男性吸烟率达63％，占全球10亿男性烟民的近1／3，中国也因此成为世界上最大的卷烟市场。吸烟会导致终生吸烟者的一半人死亡，每年有大约1OO万中国人死于与吸烟有关的病如肿瘤、肺气肿、心脏病和中     

Incremental net benefit in randomized clinical trials with quality-adjusted survival

Owing to induced dependent censoring, estimating mean costs and quality-adjusted survival in a cost-effectiveness comparison of two groups using standard life-table methods leads to biased results. In this paper we propose methods for estimating the difference in mean costs and the difference in mean effectiveness, together with their respective variances and covariance in the presence of dependent censoring. We consider the situation in which the measure of effectiveness is either the probability of surviving a duration of interest or mean quality-adjusted survival time over a duration of interest. The methods are illustrated in an example using an incremental net benefit analysis.     

The Yale-Brown-Cornell eating disorder scale: A new scale to assess eating disorder symptomatology

Anorectic and bulimic patients (n = 100) were interviewed using the Yale-Brown-Cornell Eating Disorder Scale (YBC-EDS). All patients reported preoccupations and rituals related to their eating disorder ranging from mild to severe symptomatology, with mean scores in the moderate range. The preoccupations were more severe than the rituals; however, the rituals were still time-consuming, distressing, and interfered with functioning. Both preoccupations and rituals were largely ego syntonic. The YBC-EDS is an easy to administer interview which characterizes and quantifies preoccupations and rituals associated with eating disorders. It is useful both for research and clinical purposes. © 1995 by John Wiley & Sons, Inc.     

A clinical trial of the American Heart Association step one diet for treatment of hypercholesterolemia

BACKGROUND. Although diet therapy is the primary treatment for hypercholesterolemia, a trial to determine the effectiveness of the new American Heart Association Step One Diet (AHA diet) in lowering cholesterol has to our knowledge never been carried out. METHODS. A clinical trial was conducted to assess the plasma lipids response and adherence to the AHA diet in 120 men and women with hypercholesterolemia. All subjects were advised to follow the AHA diet for 18 weeks. RESULTS. After 6 weeks of the AHA diet intervention, there were modest but significant reductions in plasma total cholesterol (-2.6%) and low-density lipoprotein (LDL) cholesterol (-3.5%), but no further significant reductions were observed thereafter. Rather, there was a tendency to return to and even exceed baseline levels of total cholesterol and LDL cholesterol over the subsequent 12 weeks, in spite of the subjects' reported continued adherence to the AHA diet and maintenance of weight loss throughout the entire study period. Nevertheless, 51% of the subjects had experienced improvement (-0.2% to -26.3%) in their plasma LDL cholesterol levels by the end of the study. CONCLUSIONS. A probable reason for the limited response of the diet was low baseline levels in intake of saturated fat and cholesterol by participants. The subjects who were older and had higher levels of plasma LDL cholesterol and total fat intake at baseline experienced better plasma LDL cholesterol response to the AHA diet. Thus, practicing physicians should consider assessing the baseline dietary fat and cholesterol intake of patients with hypercholesterolemia before starting the AHA diet, since patients may already be following a relatively prudent self-selected diet. Additional dietary gains in lipid management might well require a more severe restriction of dietary fats and cholesterol. Long-term efficacy of the AHA diet should also be evaluated clinically with periodic lipid profiles.     

Development and validation of an integrative scale to assess hope

Background  Hope includes the dimensions of time, goals, control, relations and personal characteristics. Existing tools that measure it vary in length and psychometric properties and cover different parts of its overall concept. Objectives  This study aimed to develop an instrument that integrates all relevant aspects of hope is concise, easy to use and shows good psychometric properties. Design  Three pre‐existing instruments (Miller Hope Scale, Herth Hope Index, Snyder Hope Scale) covering complementary and overlapping aspects of hope were administered cross‐sectionally to a general population sample (n = 489). Factor analysis was used for item reduction. Reliability and validity were tested using factor analysis and item correlations between the new scale and quality of life and depression scales. Setting and participants  The study was set in Austria. Participants were sampled from the general population using a quota sampling strategy. Results  The initial 60 items were reduced to a 23‐item scale with four dimensions: ‘trust and confidence’, ‘positive future orientation’, ‘social relations and personal value’ and ‘lack of perspective’. The new scale’s factor structure was highly stable and its internal consistency high (alpha = 0.92 for the overall scale, 0.80–0.85 for its subscales). Hope scores were negatively correlated with depression (r = −0.68) and positively with quality of life (r = 0.57), with the factor analysis and item discriminant validity supporting the new scale’s construct validity. Conclusions  The new scale comprehensively covers the concept of hope is significantly shorter than previous scales and shows satisfactory reliability and validity.     

Patients' willingness to enter clinical trials: measuring the association with perceived benefit and preference for decision participation

Patients who agree and those who refuse clinical trial entry may differ in attitudes towards decision control and the benefits associated with the trial arms. These differences, if they exist, have implications for the process of obtaining informed consent and for the generalization of the results of a clinical trial. This paper describes the development and initial application of methods designed to detect such differences. Developmental work involved creating an inventory of instruments designed to determine patients' attitudes towards participating in treatment decision making, permitting random selection of treatment, and undertaking the risks and benefits associated with the various treatments in a trial. Initial application involved modifying these instruments in terms of an actual chemotherapeutic trial for colonic adenocarcinoma, seeking responses to these measures from 60 non-eligible colorectal cancer patients, then determining whether those who would agree to trial entry differed systematically on these measures from those who indicated that they would refuse such a trial. Twenty-five of the respondents reported that, if faced with the actual decision, they would agree to trial entry: 35 would refuse. Refusers demanded more participation in decision making (Chi-square; P = 0.01) and a greater increment in treatment benefit (t-test; P = 0.0001). Twenty-two of the 35 refusers reported aversion to randomization as their primary reason for trial refusal. Since their particular content can be modified, these measures may be applicable to all clinical trials. They could be used to study the reasons patients accept or refuse trial entry and to determine if agreer-refuser attitude differences undermine the generalizability of a trials results.     

Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy

Vaccination in pregnancy is an effective strategy to prevent serious infections in mothers and their infants. Safety of this strategy is of principal importance to all stakeholders. As the number of studies assessing safety of vaccines in pregnancy increases, the need to ensure consistent collection and reporting of critical data to allow comparisons and data pooling becomes more important. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project aims to improve data collection and create a shared understanding of maternal, fetal and neonatal outcomes in order to progress the global agenda for vaccination in pregnancy.The guidance in this document has been developed to harmonize the data collected in case report forms used for safety monitoring in clinical trials of vaccination in pregnant women. Data to be collected is prioritized to allow applicability in diverse research settings, including low and middle-income countries. Standardized data will enable the research community to have a common base upon which to conduct meta-analyses, strengthening the applicability of outcomes to different settings.