Statistics, ethics and probiotica

Ethical issues involved in the design of the ‘PROPATRIA’ probiotica trial are discussed. This randomized clinical trial appeared to be well conducted according to accepted good practices. The finding that the treatment was actually rather harmful, and that despite this, and despite a built‐in interim analysis, the trial was not stopped earlier, led to strong criticism in the media. I argue that ‘accepted good practices’ need to be reconsidered in the light of this experience. First, a much stronger distinction needs to be recognized between the immediate interests of the patients being treated in the trial and the interests of future patients of future doctors elsewhere. Secondly, it is in the interests of future patients that well‐conducted clinical trials are accepted by society. As it is unavoidable that an occasional trial will result in an unpredicted severely negative outcome, ethical screening committees must ensure that those performing a trial can never be accused of putting the interest of ‘science’ above the interest of their own patients when such ‘accidents’ happen. There are two consequences of this. First, the design of a trial should also explicitly lead to minimizing the number of patients who are treated by the researchers with a potentially seriously harmful medicine. Secondly, the disadvantages of triple‐blinding far outweigh the advantages. Although it might at best only have saved a few lives if the PROPATRIA trial been re‐designed with these issues in mind, I argue that the scientific value of the trial would not have been significantly reduced; the damage to medical research, and hence to future patients, would have been substantially less. Closer inspection of the data from the PROPATRIA trial brings a new and quite unexpected failing to light. The decision for stopping the trial early was accidentally based on the one‐sided test looking in the wrong direction, partly through the inadequacy of the output of the statistical package, SPSS and partly through lack of statistical expertise on the part of the users. If the envisaged one‐sided stopping rule had been used correctly, the trial would in fact have been terminated at the time of the interim analysis ‘for futility’; it was at this moment highly unlikely that a significant end‐result in favour of probiotica was going to be attained. The decision to continue the trial was a result of looking at the test statistic ‘in the wrong direction’. In effect, the trial was continued because there was still a good chance to show that probiotica is actually very harmful. I recommend that data‐monitoring committees should always be advised by a professional statistician, who is not blinded to the treatment allocation.     

计算机病毒注入方式及临床症状

本文简要探讨了病毒的注入方式及临床症状,旨在提高用户对病毒的诊断能力和防范能力。     

ICU临床带教心得

目的:探讨ICU护生带教方法与带教心得。方法:采用"总带教与带教老师相结合"的教学模式对护生进行带教。结果:通过教学满意度反馈表调查显示对ICU教学满意度达到95%以上。     

诊所式法律教育模式本土化过程中的困境与解决对策分析

诊所式法律教育作为一种新兴的法律教育模式,起源于美国,它借鉴了医学院学生在医疗诊所临床实习的模式,倡导在实践中学习法律和律师的执业技能。它于2000年被引入中国,至今已被国内多所高校开设及实践。作为一种舶来品,法律诊所教育在中国化的过程冲难免困境重重,诸如案源不足、师资短缺、经费投入欠缺等等。在实践过程中,我们必须深入探析导致这些困境的原因,并将这一模式与传统法学教育模式有机结合起来,形成理论教育和职业教育相统一的完善的法学教育体系。     

Composite outcome measurement in clinical research: the triumph of illusion over reality?

Abstract

Composite measures that combine different types of indicators are widely used in medical research; to evaluate health systems, as outcomes in clinical trials and patient-reported outcome measurement. The potential advantages of such indices are clear. They are used to summarise complex data and to overcome the problem of evaluating new interventions when the most important outcome is rare or likely to occur far in the future. However, many scientists question the value of composite measures, primarily due to inadequate development methodology, lack of transparency or the likelihood of producing misleading results. It is argued that the real problems with composite measurement are related to their failure to take account of measurement theory and the absence of coherent theoretical models that justify the addition of the individual indicators that are combined into the composite index. All outcome measures must be unidimensional if they are to provide meaningful data. They should also have dimensional homogeneity. Ideally, a specification equation should be developed that can predict accurately how organisations or individuals will score on an index, based on their scores on the individual indicators that make up the measure. The article concludes that composite measures should not be used as they fail to apply measurement theory and, consequently, produce invalid and misleading scores.     

冬凌草的化学和药理作用研究

介绍冬凌草的化学成分、药理作用、抗肿瘤机制、临床应用等方面的研究成果。通过文献系统地介绍了国内外目前关于冬凌草的研究。研究发现冬凌草中含有萜类、生物碱、甾体、黄酮、挥发油、氨基酸、有机酸、单糖等化学成分,并具有抗肿瘤、抗菌消炎、免疫增强、抗氧化、抗突变、降压等药理作用,而其抗肿瘤机制包括阻遏细胞周期、下调端粒酶活性、抑制细胞膜钠泵活性、诱导肿瘤细胞凋亡、逆转多药耐药等,在临床上对食管癌、贲门癌、肝癌、乳腺癌等多种癌症均具有疗效。表明冬凌草具有广泛的药理作用和良好的抗癌活性。     

Using Clinical Trials to Benchmark Effects Produced in Clinical Practice

This paper proposes an intuitive yet statistical advancement of the benchmarking method (e.g., Weersing and Weisz, 2002, Journal of Consulting and Clinical Psychology 70: 299–310) that could facilitate the assessment of pre-post treatment effectiveness of psychotherapy and other interventions delivered in clinical settings against efficacy observed in clinical trials. Primary development was in the use of the “good-enough principle” (Serlin and Lapsley, 1985 American Psychologist 40: 73–13, 1993, In: G. Keren & C. Lewis (eds.), A handbook for Data Analysis in Behavioral Sciences: Methodological Issues. Hillsdale, NJ: Lawrence Erlbaum Associated, pp. 199–228), which allowed for setting a clinically relevant margin between the benchmarks and the effect sizes observed in clinical settings so as to avoid attaining statistical significance with clinically trivial differences. Examples are given using clinical trials benchmarks of adult depression treatment, followed by instructions and limitations for its use.     

A Bayesian adaptive design in clinical trials for continuous responses

Adaptive design is a popular concept in several clinical trials, especially in phase III trials. The idea is to allocate treatments to the entering patients according to the state of art of the present data, i.e., to allocate a larger number of patients to the better treatment. The present paper provides a Bayesian formulation of an adaptive allocation design for clinical trials that considers all the continuous responses along with the associated covariates for future allocation. Some Bayesian inferences followed by the allocation are discussed along with a Bayesian prediction for future allocation. The convergence of the allocation probabilities is also discussed along with some related logistics of the design.     

Rules of engagement

Collaborative research between universities and pharmaceutical companies is a form of public?–?private sector partnership that raises important issues of governance and research integrity. The article analyses this from a stakeholder perspective with particular reference to clinical trial collaborations. Constraints and pressures on universities involved in collaborative projects are identified, together with implications for research integrity. A stakeholder systems model is offered as a means of identifying and reconciling disparate stakeholder perspectives, and its organizational justice dimensions enable evaluation of perceptions of fairness in system operation. The article contends incorporation of stakeholder views on system rationale, process and evaluation can enhance effectiveness, social responsibility and stakeholder commitment.     

虚拟现实技术在未来临床实践教学过程中的辅助应用

目前,医学院校临床实践教学存在诸多问题,已经影响了学生的教学质量,为了提高医学院校临床实践教学的质量,提高学生的临床思维及技能,应该改变传统临床实践教学模式,尝试在校园网平台下建设虚拟临床实践教学场景。文章着重介绍了影响医学院校大学生实践能力培养的因素以及虚拟环境在临床实践教学过程中的现实意义以及应用价值。