药品价格指数的方法学综述

目的:综述药品价格指数的研究方法,为药品价格指数实证研究提供方法学借鉴。方法:以近年来的国内外研究文献为基础,从指数方法(公式)、药品产品的定义、价格和数量计量单位三个方面进行综述,并对选择不同方法的优缺点以及测量偏倚进行评析。结果:价格指数的结果会随着指数公式所选择的权重、产品的定义以及价格和数量计量单位的不同而不同。在指数公式的选择中是否考虑了新产品上市和老产品退市的产品更新换代问题以及产品的质量变化问题等同样会使得指数结果具有较大差异。结论:药品价格指数的研究方法还有待进一步研究完善,学术界应致力于对价格指数进行更深入的研究,以达到更精确的测量。在实证分析中尽可能采用多种方法进行计算,以更加准确地反映药品价格水平的变化。     

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2012

Background:

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2012. This is an extension of the previously reported study of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, which found that over three-quarters of all these trials were disclosed within 12 months and almost 90% were disclosed by the end of the study.

Methods:

The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2012, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2014.

Outcome measures and results:

The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2014 (end of survey). Of the completed trials associated with 23 new medicines licensed to 17 different companies in 2012, results of 90% (307/340) had been disclosed within 12 months, and results of 92% (312/340) had been disclosed by 31 July 2014.

Conclusions:

The disclosure rate within 12 months of 90% suggests the industry is now achieving disclosure in a timely manner more consistently than before. The overall disclosure rate at study end of 92% indicates that the improvement in transparency amongst company-sponsored trials has been maintained in the trials associated with new medicines approved in 2012.     

Reply to ‘Indication bias or protopathic bias?’

Aim

The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain.

Methods

We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression.

Results

A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion.

Conclusions

The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions.     

Critical appraisal training increases understanding and confidence and enhances the use of evidence in diverse categories of learners

Background

Training in evidence‐based medicine is most commonly offered to physicians, medical students and health‐care decision‐makers.

Setting and participants

We partnered with community organizations to recruit participants and develop trainings for consumers, non‐physician health‐care providers and journalists in California.

Intervention

We conducted half‐day and one‐day workshops in critical appraisal of health evidence. Workshops consisted of didactic presentations, small‐group practice sessions and class discussions.

Outcome measures

We measured knowledge and confidence immediately before and after the workshops and at follow‐up 6 months later. We also asked participants to describe their use of health evidence before the workshops and at follow‐up.

Results

At baseline, 41% of the consumers, 45% of the providers and 57% of the journalists correctly answered questions about health evidence. Scores increased by about 20% (P < 0.05) in all groups at the end of the workshops and remained significantly over baseline at follow‐up. At baseline, 26% of the participants were confident in their understanding of critical appraisal concepts, significantly increasing to 54% after the workshops and sustained (53%) at follow‐up. During discussions, participants’ comments often focused on funding and the potential effects of financial conflicts of interest on study findings. Participants did not use evidence more frequently at follow‐up but said that they applied workshop skills in evaluating research, communicating with others and making decisions about health care.

Conclusion

It is possible to successfully conduct critical appraisal workshops to aid health‐related decision making for groups who have previously not had access to this kind of training.     

The Role of Intuitive Cognition in Radiologic Decision Making

The decision making involved in radiologic interpretation entails distinct cognitive pathways. On one side is analytic reasoning, which represents a deliberate, stepwise process integrating discrete data to formulate an interpretation, in which a range of diagnostic possibilities are directly compared. On the other side is intuition, which represents an automatic, rapid, and holistic form of decision making that generates an interpretation absent the sequential processing of data and direct comparison of possibilities. Nonexpert intuitive cognition often reflects domain-independent heuristics (ie, mental rules of thumb) that are often effective but prone to bias and systematic error. In contrast, expert intuition reflects the domain-specific skills developed among highly experienced practitioners who have gained deep knowledge in a given task domain from extensive practice and feedback. In this article, the authors define intuitive cognition, show evidence for its pervasive use among experts in a variety of fields, and explain its strengths and weaknesses relative to deliberate reasoning. Developing expert intuition requires the opportunity to learn from reliable feedback, and the authors describe various measures that can be used by radiology departments to foster such opportunities. Finally, the authors discuss implications for diagnostic performance and error reduction in clinical radiology.     

How experience shapes memory for faces: An event-related potential study on the own-age bias

Young adults more accurately remember own-age than older faces. We tested whether this own-age bias (OAB) is reduced by increased experience. Young experts (geriatric nurses) and controls performed a recognition experiment with young and old faces. Critically, while control participants demonstrated better memory for young faces, no OAB was observed in the experts. Event-related potentials revealed larger N170 and P2 amplitudes for young than old faces in both groups, suggesting no group differences during early perceptual processing. At test, N250 repetition effects were more anteriorily distributed for own- than other-age faces in control participants, whereas experts showed no corresponding effects. A larger late positive component (LPC) for old than young faces was observed in controls, but not in experts. Larger LPCs may reflect prolonged stimulus processing compromising memory retrieval. In sum, experience with other-age faces does not affect early perceptual processing, but modulates later stages related to memory retrieval.     

Dissecting the Roles of Supervised and Unsupervised Learning in Perceptual Discrimination Judgments

Our ability to compare sensory stimuli is a fundamental cognitive function, which is known to be affected by two biases: choice bias, which reflects a preference for a given response, and contraction bias, which reflects a tendency to perceive stimuli as similar to previous ones. To test whether both reflect supervised processes, we designed feedback protocols aimed to modify them and tested them in human participants. Choice bias was readily modifiable. However, contraction bias was not. To compare these results to those predicted from an optimal supervised process, we studied a noise-matched optimal linear discriminator (Perceptron). In this model, both biases were substantially modified, indicating that the “resilience” of contraction bias to feedback does not maximize performance. These results suggest that perceptual discrimination is a hierarchical, two-stage process. In the first, stimulus statistics are learned and integrated with representations in an unsupervised process that is impenetrable to external feedback. In the second, a binary judgment, learned in a supervised way, is applied to the combined percept.SIGNIFICANCE STATEMENT The seemingly effortless process of inferring physical reality from the sensory input is highly influenced by previous knowledge, leading to perceptual biases. Two common ones are contraction bias (the tendency to perceive stimuli as similar to previous ones) and choice bias (the tendency to prefer a specific response). Combining human psychophysical experiments with computational modeling we show that they reflect two different learning processes. Contraction bias reflects unsupervised learning of stimuli statistics, whereas choice bias results from supervised or reinforcement learning. This dissociation reveals a hierarchical, two-stage process. The first, where stimuli statistics are learned and integrated with representations, is unsupervised. The second, where a binary judgment is applied to the combined percept, is learned in a supervised way.     

Mind’s eye: The impact of spider presence and cognitive therapy on size estimation biases in spider phobia

The present study assessed the circumstances under which size estimation biases in spider phobia occur, and whether such biases are modifiable by treatment. Women with (n = 67) and without (n = 33) spider phobia approached a spider during a behavioral approach test (BAT). They provided size estimates of the spider both during and shortly after the BAT (with the spider in view, or not in view, respectively). Phobic women then received cognitive therapy or a placebo treatment and one week later they underwent a second BAT and provided size estimates of the same spider during and after the BAT. Phobic women reported larger size estimates than non-phobic women after, but not during, the BAT. Size estimates after, but not during, the BAT correlated with self-reported fear but not avoidance. Size estimates after, but not during, the BAT reduced from the first to second BAT in phobic women; an effect evident in both the cognitive therapy and placebo treatment conditions. Changes in size estimates were not associated with treatment-induced reductions in fear or avoidance. These results suggest that estimation biases in spider phobia are likely driven by non-perceptual processes. The clinical utility of size estimation measures is discussed.