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从一篇拉伸的临床研究,带你6步细说系统回顾类文献的解读过程。

 林涔涔 2018-04-24


之前的文章介绍了如何查阅文献,这能让你找到更多和更精确的资料来解决自己在临床上遇到的问题。那么这篇文章,将告诉你如何甄别文献的质量和可信度。


医学文献的类型林林总总,但归纳起来就这么几个(图1)

  • Meta-Analysis 荟萃分析

  • Systematic Review系统性回顾

  • Practice Guideline临床实践指南

  • Randomized Controlled Trial随机对照研究

  • Cohort Study队列研究

  • Case Control Study病例对照研究

  • Case Report病例报告


简单的说,越在金字塔顶层,可信度越高,其结果越可在临床复制。今天我们就介绍处于金字塔塔尖的荟萃分析。

图1 不同的文献类型



Meta-Analysis Definition 荟萃分析定义

A subset of systematic reviews; a method for systematically combining pertinent qualitative and quantitative study data from several selected studies to develop a single conclusion that has greater statistical power. This conclusion is statistically stronger than the analysis of any single study, due to increased numbers of subjects, greater diversity among subjects, or accumulated effects and results.

荟萃分析为系统性回顾的一种。从入选的临床研究中,将具有一定相关性的定性和定量研究进行系统性的汇总,并形成一个具统计学效力的单一结论。因为荟萃分析大大增加受试者数量,使得受试者更具多样性以及累积更多结果和疗效,所以,其得出的结论在统计学上的效力强于任何一个单一性研究。


对于系统性回顾,因为已经处于金字塔的塔尖,所以我们的问题就非常直接,那就是:文献中得出的结论是否有效?能否指导临床实践?


让我们一步一步来解释。我们以Stretch for the treatment and prevention of contractures(Review)拉伸对肌肉挛缩的治疗和预防(系统性回顾)为例,怎么得出你自己的结论。为加强理解,建议去物理治疗师之家下载后,再阅读此文。

以该文献为例,原文去“微社区”物理治疗师之家索取



首先,就像你查文献时问自己的PICO问题一样,对该文献也以PICO模式归纳一下作者的问题,看作者的思路是否清晰。

第一步

What question (PICO) did the systematic review address?

该系统性回顾主要针对什么PICO问题?

What is best?

最佳标准是什么?

Where do I find the information?

在哪里可以找到符合最佳标准的信息?

The main question being addressed should be clearly stated. The   exposure, such as a therapy or diagnostic test, and the outcome(s) of   interest will often be expressed in terms of a simple relationship.

应该清晰阐述主要问题。各个要素(例如治疗,诊断和结果等)之间的关系描述简单直接。

The Title, Abstract or   final paragraph of the   Introduction should clearly state the   question. If you still cannot ascertain what the focused question is after   reading these sections, search for another paper!

标题摘要或者简介最后的图片中应该清晰的阐明问题。如果你读完这些内容,仍不清楚作者针对什么问题,那么请查找其他文献。

This   paper: Yes ✔ No        Unclear   

Comment:   该文献作者针对的临床问题非常具体清晰。(图2)

图2 该文献作者的PICO非常清晰


P(Population or Problem): people with, or at risk of developing, contractures

I(Intervention): Stretch

C(comparator): no stretch

O(Outcome): joint mobility, quality of life, pain, activity limitations, participation restrictions, spasticity and adverse events



第二步

Is it   unlikely that important, relevant studies were missed?

对重要的相关性研究,作者是否有遗漏?

What   is best?

最佳标准是什么?

Where   do I find the information?

我在哪里可以找到符合标准的信息?

The starting point for comprehensive   search for all relevant studies is the major bibliographic databases (e.g.,   Medline, Cochrane, EMBASE, etc) but should also include a search of reference   lists from relevant studies, and contact with experts, particularly to   inquire about unpublished studies. The search should not be limited to   English language only.  The search   strategy should include both MESH terms and text words.

对相关性研究的搜索应开始于主要的各书目数据库(例如,Medline, Cochrane, EMBASE等),但也应该搜索这些相关性研究的参考文献,同时应该联系原作者,特别是要询问一些尚未发表的相关文献情况。作者不应该仅搜索英文文献。作者的搜索策略不仅包含MESH术语,也包含普通词条。

The Methods section should describe the search strategy,   including the terms used, in some detail. The Results section   will outline the number of titles and abstracts reviewed, the number of   full-text studies retrieved, and the number of studies excluded together with   the reasons for exclusion. This information may be presented in a figure or   flow chart. 

方法中,作者应该描述搜索策略,包括对使用的术语有些较为详细的说明。在结果中,作者应该列出阅读过的文献题目和摘要的数目,以及被排除在外的文献数目和排除的原因。这些信息应该用一张图表或流程图展示。

This   paper: Yes ✔      No        Unclear   

Comment:对搜索的数据库及文献的来源做详细的阐述(图3)

图3 数据来源毫不含糊,清楚说明


第三步

Were the criteria used to select   articles for inclusion appropriate?

用于文献选择的入选标准合适吗?

What   is best?

最佳标准是什么?

Where   do I find the information?

我在哪里可以找到符合标准的信息?

The inclusion or exclusion of studies in a systematic review should be   clearly defined a priori. The eligibility criteria used should specify the   patients, interventions or exposures and outcomes of interest.  In many cases the type of study design will   also be a key component of the eligibility criteria.

系统性回顾中文献入选和排除标准的定义应该清晰明确。符合要求的标准应该包括具体的患者,具体的干预措施和具体的结果。在许多情况下,何种类型的研究设计,也是判断文献入选或排除标准是否符合要求的关键因素。

The Methods section should describe in detail the inclusion and   exclusion criteria. Normally, this will include the study design.

方法中,应该对文献入选和排除标准有清晰的描述。通常,也会包含研究设计的内容。

This   paper: Yes ✔      No        Unclear   

Comment:   该文献在方法中对入选标准的描述非常清晰。(图4)

图4 入选标准的描述清晰,明确


第四步

Were the included studies   sufficiently valid for the type of question asked?

对于作者提出的问题,入选的研究是否足够有效?

What   is best?

最佳标准是什么?

Where   do I find the information?

我在哪里可以找到符合标准的信息?

The article should describe how   the quality of each study was assessed using predetermined quality criteria   appropriate to the type of clinical question (e.g., randomization, blinding   and completeness of follow-up) 

作者应该说明如何通过一些预先设定的标准(例如随机,双盲和随访的完整性等)来判断所采用文献的质量。


The Methods section should describe   the assessment of quality and the criteria used. The Results   section should provide information on the quality of the   individual studies. 

方法中应该描述所引用文献质量的评估标准。在结果中应该提供关于单个研究的文献质量的具体信息。

This   paper: Yes ✔     No        Unclear   

Comment:详细说明每个研究的入选标准(图5)

图5 详细列出入选的每个研究的具体信息


第五步

Were the results similar from study   to study?

各研究之间的结果是否相似?

What   is best?

最佳标准是什么?

Where   do I find the information?

我在哪里可以找到符合标准的信息?

Ideally, the results of the   different studies should be similar or homogeneous. If heterogeneity exists   the authors may estimate whether the differences are significant (chi-square   test). Possible reasons for the heterogeneity should be explored.

最理想的是,不同研究之间的结果应该是相似或同质的。如果有异质性存在,作者应该评估这种异质性是否具有显著性(用卡方检验)。应该说明造成这些差异的原因。

The Results section   should state whether the results are heterogeneous and discuss possible   reasons. The forest plot should show the results of the chi-square test for heterogeneity and if discuss reasons for   heterogeneity, if present.

结果中应该陈述结果是否存在异质性,并讨论异质性存在的原因。森林图应显示对异质性进行卡方检验的结果,并讨论异质性的原因。

This   paper: Yes ✔    No        Unclear   

Comment:对每个亚组的森林图分析,详细解释各研究之间存在的差异(图6)

图6 使用经典森林图呈现研究结果


第六步

What were the results?研究结果是什么?

How are   the results presented?研究结果如何呈现?

A systematic review provides a   summary of the data from the results of a number of individual studies.  If the results of the individual studies   are similar, a statistical method (called meta-analysis) is used to combine   the results from the individual studies and an overall summary estimate is   calculated. The meta-analysis gives weighted values to each of the individual   studies according to their size. The individual results of the studies need   to be expressed in a standard way, such as relative risk, odds ratio or mean   difference between the groups. Results are traditionally displayed in a   figure, like the one below, called a forest plot.

系统性回顾提供一定数量单个研究的数据汇总。如果这些研究的结果相似,那么可以使用荟萃分析(一种统计方法)综合所有单个研究的结果并给出一个总体的概括性评估。荟萃分析会根据单个研究的样本数量给与不同的权重。单个研究的结果应该用标准化的方式进行描述,例如在各组之间使用相对风险,比值比或者平均标准差等专业标准。结果通常用图表的形式展现,例如下面这张森林图。

                                                                                  

The forest   plot depicted above represents a meta-analysis of 5 trials that assessed the   effects of a hypothetical treatment on mortality. Individual studies are   represented by a black square and a horizontal line, which corresponds to the   point estimate and 95% confidence interval of the odds ratio. The size of the   black square reflects the weight of the study in the meta-analysis. The solid   vertical line corresponds to ‘no effect’ of treatment - an odds ratio of   1.0.  When the confidence interval   includes 1 it indicates that the result is not significant at conventional   levels (P>0.05).

这张森林图描述了5个评估某假设性治疗对死亡率影响的荟萃分析结果。单个研究用黑色方块表示。平行线(横线)代表估值点以及比值比的95%可信区间。黑色方块的大小反映在单个研究在该荟萃分析中的权重。实心的垂直线代表治疗效果为零,也就是比值比为1。当可信区间包括1时,这表明跟传统方法相比,结果并不具有显著性(p值大于0.05)。因此,黑色方块越偏向左侧,则越有利于该假设性治疗。黑色方块越偏向右侧,则越不利于该假设性治疗。

The diamond   at the bottom represents the combined or pooled odds ratio of all 5 trials   with its 95% confidence interval. In this case, it shows that the treatment   reduces mortality by 34% (OR 0.66 95% CI 0.56 to 0.78). Notice that the   diamond does not overlap the ‘no effect’ line (the confidence interval   doesn’t include 1) so we can be assured that the pooled OR is statistically   significant. The test for overall effect also indicates statistical   significance (p<>

图表下方的钻石形代表所有5个研究95%可信区间的比值比汇总结果。在这个例子中,表明该治疗方法能够降低34%的死亡率(比值比为 0.66, 95%的可信区间在0.56和0.78之间)。注意,钻石形并不和“效果为零”的垂直线相重叠(其可信区间并不包含1)。所以我们可以确定总体的比值比(OR)达到统计学上的差异。对整体治疗效果的检验也达到统计学差异(p值小于0.0001)

Exploring heterogeneity对异质性的说明

Heterogeneity   can be assessed using the “eyeball” test or more formally with statistical   tests, such as the Cochran Q test. With the “eyeball” test one looks for   overlap of the confidence intervals of the trials with the summary estimate.   In the example above note that the dotted line running vertically through the   combined odds ratio crosses the horizontal lines of all the individual   studies indicating that the studies are homogenous. Heterogeneity can also be   assessed using the Cochran chi-square (Cochran Q). If Cochran Q is   statistically significant there is definite heterogeneity. If Cochran Q is   not statistically significant but the ratio of Cochran Q and the degrees of   freedom (Q/df) is > 1 there is possible heterogeneity. If Cochran Q is not   statistically significant and Q/df is < 1="" then="" heterogeneity="" is="" very=""  ="" unlikely.="" in="" the="" example="" above="" q/df="" is=""><1 (0.92/4="0.23)" and="" the="" p-value=""  ="" is="" not="" significant="" (0.92)="" indicating="" no="">

异质性可以用“eyeball”检验以及其他正式的统计学检验,例如Cochran Q检验来评估。用“eyeball”检验时,我们试图寻找已具概括性评估的各研究的可信区间的重叠情况。在上述的例子中,垂直的虚线穿过总体比值比并跨过各个研究的平行线,这表明这些研究之间是具有同质性。异质性也可以通过Cochran Q检验来评估。如果Cochran Q检验的结果具有统计学差异,那么各研究之间具有异质性。如果Cochran Q检验没有统计学差异但是Cochran Q和自由度之比大于1,表明之间可能存在异质性。如果Cochran Q检验没有统计学差异但是Cochran Q和自由度之比小于1,表明之间存在异质性的可能性很小。在上面的这个例子中Q/df 的比值 <1 (0.92/4="">

Note: The level of   significance for Cochran Q is often set at 0.1 due to the low power of the   test to detect heterogeneity.

注意:因为Cochran Q检验对于检查异质性的能力偏弱,故该检验的差异水平经常设为0.1。


再回到我们的例子,结论已经非常明显(图7)。正如我们上述分析的那样,这篇系统性回顾科学而又严谨,所以在最后的结论中使用了“sufficiently robust”这样的字眼。他是有强大的底气的。


图7 结论的得出高度可信


通过这一步步的分析,最后老编认为像这种文章得出的结论是完全可以指导你的临床实践的。


本文的案例,文献Stretch for the treatment and prevention of contractures(Review)拉伸对肌肉挛缩的治疗和预防(系统性回顾),请点击“微社区”进入物理治疗师之家索取。


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