1、使用GRADEpro評價證據(jù)質(zhì)量,2011年11月,GRADE系統(tǒng)簡介,GRADE（Grading of Recommendations Assessment, Development and Evaluation）是由2000年建立的GRADE工作組提出的一套評級系統(tǒng)。 GRADE系統(tǒng)使用易于理解的方式評價證據(jù)質(zhì)量和推薦等級，目前已被世界衛(wèi)生組織（WHO）、Cochrane協(xié)作網(wǎng)等一批著名機(jī)構(gòu)所采用。,GRADE系統(tǒng)較之其他系統(tǒng)的優(yōu)勢,由一個具有廣泛代表性的國際指南制定小組制定 明確界定了證據(jù)質(zhì)量和推薦強(qiáng)度 清楚評價了不同治療方案的重要結(jié)局 對不同級別證據(jù)的升級與降級有明確、綜合的標(biāo)準(zhǔn) 從證

2、據(jù)到推薦全過程透明 明確承認(rèn)價值觀和意愿 就推薦意見的強(qiáng)弱，分別從臨床醫(yī)生、患者、政策制定者角度做了明確實(shí)用的詮釋 適用于制作系統(tǒng)評價、衛(wèi)生技術(shù)評估及指南,證據(jù)質(zhì)量（GRADEpro）,為達(dá)到透明和簡化的目標(biāo)， GRADE系統(tǒng)將證據(jù)質(zhì)量分為高、 中、 低、 極低 4 級。一些使用GRADE系統(tǒng)的組織甚至把低和極低歸為一級。,推薦等級,使用GRADE系統(tǒng)時，指南小組 用“強(qiáng)推薦”表示他們確信相關(guān)的干預(yù)措施利大于弊。 用“弱推薦”表示干預(yù)措施有可能利大于弊，但他們把握不大。,GRADE中的證據(jù)質(zhì)量和推薦等級,關(guān)鍵步驟一 導(dǎo)入RevMan文件,關(guān)鍵步驟二 判斷結(jié)局的重要程度,GRADE 系統(tǒng)建議采用

3、 9 級分級判斷結(jié)局的重要程度: 13：不重要結(jié)局（NOT IMPORTANT） 46：重要結(jié)局（IMPORTANT） 79：關(guān)鍵結(jié)局（CRITICAL）,關(guān)鍵步驟三 選擇研究設(shè)計(jì)類型,按研究設(shè)計(jì)方法劃分 隨機(jī)試驗(yàn)質(zhì)量等級最高，為高； 觀察性研究 （包括隊(duì)列研究、病例 - 對照研究、病例 - 歷史對照研究）質(zhì)量等級低，為低； 病例報告、病例分析等其他研究質(zhì)量等級非常低，為極低。,關(guān)鍵步驟四 評價證據(jù)質(zhì)量,基于研究設(shè)計(jì)可因5 條降級因素和 4 條升級因素上升或下降級別。,決定證據(jù)質(zhì)量的因素,可能降低證據(jù)質(zhì)量的因素 研究的局限性 結(jié)果不一致 間接證據(jù) 精確度不夠 發(fā)表偏倚 可能增加證據(jù)質(zhì)量的因素

4、效應(yīng)值很大 可能的混雜因素會降低療效 劑量-效應(yīng)關(guān)系,研究設(shè)計(jì)與證據(jù)質(zhì)量,高：為不降級的隨機(jī)試驗(yàn)和升 2 級的觀察性研究； 中：為降級的隨機(jī)試驗(yàn)和升 1 級的觀察性研究； 低：降 2 級的隨機(jī)試驗(yàn)和沒有升降級的觀察性研究； 非常低：降3級的隨機(jī)試驗(yàn)、 降1級的觀察性研究、 病例分析/病例報告。,幫助教程要點(diǎn),研究的局限性（Risk of bias）,這些局限性包括（RCTs） 隱藏分組缺失 盲法缺失（特別是結(jié)局指標(biāo)為主觀性指標(biāo)且對其的評估極易受偏倚影響時） 失訪過多 未進(jìn)行意向性分析、觀 察到療效就過早終止試驗(yàn) 或未報道結(jié)果（通常是未觀察到療效的一些研究）,To rate study limi

5、tations:,If you think any limitations were negligible choose no If you think there were serious limitations choose serious this will downgrade the quality of evidence for this outcome by 1 level If you think there were very serious limitations choose very serious this will downgrade the quality of e

6、vidence for this outcome by 2 levels,結(jié)果不一致（ Inconsistency）,Inconsistency may arise from differences in: populations (e.g. drugs may have larger relative effects in sicker populations) interventions (e.g. larger effects with higher drug doses) outcomes (e.g. diminishing treatment effect with time) 差異

7、可能源于人群（如藥物對重癥人群的療效可能相對顯著）、干預(yù)措施（如較高藥物劑量會使療效更顯著）或結(jié)局指標(biāo)（如隨時間推移療效降低）。,I2,One set of criteria would say that an I2 of less than 40% is low 3060% may be moderate 5090% may be substantial 75100% is considerable,To rate inconsistency:,If you think any inconsistency was negligible choose no If you think there

8、 was serious inconsistency choose serious this will downgrade the quality of evidence for this outcome by 1 level If you think there was very serious inconsistency choose very serious this will downgrade the quality of evidence for this outcome by 2 levels,間接證據(jù)（ Indirectness),There are two types of

9、indirectness: 1. Indirect comparison 2. Indirect population intervention comparator outcome,To rate indirectness:,If you think the evidence is direct choose no If you have serious doubts about directness choose serious this will downgrade the evidence for this outcome by 1 level If you have very ser

10、ious doubts about directness choose very serious this will downgrade the evidence for this outcome by 2 levels,精確度不夠（Imprecision ）,當(dāng)研究納入的患者和觀察事件相對較少而致可信區(qū)間較寬時，指南小組將降低該研究的證據(jù)質(zhì)量。 A threshold rule-of-thumb value Total number of events is less than 300（dichotomous） Total population size is less than 400（c

11、ontinuous）,To rate imprecision:,If you think the results were precise choose no If there was serious imprecision choose serious this will downgrade the quality of evidence for this outcome by 1 level If there was very serious imprecision choose very serious this will downgrade the quality of evidenc

12、e for this outcome by 2 levels,發(fā)表偏倚（ Publication bias ）,Publication bias arises when investigators fail to report studies they have undertaken (typically those that show no effect). Methods to detect the possibility of publication bias in systematic reviews exist, although authors of the reviews and

13、 guideline panels must often guess about the likelihood of publication bias. A prototypical situation that should elicit suspicion of publication bias occurs when published evidence is limited to a small number of trials, all of which are showing benefits of the studied intervention. 若研究者未能發(fā)表研究（通常是陰

14、性結(jié)果的研究）時，證據(jù)質(zhì)量亦會減弱。典型情況是當(dāng)公開的證據(jù)僅局限于少數(shù)試驗(yàn)而這些試驗(yàn)全部由企業(yè)贊助，此時不得不質(zhì)疑存在發(fā)表偏倚。,Funnel Plot,To rate probability of the publication bias:,If you think there is no evidence of publication bias choose unlikely If there is high probability of publication bias choose likely this will downgrade the quality of evidence f

15、or this outcome by 1 level If there is very high probability of publication bias choose very likely this will downgrade the quality of evidence for this outcome by 2 levels,效應(yīng)值很大（Large effect）,療效越顯著，證據(jù)越有力。,To rate magnitude of the effect:,If the effect was not large (RR between 0.5 and 2.0) choose n

16、o If the effect was large (RR either 2.0 or 2 or 5.0 or 5 or 0.2this will upgrade the quality of evidence for this outcome by 2 levels,可能的混雜因素會降低療效（Plausible confounding would change the effect）,On occasion, all plausible confounding from observational studies or randomised trials may be working to

17、reduce the demonstrated effect or increase the effect if no effect was observed. For example, if only sicker patients receive an experimental intervention or exposure, yet they still fare better, it is likely that the actual intervention or exposure effect is larger than the data suggest.,To rate th

18、e effect of all plausible residual confounding:,If there is no evidence that the influence of all plausible confounding would reduce a demonstrated effect or suggest a spurious effect when results show no effect choose no If there is evidence that the influence of all plausible confounding would red

19、uce a demonstrated effect or suggest a spurious effect when results show no effect choose yesthis will upgrade the quality of evidence for this outcome by 1 level,劑量-效應(yīng)關(guān)系（Dose-response gradi）,The presence of a dose-response gradient may increase our confidence in the findings of observational studie

20、s and thereby increase the quality of evidence.,To rate the presence of dose-response gradient:,If there is no evidence of dose-response gradient choose no If there is evidence of dose-response gradient choose yesthis will upgrade the quality of evidence for this outcome by 1 level,評級流程,關(guān)鍵步驟五 完善數(shù)據(jù),關(guān)鍵步驟六 生成表格,Evidence Profile vs. Summary of Findings Table,GRADE Evidence profile Particularly useful for guideline developers Presents information about the body of evidence (e.g. number of studies), the judgments