使用GRADEro評價證據(jù)質(zhì)量

使用GRADEpro評價證據(jù)質(zhì)量

武漢大學公共衛(wèi)生學院流行病教研室2011年11月GRADE系統(tǒng)簡介GRADE（GradingofRecommendationsAssessment,DevelopmentandEvaluation）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、綜合的標準從證據(jù)到推薦全過程透明明確承認價值觀和意愿就推薦意見的強弱，分別從臨床醫(yī)生、患者、政策制定者角度做了明確實用的詮釋適用于制作系統(tǒng)評價、衛(wèi)生技術評估及指南證據(jù)質(zhì)量（GRADEpro）為達到透明和簡化的目標，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“強推薦”表示他們確信相關的干預措施利大于弊。用“弱推薦”表示干預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

符號字母/數(shù)字證據(jù)質(zhì)量

高質(zhì)量⊕⊕⊕⊕A

中等質(zhì)量⊕⊕⊕○B(yǎng)

低質(zhì)量⊕⊕○○C

極低質(zhì)量⊕○○○D推薦等級

支持使用某療法的強推薦↑↑1

支持使用某療法的弱推薦↑？2

反對使用某療法的強推薦↓↓1

反對使用某療法的弱推薦↓？2關鍵步驟一導入RevMan文件關鍵步驟二判斷結(jié)局的重要程度GRADE系統(tǒng)建議采用9級分級判斷結(jié)局的重要程度:1—3：不重要結(jié)局（NOTIMPORTANT）4—6：重要結(jié)局（IMPORTANT）7—9：關鍵結(jié)局（CRITICAL）關鍵步驟三選擇研究設計類型按研究設計方法劃分隨機試驗質(zhì)量等級最高，為高；觀察性研究（包括隊列研究、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。關鍵步驟四四評價證證據(jù)質(zhì)量基于研究設設計可因5條降級因素素和4條升級因素素上升或下下降級別。。決定證據(jù)質(zhì)質(zhì)量的因素素可能降低證證據(jù)質(zhì)量的的因素研究的局限限性結(jié)果不一致致間接證據(jù)精確度不夠夠發(fā)表偏倚可能增加證證據(jù)質(zhì)量的的因素效應值很大大可能的混雜雜因素會降降低療效劑量-效應關系研究設計與與證據(jù)質(zhì)量量高：為不降降級的隨機機試驗和升升2級的觀察性性研究；中：為降級級的隨機試試驗和升1級的觀察性性研究；低：降2級的隨機試試驗和沒有有升降級的的觀察性研研究；非常低：降降3級的隨機試試驗、降降1級的觀察性性研究、病病例分析析/病例報告。。幫助教程要要點研究的局限限性（Riskofbias）這些局限性性包括（RCTs）隱藏分組缺缺失盲法缺失（（特別是結(jié)結(jié)局指標為為主觀性指指標且對其其的評估極極易受偏倚倚影響時））失訪過多未進行意向向性分析、、觀察到療效就就過早終止止試驗或未報道結(jié)結(jié)果（通常常是未觀察察到療效的的一些研究究）Toratestudylimitations:IfyouthinkanylimitationswerenegligiblechoosenoIfyouthinktherewereseriouslimitationschooseserious?thiswilldowngradethequalityofevidenceforthisoutcomeby1level?Ifyouthinktherewereveryseriouslimitationschooseveryserious?thiswilldowngradethequalityofevidenceforthisoutcomeby2levels?結(jié)果不一致致（Inconsistency）Inconsistencymayarisefromdifferencesin:populations(e.g.drugsmayhavelargerrelativeeffectsinsickerpopulations)interventions(e.g.largereffectswithhigherdrugdoses)outcomes(e.g.diminishingtreatmenteffectwithtime)差異可能源源于人群（（如藥物對對重癥人群群的療效可可能相對顯顯著）、干干預措施（（如較高藥藥物劑量會會使療效更更顯著）或或結(jié)局指標標（如隨時時間推移療療效降低））。I2OnesetofcriteriawouldsaythatanI2oflessthan40%islow30～60%maybemoderate50～90%maybesubstantial75～100%isconsiderableTorateinconsistency:IfyouthinkanyinconsistencywasnegligiblechoosenoIfyouthinktherewasseriousinconsistencychooseserious?thiswilldowngradethequalityofevidenceforthisoutcomeby1level?Ifyouthinktherewasveryseriousinconsistencychooseveryserious?thiswilldowngradethequalityofevidenceforthisoutcomeby2levels?間接證據(jù)（（Indirectness)Therearetwotypesofindirectness:1.Indirectcomparison2.IndirectpopulationinterventioncomparatoroutcomeTorateindirectness:IfyouthinktheevidenceisdirectchoosenoIfyouhaveseriousdoubtsaboutdirectnesschooseserious?thiswilldowngradetheevidenceforthisoutcomeby1level?Ifyouhaveveryseriousdoubtsaboutdirectnesschooseveryserious?thiswilldowngradetheevidenceforthisoutcomeby2levels?精確度不夠夠（Imprecision）當研究納入入的患者和和觀察事件件相對較少少而致可信信區(qū)間較寬寬時，指南南小組將降降低該研究究的證據(jù)質(zhì)質(zhì)量。Athresholdrule-of-thumbvalueTotalnumberofeventsislessthan300（dichotomous）Totalpopulationsizeislessthan400（continuous）Torateimprecision:IfyouthinktheresultswereprecisechoosenoIftherewasseriousimprecisionchooseserious?thiswilldowngradethequalityofevidenceforthisoutcomeby1level?Iftherewasveryseriousimprecisionchooseveryserious?thiswilldowngradethequalityofevidenceforthisoutcomeby2levels?發(fā)表偏倚（（Publicationbias）Publicationbiasariseswheninvestigatorsfailtoreportstudiestheyhaveundertaken(typicallythosethatshownoeffect).Methodstodetectthepossibilityofpublicationbiasinsystematicreviewsexist,althoughauthorsofthereviewsandguidelinepanelsmustoftenguessaboutthelikelihoodofpublicationbias.Aprototypicalsituationthatshouldelicitsuspicionofpublicationbiasoccurswhenpublishedevidenceislimitedtoasmallnumberoftrials,allofwhichareshowingbenefitsofthestudiedintervention.若研研究究者者未未能能發(fā)發(fā)表表研研究究（（通通常常是是陰陰性性結(jié)結(jié)果果的的研研究究））時時，，證證據(jù)據(jù)質(zhì)質(zhì)量量亦亦會會減減弱弱。。典典型型情情況況是是當當公公開開的的證證據(jù)據(jù)僅僅局局限限于于少少數(shù)數(shù)試試驗驗而而這這些些試試驗驗全全部部由由企企業(yè)業(yè)贊贊助助，，此此時時不不得得不不質(zhì)質(zhì)疑疑存存在在發(fā)發(fā)表表偏偏倚倚。。FunnelPlotTorateprobabilityofthepublicationbias:IfyouthinkthereisnoevidenceofpublicationbiaschooseunlikelyIfthereishighprobabilityofpublicationbiaschooselikely?thiswilldowngradethequalityofevidenceforthisoutcomeby1level?Ifthereisveryhighprobabilityofpublicationbiaschooseverylikely?thiswilldowngradethequalityofevidenceforthisoutcomeby2levels?效應應值值很很大大（（Largeeffect）療效效越越顯顯著著，，證證據(jù)據(jù)越越有有力力。。Toratemagnitudeoftheeffect:Iftheeffectwasnotlarge(RRbetween0.5and2.0)choosenoIftheeffectwaslarge(RReither>2.0or<0.5basedonconsistentevidencefromatleast2studies,withnoplausibleconfounders)chooseRR>2or<0.5?thiswillupgradethequalityofevidenceforthisoutcomeby1level?Iftheeffectwasverylarge(RReither>5.0or<0.2basedondirectevidencewithnomajorthreatstovalidity)chooseRR>5or<0.2?thiswillupgradethequalityofevidenceforthisoutcomeby2levels?可能能的的混混雜雜因因素素會會降降低低療療效效（Plausibleconfoundingwouldchangetheeffect）Onoccasion,allplausibleconfoundingfromobservationalstudiesorrandomisedtrialsmaybeworkingtoreducethedemonstratedeffectorincreasetheeffectifnoeffectwasobserved.Forexample,ifonlysickerpatientsreceiveanexperimentalinterventionorexposure,yettheystillfarebetter,itislikelythattheactualinterventionorexposureeffectislargerthanthedatasuggest.Toratetheeffectofallplausibleresidualconfounding:IfthereisnoevidencethattheinfluenceofallplausibleconfoundingwouldreduceademonstratedeffectorsuggestaspuriouseffectwhenresultsshownoeffectchoosenoIfthereisevidencethattheinfluenceofallplausibleconfoundingwouldreduceademonstratedeffectorsuggestaspuriouseffectwhenresultsshownoeffectchooseyes?thiswillupgradethequalityofevidenceforthisoutcomeby1level?劑量量-效應應關關系系（（Dose-responsegradi）Thepresenceofadose-responsegradientmayincreaseourconfidenceinthefindingsofobservationalstudiesandtherebyincreasethequalityofevidence.Toratethepresenceofdose-responsegradient:Ifthereisnoevidenceofdose-responsegradientchoosenoIfthereisevidenceofdose-responsegradientchooseyes?thiswillupgradethequalityofevidenceforthisoutcomeby1level?評級級流流程程關鍵鍵步步驟驟五五完完善善數(shù)數(shù)據(jù)據(jù)關鍵鍵步步驟驟六六生生成成表表格格EvidenceProfilevs.SummaryofFindingsTableGRADEEvidenceprofileParticularlyusefulforguidelinedevelopersPresentsinformationaboutthebodyofevidence(e.g.numberofstudies),thejudgmentsabouttheunderlyingqualityofevidence,keystatistical