Evidence-basedEtiology/Harm

病因研究與循證醫(yī)學(xué)實踐Evidence-basedEtiology/Harm學(xué)習(xí)目標(biāo)掌握評價病因性研究真實性原則(Validity)掌握評價病因性研究重要性原則(Importance)學(xué)會應(yīng)用病因性研究證據(jù)的結(jié)果，解決臨床問題(Applying)學(xué)習(xí)目標(biāo)掌握評價病因性研究真實性原則(Validity)病因性研究基本知識病因性研究基本概念與病因相關(guān)的臨床問題病因性研究的主要方法病因/不良反應(yīng)研究證據(jù)的分級病因性研究常用統(tǒng)計學(xué)指標(biāo)病因性研究基本知識病因性研究基本概念病因性研究基本概念（1）病因是指引起人體發(fā)生疾病的原因。病因?qū)W是指研究疾病病因的科學(xué)。病因：致病因素（直接、間接、危險因素）研究內(nèi)容：用流行病學(xué)方法研究并驗證危險因素是否與疾病發(fā)生有因果關(guān)系，且評估因果聯(lián)系的強弱。例“吸煙與肺癌關(guān)系”病因性研究基本概念（1）病因是指引起人體發(fā)生疾病的原因。病因病因性研究基本概念（2）不良反應(yīng)的研究實質(zhì)上也是病因?qū)W研究

“因”：造成不良反應(yīng)的各種因素，如各種治療措施（藥物，手術(shù)）醫(yī)療過程中臨床醫(yī)師經(jīng)常需要考慮某種危險因素或治療措施是否對患者有害。利是否大于弊？用他人的研究結(jié)果來回答提出的問題

真實性重要性實用性病因性研究基本概念（2）不良反應(yīng)的研究實質(zhì)上也是病因?qū)W研究與病因相關(guān)的臨床問題該疾病是什么原因造成的？該藥物或治療措施會導(dǎo)致什么不良反應(yīng)嗎？是否需要停藥？DoesexposuretoaluminumcauseAlzheimer’sdementia?Dostatinscausecancer?與病因相關(guān)的臨床問題該疾病是什么原因造成的？病因性研究的主要方法病因性研究的主要方法病因性研究常用統(tǒng)計學(xué)指標(biāo)因果相關(guān)性強度的指標(biāo)RR(前瞻性)RCT,cohortstudyOR(回顧性）case-controlstudyNNH(numberneededtoharm)clinicalimportance暴露多少研究對象可導(dǎo)致1例發(fā)?。犃醒芯浚┌l(fā)生1例不良反應(yīng)所需治療的病例數(shù)（臨床研究）病因性研究常用統(tǒng)計學(xué)指標(biāo)因果相關(guān)性強度的指標(biāo)因果相關(guān)性強度的指標(biāo)當(dāng)所研究疾病的發(fā)病率較低時，OR近似于RR，故在回顧性研究中可用OR估計RR,其解釋與RR同，易于統(tǒng)計分析RR或OR愈高，則因果關(guān)系強度愈強RR或OR有多大才有意義，無一定的標(biāo)準(zhǔn)1.2-1.5:弱聯(lián)系1.6-2.9:中等聯(lián)系

>3.0:強聯(lián)系因果相關(guān)性強度的指標(biāo)當(dāng)所研究疾病的發(fā)病率較低時，OR近似于R可信區(qū)間ConfidenceInterval因果關(guān)系的強度外，評價精確度按一定的概率去估計總體參數(shù)所在的范圍95％的可信區(qū)間循證醫(yī)學(xué)－估計總體參數(shù)－假設(shè)檢驗：RR可信區(qū)間ConfidenceInterval因果關(guān)系的強度有關(guān)指標(biāo)的計算1.OddsRatio

2.RelativeRisk3.RiskReduction/Increase

4.NumberNeededtoTreat/Harm

有關(guān)指標(biāo)的計算1.OddsRatio2.Relati循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件證據(jù)的強度證據(jù)的強度TheConfusionMatrix+veEvent-veEventTotalExperimentABA+ＢControlCDC+DAlsoknownasthe2x2tableTheConfusionMatrix+veEvent-EventRateEER=A/(A+B)

試驗組事件發(fā)生率CER=C/(C+D)

對照組事件發(fā)生率+veEvent-veEventTotalExperimentABA+ＢControlCDC+DEventRateEER=A/(A+B)+veERRandORRR=EER/CER

相對危險度OR=AD/BC

比值比+veEvent-veEventTotalExperimentABA+ＢControlCDC+DRRandORRR=EER/CER+veEveRelativeRiskReductionRRR=(CER-EER)/CER

=1–RR

相對危險度減少率+veEvent-veEventTotalExperimentABA+ＢControlCDC+DRelativeRiskReductionRRR=(C(Absolute)RiskReductionARR=CER-EER絕對危險度減少率+veEvent-veEventTotalExperimentABA+ＢControlCDC+D(Absolute)RiskReductionARR=NumberNeededtoTreatNNT =1/ARR得到1例有利結(jié)果需要防治的病例數(shù)+veEvent-veEventTotalExperimentABA+ＢControlCDC+DNumberNeededtoTreatNNT =1舉例：

ActivatedProteinCforSevereSepsisBleedNobleedTotalAPC30820850Control17823840APC=ActivatedProteinCEfficacyandsafetyofrecombinanthumanactivatedproteinCforseveresepsis.NEnglJMed.2001Mar8;344(10):699-709舉例：

ActivatedProteinCforSeEventRatesandOddsEER =A/(A+B) =30/850=0.035CER =C/(C+D) =17/840=0.020EEO=A/B =30/820=0.037CEO=C/D =17/823=0.021+veEvent-veEventTotalExperimentABA+ＢControlCDC+DBleedNobleedTotalAPC30820850Control17823840OR =EEO/CEO =0.037/0.021=1.77RR =EER/CER =0.035/0.020=1.744RRI =(EER–CER)/CER =0.015/0.020=0.744 =74%ARI =EER–CER =0.035–0.020=0.015

NNH =1/ARI =66EventRatesandOddsEER =A/Risk-BenefitRatioNNT =1/ARR=1/0.06 =16(治療16個獲益1個：存活)

反映有利結(jié)果（越小越好）NNH =1/ARI=1/0.015 =66(治療66個損害1個：嚴(yán)重出血)

反映不良反應(yīng)（越大越好）Risk-BenefitRatio =NNT/NNH =16/66 =1/4DeadNotdeadTotalAPC210640850Control259581840BleedNobleedTotalAPC30820850Control17823840Risk-BenefitRatioNNT =1/A怎樣解決臨床問題？

Howtosolveaclinicalproblem?怎樣解決臨床問題？

Howtosolveaclini臨床病案（ClinicalScenario）84歲的男性，近期記憶力明顯下降.高血壓病，高膽固醇血癥。右眼白內(nèi)障術(shù)后2天，出現(xiàn)易激、譫妄和性格改變。無感染，貧血及代謝異常的臨床證據(jù)。心理衛(wèi)生中心會診：抗精神病藥物氟哌啶醇,haloperidol,奮乃靜perphenazine,奧氮平,olanzapine臨床病案（ClinicalScenario）84歲的男性，臨床問題（InitialQuestion）老年患者中，用傳統(tǒng)性抗精神病藥物（如氟哌啶醇,haloperidol,奮乃靜perphenazine,）是否會增加死亡風(fēng)險性？非典型性抗精神病藥物(如奧氮平,olanzapine,）是否對老年人更安全？臨床問題（InitialQuestion）老年患者中，用傳第一步提出問題(AskClinicalQuestions)Initialquestion:Framingtheinitialquestion:answerablePatients(population)Intervention/exposureComparisonOutcomePICO第一步提出問題(AskClinicalQuestion轉(zhuǎn)變成可以回答的臨床問題

Framingthequestion患者類型(P)elderlypatients干預(yù)措施(I)haloperidolorperphenazine對照措施(C)olanzapine臨床結(jié)局(O)death轉(zhuǎn)變成可以回答的臨床問題

Framingthequest第二步查詢證據(jù)(AcquireEvidence)PICO:keywordsTypeofquestion：harm-Bestevidence

Levelsofevidence-OptimalsourceofevidenceSearchingworthwhile?第二步查詢證據(jù)(AcquireEvidence)PIC病因/不良反應(yīng)研究常用數(shù)據(jù)庫BestEvidence（ACPjournalclub,EBM)UptoDateMedlinePubMed:clinicalquery-etiologySumsearchOvid循證醫(yī)學(xué)數(shù)據(jù)庫(多庫同時檢索)ACPjournalclub,CochraneLibrary(CDSR,CCTR,DARE),Medline,EMBASE病因/不良反應(yīng)研究常用數(shù)據(jù)庫BestEvidence（AC系統(tǒng)評價資料庫(CochraneDatabaseofSystematicReview,CDSR)療效評價文摘庫(DatabaseofAbstractsofReviewsofEffectiveness,DARE)臨床對照試驗注冊資料庫(CochraneControlledTrialsRegister,CCTR)方法學(xué)數(shù)據(jù)庫(CochraneMethodologyDatabase)系統(tǒng)評價資料庫(CochraneDatabaseofS檢索方法選擇數(shù)據(jù)庫：ACPjournalclub（oviddatabase,bestevidence）在search中，鍵入關(guān)鍵詞olanzapine－etiology（病因?qū)W）檢索結(jié)果：1篇文獻（摘要）找到全文檢索方法選擇數(shù)據(jù)庫：ACPjournalclub（ovi循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件篩選結(jié)果ACPjournalClubsummary:ConventionalantipsychoticdrugsincreasedriskfordeathmorethandidatypicalantipsychoticdrugsinelderlypatientsACPJournalClub.2007;147:23.SchneeweissS,SetoguchiS,BrookhartA,DormuthC,WangPS.Riskofdeathassociatedwiththeuseofconventionalversusatypicalantipsychoticdrugsamongelderlypatients.CMAJ.2007;176:627-32篩選結(jié)果ACPjournalClubsummary:循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件研究詳情Background:Publichealthadvisorieshavewarnedthattheuseofatypicalantipsychoticmedicationsincreasestheriskofdeathamongelderlypatients.Weassessedtheshort-termmortalityinapopulation-basedcohortofelderlypeopleinBritishColumbiawhowereprescribedconventionalandatypicalantipsychoticmedications.Methods:WeusedlinkedhealthcareutilizationdataofallBCresidentstoidentifyacohortofpeopleaged65years

andolderwhobegantakingantipsychoticmedicationsbetweenJanuary1996andDecember2004andwerefreeofcancer.Wecomparedthe180-dayall-causemortalitybetweenresidentstakingconventionalantipsychoticmedicationsandthosetakingatypicalantipsychoticmedications.

研究詳情Background:PublichealthResults:Of37241elderlypeopleinthestudycohort,12882wereprescribedaconventionalantipsychoticmedicationand24359anatypicalformulation.Withinthefirst180daysofuse,1822patients(14.1%)intheconventionaldruggroupdied,comparedwith2337(9.6%)intheatypicaldruggroup(mortalityratio1.47,95%confidenceinterval[CI]1.39–1.56).Multivariableadjustmentresultedina180-daymortalityratioof1.32(1.23–1.42).Incomparisonwithrisperidone（利培酮）,haloperidol（氟哌啶醇）wasassociatedwiththegreatestincreaseinmortality(mortalityratio

2.14,95%CI1.86–2.45)andloxapine（洛沙平）thelowest(mortalityratio1.29,95%CI1.19–1.40).Thegreatestincreaseinmortalityoccurredamongpeopletakinghigher(abovemedian)dosesofconventionalantipsychoticmedications(mortalityratio1.67,95%CI1.50–1.86)andduringthefirst40daysafterthestartofdrugtherapy(mortalityratio1.60,95%CI1.42–1.80).Resultswereconfirmedinpropensityscoreanalysesandinstrumentalvariableestimation,minimizingresidualconfounding.Results:Of37241elderlypeop結(jié)論Interpretation:Amongelderlypatients,theriskofdeathassociatedwithconventionalantipsychoticmedicationsiscomparabletoandpossiblygreaterthantheriskofdeathassociatedwithatypicalantipsychoticmedications.Untilfurtherevidenceisavailable,physiciansshouldconsiderallantipsychoticmedicationstobeequallyriskyinelderlypatients.結(jié)論Interpretation:Amongelderl第三步評價證據(jù)AppraiseEvidence證據(jù)的真實性Aretheresultsvalid?證據(jù)的重要性Whataretheresults?第三步評價證據(jù)AppraiseEvidence證據(jù)的真證據(jù)的真實性

Aretheresultsvalid?證據(jù)的真實性

Aretheresultsvalid?1研究方法的論證強度

TypeofReportsonEtiology/Harm哪種研究方法？論證強度如何？是否源于真正的人體試驗？

Werethereclearlydefinedgroupsofpatients,similarinallimportantwaysotherthanexposuretothetreatmentorothercause?1研究方法的論證強度

TypeofReportson本研究Objective:Inelderlypatients,associationofconventionaloratypicalantipsychoticdrugs(APDs)withdeath?Design:CohortstudyParticipants:37241patients65yofageoralconventional(n=12882,meanage80y)

atypical(n=24359,meanage80y).Exclusioncriteria:canceranduseofAPDsintheyearbeforetheindexdate.本研究Objective:Inelderlypatie2兩組結(jié)局暴露因素的測量方法是否一致？Weretreatments/exposuresandclinicaloutcomesmeasuredinthesamewaysinbothgroups?(Wastheassessmentofoutcomeseitherobjectiveorblindedtoexposure?)Weretheoutcomesandexposuresmeasuredinthesamewayinthegroupsbeingcompared?2兩組結(jié)局暴露因素的測量方法是否一致？WeretreatCohortStudySurveillancebias:監(jiān)測偏倚偏倚的控制－客觀指標(biāo)（Objectiveoutcome）：病死率－主觀指標(biāo)（Subjectiveoutcome）:Blinding舉例：乙型肝炎與肝癌關(guān)系的研究

CohortStudySurveillancebias:3.隨訪時間及失訪率Wasthefollow-upofthestudypatientssufficientlylong(fortheoutcometooccur)andcomplete?舉例：HP與胃癌：5年（無差異），10

年（顯著差異）失訪超過20％？--結(jié)果將失去真實性3.隨訪時間及失訪率Wasthefollow-upo4病因/不良反應(yīng)研究結(jié)果是否符合病因診斷原則Dotheresultsoftheharmstudysatisfysomeofthediagnostictestsforcausation?4病因/不良反應(yīng)研究結(jié)果是否符合病因診斷原則DotheIsitclearthattheexposureprecededtheonsetoftheoutcome?

因果效應(yīng)的先后順序－僅見于前瞻性研究Isthereadose–responsegradient?

因果效應(yīng)的相關(guān)程度，劑量依賴（吸煙與肺癌）Isthereanypositiveevidencefroma

“dechallenge–rechallenge”

study?

符合流行病學(xué)規(guī)律-危險因素減弱，發(fā)病減少IsitclearthattheexposureIstheassociationconsistentfromstudytostudy?

不同研究，結(jié)果一致（HP與胃癌）Doestheassociationmakebiologicalsense?

充分的生物學(xué)依據(jù)（CCB與癌癥，壞血病與水果蔬菜）IstheassociationconsistentKeyPoints1.Werethereclearlydefinedgroupsofpatients,similarinallimportantwaysotherthanexposuretothetreatmentorothercause?

研究方法的論證強度2.Weretreatments/exposuresandclinicaloutcomesmeasuredinthesamewaysinbothgroups?

測量方法一致3.Wasthefollow-upofthestudypatientssufficientlylong(fortheoutcometooccur)andcomplete?

隨訪時間及失訪率KeyPoints1.Werethereclearl證據(jù)的重要性

Whataretheresults?證據(jù)的重要性

Whataretheresults?1.因果聯(lián)系強度Whatisthemagnitudeoftheassociationbetweentheexposureandoutcome?Howstrongistheassociationbetweenexposureandoutcome?RR

ORNNH1.因果聯(lián)系強度Whatisthemagnitude2.結(jié)果是否準(zhǔn)確？Whatistheprecisionoftheestimateoftheassociationbetweentheexposureandoutcome?Howpreciseistheestimateofrisk?95%CI2.結(jié)果是否準(zhǔn)確？WhatistheprecisioConventionalAPDvsAtypicalAPD

AssociationwithdeathConventionalAPDvsAtypicalA第四步應(yīng)用證據(jù)

HowcanIapplytheresultstomypatient?第四步應(yīng)用證據(jù)

HowcanIapplythere病情相似Isourpatientsodifferentfromthoseincludedinthestudythatitsresultscannotapply?Werethestudypatientssimilartomypatient?基于納入和排除標(biāo)準(zhǔn)病情相似Isourpatientsodifferen本研究Patients:>65yofage,60-65%womenUsed1medicalservice,andfilled1prescriptioninthetwo6-monthintervalsbeforetheindexdate.Exclusioncriteria:canceranduseofAPDsintheyearbeforetheindexdate.AtypicalAPDs:risperidone,quetiapine,olanzapine,andclozapineConventionalAPDs:loxapine,haloperidol,chlorpromazine,trifluoperazine,thioridazine,pimozide,promazine,perphenazine,fluphenazine,mesoridazine,andthiothixene.本研究Patients:>65yofage,6權(quán)衡利弊Whatisourpatient’sriskofbenefitandharmfromtheagent?NNTandNNH權(quán)衡利弊Whatisourpatient’srisk舉例一項心律失常抑制試驗（CAST):

恩卡尼/氟卡尼與安慰劑：10月隨訪，病死率分別為7.7%和3.0%，NNH＝21（平均每21個患者服此藥，將有1人發(fā)生額外死亡）NSIAD與消化道出血：NNH＝2000（每2000

人服NSAIDs，預(yù)期增加1例消化道出血患者）舉例一項心律失常抑制試驗（CAST):本病案使用傳統(tǒng)和非典型性抗精神病藥物

NNT/NNH

作者未進行計算和分析查詢其他證據(jù)本病案使用傳統(tǒng)和非典型性抗精神病藥物患者的價值觀和愿望Whatareourpatient’spreferences,concerns,andexpectationsfromthistreatment?1、為了避免疾病的進展而接受治療，可能帶來不良反應(yīng)

2、寧愿冒疾病進展的風(fēng)險而不接受治療

3、關(guān)注費用

4、無所謂的態(tài)度患者的價值觀和愿望Whatareourpatient’其他可替代的療法Whatalternativetreatmentsareavailable?---當(dāng)危險因素或治療措施的危險明確而且巨大，則應(yīng)立即脫離危險因素或終止治療。舉例

β-blockersforhypertensioninpatientswithasthma

治療高血壓的β受體阻滯劑能加重支氣管痙攣；血管緊張素轉(zhuǎn)換酶抑制劑巰甲丙脯酸、依那普利等，既能降壓，又不誘發(fā)支氣管痙攣，其他可替代的療法Whatalternativetreat本病案：臨床決策對該患者選擇哪類抗精神病藥?本病案：臨床決策對該患者選擇哪類抗精神病藥?Evidence-basedpracticeinrealtime直接查詢已經(jīng)評價過的高質(zhì)量的綜合臨床證據(jù)(preappraisedevidence)，如選擇數(shù)據(jù)庫“ACPjournalclub”,“臨床證據(jù)”（clinicalevidence，）等進行查詢。這些信息資源一般收集高質(zhì)量且臨床實用性強的研究，已經(jīng)對某種病因性研究的價值進行了總結(jié)。使用已評價過的高質(zhì)量證據(jù)，臨床醫(yī)師可在30秒內(nèi)找到擬解決問題的答案，特別適用于在床旁實踐循證醫(yī)學(xué)Evidence-basedpracticeinrea知識回顧KnowledgeReview知識回顧KnowledgeReviewEvidence-basedEtiology/Harm

病因研究與循證醫(yī)學(xué)實踐Evidence-basedEtiology/Harm學(xué)習(xí)目標(biāo)掌握評價病因性研究真實性原則(Validity)掌握評價病因性研究重要性原則(Importance)學(xué)會應(yīng)用病因性研究證據(jù)的結(jié)果，解決臨床問題(Applying)學(xué)習(xí)目標(biāo)掌握評價病因性研究真實性原則(Validity)病因性研究基本知識病因性研究基本概念與病因相關(guān)的臨床問題病因性研究的主要方法病因/不良反應(yīng)研究證據(jù)的分級病因性研究常用統(tǒng)計學(xué)指標(biāo)病因性研究基本知識病因性研究基本概念病因性研究基本概念（1）病因是指引起人體發(fā)生疾病的原因。病因?qū)W是指研究疾病病因的科學(xué)。病因：致病因素（直接、間接、危險因素）研究內(nèi)容：用流行病學(xué)方法研究并驗證危險因素是否與疾病發(fā)生有因果關(guān)系，且評估因果聯(lián)系的強弱。例“吸煙與肺癌關(guān)系”病因性研究基本概念（1）病因是指引起人體發(fā)生疾病的原因。病因病因性研究基本概念（2）不良反應(yīng)的研究實質(zhì)上也是病因?qū)W研究

“因”：造成不良反應(yīng)的各種因素，如各種治療措施（藥物，手術(shù)）醫(yī)療過程中臨床醫(yī)師經(jīng)常需要考慮某種危險因素或治療措施是否對患者有害。利是否大于弊？用他人的研究結(jié)果來回答提出的問題

真實性重要性實用性病因性研究基本概念（2）不良反應(yīng)的研究實質(zhì)上也是病因?qū)W研究與病因相關(guān)的臨床問題該疾病是什么原因造成的？該藥物或治療措施會導(dǎo)致什么不良反應(yīng)嗎？是否需要停藥？DoesexposuretoaluminumcauseAlzheimer’sdementia?Dostatinscausecancer?與病因相關(guān)的臨床問題該疾病是什么原因造成的？病因性研究的主要方法病因性研究的主要方法病因性研究常用統(tǒng)計學(xué)指標(biāo)因果相關(guān)性強度的指標(biāo)RR(前瞻性)RCT,cohortstudyOR(回顧性）case-controlstudyNNH(numberneededtoharm)clinicalimportance暴露多少研究對象可導(dǎo)致1例發(fā)?。犃醒芯浚┌l(fā)生1例不良反應(yīng)所需治療的病例數(shù)（臨床研究）病因性研究常用統(tǒng)計學(xué)指標(biāo)因果相關(guān)性強度的指標(biāo)因果相關(guān)性強度的指標(biāo)當(dāng)所研究疾病的發(fā)病率較低時，OR近似于RR，故在回顧性研究中可用OR估計RR,其解釋與RR同，易于統(tǒng)計分析RR或OR愈高，則因果關(guān)系強度愈強RR或OR有多大才有意義，無一定的標(biāo)準(zhǔn)1.2-1.5:弱聯(lián)系1.6-2.9:中等聯(lián)系

>3.0:強聯(lián)系因果相關(guān)性強度的指標(biāo)當(dāng)所研究疾病的發(fā)病率較低時，OR近似于R可信區(qū)間ConfidenceInterval因果關(guān)系的強度外，評價精確度按一定的概率去估計總體參數(shù)所在的范圍95％的可信區(qū)間循證醫(yī)學(xué)－估計總體參數(shù)－假設(shè)檢驗：RR可信區(qū)間ConfidenceInterval因果關(guān)系的強度有關(guān)指標(biāo)的計算1.OddsRatio

2.RelativeRisk3.RiskReduction/Increase

4.NumberNeededtoTreat/Harm

有關(guān)指標(biāo)的計算1.OddsRatio2.Relati循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件證據(jù)的強度證據(jù)的強度TheConfusionMatrix+veEvent-veEventTotalExperimentABA+ＢControlCDC+DAlsoknownasthe2x2tableTheConfusionMatrix+veEvent-EventRateEER=A/(A+B)

試驗組事件發(fā)生率CER=C/(C+D)

對照組事件發(fā)生率+veEvent-veEventTotalExperimentABA+ＢControlCDC+DEventRateEER=A/(A+B)+veERRandORRR=EER/CER

相對危險度OR=AD/BC

比值比+veEvent-veEventTotalExperimentABA+ＢControlCDC+DRRandORRR=EER/CER+veEveRelativeRiskReductionRRR=(CER-EER)/CER

=1–RR

相對危險度減少率+veEvent-veEventTotalExperimentABA+ＢControlCDC+DRelativeRiskReductionRRR=(C(Absolute)RiskReductionARR=CER-EER絕對危險度減少率+veEvent-veEventTotalExperimentABA+ＢControlCDC+D(Absolute)RiskReductionARR=NumberNeededtoTreatNNT =1/ARR得到1例有利結(jié)果需要防治的病例數(shù)+veEvent-veEventTotalExperimentABA+ＢControlCDC+DNumberNeededtoTreatNNT =1舉例：

ActivatedProteinCforSevereSepsisBleedNobleedTotalAPC30820850Control17823840APC=ActivatedProteinCEfficacyandsafetyofrecombinanthumanactivatedproteinCforseveresepsis.NEnglJMed.2001Mar8;344(10):699-709舉例：

ActivatedProteinCforSeEventRatesandOddsEER =A/(A+B) =30/850=0.035CER =C/(C+D) =17/840=0.020EEO=A/B =30/820=0.037CEO=C/D =17/823=0.021+veEvent-veEventTotalExperimentABA+ＢControlCDC+DBleedNobleedTotalAPC30820850Control17823840OR =EEO/CEO =0.037/0.021=1.77RR =EER/CER =0.035/0.020=1.744RRI =(EER–CER)/CER =0.015/0.020=0.744 =74%ARI =EER–CER =0.035–0.020=0.015

NNH =1/ARI =66EventRatesandOddsEER =A/Risk-BenefitRatioNNT =1/ARR=1/0.06 =16(治療16個獲益1個：存活)

反映有利結(jié)果（越小越好）NNH =1/ARI=1/0.015 =66(治療66個損害1個：嚴(yán)重出血)

反映不良反應(yīng)（越大越好）Risk-BenefitRatio =NNT/NNH =16/66 =1/4DeadNotdeadTotalAPC210640850Control259581840BleedNobleedTotalAPC30820850Control17823840Risk-BenefitRatioNNT =1/A怎樣解決臨床問題？

Howtosolveaclinicalproblem?怎樣解決臨床問題？

Howtosolveaclini臨床病案（ClinicalScenario）84歲的男性，近期記憶力明顯下降.高血壓病，高膽固醇血癥。右眼白內(nèi)障術(shù)后2天，出現(xiàn)易激、譫妄和性格改變。無感染，貧血及代謝異常的臨床證據(jù)。心理衛(wèi)生中心會診：抗精神病藥物氟哌啶醇,haloperidol,奮乃靜perphenazine,奧氮平,olanzapine臨床病案（ClinicalScenario）84歲的男性，臨床問題（InitialQuestion）老年患者中，用傳統(tǒng)性抗精神病藥物（如氟哌啶醇,haloperidol,奮乃靜perphenazine,）是否會增加死亡風(fēng)險性？非典型性抗精神病藥物(如奧氮平,olanzapine,）是否對老年人更安全？臨床問題（InitialQuestion）老年患者中，用傳第一步提出問題(AskClinicalQuestions)Initialquestion:Framingtheinitialquestion:answerablePatients(population)Intervention/exposureComparisonOutcomePICO第一步提出問題(AskClinicalQuestion轉(zhuǎn)變成可以回答的臨床問題

Framingthequestion患者類型(P)elderlypatients干預(yù)措施(I)haloperidolorperphenazine對照措施(C)olanzapine臨床結(jié)局(O)death轉(zhuǎn)變成可以回答的臨床問題

Framingthequest第二步查詢證據(jù)(AcquireEvidence)PICO:keywordsTypeofquestion：harm-Bestevidence

Levelsofevidence-OptimalsourceofevidenceSearchingworthwhile?第二步查詢證據(jù)(AcquireEvidence)PIC病因/不良反應(yīng)研究常用數(shù)據(jù)庫BestEvidence（ACPjournalclub,EBM)UptoDateMedlinePubMed:clinicalquery-etiologySumsearchOvid循證醫(yī)學(xué)數(shù)據(jù)庫(多庫同時檢索)ACPjournalclub,CochraneLibrary(CDSR,CCTR,DARE),Medline,EMBASE病因/不良反應(yīng)研究常用數(shù)據(jù)庫BestEvidence（AC系統(tǒng)評價資料庫(CochraneDatabaseofSystematicReview,CDSR)療效評價文摘庫(DatabaseofAbstractsofReviewsofEffectiveness,DARE)臨床對照試驗注冊資料庫(CochraneControlledTrialsRegister,CCTR)方法學(xué)數(shù)據(jù)庫(CochraneMethodologyDatabase)系統(tǒng)評價資料庫(CochraneDatabaseofS檢索方法選擇數(shù)據(jù)庫：ACPjournalclub（oviddatabase,bestevidence）在search中，鍵入關(guān)鍵詞olanzapine－etiology（病因?qū)W）檢索結(jié)果：1篇文獻（摘要）找到全文檢索方法選擇數(shù)據(jù)庫：ACPjournalclub（ovi循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件篩選結(jié)果ACPjournalClubsummary:ConventionalantipsychoticdrugsincreasedriskfordeathmorethandidatypicalantipsychoticdrugsinelderlypatientsACPJournalClub.2007;147:23.SchneeweissS,SetoguchiS,BrookhartA,DormuthC,WangPS.Riskofdeathassociatedwiththeuseofconventionalversusatypicalantipsychoticdrugsamongelderlypatients.CMAJ.2007;176:627-32篩選結(jié)果ACPjournalClubsummary:循證醫(yī)學(xué)_病因?qū)W研究和循證醫(yī)學(xué)實踐_新_研課件研究詳情Background:Publichealthadvisorieshavewarnedthattheuseofatypicalantipsychoticmedicationsincreasestheriskofdeathamongelderlypatients.Weassessedtheshort-termmortalityinapopulation-basedcohortofelderlypeopleinBritishColumbiawhowereprescribedconventionalandatypicalantipsychoticmedications.Methods:WeusedlinkedhealthcareutilizationdataofallBCresidentstoidentifyacohortofpeopleaged65years

andolderwhobegantakingantipsychoticmedicationsbetweenJanuary1996andDecember2004andwerefreeofcancer.Wecomparedthe180-dayall-causemortalitybetweenresidentstakingconventionalantipsychoticmedicationsandthosetakingatypicalantipsychoticmedications.

研究詳情Background:PublichealthResults:Of37241elderlypeopleinthestudycohort,12882wereprescribedaconventionalantipsychoticmedicationand24359anatypicalformulation.Withinthefirst180daysofuse,1822patients(14.1%)intheconventionaldruggroupdied,comparedwith2337(9.6%)intheatypicaldruggroup(mortalityratio1.47,95%confidenceinterval[CI]1.39–1.56).Multivariableadjustmentresultedina180-daymortalityratioof1.32(1.23–1.42).Incomparisonwithrisperidone（利培酮）,haloperidol（氟哌啶醇）wasassociatedwiththegreatestincreaseinmortality(mortalityratio

2.14,95%CI1.86–2.45)andloxapine（洛沙平）thelowest(mortalityratio1.29,95%CI1.19–1.40).Thegreatestincreaseinmortalityoccurredamongpeopletakinghigher(abovemedian)dosesofconventionalantipsychoticmedications(mortalityratio1.67,95%CI1.50–1.86)andduringthefirst40daysafterthestartofdrugtherapy(mortalityratio1.60,95%CI1.42–1.80).Resultswereconfirmedinpropensityscoreanalysesandinstrumentalvariableestimation,minimizingresidualconfounding.Results:Of37241elderlypeop結(jié)論Interpretation:Amongelderlypatients,theriskofdeathassociatedwithconventionalantipsychoticmedicationsiscomparabletoandpossiblygreaterthantheriskofdeathassociatedwithatypicalantipsychoticmedications.Untilfurtherevidenceisavailable,physiciansshouldconsiderallantipsychoticmedicationstobeequallyriskyinelderlypatients.結(jié)論Interpretation:Amongelderl第三步評價證據(jù)AppraiseEvidence證據(jù)的真實性Aretheresultsvalid?證據(jù)的重要性Whataretheresults?第三步評價證據(jù)AppraiseEvidence證據(jù)的真證據(jù)的真實性

Aretheresultsvalid?證據(jù)的真實性

Aretheresultsvalid?1研究方法的論證強度

TypeofReportsonEtiology/Harm哪種研究方法？論證強度如何？是否源于真正的人體試驗？

Werethereclearlydefinedgroupsofpatients,similarinallimportantwaysotherthanexposuretothetreatmentorothercause?1研究方法的論證強度

TypeofReportson本研究Objective:Inelderlypatients,associationofconventionaloratypicalantipsychoticdrugs(APDs)withdeath?Design:CohortstudyParticipants:37241patients65yofageoralconventional(n=12882,meanage80y)

atypical(n=24359,meanage80y).Exclusioncriteria:canceranduseofAPDsintheyearbeforetheindexdate.本研究Objective:Inelderlypatie2兩組結(jié)局暴露因素的測量方法是否一致？Weretreatments/exposuresandclinicaloutcomesmeasuredinthesamewaysinbothgroups?(Wastheassessmentofoutcomeseitherobjectiveorblindedtoexposure?)Weretheoutcomesandexposuresmeasuredinthesamewayinthegroupsbeingcompared?2兩組結(jié)局暴露因素的測量方法是否一致？WeretreatCohortStudySurveillancebias:監(jiān)測偏倚偏倚的控制－客觀指標(biāo)（Objectiveoutcome）：病死率－主觀指標(biāo)（Subjectiveoutcome）:Blinding舉例：乙型肝炎與肝癌關(guān)系的研究

CohortStudySurveillancebias:3.隨訪時間及失訪率Wasthefollow-upofthestudypatientssufficientlylong(fortheoutcometooccur)andcomplete?舉例：HP與胃癌：5年（無差異），10

年（顯著差異）失訪超過20％？--結(jié)果將失去真實性3.隨訪時間及失訪率Wasthefollow-upo4病因/不良反應(yīng)研究結(jié)果是否符合病因診斷原則Dotheresultsoftheharmstudysatisfysomeofthediagnostictestsforcausation?4病因/不良反應(yīng)研究結(jié)果是否符合病因診斷原則DotheIsitclearthattheexposureprecededtheonsetoftheoutcome?

因果效應(yīng)的先后順序－僅見于前瞻性研究Isthereadose–responsegradient?

因果效應(yīng)的相關(guān)程度，劑量依賴（吸煙與肺癌）Isthereanypositiveevidencefroma

“dechallenge–rechallenge”

study?

符合流行病學(xué)規(guī)律-危險因素減弱，發(fā)病減少IsitclearthattheexposureIstheassociationconsistentfromstudytostudy?

不同研究，結(jié)果一致（HP與胃癌）Doestheassociationmakebiologicalsense?

充分的生物學(xué)依據(jù)（CCB與癌癥，壞血病與水果蔬菜）IstheassociationconsistentKeyPoints1.Werethereclearlydefinedgroupsofpatients,similarinallimportantwaysotherthanexposuretothetreatmentorothercause?

研究方法的論證強度2.Weretreatments/exposuresandclinicaloutcomesmeasuredinthesamewaysinbothgroups?

測量方法一致3.Wast