病例對照與回顧性隊列研究

RobertE.Fontaine,MD,MScBao-PingZhu,MD,MSUSExpertAdvisorstoChineseFETP病例對照與回憶性隊列研究

Case-ControlandRetrospectiveCohortStudiesEpidemiology:

The“CDC〞ApproachC = Count2D = DivideC = CompareProposedby:WilliamFoege,MD,MPH,Director,USCDC(1977-1983)WilliamFoege,MD,MPHCase-controlCohortIndividualsInterventionRetrospectiveProspectiveDescriptivePopulationsAnalyticalObservationalCase-seriesCross-sectionalEcologicClinicaltrials流行病學研究Epidemiologicalstudies有了初步假設，并已經(jīng)進行了以下步驟。下一步要做什么？Youhaveahypothesisandthefollowing.Whatnext?疾病特征DiseaseCharacteristics+時間分布Timedistribution+地區(qū)分布Placedistribution+人群分布Persondistribution+通過訪談建立假設Hypothesisgeneratinginterviews+考慮異常值Outliers=得到關于暴露的假設possibleexposure針對假設的暴露因素，對率進行比較WecompareratesbyourhypothesizedexposuresWhatdoweneedtodothis?對可疑的暴露進行準確的測量Weobtainaccuratemeasurementsontheexposureofinterest訪談Interviews查閱記錄Writtenrecords測量Measurements實驗室檢測Laboratorytests環(huán)境數(shù)據(jù)Environmentaldata在病例對照和回憶隊列研究中，從疾病開始，回溯暴露Incase-controlandretrospectivecohortstudieswebeginwiththediseaseandlookbacktotheexposure.ExposureDiseaseTime

Referent

exposure

periodStudybegins在人群中，某種暴露與疾病的關系TherelationshipbetweenexposureandcasesinapopulationDisease

疾病Exposure

暴露+-Total

合計罹患率ARx+ABA+BA/(A+B)Reference

參照-CDC+DC/(C+D)Total

合計A+CB+DA+B+C+D人群罹患率PopulationAR=(A+C)/(A+B+C+D)根據(jù)人群數(shù)據(jù)進行一些根本的流行病學比較BasicepidemiologiccomparisonsfromthepopulationdataRiskDifference: [A/(A+B)]–[C/(C+D)]RiskRatio: [A/(A+B)]/[C/(C+D)]=(AC+AD)/(AC+BC)OddsRatio: (A/B)/(C/D)=(A/C)/(B/D)=AD/BCDisease

疾病Exposure

暴露+-Total

合計罹患率ARx+ABA+BA/(A+B)Reference

參照-CDC+DC/(C+D)Total

合計A+CB+DA+B+C+DDisease

疾病Exposure

暴露+-Total

合計ARx+50950100050/1000Reference

參照-10990100010/1000Total

合計601940200060/2000Riskdifference:[50/1000]–[10/1000]=40/1000RiskRatio:[50/1000]/[10/1000]=5.0根據(jù)人群數(shù)據(jù)進行一些根本的流行病學比較Basicepidemiologiccomparisonsfromthepopulationdata從同一2X2表也可以計算奧值和奧值比Oddsandoddsratiosmaybecalculatedfromthesame2x2tableDisease

疾病Exposure

暴露+-疾病奧值Oddsofdisease+ABA/B-(Reference

參照)CDC/D暴露奧值OddsofexposureA/CB/D暴露的奧值比Oddsratioexposure=(A/C)/(B/D)=AD/BC疾病的奧值比Oddsratiodisease=(A/B)/(C/D)=(A/D)/(B/C)=AD/BC暴露奧值與疾病奧值完全相等OddsratiosfromexposureordiseaseoddsareidenticalDisease

疾病Exposure

暴露+-Oddsofdisease+509505/95=1/19Reference

參照-109901/99Oddsofexposure5/195/99OddsRatioexposure=(5)/(95/99)=5*99/95=99/19OddsRatiodisease=(1/19)/(1/99)=99/19OR也是病例與非病例的交叉乘積比TheORcanbecalculatedbythecrossproductofcasesandnotillDisease

疾病Exposure

暴露+-Total

合計+ABA+BReference

參照-CDC+DTotal

合計A+CB+DA+B+C+DADBCOR=(A/B)/(C/D)=(A/C)/(B/D)=RR是疾病與合計之間的交叉乘積比TheRRcanbecalculatedbythecrossproductofcasesandtotalsDisease

疾病Exposure

暴露+-Total

合計+ABA+BReference

參照-CDC+DTotal

合計A+CB+DA+B+C+DRR=[A/(A+B)]/[C/(C+D)]=[A(C+D)]/[C(A+B)]=AC+ADAC+BC奧值比與危險比之間的關系RelationshipoftheoddsratiototheriskratioWhenRR>1,OR>RRWhenRR<1,OR<RRWhenRR=1,OR=RR=101∞RRORRROR假設為稀有疾病，AC很小，ORRRIfthediseaseisrarethetermACissmallandtheORandRRarenearlyidenticalDisease疾病Exposure

暴露+-Total

合計ARx+ABA+BA/(A+B)Reference

參照-CDC+DC/(C+D)Total

合計A+CB+DA+B+C+DRiskRatio: [A/(A+B)]/[C/(C+D)]=(AC+AD)/(AC+BC)OddsRatio: (A/B)/(C/D)=(A/C)/(B/D)=AD/BCAC+ADAC+BCADBCRRORDisease疾病Exposure

暴露+-Total

合計+59951000Reference

參照-19991000Total

合計a+cb+da+b+c+dDisease疾病Exposure

暴露+-Total

合計+509501000Reference

參照-109901000Total

合計a+cb+da+b+c+d5(999)1(995)5+5(999)5+1(995)50(990)10(950)500+50(990)500+10(950)499599550001000495009500=5.02=5.0=5.2=5.05000010000假設為稀有疾病，AC很小，ORRRIfthediseaseisrarethetermACissmallandtheORandRRarenearlyidentical病例對照與回憶性隊列研究的比較Howarecasecontrolstudiesandretrospectivecohortstudysimilar?Disease

疾病Exposure

暴露+-Total

合計+ABA+BReference

參照-CDC+DTotal

合計A+CB+DA+B+C+D回憶性隊列研究從暴露開始進行抽樣

AretrospectivecohortstudysamplesbyexposureDisease

疾病Exposure

暴露+-Total

合計+AB(A+B)kReference

參照-CD(C+D)jTotal

合計k=proportionofexposedpersonssampledj=proportionofunexposedpersonssampledThisresultsinthefollowingdistributioninsidethetable.Disease

疾病Exposure

暴露+-Total

合計+AkBk(A+B)kReference

參照-CjDj(C+D)jTotal

合計A+CB+DA+B+C+D抽樣比例約除，得到人群的RD,RR,OR

ThesamplefractionscancelleavinguswiththeRD,RR,andORofthepopulationDisease

疾病Exposure

暴露+-Total

合計+AkBk(A+B)kReference

參照-CjDj(C+D)jTotal

合計A+CB+DA+B+C+DRD=[Ak/(A+B)k]-[Cj/(C+D)j] =[A/(A+B)]-[C/(C+D)]RR=[Ak/(A+B)k]/[Cj/(C+D)j] =[A/(A+B)]/[C/(C+D)] =(AC+AD)/(AC+BC)OR=(Ak/Bk)/(Cj/Dj)=(A/B)/(C/D)=AD/BC病例對照研究是從疾病狀態(tài)開始抽樣Acasecontrolstudysamplesbydiseasestatus.Disease

疾病Exposure

暴露+-Total

合計+A+BReference

參照-C+DTotal

合計(A+C)k(B+D)jA+B+C+Dk=proportionofdiseasedpersonssampledj=proportionofwellpersonssampledDisease

疾病Exposure

暴露+-Total

合計+AkBjA+BReference

參照-CkDjC+DTotal

合計(A+C)k(B+D)jA+B+C+D病例對照研究是從疾病狀態(tài)開始抽樣Acasecontrolstudysamplesbydiseasestatus.抽樣比例約除，得到人群的OR

Again,thesamplingfractionscancelleavingtheORofthepopulationDisease

疾病Exposure

暴露+-Total

合計+AkBjA+BReference

參照-CkDjC+DTotal

合計(A+C)k(B+D)jA+B+C+DOR=(Ak/Bj)/(Ck/Dj)=ADjk/BCjk=AD/BC假定在人群中隨機抽取樣本作為對照Supposethatyouuseascontrolsasampleofthepopulation.Disease

疾病Exposure

暴露+-Total

合計+AkBj(A+B)jReference

參照-CkDj(C+D)jTotal

合計(A+C)k(B+D)j(A+B+C+D)j這種研究稱為“疾病-參比研究〞Thisisacase-base(orcase-referent,case-cohort)studyDisease

疾病Exposure

暴露+-Total

合計+AkB(A+B)jReference

參照-CkD(C+D)jTotal

合計(A+C)k(B+D)(A+B+C+D)j此時，交叉積比是人群RR，而非OR

NoticethatthecrossproductisnowaRRandnotanORDisease

疾病Exposure

暴露+-Total

合計+AkB(A+B)jReference

參照-CkD(C+D)jTotal

合計(A+C)k(B+D)(A+B+C+D)jCrossProduct=Ak(C+D)j/Ck(A+B)j =Ak(C+D)j/Ck(A+B)j =[A/(A+B)]/[C/(C+D)] =A(C+D)/C(A+B)=RR病例對照，或回憶性隊列研究？要考慮：時間，花費，精確度Case-controlorretrospectivecohort?Time,cost,andaccuracy50casesamong200persons50casesamong2000persons500casesamong2000persons病例對照研究的主要步驟Majorstepsincase-controlstudy定義并選擇病例Defineandselectcases定義并選擇對照Defineandselectcontrols確定暴露Ascertainexposures比較病例和對照的暴露史Compareexposureincasesandcontrols對照代表病例所來自的人群Acontrolisarepresentativeofthepopulationfromwhichthecasescame.Disease

疾病Exposure

暴露CaseControlTotal

合計+aba+b-cdc+dTotal

合計a+cb+da+b+c+d不要與實驗研究中的對照組相混淆Donotconfusewithexperimentalcontrols.病例定義Casedefinition2007年北京市朝陽區(qū)常住人口中實驗室確診的腦膜炎球菌疾病。“Laboratory-confirmedmeningococcaldiseaseduring2007inregularresidentsofChaoyangDistrict,Beijing.〞對照定義Controldefinition2007年北京市朝陽區(qū)常住人口中未發(fā)生腦膜炎球菌疾病的居民?！癛egularresidentsofChaoyangDistrict,Beijingduring1997andnotsufferingfrommeningococcaldisease.〞選擇對照的原那么PrinciplesofControlSelection與病例來源于同一人群Fromsametargetpopulationascases對照的選擇應該獨立于暴露狀態(tài)Selectedindependentlyofexposurestatus.如果對照發(fā)病，那么他們就會是病例Iftheyhaddevelopedillness,theywouldhavebeenacase.信息與病例具有可比性Comparableinformationtocases對照與病例應該有相同的暴露時機Theymusthavethesameopportunityforexposureasacase病例與對照具有相同的入選標準Usethesameinclusionandexclusioncriteria.病例對照研究中，設立對照組的目的Case-controlstudy:Purposeofthecomparison(control)group“設立對照組的目的是提供病例的源人群中暴露因素分布的估計。〞“Thecomparison(Control)groupservestoprovideanestimateoftheexposuredistributioninthestudybasefromwhichthecasesoriginate.〞-RothmanKJ,1986ExtraSlides橫斷面研究Cross-SectionalStudies橫斷面研究與病例對照、回憶性隊列研究有何不同？Whatisthedifferencebetweenacase-control,aretrospectivecohort,andacross-sectionalstudy?Disease

疾病Exposure

暴露+-Total

合計+AAA+BReference

參照-CDC+DTotal

合計A+CB+DA+B+C+D人群中疾病與暴露的分布病例對照或回憶性隊列研究那么根據(jù)疾病或暴露狀態(tài)來抽樣Case-controlandretrospectivecohortstudiessamplebycaseorexposurestatusDisease

疾病Exposure

暴露+-Total

合計+AjBj(A+B)jReference

參照-CjDj(C+D)jTotal

合計(A+C)j(B+D)j(A+B+C+D)j橫斷面研究：從全人群中進行抽樣Inacross-sectionalstudytheentirepopulationissampledDisease

疾病Exposure

暴露+-Total

合計+ABA+BReference

參照-CDC+DTotal

合計A+CB+D(A+B+C+D)j抽樣后再去調(diào)查，確定疾病和暴露狀態(tài)DiseaseorexposurestatusaredeterminedduringorafterthesamplingDisease

疾病Exposure

暴露+-Total

合計+???Reference

參照-???Total

合計??(A+B+C+D)j劑量反響關系

Dose-responserelationship暴露水平在兩個以上ExposuresmaytakeonseverallevelsofintensityDisease

疾病Exposure

暴露+-Total

合計+++a3b3a3+b3++a2b2a2+b2+a1b1a1+b1Reference

參照-a0b0a0+b0Total

合計ΣaΣbΣa+Σb每個暴露水平都應與一個共同參照水平比較EachlevelneedstobecomparedtothesamecommonreferencelevelDisease

疾病Exposure

暴露+-Total

合計+++a3b3a3+b3++a2b2a2+b2+a1b1a1+b1Reference

參照-a0b0a0+b0Total

合計ΣaΣbΣ(a+b)OR=a3b0/b3a0RR =[a3/(a3+b3)]/[a0/(a0+b0)] =[a3(a0+b0)/a0(a3+b3)]Disease

疾病Exposure

暴露+-Total

合計+++a3b3a3+b3++a2b2a2+b2+a1b1a1+b1Reference

參照-a0b0a0+b0Total

合計ΣaΣbΣ(a+b)OR=a2b0/b2a0RR =[a2/(a2+b2)]/[a0/(a0+b0)] =[a2(a0+b0)/a0(a2+b2)]每個暴露水平都應與一個共同參照水平比較Eachlevelneedstobecomparedtothesamecommonreferencelevel病例對照與回憶性隊列研究比較

Case-controlvs.RetrospectiveCohortStudies病例對照與回憶性隊列研究有何類似之處？Howarecase-controlandretrospectivecohortstudiessimilar?病例Cases暴露Exposure+-合計Total+aba+b-cdc+d合計Alla+cb+da+b+c+d累計發(fā)病病例Cumulativeincidence用2x2表來表示2x2tablearrangement疾病和暴露均已發(fā)生Bothdisease&exposurehavealreadyoccurred病例對照與回憶性隊列研究有何不同之處？Howdocasecontrolandretrospectivecohortst