匹配病例对照研究的分析Analysis-of-matched-case-control-stud

1、匹配病例对照研究的分析Analysis of matched case control studies伊万 胡廷- 世界卫生组织 Dr Yvan Hutin WHO包办婚姻 Arranged marriage1精选ppt课件可从本讲座中获得的能力Competency to be gained from this lecture匹配病例对照研究的设计和分析Design and analyze a matched case control study 2精选ppt课件关键内容 Key elements匹配的概念 The concept of matching匹配的分析 The matched an

2、alysis匹配的优缺点 Pro and cons of matching 3精选ppt课件控制混杂因素Controlling a confounding factor分层 Stratification限制 Restriction匹配 Matching 随机 Randomization 多因素分析 Multivariate analysis4精选ppt课件匹配定义 Matching: Definition产生病例和对照之间的联系 Creation of a link between cases and controls这种联系是 This link is:基于共同的特点 Based upon

3、common characteristics在研究设计时产生 Created when the study is designed分析时也应保持联系 Kept through the analysis5精选ppt课件非匹配的对照组 Unmatched control group病例 Cases对照 Controls病例 Bag of cases 对照 Bag of controls 6精选ppt课件匹配的对照组 Matched control group病例 Cases对照 Controls病例与对照的对子不能分开 Sets of cases and controls that cannot

4、be dissociated7精选ppt课件匹配概念：Matching: concept可能存在混杂 Confounding is anticipated调整将是必须的 Adjustment will be necessary对设想的层做好准备 Preparation of the strata a priori病例和对照入选 Recruitment of cases and controls 按层 By strata 保证层内有足够的样本量 To insure sufficient strata size8精选ppt课件为什么要匹配？ Why matching?如果病例和对照在匹配因素方面相

5、同 If cases and controls are similar for the matching variables,那么病例对照间的不同就是其他因素造成的而不是匹配因素（混杂因素）Then, differences must be otherwise explained.9精选ppt课件结果. Consequences.问题 The problem:混杂 Confounding解决的同时可能伴有其他问题 Is solved with another problem:引入了更多地混杂 Introduction of more confounding, 分层分析可以消除这些问题 so t

6、hat stratified analysis can eliminate it.10精选ppt课件匹配标准 Matching criteria潜在的混杂因素 Potential confounding factors与暴露存在关联 Associated with exposure与结局存在关联 Associated with the outcome标准 Criteria 独特 Unique多种 Multiple必要 Always justified11精选ppt课件匹配策略的类型Types of matching strategies频数匹配 Frequency matching层较大 La

7、rge strata集合匹配 Set matching 层较小 Small strata有时候非常小（1：1配对匹配） Sometimes very small (1/1: pairs)12精选ppt课件Chipat riverExample of frequency matching: Attack rate of acute hepatitis (E) by residence, Baripada, Orissa, India, 20040 - 0.9 / 10001 - 9.9 / 100010 -19.9 / 100020+ / 1000Attack rate Underground

8、water supplyPump from river bed13精选ppt课件频数匹配 - Frequency matching exampleResidence is a possible confounding factorAssociated with diseaseProbably associated with exposureFrequency-matching by areaEach area, numbers of controls= Number of casesAnalysis stratified by area14精选ppt课件Distribution of chol

9、era cases by households, Parpatia Village, Orissa, India 2003Household with no casesHousehold with 1 case (Triangle: Index)Household with 2 casesHousehold with 3 casesTube wellProtected wellUnprotected wellDry riverbed15精选ppt课件集合匹配 - Set matching exampleResidence is a possible confounding factorAsso

10、ciated with diseaseProbably associated with exposureSet-matching by neighbourhoodFor each case, two controls in adjacent housesAnalysis matched by set16精选ppt课件匹配：不正确的想法Matching: False pre-conceived ideas 所有病例对照研究都需要匹配 Matching is necessary for all case-control studies必须对年龄和性别进行匹配 Matching needs to b

11、e done on age and sex匹配是对病例和对照数量上的调整 Matching is a way to adjust the number of controls on the number of cases17精选ppt课件匹配：真实的描述Matching: True statements匹配可能会给你带来麻烦 Matching can put you in trouble 匹配能够使你很快找到对照 Matching can be useful to quickly recruit controls 18精选ppt课件关联指标的计算 Calculation of measures

12、 of association 相对危险 Relative risk 比值比 Odds ratio当疾病罕见时，可用比值比来估计相对危险 Approximation of relative risk if disease is rare非匹配时的计算公式： OR = ad/bc Formula = ad/bc if unmatched匹配时的计算公式较复杂 More complex if matched患病率比 Prevalence ratio 19精选ppt课件病例 Case 对照 Control合计 Total暴露 ExposedabN/A非暴露 Non-exposedcdN/A合计 To

13、tala+cb+dN/A病例中暴露比值 Odds of exposure among cases= a/c病例对照研究中OR的计算 Calculation of the odds ratio in a case control study对照中暴露比值 Odds of exposure among controls = b/d比值比 Odds ratio: ad/bc20精选ppt课件匹配策略与对应的分析 Matching strategies and corresponding analysis策略 Strategies频数匹配 Frequency matching层较大 Large str

14、ata集合匹配 Set matching 层较小 Small strata有时候非常小（1：1配对匹配） Sometimes very small (1/1: pairs)分析 Analysis混杂因素的分层分析 Stratified analysis as for confounding factors如果是1：1配对匹配，则每一层的样本量是 2 If pair matching, then strata size is 221精选ppt课件OR M-H=ai.di) / Tibi.ci) / TiMantel-Haenszel 调整在分层分析中的应用 Mantel-Haenszel adj

15、usted odds ratio applying to stratified analysis22精选ppt课件一致的对子 Concordant pairs病例与对照有相同的暴露 Cases and controls have the same exposuread 和 bc对计算没有贡献 No ad and bc: no input to the calculationCasesControlsTotalExposed112Nonexposed000合计 Total112CasesControlsTotalExposed000Nonexposed 112 Total112配对病例对照研究的

16、分析（1：1） Matched analysis by set (Pairs of 1 case / 1 control)无作用 No effect无作用 No effect23精选ppt课件CasesControlsTotalExposed101Non exposed011Total112CasesControlsTotalExposed011Non exposed 101 Total112配对病例对照研究的分析（1：1） Matched analysis by set (Pairs of 1 case / 1 control)不一致的对子 Discordant pairs病例与对照有相同的

17、暴露 Cases and controls have different exposuresad 和 bc对计算有贡献 ads and bcs: input to the calculation正相关 Positive association负相关 Negative association24精选ppt课件OR M-H=S病例暴露（对照不暴露）不一致的对子数S Discordant sets case exposed 对照暴露（病例不暴露）不一致的对子数 Discordant sets control exposed在这种情况下就是配对的ORbecomes the matched odds r

18、atio25精选ppt课件使用纸夹将相关对子夹起来，帮助分析and the analysis can be done with paper clips!一致对子的调查表： 垃圾！ Concordant questionnaire: trash不一致对子的调查表 放在天平的两端 Discordant questionnaires : on the scale“病例暴露”（而对照不暴露）的不一致对子放在正相关一边 The exposed case pairs weigh for a positive association“对照暴露”（而病例不暴露）的不一致对子放在负相关一边 The expose

19、d control pairs weigh for a negative association26精选ppt课件1:M (M1) 病例对照研究的分析 Analysis of matched case control studies with 1 control per case根据病例和对照暴露状态挑选集合 Sort out the sets according to the exposure status of the cases and controls对集合内的每一类型对子进行计数 Count reconstituted case-control pairs for each type

20、 of set将集合内不一致“对子数”乘以（符合该集合）的对子总数 Multiply the number of discordant pairs in each type of set by the number of sets然后用f/g这个公式来计算OR Calculate odds ratio using the f/g formula例如1个病例/2个对照 Example for 1 case / 2 controls暴露病例的集合 Sets with case exposed: +/+, +/+-, +/-未暴露病例的集合 Sets with case unexposed: -/+

21、, -/+-, -/-27精选ppt课件CasesControlsTotal暴露ExposedabL1非暴露UnexposedcdL0合计TotalC1C0TOdds ratio: ad/bc传统的四格表 The old 2 x 2 table.28精选ppt课件 ControlsExposedUnexposedTotalExposedefaUnexposed ghcTotalbdP (T/2) Odds ratio: f/gCases变成对子就很难认识了！. is difficult to recognize!29精选ppt课件Chi2 McN=(f - g) 2(f+g)The Mac N

22、emar chi-square30精选ppt课件匹配病例对照研究的分析：从概念到数据管理 Analysis of matched case control studies: From concepts to database management在研究设计里就将病例和对照联系在一起Link between sets of cases and controls in the study design在分析中使用这些联系 Use of this link in the data analysis频数匹配的分层分析 Stratification (Frequency matching)集合匹配的匹配

23、分析 Matched analysis (Set matching)配对匹配的匹配分析Paired analysis (Case control pairs)在数据库中要有识别这种联系的变量 Need to materialize this link in the dataset to prepare the data analysis31精选ppt课件匹配变量The matched set variable是一个另加的变量 Extra variable每个病例-对照的识别号 Identifier for each case-control在频数匹配中是“层” Stratum (Frequen

24、cy matching)在集合匹配中是“集合” Set (Case control sets)在配对匹配是“对子” Pair (Case control pairs)在每一“层/集合/对子”内中，所有病例和对照的这个变量值都是相同的 All cases and controls belonging to the same stratum/ set/ pair share the same value for the matched set variable在不同的“层/集合/对子”，这个变量值不同 Each stratum/ set/ pair have a unique value32精选p

25、pt课件2个集合的1:3集合匹配数据库变量结构Database structure for 2 sets of one case and three controls IDSetStatusAge Sex SES1111213212131331211134121013521422262244227224022822412233精选ppt课件4个对子的配对匹配数据库变量结构Database structure for 4 pairs of one case and one controlIDPairStatusAge Sex SES11112132121313321222742222275314

26、22263244227415421842552134精选ppt课件匹配：优点Matching: Advantages易于沟通 Is easy to communicate对很强地混杂有用处 Is useful for strong confounding factors能增加小型研究的效率 Can increase the power of small studies能较容易地选择对照 Can ease control recruitment如果只有一个研究因素，则有用处 Is useful if only one factor is studied匹配后，仍可以识别效应修饰因子 Allows

27、 looking for effect modification with matching criteria 35精选ppt课件匹配：不方便的方面Matching: Inconvenience必须使作者清楚 Must be understood by the author在不存在混杂情况下导致不利 Is deleterious in the absence of confounding可降低研究效率 Can decrease power造成对照选择的复杂 Can complicate control recruitment存在多个危险因素时，作用有限 Is limiting if more

28、than one factor不再能对匹配因素进行关联性分析 Does not allow examining the association with the matching criteria36精选ppt课件匹配变量与暴露有关，但与疾病无关时（匹配过度）Matching with a variable associated with exposure, but not with illness (Overmatching)减少了变异度 Reduces variability增加了一致地对子 Increases the number of concordant pairs造成有害的结果 H

29、as deleterious consequences:如果匹配分析：降低了研究效率 If matched analysis: reduction of power如果不匹配分析：OR将偏向1If match broken: Odds ratio biased towards one37精选ppt课件隐藏地匹配（“秘密匹配”）Hidden matching (“Crypto-matching”)一些对照的选择策略造成事实上的匹配 Some control recruitment strategies consist de facto in matching邻居对照 Neighbourhood

30、controls 朋友对照 Friends controls必须发现这样的匹配，并在分析中加以考虑 Matching must be identified and taken into account in the analysis38精选ppt课件匹配的操作性原因Matching for operational reasons暴发调查的情况下 Outbreak investigation setting朋友和邻居对照是常见的选择 Friends or neighbours controls are a common choice优点：Advantages:更快地找到对照 Allows ide

31、ntifying controls fast可以大体上控制混杂 Will take care of gross confounding factors 可导致一些过度匹配，但使调查者处于安全地带 May results in some overmatching, which places the investigator on “the safe side”39精选ppt课件打破匹配 Breaking the match合理性 Rationale匹配会限制分析 Matching may limit the analysis匹配也许只是为了操作方便 Matching may have been decided for operational purposes only处理过程 Procedure进行匹配的分析 Conduct matched analysis再进行非匹配的分析 Conduct unmatched analysis如果两者结果类似，可以打破匹配分析 Break the match if the results are unchanged 40精选ppt课件结论Ta