實(shí)驗(yàn)流行病學(xué)

1、department of epidemiology public health college of harbin medical university1實(shí)驗(yàn)流行病學(xué)研究實(shí)驗(yàn)流行病學(xué)研究experimental epidemiology哈爾濱醫(yī)科大學(xué)流行病學(xué)教研室哈爾濱醫(yī)科大學(xué)流行病學(xué)教研室 department of epidemiology ，harbin medical universitydepartment of epidemiology public health college of harbin medical university2橫斷面研究監(jiān)測(cè)生態(tài)學(xué)研究病例對(duì)照研究隊(duì)列研

2、究描述性研究分析性研究臨床試驗(yàn)現(xiàn)場(chǎng)試驗(yàn)社區(qū)干預(yù)項(xiàng)目理論流行病學(xué)流行病學(xué)研究方法觀察性研究實(shí)驗(yàn)性研究理論性研究驗(yàn)證假設(shè)驗(yàn)證假設(shè) 檢驗(yàn)假設(shè)檢驗(yàn)假設(shè)產(chǎn)生假設(shè)產(chǎn)生假設(shè)流行病學(xué)研究方法流行病學(xué)研究方法 research method of epidemiology department of epidemiology public health college of harbin medical university3james lind (1716-1794)維維c 缺乏壞血病缺乏壞血病 (1747)vitamin c deficiency-scurvy第一節(jié)第一節(jié) 概概 述述overview dep

3、artment of epidemiology public health college of harbin medical university4edward salk脊髓灰質(zhì)炎疫苗(poliomyelitis vaccine)現(xiàn)場(chǎng)試驗(yàn) (1955)美國(guó)+加拿大疫苗組(vaccine)安慰獎(jiǎng)200,745 人，安慰劑組（placebo）201,229 人保護(hù)率(protective rate)：60-90%thomas francis,jrdepartment of epidemiology public health college of harbin medical universit

4、y5 一、定義一、定義 (definition)ppatients or health adults) were randomly divided into experiment group and control group，intervention was given to the individuals of experiment group ，and the outcomes of two groups were followed up and compared in order to determine effect of intervention. p將研究對(duì)象（病人或正常將研究對(duì)

5、象（病人或正常人）隨機(jī)分配給實(shí)驗(yàn)組和人）隨機(jī)分配給實(shí)驗(yàn)組和對(duì)照組，將干預(yù)措施對(duì)照組，將干預(yù)措施 給給予實(shí)驗(yàn)組人群后，隨訪觀予實(shí)驗(yàn)組人群后，隨訪觀察察(follow up)(follow up)一段時(shí)間一段時(shí)間并比較兩組人群的結(jié)局并比較兩組人群的結(jié)局, , 以便確定干預(yù)措施的效果。以便確定干預(yù)措施的效果。department of epidemiology public health college of harbin medical university6二、基本原則二、基本原則 (basic principle)p對(duì)照的原則對(duì)照的原則 control p隨機(jī)的原則隨機(jī)的原則 randomiz

6、ationp盲法的原則盲法的原則 blindingp重復(fù)的原則重復(fù)的原則 duplication department of epidemiology public health college of harbin medical university7the research question cannot be answered by observational studies earlier observational studies have not answered the research question existing knowledge is not sufficient

7、to determine clinical or public health policy an experiment is likely to provide an important extension of this knowledge when to choose an experimental design? department of epidemiology public health college of harbin medical university8三、基本特征三、基本特征 (basic characteristic)前瞻前瞻 前瞻性研究前瞻性研究干預(yù)干預(yù) 施加一種或多

8、種人施加一種或多種人為干預(yù)處理為干預(yù)處理隨機(jī)隨機(jī) 研究對(duì)象隨機(jī)分配研究對(duì)象隨機(jī)分配到比較組到比較組對(duì)照對(duì)照 有平行的或可比的有平行的或可比的實(shí)驗(yàn)組和對(duì)照組實(shí)驗(yàn)組和對(duì)照組prospective intervention or treatmentrandom allocationparalleled control groupdepartment of epidemiology public health college of harbin medical university9四、實(shí)驗(yàn)流行病學(xué)的類(lèi)型四、實(shí)驗(yàn)流行病學(xué)的類(lèi)型(t(types of experimental epidemiology)

9、 pclinical trialpfield trial or field experiment pcommunity trial.p臨床試驗(yàn) p現(xiàn)場(chǎng)試驗(yàn)p社區(qū)試驗(yàn)department of epidemiology public health college of harbin medical university10(一一)個(gè)體試驗(yàn)個(gè)體試驗(yàn) (individual trial)研究對(duì)象研究對(duì)象（未患病者）（未患病者）實(shí)驗(yàn)組實(shí)驗(yàn)組（干預(yù)組）（干預(yù)組）對(duì)照組對(duì)照組有效有效無(wú)效無(wú)效有效有效無(wú)效無(wú)效department of epidemiology public health college o

10、f harbin medical university11（二）社區(qū)試驗(yàn)（二）社區(qū)試驗(yàn) (community trial)department of epidemiology public health college of harbin medical university12field trial or field experiment effect of hepatitis b vaccine against hepatitis b infections of hepatitis b childrenexperiment group ( vaccine)control group (pl

11、acebo)follow up 10 year (randomly) department of epidemiology public health college of harbin medical university13 community trial (community intervention trial) fluoridation of drinking water to prevent saprodontia (randomly) communitiesprevalence of saprodontiafluoridation of drinking waterno fluo

12、ridation of drinking water community acommunity bdepartment of epidemiology public health college of harbin medical university14（三）臨床試驗(yàn)（三）臨床試驗(yàn) (clinical trial)研究對(duì)象研究對(duì)象（病人）（病人）實(shí)驗(yàn)組實(shí)驗(yàn)組（干預(yù)組）（干預(yù)組）對(duì)照組對(duì)照組有效有效無(wú)效無(wú)效有效有效無(wú)效無(wú)效department of epidemiology public health college of harbin medical university15 clinica

13、l trial therapeutic efficacy of drug aeffects of drug apatientsexperiment group (drug a)control group (placebo)follow up (randomly) department of epidemiology public health college of harbin medical university16phases of clinical trials (fda) phase 1: safety, clinical pharmacology and toxicology 15-

14、30 people what dosage is safe? how should treatment be given? how does treatment affect the body? phase 2: efficacy,initial investigation for treatment effect less than 100 people does treatment do what it is supposed to? how does treatment affect the body?department of epidemiology public health co

15、llege of harbin medical university17 phase 3: effectiveness, full scale evaluation of treatment; licensing approval from 100 to thousands of people compare new treatment with current standard phase 4: post marketing surveillance, monitor adverse reactions from hundreds to thousands of people usually

16、 takes place after drug is approved used to further evaluate long-term safety and effectiveness of new treatmentdepartment of epidemiology public health college of harbin medical university18應(yīng)該注意的問(wèn)題應(yīng)該注意的問(wèn)題 issues should be paid attention top臨床依從性 cliccal compliancep臨床不一致性 clinical disagreementp安慰劑效應(yīng)

17、 placebo effectp向均數(shù)回歸 regression to the meandepartment of epidemiology public health college of harbin medical university19現(xiàn)場(chǎng)試驗(yàn)與臨床試驗(yàn)比較現(xiàn)場(chǎng)試驗(yàn)與臨床試驗(yàn)比較注意注意 !difference between filed trial and clinical trialdepartment of epidemiology public health college of harbin medical university20現(xiàn)場(chǎng)試驗(yàn)與臨床試驗(yàn)比較 differenc

18、e between filed trial and clinical trialdepartment of epidemiology public health college of harbin medical university21真實(shí)驗(yàn)真實(shí)驗(yàn) true experiment按所具備設(shè)計(jì)的基本特征按所具備設(shè)計(jì)的基本特征 （basic features）真實(shí)驗(yàn)真實(shí)驗(yàn)(true experiment)對(duì)照 前瞻 干預(yù) 隨機(jī)randomizationprospective control intervention department of epidemiology public health

19、 college of harbin medical university22類(lèi)實(shí)驗(yàn)類(lèi)實(shí)驗(yàn) quasi-experiment按所具備設(shè)計(jì)的基本特征按所具備設(shè)計(jì)的基本特征（basic features）類(lèi)實(shí)驗(yàn)類(lèi)實(shí)驗(yàn)(quasi-experiment)真實(shí)驗(yàn)真實(shí)驗(yàn)(true experiment)對(duì)照對(duì)照前瞻前瞻干預(yù)干預(yù)隨機(jī)隨機(jī)p不設(shè)對(duì)照組不設(shè)對(duì)照組 （without control group）l自身前后比較l與已知干預(yù)措施比較p設(shè)對(duì)照組設(shè)對(duì)照組 （with control group）l不能隨機(jī)分組department of epidemiology public health college

20、 of harbin medical university23第二節(jié)第二節(jié) 研究設(shè)計(jì)與實(shí)施研究設(shè)計(jì)與實(shí)施 design and execution department of epidemiology public health college of harbin medical university24p一一 明確研究目的明確研究目的p二二 研究對(duì)象的選擇研究對(duì)象的選擇p三三 確定實(shí)驗(yàn)現(xiàn)場(chǎng)確定實(shí)驗(yàn)現(xiàn)場(chǎng)p四四 樣本大小的確定樣本大小的確定ppurpose pobjectpexperimental spot psample department of epidemiology public he

21、alth college of harbin medical university25四、樣本量估計(jì)四、樣本量估計(jì) （estimate the quantity of the samples）p非連續(xù)變量非連續(xù)變量 non-continuous variable p連續(xù)變量連續(xù)變量 continuous variable 22122211)pp()p1(p)p1(pz)p1(p2zn222)(2dzznadepartment of epidemiology public health college of harbin medical university26五、隨機(jī)化分組五、隨機(jī)化分組 （r

22、andomization）p簡(jiǎn)單隨機(jī)分組簡(jiǎn)單隨機(jī)分組 simple randomizationp分層隨機(jī)分組分層隨機(jī)分組 stratified randomizationp整群隨機(jī)分組整群隨機(jī)分組 cluster randomizationdepartment of epidemiology public health college of harbin medical university27簡(jiǎn)單隨機(jī)分組簡(jiǎn)單隨機(jī)分組 (simple randomization)department of epidemiology public health college of harbin medical

23、 university28 simple randomizationdepartment of epidemiology public health college of harbin medical university29分層隨機(jī)分組分層隨機(jī)分組 (stratified randomization)總總體體層層層層層層可按年齡、性可按年齡、性別、種族、教別、種族、教育水平等分層育水平等分層在各層內(nèi)再在各層內(nèi)再進(jìn)行簡(jiǎn)單隨進(jìn)行簡(jiǎn)單隨機(jī)分組機(jī)分組department of epidemiology public health college of harbin medical universit

24、y30 stratification randomization categorizing subjects into subgroups by specific characteristics enables researchers to look into separate subgroups to see whether differences existdepartment of epidemiology public health college of harbin medical university31整群隨機(jī)分組整群隨機(jī)分組 (cluster randomization)p以家

25、庭、學(xué)校、醫(yī)以家庭、學(xué)校、醫(yī)院、村莊或居民區(qū)院、村莊或居民區(qū)等為單位隨機(jī)分組等為單位隨機(jī)分組p要保證組間可比性要保證組間可比性pbase on family, hospital, communication, school, and village. pcomparability department of epidemiology public health college of harbin medical university32 六、設(shè)立對(duì)照對(duì)照 (control)p不能預(yù)知的結(jié)局不能預(yù)知的結(jié)局 un-predicable outcomep霍桑效應(yīng)霍桑效應(yīng) hawthorne effe

26、ctp安慰劑效應(yīng)安慰劑效應(yīng) placebo effectp潛在的未知因素的影響潛在的未知因素的影響 unknown factordepartment of epidemiology public health college of harbin medical university33 六、設(shè)立對(duì)照對(duì)照 (control) （means）l 安慰劑對(duì)照安慰劑對(duì)照 （placebo control）l 自身對(duì)照自身對(duì)照 （own control）l 交叉對(duì)照交叉對(duì)照 （cross-over control）department of epidemiology public health coll

27、ege of harbin medical university34交叉對(duì)照對(duì)照交叉對(duì)照對(duì)照cross-over controla療法b療法b療法a療法 phase interval phasedepartment of epidemiology public health college of harbin medical university35八、盲法的應(yīng)用八、盲法的應(yīng)用 (blinding application) 單盲（單盲（single blind） 研究對(duì)象不知分組情況研究對(duì)象不知分組情況 雙盲（雙盲（double blind） 研究對(duì)象、研究者不知分組情況研究對(duì)象、研究者不知分

28、組情況 三盲（三盲（triple blind） 研究對(duì)、研究者、負(fù)責(zé)資料收集者不研究對(duì)、研究者、負(fù)責(zé)資料收集者不知分組情況知分組情況開(kāi)放試驗(yàn)開(kāi)放試驗(yàn) (open trial)department of epidemiology public health college of harbin medical university36department of epidemiology public health college of harbin medical university37博君一笑：雙盲實(shí)驗(yàn)博君一笑：雙盲實(shí)驗(yàn)department of epidemiology public hea

29、lth college of harbin medical university38單盲單盲(single blind)department of epidemiology public health college of harbin medical university39雙盲雙盲(double blind)department of epidemiology public health college of harbin medical university40三盲三盲(triple blind)department of epidemiology public health colle

30、ge of harbin medical university41三盲研究三盲研究 (triple blind)department of epidemiology public health college of harbin medical university42開(kāi)放試驗(yàn)開(kāi)放試驗(yàn)(open trial)不可能實(shí)現(xiàn)盲法不可能實(shí)現(xiàn)盲法外科手術(shù)外科手術(shù)（surgery）鍛煉鍛煉鍛煉鍛煉（exercise）飲食飲食（diet）教育教育（education）department of epidemiology public health college of harbin medical univ

31、ersity43第三節(jié)第三節(jié) 資料的收集與分析資料的收集與分析 data collect and analyzedepartment of epidemiology public health college of harbin medical university44p排除 exclusionp退出 withdrawaln不合格 ineligibilityn不依從 noncompliancen失訪 loss to follow-up一、偏倚的防止一、偏倚的防止 （bias avoiding）department of epidemiology public health college of

32、 harbin medical university45二、評(píng)價(jià)指標(biāo)選擇的基本原則二、評(píng)價(jià)指標(biāo)選擇的基本原則( (basic principle of evaluate standardization selection)p客觀的定量指標(biāo)客觀的定量指標(biāo)p較高的真實(shí)性和可較高的真實(shí)性和可靠性靠性p易于觀察和測(cè)量且易于觀察和測(cè)量且易于為受試者所接易于為受試者所接受受pobjective pvalidity and reliability pacceptability and easy observedepartment of epidemiology public health college o

33、f harbin medical university46%100治療的總例數(shù)治療有效例數(shù)有效率%100治療人數(shù)治愈人數(shù)治愈率%100某病受治療人數(shù)因某病死亡人數(shù)病死率%100nnn年的病例數(shù)隨訪滿(mǎn)年存活的病例數(shù)年生存率三、實(shí)驗(yàn)效果的主要評(píng)價(jià)指標(biāo)三、實(shí)驗(yàn)效果的主要評(píng)價(jià)指標(biāo)(evaluate standardization of efficacy of experiment )department of epidemiology public health college of harbin medical university47%100檢查總?cè)藬?shù)抗體陽(yáng)性人數(shù)抗體陽(yáng)性率率死亡實(shí)驗(yàn)組發(fā)病率死亡對(duì)

34、照組發(fā)病)()(效果指數(shù)index of effectiveness，iecmlog2）（抗體幾何平均滴度（antigmtdepartment of epidemiology public health college of harbin medical university48四、研究中的倫理問(wèn)題四、研究中的倫理問(wèn)題(ethics in the research)p研究必須具有科研依據(jù)研究必須具有科研依據(jù)p公平選擇研究對(duì)象公平選擇研究對(duì)象p獲得社區(qū)的知情同意獲得社區(qū)的知情同意p“延誤延誤”的問(wèn)題的問(wèn)題p“善后善后”處理處理pmust be scientificpselect object fairly phave permission to know the fact pdelay problemptry our best to do the finishing-up department of epidemiology public health college of harbin medical university49第四節(jié)第四節(jié) 實(shí)驗(yàn)流行病學(xué)優(yōu)缺點(diǎn)實(shí)驗(yàn)流行病