实验流行病学

1、department of epidemiology public health college of harbin medical university1实验流行病学研究实验流行病学研究experimental epidemiology哈尔滨医科大学流行病学教研室哈尔滨医科大学流行病学教研室 department of epidemiology ，harbin medical universitydepartment of epidemiology public health college of harbin medical university2横断面研究监测生态学研究病例对照研究队列研

2、究描述性研究分析性研究临床试验现场试验社区干预项目理论流行病学流行病学研究方法观察性研究实验性研究理论性研究验证假设验证假设 检验假设检验假设产生假设产生假设流行病学研究方法流行病学研究方法 research method of epidemiology department of epidemiology public health college of harbin medical university3james lind (1716-1794)维维c 缺乏坏血病缺乏坏血病 (1747)vitamin c deficiency-scurvy第一节第一节 概概 述述overview dep

3、artment of epidemiology public health college of harbin medical university4edward salk脊髓灰质炎疫苗(poliomyelitis vaccine)现场试验 (1955)美国+加拿大疫苗组(vaccine)安慰奖200,745 人，安慰剂组（placebo）201,229 人保护率(protective rate)：60-90%thomas francis,jrdepartment of epidemiology public health college of harbin medical universit

4、y5 一、定义一、定义 (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将研究对象（病人或正常将研究对

5、象（病人或正常人）随机分配给实验组和人）随机分配给实验组和对照组，将干预措施对照组，将干预措施 给给予实验组人群后，随访观予实验组人群后，随访观察察(follow up)(follow up)一段时间一段时间并比较两组人群的结局并比较两组人群的结局, , 以便确定干预措施的效果。以便确定干预措施的效果。department of epidemiology public health college of harbin medical university6二、基本原则二、基本原则 (basic principle)p对照的原则对照的原则 control p随机的原则随机的原则 randomiz

6、ationp盲法的原则盲法的原则 blindingp重复的原则重复的原则 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预干预 施加一种或多

8、种人施加一种或多种人为干预处理为干预处理随机随机 研究对象随机分配研究对象随机分配到比较组到比较组对照对照 有平行的或可比的有平行的或可比的实验组和对照组实验组和对照组prospective intervention or treatmentrandom allocationparalleled control groupdepartment of epidemiology public health college of harbin medical university9四、实验流行病学的类型四、实验流行病学的类型(t(types of experimental epidemiology)

9、 pclinical trialpfield trial or field experiment pcommunity trial.p临床试验 p现场试验p社区试验department of epidemiology public health college of harbin medical university10(一一)个体试验个体试验 (individual trial)研究对象研究对象（未患病者）（未患病者）实验组实验组（干预组）（干预组）对照组对照组有效有效无效无效有效有效无效无效department of epidemiology public health college o

10、f harbin medical university11（二）社区试验（二）社区试验 (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）临床试验（三）临床试验 (clinical trial)研究对象研究对象（病人）（病人）实验组实验组（干预组）（干预组）对照组对照组有效有效无效无效有效有效无效无效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应该注意的问题应该注意的问题 issues should be paid attention top临床依从性 cliccal compliancep临床不一致性 clinical disagreementp安慰剂效应

17、 placebo effectp向均数回归 regression to the meandepartment of epidemiology public health college of harbin medical university19现场试验与临床试验比较现场试验与临床试验比较注意注意 !difference between filed trial and clinical trialdepartment of epidemiology public health college of harbin medical university20现场试验与临床试验比较 differenc

18、e between filed trial and clinical trialdepartment of epidemiology public health college of harbin medical university21真实验真实验 true experiment按所具备设计的基本特征按所具备设计的基本特征 （basic features）真实验真实验(true experiment)对照 前瞻 干预 随机randomizationprospective control intervention department of epidemiology public health

19、 college of harbin medical university22类实验类实验 quasi-experiment按所具备设计的基本特征按所具备设计的基本特征（basic features）类实验类实验(quasi-experiment)真实验真实验(true experiment)对照对照前瞻前瞻干预干预随机随机p不设对照组不设对照组 （without control group）l自身前后比较l与已知干预措施比较p设对照组设对照组 （with control group）l不能随机分组department of epidemiology public health college

20、 of harbin medical university23第二节第二节 研究设计与实施研究设计与实施 design and execution department of epidemiology public health college of harbin medical university24p一一 明确研究目的明确研究目的p二二 研究对象的选择研究对象的选择p三三 确定实验现场确定实验现场p四四 样本大小的确定样本大小的确定ppurpose pobjectpexperimental spot psample department of epidemiology public he

21、alth college of harbin medical university25四、样本量估计四、样本量估计 （estimate the quantity of the samples）p非连续变量非连续变量 non-continuous variable p连续变量连续变量 continuous variable 22122211)pp()p1(p)p1(pz)p1(p2zn222)(2dzznadepartment of epidemiology public health college of harbin medical university26五、随机化分组五、随机化分组 （r

22、andomization）p简单随机分组简单随机分组 simple randomizationp分层随机分组分层随机分组 stratified randomizationp整群随机分组整群随机分组 cluster randomizationdepartment of epidemiology public health college of harbin medical university27简单随机分组简单随机分组 (simple randomization)department of epidemiology public health college of harbin medical

23、 university28 simple randomizationdepartment of epidemiology public health college of harbin medical university29分层随机分组分层随机分组 (stratified randomization)总总体体层层层层层层可按年龄、性可按年龄、性别、种族、教别、种族、教育水平等分层育水平等分层在各层内再在各层内再进行简单随进行简单随机分组机分组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整群随机分组整群随机分组 (cluster randomization)p以家

25、庭、学校、医以家庭、学校、医院、村庄或居民区院、村庄或居民区等为单位随机分组等为单位随机分组p要保证组间可比性要保证组间可比性pbase on family, hospital, communication, school, and village. pcomparability department of epidemiology public health college of harbin medical university32 六、设立对照对照 (control)p不能预知的结局不能预知的结局 un-predicable outcomep霍桑效应霍桑效应 hawthorne effe

26、ctp安慰剂效应安慰剂效应 placebo effectp潜在的未知因素的影响潜在的未知因素的影响 unknown factordepartment of epidemiology public health college of harbin medical university33 六、设立对照对照 (control) （means）l 安慰剂对照安慰剂对照 （placebo control）l 自身对照自身对照 （own control）l 交叉对照交叉对照 （cross-over control）department of epidemiology public health coll

27、ege of harbin medical university34交叉对照对照交叉对照对照cross-over controla疗法b疗法b疗法a疗法 phase interval phasedepartment of epidemiology public health college of harbin medical university35八、盲法的应用八、盲法的应用 (blinding application) 单盲（单盲（single blind） 研究对象不知分组情况研究对象不知分组情况 双盲（双盲（double blind） 研究对象、研究者不知分组情况研究对象、研究者不知分

28、组情况 三盲（三盲（triple blind） 研究对、研究者、负责资料收集者不研究对、研究者、负责资料收集者不知分组情况知分组情况开放试验开放试验 (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：双盲实验博君一笑：双盲实验department of epidemiology public hea

29、lth college of harbin medical university38单盲单盲(single blind)department of epidemiology public health college of harbin medical university39双盲双盲(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开放试验开放试验(open trial)不可能实现盲法不可能实现盲法外科手术外科手术（surgery）锻炼锻炼锻炼锻炼（exercise）饮食饮食（diet）教育教育（education）department of epidemiology public health college of harbin medical univ

31、ersity43第三节第三节 资料的收集与分析资料的收集与分析 data collect and analyzedepartment of epidemiology public health college of harbin medical university44p排除 exclusionp退出 withdrawaln不合格 ineligibilityn不依从 noncompliancen失访 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、评价指标选择的基本原则二、评价指标选择的基本原则( (basic principle of evaluate standardization selection)p客观的定量指标客观的定量指标p较高的真实性和可较高的真实性和可靠性靠性p易于观察和测量且易于观察和测量且易于为受试者所接易于为受试者所接受受pobjective pvalidity and reliability pacceptability and easy observedepartment of epidemiology public health college o

33、f harbin medical university46%100治疗的总例数治疗有效例数有效率%100治疗人数治愈人数治愈率%100某病受治疗人数因某病死亡人数病死率%100nnn年的病例数随访满年存活的病例数年生存率三、实验效果的主要评价指标三、实验效果的主要评价指标(evaluate standardization of efficacy of experiment )department of epidemiology public health college of harbin medical university47%100检查总人数抗体阳性人数抗体阳性率率死亡实验组发病率死亡对

34、照组发病)()(效果指数index of effectiveness，iecmlog2）（抗体几何平均滴度（antigmtdepartment of epidemiology public health college of harbin medical university48四、研究中的伦理问题四、研究中的伦理问题(ethics in the research)p研究必须具有科研依据研究必须具有科研依据p公平选择研究对象公平选择研究对象p获得社区的知情同意获得社区的知情同意p“延误延误”的问题的问题p“善后善后”处理处理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第四节第四节 实验流行病学优缺点实验流行病