实验流行病学.ppt

1、1,实验流行病学研究 Experimental Epidemiology,哈尔滨医科大学流行病学教研室 Department of epidemiology ，Harbin Medical University,2,理论流行病学,流行病学研究方法 Research Method of Epidemiology,3,James Lind (1716-1794) 维C 缺乏坏血病 (1747) Vitamin C deficiency-scurvy,第一节 概 述 Overview,4,Edward Salk,脊髓灰质炎疫苗(poliomyelitis vaccine)现场试验 (1955)美国+

2、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,Jr,5,一、定义 (definition),Patients 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

3、 were followed up and compared in order to determine effect of intervention.,将研究对象（病人或正常人）随机分配给实验组和对照组，将干预措施 给予实验组人群后，随访观察(follow up)一段时间并比较两组人群的结局, 以便确定干预措施的效果。,6,二、基本原则 (basic principle),对照的原则 control 随机的原则 randomization 盲法的原则 blinding 重复的原则 duplication,7,The research question cannot be answered b

4、y observational studies Earlier observational studies have not answered the research question Existing knowledge is not sufficient 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?,8,三、基本特征

5、 (basic characteristic),前瞻 前瞻性研究 干预 施加一种或多种人为干预处理 随机 研究对象随机分配到比较组 对照 有平行的或可比的实验组和对照组,Prospective Intervention or treatment Random allocation Paralleled control group,9,四、实验流行病学的类型 (types of experimental epidemiology),Clinical trial Field trial or field experiment Community trial.,临床试验 现场试验 社区试验,10,(

6、一)个体试验 (individual trial),研究对象 （未患病者）,实验组 （干预组）,对照组,有效,无效,有效,无效,11,（二）社区试验 (community trial),12,Field Trial or Field Experiment Effect of Hepatitis B Vaccine Against Hepatitis B,infections of hepatitis B,(randomly),13,Community Trial (community intervention trial) Fluoridation of Drinking Water to P

7、revent Saprodontia,(randomly),communities,Prevalence of saprodontia,14,（三）临床试验 (clinical trial),15,Clinical Trial Therapeutic Efficacy of Drug A,effects of Drug A,patients,experiment group (Drug A),control group (placebo),follow up,(randomly),16,Phases of Clinical Trials (FDA),Phase 1: Safety, Clini

8、cal pharmacology and toxicology 15-30 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?,17,Phas

9、e 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 takes place after drug is approved Used

10、to further evaluate long-term safety and effectiveness of new treatment,18,应该注意的问题 Issues should be paid attention to,临床依从性 cliccal compliance 临床不一致性 clinical disagreement 安慰剂效应 placebo effect 向均数回归 regression to the mean,19,现场试验与临床试验比较,注意 !,Difference Between Filed Trial and Clinical Trial,20,现场试验与

11、临床试验比较 Difference Between Filed Trial and Clinical Trial,21,真实验 true experiment,按所具备设计的基本特征 （basic features）,真实验 (true experiment),对照 前瞻 干预 随机,randomization,prospective,control,intervention,22,类实验 quasi-experiment,按所具备设计的基本特征（basic features）,不设对照组 （without control group） 自身前后比较 与已知干预措施比较 设对照组 （with

12、control group） 不能随机分组,23,第二节 研究设计与实施 Design and Execution,24,一 明确研究目的 二 研究对象的选择 三 确定实验现场 四 样本大小的确定,Purpose Object Experimental spot Sample,25,四、样本量估计 （estimate the quantity of the samples）,非连续变量 Non-continuous variable 连续变量 Continuous variable,26,五、随机化分组 （randomization）,简单随机分组 Simple Randomization 分

13、层随机分组 Stratified Randomization 整群随机分组 Cluster Randomization,27,简单随机分组 (simple Randomization),28,Simple Randomization,29,分层随机分组 (stratified randomization),总体,层,层,层,可按年龄、性别、种族、教育水平等分层,在各层内再进行简单随机分组,30,Stratification Randomization Categorizing subjects into subgroups by specific characteristics Enables

14、 researchers to look into separate subgroups to see whether differences exist,31,整群随机分组 (cluster randomization),以家庭、学校、医院、村庄或居民区等为单位随机分组 要保证组间可比性,Base on family, hospital, communication, school, and village. comparability,32,六、设立对照 (control),不能预知的结局 Un-predicable outcome 霍桑效应 Hawthorne effect 安慰剂效应

15、Placebo effect 潜在的未知因素的影响 Unknown factor,33,六、设立对照 (control),方 式 （means） 安慰剂对照 （placebo control） 自身对照 （own control） 交叉对照 （cross-over control）,34,交叉对照对照 cross-over control,A疗法,B疗法,第一阶段 间歇时间 第二阶段,B疗法,A疗法,甲组,乙组,time,Phase Interval Phase,35,八、盲法的应用 (blinding application),单盲（single blind） 研究对象不知分组情况 双盲（d

16、ouble blind） 研究对象、研究者不知分组情况 三盲（triple blind） 研究对、研究者、负责资料收集者不知分组情况,开放试验 (open trial),36,37,博君一笑：双盲实验,38,单盲 (single blind),39,双盲 (double blind),40,三盲 (triple blind),41,三盲研究 (triple blind),42,开放试验 (open trial),不可能实现盲法 外科手术（surgery） 锻炼锻炼（exercise） 饮食（diet） 教育（education） ,43,第三节 资料的收集与分析 Data Collect an

17、d Analyze,44,排除 exclusion 退出 withdrawal 不合格 ineligibility 不依从 noncompliance 失访 loss to follow-up,一、偏倚的防止 （bias avoiding）,45,二、评价指标选择的基本原则 (basic principle of evaluate standardization selection),客观的定量指标 较高的真实性和可靠性 易于观察和测量且易于为受试者所接受,objective validity and reliability acceptability and easy observe,46,

18、三、实验效果的主要评价指标 (evaluate standardization of efficacy of experiment ),47,效果指数 Index of effectiveness，IE,48,四、研究中的伦理问题 (ethics in the research),研究必须具有科研依据 公平选择研究对象 获得社区的知情同意 “延误”的问题 “善后”处理,Must be scientific Select object fairly Have permission to know the fact Delay problem Try our best to do the finishing-up,49,第四节 实验流行病学优缺点 Advantage and Limitation,50,优点 （Advantage）,为前瞻性研究，不存在回忆偏倚 研究对象是随机抽样，随机分组，均衡性较好，具有较高的可比性，减少了混杂偏倚 随访将每个研究对象的反应和结局，实验组和对照