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1、第第五五章章 广东药学院广东药学院 姚振江姚振江Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.学习目的学习目的F实验流行病学的实验流行病学的定义定义F实验流行病学的实验流行病学的特点特点F实验流行病学的实验流行病学的分类分类F实验流行病学的实验流行病学的设计设计F实验流行病学的实验流行病学的强势与弱势强势与弱势Evaluation only.Created with Aspose.Slides for .NET 3
2、.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.推荐参考文献推荐参考文献吴涛吴涛, 詹思延詹思延, 李李立明立明. 流行病学实流行病学实验研究发展历史验研究发展历史. 中华流行病学杂志中华流行病学杂志 2004; 25(7): 633-636.5第五章第五章实验流行病学研究实验流行病学研究(experimental study)历史发展Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-
3、2011 Aspose Pty Ltd.1747年年苏格兰医师苏格兰医师James Lind首次对比研究首次对比研究了用桔子、柠檬及其他干预治疗坏血病的了用桔子、柠檬及其他干预治疗坏血病的疗效疗效5第五章第五章实验流行病学研究实验流行病学研究Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.OnMay20,1747heisreadytobeginthefirstclinicalnutritionexperiment.E
4、valuation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.group1drankonequartofcideradaygroup2gargledwithsulfuricacidgroup3hadtwospoonfulsofvinegar,3timesadaygroup4drank1/2-pintseawateradaygroup5drankbarleywatergroup6atetwoorangesand1lemonadayHo
5、w did he conduct his experiment?Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.What happened?Onlysailorswhoatetheorangesandlemonfeltbetter.Infact,inonlysixdaystheyfeltgreatandwereabletostartworkingagain.Theothersailorsintheexperiment
6、feltworse.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.1816年 法国Hamilton医师首次报道了爱丁堡的一项大型对照实验，评价放血疗法的效果，这是迄今为止有关采用交替法产生对照的最早记载之一。 It had been so arranged, that this number was admitted, alternately, in such a manner that each of us ha
7、d one third of the whole. The sick were indiscriminately received, and were attended as nearly as possible with the same care and accommodated with the same comforts. One third of the whole were soldiers of the 61st Regiment, the remainder of my own (the 42nd) Regiment. Neither Mr Anderson nor I eve
8、r once employed the lancet. He lost two, I four cases; whilst out of the other third treated with bloodletting by the third surgeon thirty five patients died. Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.1898年丹麦医师Fibiger通过半随机对照实验验证
9、血清治疗白喉的效果。8outof239patientsintheserumtreatedgroupand30outof245inthecontrolgroupdied.Noformalstatisticalanalysiswasperformedbutnoobjectioncanberaisedagainstthestatisticalsignificanceofthenumbers,whichweredeemedcorrectbyaninspectorofthesickbenefitassociation(in1900Pearsoninventedthe2test,10whichwouldh
10、aveshownP=0.0003).Therateofserumsicknesswashighat60%.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Tables - 2-by-2 unstratified11:44:19, 2011-4-22|+-|Total-+-+-+|8231|239-|30215|245-+-+-Total|38446|484Tests of significanceFisherexac
11、ttest(onetailed):0.000187Fisherexacttest(twotailed):0.000289Uncorrectedchi-square:13.24p-value:0.000275YatescorrectedChi-square:12.04p-value:0.000522Measures of exposure effect 95% CIRiskratio:0.270.13,0.58Oddsratio:0.250.11,0.55Riskdifference:-0.09-0.14,-0.04Proportionalattributablerisk:-2.66-6.82,
12、-0.71Populationproportionalattr.risk:-0.56-0.76,-0.26Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.1948年英国医学研究委员会领导开展了世界第一个临床随机对照实验（RandomizedcontroledTrial，RCT），由英国统计学家Hill评估了链霉素治疗肺结核的疗效。Evaluation only.Created with Aspose.Slides f
13、or .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.First “modern” RCT - 1948The hero was Austin Bradford HillThe hero was Austin Bradford HillEvaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Francis TM, Napier JA, Vo
14、ight RB et alEvaluationofthe1954fieldtrialofpoliomyelitisvaccineFinal Report Ann Arbor University Michigan 1957Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.1954fieldtrialofpoliomyelitisvaccineEvaluation only.Created with Aspose.Sli
15、des for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Results of vaccine trialsThe randomized, controlled experimentSizeSizeRate (per 100,000)Rate (per 100,000)TreatmentTreatment200,000200,0002828ControlControl200,000200,0007171No consentNo consent350,000350,0004646The Observed
16、Control studySizeSizeRate (per 100,000)Rate (per 100,000)Grade 2 (vaccine)Grade 2 (vaccine)225,000225,0002525Grade 1, 3 (control)Grade 1, 3 (control)725,000725,0005454Grade 2 (no consent)Grade 2 (no consent)125,000125,0004444Source: Thomas Francis, J r., “An evaluation of the 1954 Poliomyelitis vacc
17、ine trials-summary report,” American Journal of Public Health vol 45 (1955) pp. 1-63.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd. 实验流行病学实验流行病学(experimental epidemiology) 以人群为研究对象的实验研究 : 又称： 流行病学实验流行病学实验（epidemiological experiment）
18、 干预研究干预研究（intervention study ）Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学(experimental epidemiology)将来自同一总体的将来自同一总体的研究人群研究人群随机随机分为分为实验组实验组和和对照组对照组，研究者对实验组人群施，研究者对实验组人群施加某种加某种干预干预措施后，措施后，随访随访并并比较两组人群比较两组人群的发病的发病
19、(死亡死亡)情况或健康状况有无差别及情况或健康状况有无差别及差别大小差别大小，从而判断干预措施效果的，从而判断干预措施效果的一种一种前瞻性、实验性研究方法前瞻性、实验性研究方法。Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.随访观察随访观察结局事件不发生结局事件不发生结局事件发生结局事件发生结局事件不发生结局事件不发生随随机机分分组组实验流行病学研究原理示意图实验流行病学研究原理示意图Evaluation only
20、.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学主要特点主要特点对照对照前瞻前瞻干预干预随机随机Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学对照对照前瞻前瞻干预干预随机随机与观察性研究进行比
21、较与观察性研究进行比较描述性研究描述性研究分析性研究分析性研究队列研究队列研究病例对照研究病例对照研究为什么要设立对照为什么要设立对照?因果性实验中的对照法则因果性实验中的对照法则设立对照设立对照Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.对照对照前瞻前瞻干预干预随机随机为什么要设立对照为什么要设立对照?影响实验流行病学研究效应的主要因素影响实验流行病学研究效应的主要因素不能预知的结局不能预知的结局霍桑效应霍桑效
22、应(Hawthorne effect)安慰剂效应安慰剂效应(placebo effect)潜在的未知因素的影响潜在的未知因素的影响设立对照的方式设立对照的方式标准方法对照标准方法对照安慰剂对照安慰剂对照自身对照自身对照交叉对照交叉对照Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学随访结局指标随访结局指标前因后果前因后果对照对照前瞻前瞻干预干预随机随机与观察性研究进行比较与观察性
23、研究进行比较描述性研究描述性研究分析性研究分析性研究队列研究队列研究病例对照研究病例对照研究Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学p暴露暴露p研究者施加研究者施加对照对照前瞻前瞻干预干预随机随机与观察性研究进行比较与观察性研究进行比较描述性研究描述性研究分析性研究分析性研究队列研究队列研究病例对照研究病例对照研究Evaluation only.Created with
24、Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.盲法盲法 (blinding)减少研究对象和研究者主观因素的影响(信息偏倚)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client
25、Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Justkidding：双盲实验患者家属：医生,流行病学家采用的双盲试验是这个意思吗？医生患者护士Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.单盲单盲(single blind)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profi
26、le 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.双盲双盲(double blind)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.三盲三盲(triple blind)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspos
27、e Pty Ltd.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锻炼锻炼饮食饮食教育教育Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.即使是药物也很难完全做到盲法即使是药物也很难完全做到盲法药物的气味、味觉、感觉药物的气味、味觉、感觉副作用副作用检验结果检验结果对药物进行化验对药物进行化验Evaluation only.Created with Aspose.Slides f
28、or .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.p来自总体的随机抽样人群来自总体的随机抽样人群p随机分配到实验组和对照组随机分配到实验组和对照组5第五章第五章实验流行病学实验流行病学对照对照前瞻前瞻干预干预随机随机与观察性研究进行比较与观察性研究进行比较描述性研究描述性研究分析性研究分析性研究队列研究队列研究病例对照研究病例对照研究Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyrigh
29、t 2004-2011 Aspose Pty Ltd.控制混杂的方法控制混杂的方法研究设计阶段研究设计阶段随机化随机化限制限制匹配匹配资料分析阶段资料分析阶段分层分析分层分析多变量分析多变量分析Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.对照对照前瞻前瞻干预干预随机随机可比的对照可比的对照有效的对照有效的对照组间非处理因素可比组间非处理因素可比组间效应测量可比组间效应测量可比随机分配随机分配盲法盲法保证基线组间平
30、衡保证基线组间平衡保证随访过程中组间平衡保证随访过程中组间平衡Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学真实验真实验(true experiment)对对照照前前瞻瞻干干预预随随机机描述性研究描述性研究 -分析性研究分析性研究 队列研究队列研究 + 病例对照研究病例对照研究 ( / ) +随随机机抽抽样样检检验验假假设设能能力力+Evaluation only.Create
31、d with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学真实验真实验(true experiment)对对照照前前瞻瞻干干预预随随机机类实验类实验(quasi-experiment)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病
32、学实验流行病学类实验类实验(quasi-experiment)真实验真实验(true experiment)对对照照前前瞻瞻干干预预随随机机Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.自身前后比较自身前后比较比比较较干预前干预前测量测量干预干预干预后干预后测量测量已知结果Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5
33、.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究对象研究对象试验组试验组(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发病时序发病时序工作时序工作时序5第五章第五章实验流行病学实验流行病学随随 机机分分 配配Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学实验流行病学Evaluation only.Created with Aspose.
34、Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.资料的收集资料的收集数据分析数据分析研究设计研究设计结果解释结果解释实验流行病学研究的实施实验流行病学研究的实施Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究设计研究设计明确研究目的明确研究目的选择研究对象确定实验现场设立对照确定样本大小随机化分组应用盲法暴
35、露暴露疾病疾病干预措施干预措施结局结局Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究设计研究设计明确研究目的选择研究对象选择研究对象确定实验现场设立对照确定样本大小随机化分组应用盲法对干预措施有效的人群对干预措施有效的人群预期发病率较高的人群预期发病率较高的人群干预对其无害的人群干预对其无害的人群能将实验坚持到底的人群能将实验坚持到底的人群依从性好的人群依从性好的人群排除排除(exclusions)减少结果偏倚
36、减少结果偏倚(保证内部真实性保证内部真实性)影响结果外推影响结果外推(影响外部真实性影响外部真实性)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究设计研究设计明确研究目的选择研究对象确定实验现场确定实验现场设立对照确定样本大小随机化分组应用盲法相对稳定、足够的数量相对稳定、足够的数量较高、稳定的发病率较高、稳定的发病率疫苗：近期未发生该病流行疫苗：近期未发生该病流行较好的医疗卫生条件较好的医疗卫生条件领导重视、
37、群众配合领导重视、群众配合Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究设计研究设计明确研究目的选择研究对象确定实验现场设立对照设立对照确定样本大小随机化分组应用盲法有效对照有效对照安慰剂对照安慰剂对照交叉对照交叉对照Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011
38、 Aspose Pty Ltd.研究设计研究设计明确研究目的选择研究对象确定实验现场设立对照确定样本大小确定样本大小随机化分组应用盲法干预前结局指标干预前结局指标 ，样本量，样本量 干预措施实施前后的变化干预措施实施前后的变化 ，样本量，样本量 ，样本量，样本量 (1 - ) ，样本量，样本量 单侧检验单侧检验 或双侧检验或双侧检验 研究对象分组数量研究对象分组数量Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第
39、五章第五章实验流行病学研究实验流行病学研究实例实例计数资料计数资料假设对照组的发病率为假设对照组的发病率为40%，通过干预措施发，通过干预措施发病率下降到病率下降到20%才有推广使用价值，规定才有推广使用价值，规定 =0.01（双侧），（双侧）， =0.05，问两组要观察多少人，问两组要观察多少人？ 干预措施实施前后的变化干预措施实施前后的变化 (1 - )单侧检验或双侧检验单侧检验或双侧检验研究对象分组数量研究对象分组数量Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyrig
40、ht 2004-2011 Aspose Pty Ltd.EpiCalc 2000Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.EpiCalc 2000Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.5第五章第五章实验流行病学研究实验流行病
41、学研究实例实例计量资料计量资料假设对照组血清胆固醇水平为假设对照组血清胆固醇水平为215mg/dl，合，合理膳食可以使干预组较对照组降低理膳食可以使干预组较对照组降低15mg/dl，已知，已知从其他资料获得胆固醇标准差为从其他资料获得胆固醇标准差为25mg/dl，规定，规定 =0.05（双侧），（双侧）， =0.05，计算各组样本数？，计算各组样本数？ Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.EpiCalc
42、2000Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.EpiCalc 2000Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究设计研究设计明确研究目的选择研究对象确定实验现场设立对照确定样本大小随机化分组随机化分组应用盲法简单随机分组
43、简单随机分组 分层随机分组分层随机分组整群随机分组整群随机分组Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.简单随机分组简单随机分组EpiCalc 2000Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.分层随机分组分层随机分组总总体体层
44、层层层层层可按年龄、性别、可按年龄、性别、种族、教育水平种族、教育水平等分层等分层在各层内再进行前在各层内再进行前述的简单随机分组述的简单随机分组Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.整群随机分组整群随机分组以家庭、学校、医院、村庄或居民区以家庭、学校、医院、村庄或居民区等为单位随机分组等为单位随机分组要保证组间可比性要保证组间可比性(群间变异越小越好群间变异越小越好)Evaluation only.Cre
45、ated with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.明确研究目的选择研究对象确定实验现场设立对照确定样本大小随机化分组应用盲法应用盲法研究设计研究设计单盲单盲 双盲双盲三盲三盲Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.数据分析数据分析资料整理表资料整理表结局指标p频率指标p计
46、量指标效应指标Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.数据分析数据分析频率指标频率指标治疗措施治疗措施有效率有效率治愈率治愈率病死率病死率生存率生存率复发率复发率预防措施预防措施抗体阳性率抗体阳性率发病率发病率感染率感染率资料整理表结局指标结局指标p频率指标p计量指标效应指标计量指标计量指标治疗措施治疗措施血压血压胆固醇胆固醇预防措施预防措施抗体几何平抗体几何平均滴度均滴度Evaluation only.Cr
47、eated with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.数据分析数据分析资料整理表结局指标结局指标p频率指标p计量指标效应指标组间差异的统计学检验组间差异的统计学检验Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.数据分析数据分析保护率保护率效果指数效果指数资料整理表结局指标p频率指
48、标p计量指标效应指标效应指标Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.保护率保护率 (protective rate, PR)保护功效保护功效 (protective efficacy, PE)归因保护归因保护/预防比例预防比例 (attributable protective proportion)指标涵义指标涵义对照组如果接受干预措施，则会减少的发病或死亡的比例对照组如果接受干预措施，则会减少的发病或死亡的
49、比例试验组中归因于干预措施而减少的发病或死亡的比例试验组中归因于干预措施而减少的发病或死亡的比例Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.效果指数效果指数 (index of effectiveness, IE)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 As
50、pose Pty Ltd.偏倚问题偏倚问题偏倚偏倚 (bias) 使实验流行病学研究的结果系统的偏离使实验流行病学研究的结果系统的偏离真相，即低估或高估某干预措施的效果。真相，即低估或高估某干预措施的效果。Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.偏倚问题偏倚问题选择偏倚选择偏倚信息偏倚混杂偏倚研究初期研究初期严格、正确地执行随机化分配及盲严格、正确地执行随机化分配及盲法法(隐藏隐藏分组情况分组情况)，可以最大
51、限度，可以最大限度地减少实验流行病学研究中的选择地减少实验流行病学研究中的选择偏倚偏倚反之，实验流行病学研究同样不能反之，实验流行病学研究同样不能幸免选择偏倚幸免选择偏倚Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.偏倚问题偏倚问题选择偏倚选择偏倚信息偏倚混杂偏倚随机分配后随机分配后实验流行病学研究中涉及的选择偏实验流行病学研究中涉及的选择偏倚主要来自于随机分配后的倚主要来自于随机分配后的“退出退出” (withd
52、rawal)不合格不合格(ineligibility)不依从不依从(noncompliance)失访失访(loss to follow-up)降低效率降低效率易引入选择偏倚易引入选择偏倚Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.偏倚问题偏倚问题选择偏倚选择偏倚信息偏倚混杂偏倚随机分配后随机分配后“退出退出”引起偏倚的原因引起偏倚的原因退出者发生结局事件的概率不退出者发生结局事件的概率不同于继续随访者同于继续随访
53、者(信息截尾信息截尾)信息截尾的程度在不同干预组信息截尾的程度在不同干预组间不同间不同意向性分析(intention to treat analysis)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.RCTs Basic AnalysisDichotomous (Disease Yes/No) OutcomeNRandomizeRt = a/n1Rc = c/n0RR = Rt/Rc and ARR = Rc- R
54、tEvaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Measures of Effect used in RCTs EER = 30/100= 30%CER = 40/100 = 40% EER = Experimental (or treatment) event rateCER = Control (or baseline) event rateRR = EER/CER = 30/40 = 75%RRR = 1 R
55、R = 25%ARR = CER - EER = 40 30 = 10%NNT = 1/ARR = 1/0.10 = 10Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.StatisticalAnalyses-ITTIntention-to-TreatAnalysisGoldStandardComparesoutcomesbasedonoriginalrandomizationschemeregardlessofel
56、igibility,non-compliance,cross-overs,andlost-to-follow-upPerProtocol(PP)AnalysisComparesoutcomesbasedonactualtreatmentreceivedamongthosewhowerecompliant(analysisdropsnon-compliant)AskswhetherthetreatmentworksamongonlythosethatcomplyAsTreated(AT)AnalysisComparesoutcomesbasedonactualtreatmentreceivedr
57、egardlessoforiginalassignment.Equivalenttoanalyzingthedataasacohortstudy!Askswhetherthetreatmentworksamongthosethattookit.BothPPandATapproachesignoreoriginalrandomizationandarethereforesubjecttoBIAS!Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 As
58、pose Pty Ltd.ITT vs. Per-Protocol vs. As TreatedEvaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.EffectofITTvs.PPvs.ATanalysesonanRCTofcoronaryarterybypasssurgeryversusmedicaltreatmentin767menwithstableangina.(Lancet1979;i:889-93).Allo
59、cated(vs.actual)treatmentMedical(medical)Medical(surgical)Surgical(surgical)Surgical(medical)ARR(95%CI)Subjects3235036826Deaths272156Mortality8.4%4.0%4.1%23.1%ITTanalysis7.8%(29/373)5.3%(21/394)2.4%(-1.0,6.1)PPanalysis8.4%(27/323)4.1%(15/368)4.3%(0.7,8.2)ATanalysis9.5%(33/349)4.1%(17/418)5.4%(1.9,9.
60、3)Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.偏倚问题偏倚问题选择偏倚信息偏倚信息偏倚混杂偏倚确定偏倚确定偏倚(ascertainment bias)施加干预的人施加干预的人被干预的人被干预的人判断结局的人判断结局的人分析数据的人分析数据的人(安慰剂)+Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.C
61、opyright 2004-2011 Aspose Pty Ltd.选择偏倚信息偏倚混杂偏倚混杂偏倚随机化偏倚问题偏倚问题Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Randomization beautifully solved the problem of confounding 随机分组以最美丽最简单的方式解决了混杂的问题随机分组以最美丽最简单的方式解决了混杂的问题Placebo and blinding
62、reduce selection and information bias 安慰剂和盲法协助控制选择偏倚和信息偏倚安慰剂和盲法协助控制选择偏倚和信息偏倚The scientifically most rigorous method of establishing causal relationship and forms the gold standard for evaluation of clinical effectiveness. 随机对照临床试验是在人群中建立因果关系最可靠的方随机对照临床试验是在人群中建立因果关系最可靠的方式式, 因而成了评估医学干预效果的金标准因而成了评估医学干预
63、效果的金标准Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.研究中的伦理学问题研究中的伦理学问题研究对象人研究对象人研究必须具有科学依据研究必须具有科学依据公平选择研究对象公平选择研究对象获得社区的知情同意获得社区的知情同意(informed consent)对照组的选择和对照组的选择和“善后善后”处理处理较长试验期限导致较长试验期限导致“延误延误”问题问题Evaluation only.Created with A
64、spose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd. 优缺点优优 点（点（strength） 随机分组，能够较好地控制偏倚和混杂 为前瞻性研究，因果论证强度高 有助于了解疾病的自然史 获得一种干预与多种结局的关系5第五章第五章实验流行病学研究实验流行病学研究Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd
65、. 难以保证有好的依从性 难获得一个随机的无偏样本 容易失访 费用常较观察性研究高 容易涉及伦理道德问题缺缺 点（点（weaknessweakness）5第五章第五章实验流行病学研究实验流行病学研究Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyrigh
66、t 2004-2011 Aspose Pty Ltd.马鸣岗.百日咳菌苗预防效果评价百日咳菌苗预防效果评价.见:钱宇平,主编.流行病学研究实例(第二卷).北京:人民卫生出版社.1991.p83-88.曾光.脊髓灰质炎减毒疫苗得现场试验脊髓灰质炎减毒疫苗得现场试验.见:钱宇平,李立明,主编.流行病学研究实例(第三卷).北京:人民卫生出版社.1996.97-107.于志恒.地方性甲状腺肿人群干预实验地方性甲状腺肿人群干预实验.见:钱宇平,李立明,主编.流行病学研究实例(第三卷).北京:人民卫生出版社.1996.9-20.一些经典的实验流行病学研究实例一些经典的实验流行病学研究实例Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.Evaluation only.Created with Aspose.Slides for .NET 3.5 Client Profile 5.2.0.0.Copyright 2004-2011 Aspose Pty Ltd.
