循证医学_病因学研究和循证医学实践_新_研课件

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Evidence-based Etiology / Harm,病因研究与循证医学实践,Evidence-based Etiology / Harm,学习目标,掌握评价病因性研究真实性原则,(Validity ),掌握评价病因性研究重要性原则,( Importance ),学会应用病因性研究证据的结果，解决临床问题,( Applying ),学习目标掌握评价病因性研究真实性原则(Validity ),病因性研究基本知识,病因性研究基本概念,与病因相关的临床问题,病因性研究的主要方法,病因,/,不良反应研究证据的分级,病因性研究常用统计学指标,病因性研究基本知识病因性研究基本概念,病因性研究基本概念（,1,）,病因是指引起人体发生疾病的原因。病因学是,指研究疾病病因的科学。,病因：致病因素（直接、间接、,危险因素,）,研究内容：用流行病学方法研究并验证危险因,素是否与疾病发生有因果关系，且评估因果联,系的强弱。例,“,吸烟与肺癌关系,”,病因性研究基本概念（1）病因是指引起人体发生疾病的原因。病因,病因性研究基本概念（,2,）,不良反应的研究实质上也是病因学研究,“,因,”,：造成不良反应的各种因素，如各种治疗措施（药物，手术）,医疗过程中临床医师经常需要考虑某种危险因素或治疗措施是否对患者有害。,利是否大于弊？,用他人的研究结果来回答提出的问题,真实性 重要性 实用性,病因性研究基本概念（2）不良反应的研究实质上也是病因学研究,与病因相关的临床问题,该疾病是什么原因造成的？,该药物或治疗措施会导致什么不良反应吗？是否需要停药？,Does exposure to aluminum cause,Alzheimer,s dementia?,Do statins cause cancer?,与病因相关的临床问题该疾病是什么原因造成的？,病因性研究的主要方法,病因性研究的主要方法,病因性研究常用统计学指标,因果相关性强度的指标,RR,(,前瞻性,) RCT, cohort study,OR,(,回顾性）,case-control study,NNH (number needed to harm),clinical importance,暴露多少研究对象可导致,1,例发病,（队列研究）,发生,1,例不良反应所需治疗的病例数,（临床研究）,病因性研究常用统计学指标因果相关性强度的指标,因果相关性强度的指标,当所研究疾病的发病率较低时，,OR,近似于,RR,，故在回顾性研究中可用,OR,估计,RR,其解释与,RR,同，易于统计分析,RR,或,OR,愈高，则因果关系强度愈强,RR,或,OR,有多大才有意义，无一定的标准,1.2-1.5:,弱联系,1.6-2.9:,中等联系,3.0:,强联系,因果相关性强度的指标当所研究疾病的发病率较低时，OR近似于R,可信区间,Confidence Interval,因果关系的强度外，评价,精确度,按,一定的概率,去估计总体参数所在的范,围,95,的可信区间,循证医学,估计总体参数,假设检验：,RR,可信区间Confidence Interval因果关系的强度,有关指标的计算,1. Odds Ratio,2. Relative Risk,3. Risk Reduction / Increase,4. Number Needed to Treat / Harm,有关指标的计算1. Odds Ratio 2. Relati,循证医学_病因学研究和循证医学实践_新_研课件,證據的強度,證據的強度,The Confusion Matrix,+ve Event,-ve Event,Total,Experiment,A,B,A +,Control,C,D,C + D,Also known as the 2 x 2 table,The Confusion Matrix+ve Event-,Event Rate,EER = A / (A+B),试验组事件发生率,CER,=,C,/ (,C,+,D,),对照组事件发生率,+ve Event,-ve,Event,Total,Experiment,A,B,A +,Control,C,D,C + D,Event RateEER = A / (A+B)+ve E,RR and OR,RR,=,EER,/,CER,相对危险度,OR,=,AD,/,BC,比值比,+ve Event,-ve,Event,Total,Experiment,A,B,A +,Control,C,D,C + D,RR and ORRR = EER / CER+ve Eve,Relative Risk Reduction,RRR= (CER - EER) / CER,= 1,RR,相对危险度减少率,+ve Event,-ve,Event,Total,Experiment,A,B,A +,Control,C,D,C + D,Relative Risk ReductionRRR= (C,(Absolute) Risk Reduction,ARR = CER - EER,绝对危险度减少率,+ve Event,-ve,Event,Total,Experiment,A,B,A +,Control,C,D,C + D,(Absolute) Risk ReductionARR =,Number Needed to Treat,NNT = 1 / ARR,得到,1,例有利结果需要防治的病例数,+ve Event,-ve,Event,Total,Experiment,A,B,A +,Control,C,D,C + D,Number Needed to TreatNNT = 1,举例：,Activated Protein C for Severe Sepsis,Bleed,No bleed,Total,APC,30,820,850,Control,17,823,840,APC = Activated Protein C,Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709,举例：Activated Protein C for Se,Event Rates and Odds,EER= A / (A+B),= 30 / 850 = 0.035,CER= C / (C+D),= 17 / 840 = 0.020,EEO = A / B,= 30 / 820 = 0.037,CEO = C / D,= 17 / 823 = 0.021,+ve Event,-ve Event,Total,Experiment,A,B,A +,Control,C,D,C + D,Bleed,No bleed,Total,APC,30,820,850,Control,17,823,840,OR= EEO / CEO,= 0.037 / 0.021 = 1.77,RR= EER / CER,= 0.035 / 0.020 = 1.744,RRI= (EER,CER) / CER,= 0.015 / 0.020 = 0.744,= 74 %,ARI= EER,CER,= 0.035,0.020 = 0.015,NNH= 1 / ARI,= 66,Event Rates and OddsEER= A /,Risk-Benefit Ratio,NNT = 1 / ARR = 1 / 0.06,= 16 (,治疗,16,个获益,1,个,：存活,),反映有利结果（越小越好）,NNH = 1 / ARI = 1 / 0.015,= 66 (,治疗,66,个损害,1,个,：,严重出血,),反映不良反应（越大越好）,Risk-Benefit Ratio= NNT / NNH,= 16 / 66,= 1 / 4,Dead,Not dead,Total,APC,210,640,850,Control,259,581,840,Bleed,No bleed,Total,APC,30,820,850,Control,17,823,840,Risk-Benefit RatioNNT = 1 / A,怎样解决临床问题？,How to solve a clinical problem?,怎样解决临床问题？How to solve a clini,临床病案（,Clinical Scenario,）,84,岁的男性，近期记忆力明显下降,.,高血压病，高胆固醇血症。,右眼白内障术后,2,天，,出现易激、谵妄和性格改变。,无感染，贫血及代谢异常的临床证据。,心理卫生中心会诊：,抗精神病药物,氟哌啶醇, haloperidol ,奋乃静,perphenazine,奥氮平, olanzapine,临床病案（Clinical Scenario）84岁的男性，,临床问题（,Initial Question,）,老年患者中，用,传统性抗精神病药物,（如氟哌啶醇, haloperidol ,奋乃静,perphenazine,）是否会增加死亡风险性？,非典型性抗精神病药物,(,如奥氮平, olanzapine,）是否对老年人更安全？,临床问题（Initial Question）老年患者中，用传,第一步 提出问题,(Ask Clinical Questions),Initial question:,Framing the initial question: answerable,P,atients (population),I,ntervention/exposure,C,omparison,O,utcome,PICO,第一步 提出问题(Ask Clinical Question,转变成可以回答的临床问题,Framing the question,患者类型,(,P,) elderly patients,干预措施,(,I,) haloperidol or perphenazine,对照措施,(,C,) olanzapine,临床结局,(,O,) death,转变成可以回答的临床问题Framing the quest,第二步 查询证据,(Acquire Evidence),PICO: key words,Type of question,：,harm,-,Best evidence,Levels of evidence,-,Optimal source of evidence,Searching worthwhile?,第二步 查询证据 (Acquire Evidence)PIC,病因,/,不良反应研究常用数据库,Best Evidence,（,ACP journal club, EBM),Up to Date,Medline,PubMed: clinical query-etiology,Sumsearch,Ovid,循证医学数据库,(,多库同时检索,),ACP journal club, Cochrane Library( CDSR, CCTR,DARE), Medline, EMBASE,病因/不良反应研究常用数据库Best Evidence（AC,系统评价资料库,(Cochrane Database of Systematic Review,CDSR,),疗效评价文摘库,(Database of Abstracts of Reviews of Effectiveness,DARE,),临床对照试验注册资料库,(Cochrane Controlled Trials Register,CCTR,),方法学数据库,(Cochrane Methodology Database),系统评价资料库(Cochrane Database of S,检索方法,选择数据库：,ACP journal club,（,ovid,database, best evidence,）,在,search,中，键入关键词,olanzapine,etiology,（病因学）,检索结果：,1,篇文献（摘要）,找到全文,检索方法选择数据库：ACP journal club（ovi,循证医学_病因学研究和循证医学实践_新_研课件,循证医学_病因学研究和循证医学实践_新_研课件,筛选结果,ACP journal Club,summary,:,Conventional antipsychotic drugs increased risk for death more than did atypical antipsychotic drugs in elderly patients,ACP Journal Club. 2007;147:23.,Schneeweiss S, Setoguchi S, Brookhart A, Dormuth C,Wang PS.,Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients,.,CMAJ.2007;176:627-32,筛选结果ACP journal Club summary:,循证医学_病因学研究和循证医学实践_新_研课件,研究详情,Background:,Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the,short-term mortality,in a,population-based cohort,of,elderly people,in British Columbia who were prescribed,conventional,and,atypical,antipsychotic medications.,Methods:,We used linked health care utilization data of all BC residents to identify a,cohort,of people aged,65 years,and older,who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the,180-day all-cause mortality,between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications.,研究详情Background: Public health,Results:,Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients,(14.1%),in the conventional drug group died, compared with 2337,(9.6%),in the atypical drug group (,mortality ratio 1.47, 95% confidence interval CI 1.39,1.56). Multivariable adjustment resulted in a 180-day mortality ratio of,1.32,(1.23,1.42). In comparison with risperidone,（,利培酮,）, haloperidol,（,氟哌啶醇,）,was associated with the greatest increase in mortality (mortality ratio,2.14, 95% CI 1.86,2.45) and loxapine,（,洛沙平,）,the lowest (mortality ratio,1.29, 95% CI 1.19,1.40). The greatest increase in mortality occurred among people,taking higher,(above median),doses,of conventional antipsychotic medications (mortality ratio,1.67, 95% CI 1.50,1.86) and,during the first 40 days,after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42,1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding.,Results:Of 37 241 elderly peop,结论,Interpretation:,Among elderly patients, the risk of death associated with,conventional antipsychotic,medications is comparable to and possibly greater than the risk of death associated with,atypical antipsychotic medications,. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients.,结论Interpretation: Among elderl,第三步 评价证据,Appraise Evidence,证据的,真实性,Are the results valid?,证据的,重要性,What are the results?,第三步 评价证据 Appraise Evidence证据的真,证据的真实性,Are the results valid?,证据的真实性Are the results valid?,1,研究方法的论证强度,Type of Reports on Etiology/Harm,哪种研究方法？,论证强度如何？,是否源于真正的人体试验？,Were there clearly defined groups of patients,similar in all important ways,other than exposure to the treatment or other cause?,1 研究方法的论证强度Type of Reports on,本研究,Objective,: In elderly patients, association of conventional or atypical antipsychotic drugs (APDs) with death ?,Design:,Cohort study,Participants:,37241 patients 65 y of age,oral,conventional,(,n,= 12 882, mean age 80 y),atypical,(,n,= 24 359, mean age 80 y).,Exclusion criteria: cancer and use of APDs in the year,before the index date.,本研究Objective: In elderly patie,2,两组结局暴露因素的测量方法是否一致？,Were treatments/exposures and clinical outcomes measured in the same ways in both groups,? (Was the assessment of outcomes either,objective,or,blinded to exposure,?),Were the outcomes and exposures,measured in the same way,in the groups being compared,?,2 两组结局暴露因素的测量方法是否一致？Were treat,Cohort Study,Surveillance bias:,监测偏倚,偏倚的控制,客观指标（,Objective outcome,）：病死率,主观指标（,Subjective outcome,）,: Blinding,举例：,乙型肝炎与肝癌关系的研究,Cohort StudySurveillance bias:,3.,随访时间及失访率,Was the follow-up of the study patients,sufficiently long (for the outcome to,occur) and complete?,举例：,HP,与胃癌：,5,年（无差异），,10,年（显著差异）,失访超过,20,？,-,结果将失去真实性,3. 随访时间及失访率Was the follow-up o,4,病因,/,不良反应研究结果是否符合病因诊断原则,Do the results of the harm study satisfy some of the diagnostic tests for causation?,4 病因/不良反应研究结果是否符合病因诊断原则Do the,Is it clear that the exposure preceded the onset of the outcome?,因果效应的先后顺序仅见于前瞻性研究,Is there a dose,response gradient?,因果效应的相关程度，剂量依赖（吸烟与肺癌）,Is there any positive evidence from a,“,dechallenge,rechallenge,”,study?,符合流行病学规律,-,危险因素减弱，发病减少,Is it clear that the exposure,Is the association consistent from study,to study?,不同研究，结果一致（,HP,与胃癌）,Does the association make biological,sense?,充分的生物学依据（,CCB,与癌症，坏血病与水果蔬菜）,Is the association consistent,Key Points,1. Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?,研究方法的论证强度,2. Were treatments/exposures and clinical outcomes measured in the same ways in both groups?,测量方法一致,3. Was the follow-up of the study patients sufficiently long (for the outcome to occur) and complete?,随访时间及失访率,Key Points1. Were there clearl,证据的重要性,What are the results?,证据的重要性What are the results?,1.,因果,联系强度,What is the,magnitude,of the association between the exposure and outcome?,How strong is the,association,between exposure and outcome?,RR,OR NNH,1.因果联系强度What is the magnitude,2.,结果是否,准确,？,What is the,precision,of the estimate of the,association,between the exposure and outcome?,How precise is the estimate of,risk,?,95%CI,2. 结果是否准确？What is the precisio,Conventional APD vs Atypical APDAssociation with death,Conventional APD vs Atypical A,第四步应用证据,How can I apply the results to mypatient?,第四步应用证据How can I apply the re,病情相似,Is our patient so different from those included in the study that its results cannot apply?,Were the study patients similar to my patient?,基于纳入和排除标准,病情相似Is our patient so differen,本研究,Patients: 65 y of age , 60-65% women,Used 1 medical service, and filled 1 prescription in the two 6-month intervals before the index date.,Exclusion criteria: cancer and use of APDs in the year before the index date.,Atypical APDs: risperidone, quetiapine,olanzapine, and clozapine,Conventional APDs: loxapine,haloperidol, chlorpromazine, trifluoperazine, thioridazine, pimozide, promazine,perphenazine, fluphenazine, mesoridazine, and thiothixene.,本研究Patients: 65 y of age , 6,权衡利弊,What is our patient,s risk of benefit and harm from the agent?,NNT and NNH,权衡利弊What is our patients risk,举例,一项心律失常抑制试验（,CAST):,恩卡尼,/,氟卡尼与安慰剂：,10,月随访，病死率分别为,7.7%,和,3.0%,，,NNH,21,（平均每,21,个患者服此药，将有,1,人发生额外死亡）,NSIAD,与消化道出血：,NNH,2000,（每,2000,人服,NSAIDs,，预期增加,1,例消化道出血患者）,举例一项心律失常抑制试验（CAST):,本病案,使用传统和非典型性抗精神病药物,NNT/NNH,作者未进行计算和分析,查询其他证据,本病案使用传统和非典型性抗精神病药物,患者的价值观和愿望,What are our patient,s preferences,concerns, and expectations from this treatment?,1,、为了避免疾病的进展而接受治疗，可能带来不良反应,2,、宁愿冒疾病进展的风险而不接受治疗,3,、关注费用,4,、无所谓的态度,患者的价值观和愿望What are our patient,其他可替代的疗法,What alternative treatments are,available?-,当危险因素或治疗措施的危险明确而且巨大，则应立即脱离危险因素或终止治疗。,举例,-blockers for hypertension in patients with asthma,治疗高血压的,受体阻滞剂能加重支气管痉挛；血管紧张素转换酶抑制剂巯甲丙脯酸、依那普利等，既能降压，又不诱发支气管痉挛，,其他可替代的疗法What alternative treat,本病案：临床决策,对该患者选择哪类抗精神病药,?,本病案：临床决策对该患者选择哪类抗精神病药?,Evidence-based practice in real time,直接查询,已经评价过的高质量的综合临床证据,(preappraised evidence),，如选择数据库,“,ACP journal,club,”,“,临床证据,”,（,clinical evidence,，,www.clinicalevidence.org,）等进行查询。,这些信息资源一般收集高质量且临床实用性强的研究，,已经对某种病因性研究的价值进行了总结,。,使用已评价过的高质量证据，临床医师可在,30,秒内找,到拟解决问题的答案，特别适用于在床旁实践循证医,学,Evidence-based practice in rea,知识回顾,Knowledge Review,知识回顾Knowledge Review,