1. 医学文献的有效应用 浙江大学医学部医学信息中心 胡小君

2. Prepare students to make independent, balanced clinical decisions that contribute to optimal patient outcomes. Clinical Reasoning 的纵向目标 :

3. Clinical Reasoning 的纵向目标 By end of Year 2, students should be able to: Understand patient-centered outcomes and shared medical decision-making Systematically analyze any clinical problem Make independent judgments on tests and treatments, based on published evidence Habitually seek and apply new knowledge from reliable sources

4. Core Competencies Heath Professions Education: A Bridge to Quality Institute of Medicine 2003 1.Provide patient-centered care 2. Work in interdisciplinary teams 3.Employ evidence-based practice 4.Apply quality improvement 5.Utilize informatics

5. Scientific Foundations for future Physicians Scientific Foundations for future Physicians AAMC-HHMI 2009 “science competency” (learner performance), rather than academic courses. “science competency” (learner performance), rather than academic courses.

6. Competency M8 Apply quantitative knowledge and reasoning—including integration of data, modeling, computation, and analysis—and informatics tools to diagnostic and therapeutic clinical decision making.

7. 本次课的目标 理解从文献样例中获得的两个关键概念： – 关注结果 – 从病人角度考虑医学, （ 6 “requests” ） 理解医学文献及其有效性的评价标准 –What is it? –What’s in it? –Who creates it, how and why? –What is clinical “evidence”? –What are the criteria for validity of medical literature? –Where to find the medical literature. –Matching information sources to question types: what should an MS1 read? What are the best sources for PBL? –PBL Learning issue sourcing matrix: how to use it

8. 医学结果 广义定义： results that matter to someone Patient-centered, clinical, satisfaction, cost, safety Individual and population outcomes 着眼于结果的各种器官系统及其相关状况的方法。 “Input” focus: “How are iron chelating （螯合） agents used to treat complications of thalassemia( 地中海贫 血 ) ?” Outcome focus: “What outcomes do patients with thalassemia experience under different treatment approaches?”

9. 病人参照框  Don’t kill me  Do help me  Don’t hurt me  Don’t make me feel helpless  Don’t keep me waiting  Don’t waste resources, mine or anyone else’s

10. Professionalism Our duty to patients  Know what to do  Do what is known  Understand what is done  Provide ALL and ONLY the care patients need

11. Know what to do: 3 sources of medical knowledge –What we hear –What we see –What we read

12. The Medical Literature: what is it? Definition: Experts’ systematically recorded observations relating to human illness and how to relieve it, published in generally accessible locations and forms –Media: journals, books, web sites, audio, video –Range: from single case reports to systematic syntheses of large trials –VERY LARGE!

13. The Medical Literature: What kinds do clinicians use? 作为临床医生, 我们是 “ 信息不偏食者 ” –We “consume” all different types of published information that help us care for patients –But: we prefer some types to others, when available e.g., we prefer large clinical trials to case series to guide choice of therapy

14. What kinds of information does the medical literature contain? 用三条 “ 轴 ” 简单分类 Biology (mechanism) vs. Outcomes Primary vs. Secondary Observational vs. Experimental

17. Major clinical knowledge “Domains”: –Biological knowledge: normal human biology and disease mechanisms –Outcomes knowledge: how tests and treatments perform in real patients –Both types necessary, and complementary –Major trend: clinicians increasingly favor outcomes information (when available) as a basis for specific clinical decisions –But – clinicians must judge outcome data in context of known biology

18. Based on the title, is this study an example of Outcomes or Biological clinical knowledge? Tropak MB, et al. Pharmacological enhancement of beta-hexosaminidase （ 已糖胺酶 ） activity in fibroblasts （ 纤维原细胞 ） from adult Tay-Sachs and Sandhoff Patients. J Biol Chem. 2004 Apr 2;279(14):13478-87

19. The Medical Literature: Two main article types Primary studies: initial, first-hand report of observations from a (new) data set –examples: case series, clinical trial Secondary literature: summaries or syntheses of primary studies – examples: review article, textbook chapter

20. Based on the title, is this study an example of primary or secondary literature? Khoury MJ, McCabe LL, McCabe ER. Population screening in the age of genomic medicine. N Engl J Med. 2003 Jan 2;348(1):50-8

21. The Outcomes Literature: Two main classes of study design –Observational: examples: case series, case control, cohort –Experimental: examples: Clinical Trials, RCT’s –Each has advantages and weaknesses –General preference for experimental designs to answer clinical questions

22. What is “Clinical Evidence”? Inclusive definition : All systematically collected knowledge relating to illness and its treatment “Evidence-based” medicine: care that reflects a good-faith effort to tie clinical decisions to current knowledge EBM: a method, and a movement

23. Clinical Evidence: Orthodox definition Clinical evidence comes from patient- centered clinical research which investigates the accuracy and precision of diagnostic tests, the efficacy and safety of therapeutic regimes, and the reliability of prognostic indicators. DL Sackett, Evidence-based Medicine. How to Practice & Teach EBM, 2000

24. “Evidence alone is never enough” Evidence-based Medicine (EBM) combines individual clinical expertise with the best available clinical evidence from systematic research in making decisions about the care of individual patients. Clinical expertise is the proficiency and judgment that individual clinicians acquire through knowledge, clinical experience, and practice. DL Sackett, Evidence-based Medicine. How to Practice & Teach EBM, 2000

28. Obtain current best evidence - 文献有效性分析 The hierarchy of evidence:

29. 临床证据的质量分级 A 级 : 从至少一项设计良好的大样本随机临床试验 (RCTs) 或多个随机临床试验的系统分析 ( 包括 Meta 分析 ) 中获取的 证据。A 级 : 从至少一项设计良好的大样本随机临床试验 (RCTs) 或多个随机临床试验的系统分析 ( 包括 Meta 分析 ) 中获取的 证据。 B 级 : 从一项中等规模 RCT 或由中等数量患者参与的小规 模 Meta 分析提供的证据，或从一项 RCT 提供的证据。B 级 : 从一项中等规模 RCT 或由中等数量患者参与的小规 模 Meta 分析提供的证据，或从一项 RCT 提供的证据。 C 级：有缺点的临床试验或分析性观察性研究。C 级：有缺点的临床试验或分析性观察性研究。 D 级：病例系列分析和质量较差的病例对照研究。D 级：病例系列分析和质量较差的病例对照研究。 E 级：专家个人意见、个例报告。E 级：专家个人意见、个例报告。

30. 初步判定文献的临床价值一般考虑下述几个 方面 1 ．研究结果是否具有效性 ( 内部有效性）1 ．研究结果是否具有效性 ( 内部有效性） 2. 研究效果的衡量（外部有效性）2. 研究效果的衡量（外部有效性） 3. 偏倚3. 偏倚

31. 该文献所报道的研究结果是否具有效性 （ 1 ）是否随机地将病人分配入试验组和对照组 （ 1 ）是否随机地将病人分配入试验组和对照组 （ 2 ）结果分析和报道是否包括了全部入选病人, 是否已完 成了对象的随访 （ 2 ）结果分析和报道是否包括了全部入选病人, 是否已完 成了对象的随访 （ 3 ）对医生及受试者是否实行了盲法 （ 3 ）对医生及受试者是否实行了盲法 （ 4 ）试验组和对照组其他干预因素和基线因素是否一致 可比 （ 4 ）试验组和对照组其他干预因素和基线因素是否一致 可比

32. 研究效果的衡量 （ 1 ）治疗效果的大小 （ 1 ）治疗效果的大小 （ 2 ）治疗效果的价值 （ 2 ）治疗效果的价值 （ 3 ）试验结果对病人作用的大小 （ 3 ）试验结果对病人作用的大小 （ 4 ）试验结果能否指导医疗实践 （ 4 ）试验结果能否指导医疗实践 （ 5 ）该项治疗的效益、风险和成本 （ 5 ）该项治疗的效益、风险和成本 （ Exp: 动机 —— 作者 vs 赞助者 ） （ Exp: 动机 —— 作者 vs 赞助者 ）

33. 偏倚 —— 是指各种可以导致研究结果失真的系统性误差。 选择偏倚（ Selection bias) 志愿者偏倚（ Volunteer bias ）, 也称无应答偏倚（ Non-respondent bias ） 检出偏倚（ Unmasked bias ） 幸存者偏倚（ Survivor bias ） 会员制偏倚（ Membership bias ） 测量偏倚（ Measurement bias ） 观察者偏倚（ Observer bias ） 回忆偏倚（ Recall bias ） 干预偏倚（ Intervention bias ） 随访偏倚（ Follow-up bias ） 分析偏倚（ Analysis bias ）

34. 如何有效应用医学文献 参见临床问题与资源的一般矩阵 证据资源倒金字塔