复旦大学：《循证医学》课程教学资源（参考教材）Unit 01 循证医学概论（授课老师：陈世耀）.pdf

Unit 1：循证医学概论授课老师：陈世耀一、教学目的循证医学的基本概念；实施循证医学的步骤；循证证据的分级与推荐标准。二、教学内容 1. 掌握循证医学的基本概念与三要素； 2. 了解原始研究证据类型和二次研究证据； 3. 掌握实施循证医学的步骤； 4. 熟悉快速评阅证据的方法（阅读文献 3：表 1）； 5. 熟悉证据分级水平与推荐分级（阅读文献 3：表 2，表 3）。三、教学重点：实施循证医学的步骤四、教学难点：证据的分级与推荐五、中文和英文关键词循证医学: Evidence-based medicine, 证据质量的分级与推荐：rating the quality of evidence and recommendation 六、预习《循证医学与临床实践》(第 4 版) 第 1-6 章、第 13 章、阅读文献 3：表 1- 表 3 七、讨论思考题 1. 简述实施循证医学的步骤并结合临床问题举例说明（包括用 PICO 方式构建临床问题） 2. 简述循证证据的分级标准 3. 如何成长为既具备科学临床决策能力、又有扎实临床科研功底，高水平、高素质的临床医师？八、参考书 1. 《循证医学与临床实践》(第 4 版).王吉耀主编,科学出版社,2012. 2. 王吉耀主译: Schulz KF, Grimes DA,《柳叶刀》临床研究基本概念,人民卫生出版社,2010. 九、阅读文献 1. Wang JY. Evidence-based medicine in China. Lancet 2010;375: 532–533. 2. Benjamin Djulbegovic, Gordon H Guyatt. Progress in evidence-based medicine: a quarter century on. Lancet, Published Online Feb 16,2017 3. Balshem, H, Helfand M, Holger J. Schunemann HJ, Oxman A D, Kunz R, Brozek J, et al: GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011; 64: 401-406（阅读文献：表1-表3） 4. Lee SW, Kwon JH, Lee HL, etc: Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naïve patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis. Hepatology

Comment Evidence-based medicine in China n recent decade evidence-based medicin has beer ciations in every discipline have bult only to of Evidence-Based Medicine.the china Fvidence-ba ad n na ha lournal of Evidence.Rased Medicine and the chinese with traditional Chinese medicine.Research teams in Joual of Evidence-Based Pediatrics were launched in traditional Chinese medicine have been established and 2001-06.Several organisations developed programmes the rigour of traditional medicine has been gradually to strengthen a national culture of evidence-based raised.The Chinese cinicatrial registrywasestablished medicine,including the clinical epidemiology committee in 2007 and the number of cinical trials registered in China is increasing(figure) niology Networ ver,seve concerns abou the de registere na.Firs f the Ministry of Education's virtual research centre of at their university via databases such as medline but evidence-based medicine founded in 2004,and the doctors in remote areas might not be able to access China Medical Doctor Association's evidence-based the best information resources,which,together with a medicine committeeorganised in2003. limited knowledge of English,could prevent use of the The board members ofthese organisations are located best evidence in their practice. d have sought to als the world's evide ce doe kn e ugh ot com rew ogramme ally 1009 to 2008.1880 cinical research artices we evidence-based in The New Enaland lournal of Medicine the lancet medicine have become compulsory curricula for medical and JAMA.However,only 021%of these were from students and clinical postgraduates in all universities. mainland China.'Wu and colleagues analysed randomised trials on 20 common diseases published in China's natural knowledge infrastructure database m19 200 a found that only 7%of then criteria) criteria (ac ng to an also found in Third because of a lack of fundina for investigator-led 4 andomised trials most good-quality Chinese clinical trials are pharmaceutical premarketing trials sponsored by drug companies.Such research is more likely to have outcomes that favour the sponsor's product,which publiction bias Finally,athough the mnese Govemment h 5 m h into a p of the low ality of trials and selective

Comment 532 www.thelancet.com Vol 375 February 13, 2010 Evidence-based medicine in China In recent decades, evidence-based medicine has been propagated rapidly in China, not only to doctors but also to nurses and other health-care professionals. The Chinese Journal of Evidence-Based Medicine, the Journal of Evidence-Based Medicine, and the Chinese Journal of Evidence-Based Pediatrics were launched in 2001–06. Several organisations developed programmes to strengthen a national culture of evidence-based medicine, including the clinical epidemiology committee of the Chinese Medical Association (established in 1993) working with the Chinese Clinical Epidemiology Network (ChinaCLEN; registered as part of the International Clinical Epidemiology Network in 1989),1 the Chinese Cochrane Centre (which became the 14th centre of the International Cochrane Collaboration in 1999),2 the Ministry of Education’s virtual research centre of evidence-based medicine founded in 2004, and the China Medical Doctor Association’s evidence-based medicine committee organised in 2003.3 The board members of these organisations are located all around China, and have sought to disseminate knowledge of evidence-based medicine throughout the country. Programmes (usually 1–3 months) organised by the Ministry of Education, continuing education programmes, and online education programmes are available. Clinical epidemiology and evidence-based medicine have become compulsory curricula for medical students and clinical postgraduates in all universities. Medical associations in every discipline have built clinical guidelines for common diseases according to the evidence to inform clinical decision making and teaching. Evidence-based medicine has also engaged with traditional Chinese medicine. Research teams in traditional Chinese medicine have been established and the rigour of traditional medicine has been gradually raised. The Chinese clinical trial registry4 was established in 2007 and the number of clinical trials registered in China is increasing (fi gure).5 There are, however, several concerns about the develop ment of evidence-based medicine in China. First, access to scientifi c evidence is not equal in all regions. Doctors from developed areas and large cities, such as Shanghai and Beijing, can search the literature for free at their university via databases such as Medline. But doctors in remote areas might not be able to access the best information resources, which, together with a limited knowledge of English, could prevent use of the best evidence in their practice. Second, most of the world’s clinical evidence does not come from China. Few results from China have been included in systematic reviews6 or clinical practice guidelines. I calculated that from 1999 to 2008, 1880 clinical research articles were published in The New England Journal of Medicine, The Lancet, and JAMA. However, only 0·21% of these were from mainland China.7 Wu and colleagues8 analysed randomised trials on 20 common diseases published in China’s natural knowledge infrastructure database from 1994 to 2005, and found that only 7% of them met methodological criteria (according to Cochrane review criteria). Frequent errors in statistical analyses are also found in Chinese medical journals,9 which reduces the credibility of the evidence. Third, because of a lack of funding for investigator-led randomised trials, most good-quality Chinese clinical trials are pharmaceutical premarketing trials sponsored by drug companies. Such research is more likely to have outcomes that favour the sponsor’s product, which could result in publication bias.10 Finally, although the Chinese Government has made research into traditional medicine a priority area and randomised trials have shown effi cacy for some traditional therapies, because of the low methodological quality of trials and selective 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year 50 100 150 200 250 Numbers 300 350 400 450 500 Phase 1/2 Phase 3 Phase 4 Randomised trials Observational studies Total Figure: Growth in clinical trials in China We searched ClinicalTrials.gov5 on June 15, 2009, with the term “lead principal investigator/sponsor=China

Comment publication of positive results,the efficacy of most JiyaoWang traditional therapies is uncertain. Several factors might contribute to this situation. ogtrz0202hcnghanHopldn ang.ys-hospitalsh.cn Most active dinical researchers and physicians have little formal training in research methods.Even the fdere-d editors and peer reviewers of Chinese medical journals do not know or ignore reporting criteria, such as CONSORT,STROBE D.and PR ntial for publication, Network http://www.chinaden.org.cn trial registration has not be even th 2 http://www..comfco hrane_new (accessed 0t12.200910 y 3 eunteresnchin 4 0eci4.20091. Chi lished partly in Chine sand ar 9 the oad to by ador the advice in relevan 30:1(n WoT.LY.B bias.National level platforms need to be established for a0041046 ing in Chines consultation and administration of multicentre dlinical trials lournal editors must require documentation of ethics approval and dinical trial registration before manuscript acceptance.Joumals in China that are 6ZTadionalChreaemdcne.lanct2oog members of the ICMJEshould obey intemational criteria 12 for publication.Finally,the Chinese Government should 13 increase its support of clinical research,in the form of dlinical research grants for physicians,the creation of of ir 007.53234-42 national repositories of clinical cases and samples of c. dcte2ndnldpactke serum and tissues,and financial support for universities in remote areas to buy literature databases. There is aong waytogo before the words of a anc China ha the Fomenting a prevention revolution for HIV 2010 heralds the year set by the Un to achieve universal stay.and residence in some 57 countries Abou access to HIV prevention,treatment,care,and support.10 million people are currently denied access to life. Desnite maior achievements and heroic efforts over saving treatment the past decades by people living with HiV to assert Despite,or perhaps because of,its success,the AIDS their rights for treatment equity,to end stigma and response has itself come under attack s Coalitions of discrimination,and to ensure more inclusive approaches social conservativeshaveorchestrated a global campaign to governing the response,much remains to be against condom promotion and supported legislation done.80 countries still criminalise homosexuality." criminalising same-sex relations.Such actions increase People living with HIV face restrictions on entry, stigma and isolate people most at risk of HIV at a 533

Comment www.thelancet.com Vol 375 February 13, 2010 533 Fomenting a prevention revolution for HIV 2010 heralds the year set by the UN to achieve universal access to HIV prevention, treatment, care, and support.1 Despite major achievements and heroic eff orts over the past decades by people living with HIV to assert their rights for treatment equity, to end stigma and discrimination, and to ensure more inclusive approaches to governing the response, much remains to be done. 80 countries still criminalise homosexuality.2 People living with HIV face restrictions on entry, stay, and residence in some 57 countries.3,4 About 10 million people are currently denied access to lifesaving treatment. Despite, or perhaps because of, its success, the AIDS response has itself come under attack.5,6 Coalitions of social conservatives have orchestrated a global campaign against condom promotion and supported legislation criminalising same-sex relations.7 Such actions increase stigma and isolate people most at risk of HIV at a publication of positive results, the effi cacy of most traditional therapies is uncertain.11 Several factors might contribute to this situation. Most active clinical researchers and physicians have little formal training in research methods.12 Even the editors and peer reviewers of Chinese medical journals do not know or ignore reporting criteria, such as CONSORT, STROBE, STARD, and PRISMA.13 Preclinical trial registration has not been essential for publication, even though registration results in trials that are more rigorous, effi ciently conducted, and ethically sound.14 To counter these problems, I have several suggestions. Clinical researchers in China should be formally trained and accredited in clinical trial methodology. Reporting guidelines have been translated into Chinese and published partly in Chinese,15 and are now available online.1,7 Researchers need to improve study design by adopting the advice in relevant reporting guidelines to reduce bias. National level platforms need to be established for consultation and administration of multicentre clinical trials. Journal editors must require documentation of ethics approval and clinical trial registration before manuscript acceptance. Journals in China that are members of the ICMJE16 should obey international criteria for publication. Finally, the Chinese Government should increase its support of clinical research, in the form of clinical research grants for physicians, the creation of national repositories of clinical cases and samples of serum and tissues, and fi nancial support for universities in remote areas to buy literature databases. There is a long way to go before the words of a Lancet Editorial—“China has the opportunity to lead the world not only in research quantity, but also in quality”17—are fulfi lled. Jiyao Wang Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China wang.jiyao@zs-hospital.sh.cn I am: president of ChinaCLEN; chair of the Clinical Epidemiology Committee of the Chinese Medical Association; vice chair of the Society of Evidence-Based Medicine, Chinese Medical Doctor Association; a board member of the Ministry of Education’s virtual research centre of evidence-based medicine; and a member of the Board of Trustees, INCLEN. I thank Xue-juan Jin for collecting information to make the fi gure. 1 China Clinical Epidemiology Network. http://www.chinaclen.org.cn (accessed Dec 13, 2009). 2 Chinese Cochrane Centre. http://www.hxyx.com/cochrane_new (accessed Oct 12, 2009) (in Chinese). 3 Chinese Medical Doctor Association. http://www.cmda.gov.cn (accessed Oct 12, 2009) (in Chinese). 4 The Chinese Clinical Trial Register. http://www.chictr.org (accessed Dec 14, 2009). 5 ClinicalTrials.gov. http://www.clinicalTrials.gov (accessed June 15, 2009). 6 Straus SE, Richardson WS, Glasziou P, Haynes RB. Evidence-based medicine: therapy, 3rd edn. London, UK: Elsevier, 2005. 7 Wang JY. Follow international reporting guidelines to raise the quality of articles about clinical research in China (Commentary). Chung Hua Hsiao Hua Tsa Chih 2010; 30: 1 (in Chinese). 8 Wu T, Li Y, Bian Z, Liu G, Moher D. Randomized trials published in some Chinese journals: how many are randomized? Trials 2009; 10: 46. 9 He J, Jin Z, Yu D. Statistical reporting in Chinese biomedical journals. Lancet 2009; 373: 2091–93. 10 Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003; 326: 1167–70. 11 Tang J-L, Liu B-Y, Ma K-W. Traditional Chinese medicine. Lancet 2008; 372: 1938–40. 12 Schulz KF, Grimes DA. The Lancet handbook of essential concepts in clinical research. Philadelphia, PA, USA: Elsevier, 2006. 13 EQUATOR Network. Enhancing the quality and transparency of health research. http://www.equator-network.org (accessed Dec 13, 2009). 14 Yu H, Liu JP. A review of international clinical trial registration. Zhong Xi Yi Jie He Xue Bao 2007; 5: 234–42 (in Chinese). 15 Wang J, Gluud C, eds. Evidence based medicine and clinical practice, 2nd edn. Appendix 3 and 5. Beijing, China: Science Publisher, 2006: 383–87. 16 International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals. http://www.icmje.org (accessed Dec 13, 2009). 17 The Lancet. Reforming research in China. Lancet 2007; 369: 880

www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 1 Review Progress in evidence-based medicine: a quarter century on Benjamin Djulbegovic, Gordon H Guyatt In response to limitations in the understanding and use of published evidence, evidence-based medicine (EBM) began as a movement in the early 1990s. EBM’s initial focus was on educating clinicians in the understanding and use of published literature to optimise clinical care, including the science of systematic reviews. EBM progressed to recognise limitations of evidence alone, and has increasingly stressed the need to combine critical appraisal of the evidence with patient’s values and preferences through shared decision making. In another progress, EBM incorporated and further developed the science of producing trustworthy clinical practice guidelines pioneered by investigators in the 1980s. EBM’s enduring contributions to clinical medicine include placing the practice of medicine on a solid scientifi c basis, the development of more sophisticated hierarchies of evidence, the recognition of the crucial role of patient values and preferences in clinical decision making, and the development of the methodology for generating trustworthy recommendations. Historical origins of evidence-based medicine Since the time of Hippocrates, medicine has struggled to balance the uncontrolled experience of healers with observations obtained by rigorous investigation of claims regarding the eff ects of health interventions. During the past 300 years, demands that the practice of medicine be founded on scientifi cally trustworthy empirical evidence have become increasingly vocal. Pioneers, including Rudolph Virchow, Claude Bernard, and Louis Pasteur, championed science in medicine in Europe, and the Flexner report in the early 20th century cemented scientifi c inquiry as a bedrock of American medicine. Although one can identify attempts to obtain accurate observational data in the work of Pierre-CharlesAlexandre Louis and John Snow in the mid-19th century, and the use of clinical trials in James Lind’s famous study of scurvy in the British navy,1 the focus of most of these innovators was on physiological and basic research as a foundation for clinical practice, rather than the empirical assessment of diagnostic testing, prognosis, and therapeutic eff ect. Indeed, it was not until 1962, with the passage of the US Food and Drug Administration Kefauver-Harris Act in the USA, that rigorous empirical testing of clinical trials in human beings was legally required to establish claims regarding drug effi cacy;2 other countries followed soon thereafter. Although these regulatory developments established the necessity for well done clinical trials demonstrating the effi cacy and safety of new pharmaceutical innovations, unsystematic, uncontrolled clinical experience and physiological reasoning maintained their dominance as drivers of clinical practice. In the 1970s and 1980s, David Sackett, David Eddy, and Archie Cochrane (among others) highlighted the need for strengthening the empirical practice of medicine and proposed initial evidentiary rules for guiding clinical decisions.3–7 In 1991, one of us (GHG) introduced the term evidence-based medicine (EBM),8 with a focus on educating front-line clinicians in assessing the credibility of research evidence, Published Online February 16, 2017 http://dx.doi.org/10.1016/ S0140-6736(16)31592-6 University of South Florida Program for Comparative Effectiveness Research, and Division of Evidence Based Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA (Prof B Djulbegovic MD); H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA (Prof B Djulbegovic); Tampa General Hospital, Tampa, FL, USA (Prof B Djulbegovic); and Department of Clinical Epidemiology and Biostatistics, and Department of Medicine, McMaster University, Hamilton, ON, Canada (Prof G H Guyatt MD) Correspondence to: Prof Benjamin Djulbegovic, USF Health, Program for Comparative Effectiveness Research, University of South Florida, Tampa, FL 33612, USA bdjulbeg@health.usf.edu Key messages • EBM started as a movement in the early 1990s to evaluate and in turn acquire a better empirical basis for the practice of medicine • EBM originally focused on critical appraisal, development of systematic reviews, and clinical practice guidelines • These three domains coalesced in the mid-2000s and characterise the practice of EBM today • EBM has become essential for the training of young clinicians by stressing critical thinking and the importance of statistical reasoning and continuous evaluation of medical practice • EBM has contributed substantially to improvement of the quality of research by transparently documenting the problems with existing research and subsequently developing better research standards • EBM has also improved the practice of medicine by developing methods and techniques for generating systematic reviews and clinical practice guidelines • The main challenge for EBM remains how to develop a coherent theory of decision making by relating to other decision science disciplines Search strategy and selection criteria We searched PubMed for English language articles using the following search criteria: (“Evidence-Based Medicine/ ethics”[Majr] OR “Evidence-Based Medicine/history”[Majr] OR “Evidence-Based Medicine/methods”[Majr] OR “Evidence-Based Medicine/standards”[Majr] OR “Evidence-Based Medicine/statistics and numerical data”[Majr] OR “Evidence-Based Medicine/trends”[Majr]). “Evidence-Based Medicine”[Mesh] AND (critical[All Fields] AND appraisal[All Fields]). The last search was performed on April 19, 2016 (there was no restriction on the start date). 6009 hits were identifi ed. We supplemented the search by searching our personal libraries and the references of selected articles. The reviewers have also provided useful references. We selected articles of relevance for the main sections of the paper using our own judgment