實證醫學訓練 第一階段 產生問題及文獻搜尋 馬偕紀念醫院 實證醫學工作小組 方靜如 2008~2009

Presentation on theme: "實證醫學訓練 第一階段 產生問題及文獻搜尋 馬偕紀念醫院 實證醫學工作小組 方靜如 2008~2009"— Presentation transcript:

1 實證醫學訓練 第一階段 產生問題及文獻搜尋 馬偕紀念醫院 實證醫學工作小組 方靜如 2008~2009
馬偕紀念醫院 2008 PGY訓練課程 實證醫學訓練 第一階段 產生問題及文獻搜尋 馬偕紀念醫院 實證醫學工作小組 方靜如 2008~2009

2 認識證據等級 Level Therapy/Prevention, Aetiology/Harm 1a
Systematic review of RCTs + Meta-Analysis 1b Randomized controlled trial (RCT) 1c ‘All-or-none’ 2a Systematic review of cohort studies 2b Cohort study or poor RCT 2c ‘Outcomes’ research ; Ecological studies 3a Systematic review of case-control studies 3b Case-control study 4 Case series 5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles" Level Therapy/Prevention, Aetiology/Harm 1a Systematic review of RCTs + Meta-Analysis 1b Randomized controlled trial (RCT) 1c ‘All-or-none’ 2a Systematic review of cohort studies 2b Cohort study or poor RCT 2c ‘Outcomes’ research 3a Systematic review of case-control studies 3b Case-control study 4 Case series 5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles" 證據力強 設計嚴謹 偏差少 並非所有臨床問題都可找到最高等級文獻，但應盡可能使用等級高的證據來源 學員可以只先記紅色字 all-or- none: all patients died before the drug became available, but some now survive on it; or when some patients died before the drug became available, but none now die on it. 無論使用何種研究方法，但其研究結果為完全正面、完全負面或完全無效果 Outcomes research is a broad umbrella term without a consistent definition. However it tends to describe research that is concerned with the effectiveness of public-health interventions and health services; that is, the outcomes of these services. Attention is frequently focused on the affected individual − with measures such as quality of life and preferences − but outcomes research may also refer to effectiveness of health-care delivery, with measures such as cost-effectiveness, health status and disease burden. The present review details the historical background of outcomes research to reveal the origins of its diversity. The value and relevance of outcomes research, commonly employed research techniques and examples of recent publications in the area are also discussed. (Intern Med J 2003; 33: 110−118)   WHAT IS OUTCOMES RESEARCH?"Outcomes research" is a term developed in the past 15 years to describe clinical research concerning the outcomes of medical care (1, 2). Outcomes, broadly defined, can include any variable used to assess the effect of some medical treatment or intervention. "Outcomes research," however, connotes clinical research that focuses less on physiology or biochemical processes and more on clinical end points directly relevant to patients and society: mortality, quality of life, health status, functional status, and costs of care (3, 4). Outcomes research examines the effectiveness of treatment in real clinical settings of heterogeneous patient populations with barriers to treatment rather than the efficacy of treatment in the more controlled research settings with carefully selected, motivated subjects. In addition, outcomes research is concerned with a broad range of issues touching on all aspects of health care delivery, from the clinical encounter between patient and clinician to questions of the organization, financing, and regulation of the health care system. While large, population-based randomized controlled studies using outcomes important to patients (often called "effectiveness trials") are a type of outcomes research, much of outcomes research relies on observational, nonrandomized designs (5). In fact, outcomes research performed by trainees will likely be observational research because of the time and expense involved in performing effectiveness randomized controlled trials. There is a growing recognition of the need for outcomes research, both observational and experimental, to understand and improve the way health care is delivered throughout our society. Although the terms "outcomes research," "clinical epidemiology," and "health services research" have overlapping definitions, we use "outcomes research" in a broad way to include much of the disciplines of clinical epidemiology and health services research. Therefore, we define outcomes research as clinical research attempting to understand and improve the outcomes of illness and medical treatment by focusing on those outcomes important to patients and society. Although it is difficult to draw a sharp line distinguishing outcomes research from other clinical research, many important types of clinical studies are clearly not outcomes studies. For example, small clinical trials using physiologic or biochemical end points are not outcomes research. Nonetheless, faculty performing these other types of clinical research have much to contribute to training outcomes researchers, and trainees interested in other types of clinical research could benefit from many of the tools taught to outcomes researchers. Pulmonary clinicians have been doing outcomes research for at least 25 years. As one example, the Nocturnal Oxygen Therapy Trial in the 1970s used quality of life, as well as survival, as an outcome in a large effectiveness trial to demonstrate the value of oxygen therapy for patients with COPD and hypoxemia (6). The investigators used this study to describe the effect of COPD on the quality of life in these patients (7). Since that time, there has been a large body of work assessing the quality of life and functional status of patients with COPD and asthma and using these measures to determine the effectiveness of treatments (8). Critical care researchers have been among the leaders in assessing outcomes of medical care and performing risk adjustment to control for severity of illness. The APACHE score was one of the earliest validated systems to assess risk, control for severity of illness, and predict outcome (14), and the APACHE III remains one of the most comprehensive and accurate risk adjustment systems available (15). Assessing outcomes and predictors of outcomes in critical care has been an important and vital area of research for three decades. 證據力弱 設計薄弱 偏差多 表濃縮自: Oxford Centre for EBM Levels of Evidence

3 Randomized Controlled Trial (RCT) 隨機對照試驗
有病 沒病 鏈黴素 第一個隨機對照試驗在大英帝國完成，有趣的是推動這項鏈黴素研究的原因不是科學方法的進展，而是因為當時醫療人員只有全部結核病人所需要的一半鏈黴素。鏈黴素是在第二次世界大戰期間開發試驗的，戰後鏈黴素的試驗，由傷口照護轉移到結核病。大不列顛醫學研究理事會覺得最公平的分配方法就是機率，於是…第一次有了經隨機分派的治療組與控制組。(Medical Research Council. Streptomycin treatment of pulmonary tuberculosis. BMJ 1948;2:769–782.) Ann McKibbon著；楊宗翰譯。實證醫學原理與應用快速入門，p.24-25。台北市：合記，2008。 A randomized controlled study is one in which: 1. There are two groups, one treatment group and one control group. The treatment group receives the treatment under investigation, and the control group receives either no treatment or some standard default treatment. 2. Patients are randomly assigned to all groups. Assigning patients at random reduces the risk of bias and increases the probability that differences between the groups can be attributed to the treatment. Having a control group allows us to compare the treatment with alternative choices. For instance, the statement that a particular medication cures 40% of cases tells us very little unless we also know how many cases get better on their own! (Or with a different treatment). With certain research questions, randomized controlled studies cannot be done for ethical reasons. For instance, it would be unethical to attempt to measure the effect of smoking on health by asking one group to smoke two packs a day and another group to abstain, since the smoking group would be subject to unnecessary harm. Randomized controlled trials are the standard method of answering questions about the effectiveness of different therapies. If you have a therapy question, first look for a randomized controlled trial, and only go on to look for other types of studies if you don't find one. 有病 沒病 安慰劑 結核病人 SUNY Downstate EBM Tutorial: ,

4 Cohort Study 世代研究 肺癌 無肺癌 抽菸者 肺癌 無肺癌 非抽菸者
世代研究，是一種觀察性研究方法(observational study)，一群界定清楚的人 (the cohort) 被追蹤一段時間。檢驗結果( outcome) 在不同次群組之間是否有差異，例如有（或沒有）暴露在某種介入之次群組，觀察其結果發生率。世代研究大多是前瞻性的，但也有少數是回溯性的（必須相關記錄非常清楚）。(資料來源:彰基醫圖電子報第3期) A Cohort Study is a study in which patients who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation. For instance, since a randomized controlled study to test the effect of smoking on health would be unethical, a reasonable alternative would be a study that identifies two groups, a group of people who smoke and a group of people who do not, and follows them forward through time to see what health problems they develop. Cohort studies are not as reliable as randomized controlled studies, since the two groups may differ in ways other than in the variable under study. For example, if the subjects who smoke tend to have less money than the non-smokers, and thus have less access to health care, that would exaggerate the difference between the two groups. The main problem with cohort studies, however, is that they can end up taking a very long time, since the researchers have to wait for the conditions of interest to develop. Physicians are, of course, anxious to have meaningful results as soon as possible, but another disadvantage with long studies is that things tend to change over the course of the study. People die, move away, or develop other conditions, new and promising treatments arise, and so on. Even so, cohort studies are generally preferred to case control studies , since they involve far fewer statistical problems and generally produce more reliable answers. 肺癌 無肺癌 非抽菸者 SUNY Downstate EBM Tutorial: ,

5 Case Control Study 病例對照研究
癌症病人 抽菸者 非抽菸者 Case control studies are studies in which patients who already have a certain condition are compared with people who do not. For example: a study on which lung cancer patients are asked how much they smoked in the past and the answers are compared with a sample of the general population would be a case control study. Case control studies are less reliable than either randomized controlled trials or cohort studies. Just because there is a statistical relationship between two conditions does not mean that one condition actually caused the other. For instance, lung cancer rates are higher for people without a college education (who tend to smoke more), but that does not mean that someone can reduce his or her cancer risk just by getting a college education. The main advantages of case control studies are: • They can be done quickly. By asking patients about their past history, researchers can quickly discover effects that otherwise would take many years to show themselves. • Researchers don't need special methods, control groups, etc. They just take the people who show up at their institution with a particular condition and ask them a few questions. The first study to suggest a new medical conclusion will often be a case control study, perhaps designed to check on a hypothesis suggested by a case series. If possible, researchers will generally try to confirm the results with a randomized controlled trial or a cohort study. 非癌症病人 抽菸者 非抽菸者 SUNY Downstate EBM Tutorial: ,

6 Case Series and Case Report 病例系列與病例報告
Case series and case reports consist either of collections of reports on the treatment of individual patients, or of reports on a single patient. For example: one of your patients has a condition that you have never seen or heard of before and you are uncertain what to do. A search for case series or case reports may reveal information that will assist in a diagnosis. However, for any reasonably well-known condition you should be able to get better evidence. Case series and case reports, since they use no control group with which to compare outcomes, have no statistical validity . SUNY Downstate EBM Tutorial: ,

7 Systematic Review + Meta-Analysis 系統性評論 + 統合分析
(通常是RCT) 提出一個特定的臨床問題 執行完整文獻搜尋 評析設計良好且適用的研究 歸結臨床應用上的可行建議 Systematic Review Important medical questions are typically studied more than once, often by different research teams in different locations. A systematic review is a comprehensive survey of a topic in which all of the primary studies of the highest level of evidence have been systematically identified, appraised and then summarized according to an explicit and reproducible methodology. A meta-analysis is a survey in which the results of all of the included studies are similar enough statistically that the results are combined and analyzed as if they were one study. In general a good systematic review or meta-analysis will be a better guide to practice than an individual article. Pitfalls specific to meta-analysis include: 1. It's rare that the results of the different studies precisely agree, and often the number of patients in a single study is not large enough to come up with a decisive conclusion. 2. If the authors are interested in supporting a particular conclusion, they can include studies that support that conclusion and omit studies that do not. Do the authors explain in their paper exactly on what basis they included studies , and do their reasons make sense? 3. Studies that show some kind of positive effect tend to be published more often than those that do not. This means that if the authors include only published studies, several weak positive studies may seem to add up to a strong positive result. Do weak negative studies exist? This effect is known as Publication bias. 將個別研究數據進行統計學量化分析 歸結出一個證據力更強的結論 SUNY Downstate EBM Tutorial: ,

8 資料庫的選擇與使用

9 5S EBM Resources (非關證據強弱!)
愈上層 資訊精萃 簡單的關鍵字 省時搜尋與評讀 快速支援決策 由下層積累 1.systems 連結個別病歷的臨床知識與支援決策系統 整合證據提供特定臨床問題之概述與建議 UpToDate BMJ Clinical Evidence FirstConsult ACP PIER 2.summaries Filtered Resources 對單篇研究或回顧性文獻作摘要與評述 ACP Journal Club, Evidence-Based Medicine (PubMed, Ovid Medline) 3.synopses 特定臨床問題的系統性評論文獻 Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effects (PubMed, Ovid Medline): Systematic Reviews 4.syntheses 愈下層 文獻雜多 完整的關鍵字 費時搜尋與評讀 注重檢索技巧 資訊新穎 原始文獻 (PubMed, Ovid Medline, CINAHL, EMBASE Cochrane CENTRAL, Google Scholar CEPS中文電子期刊, 中文期刊篇目索引) Unfiltered Resources 5.studies Model from: Haynes, R. B. (2006). Of studies, syntheses, synopses, summaries, and systems: the "5S" evolution of information services for evidence-based health care decisions. ACP Journal Club, 145(3), A8.

10 PICO檢索示範 – 治療 P I C O 一位胃食道逆流的患者 使用proton pump inhibitor 與不使用藥物治療
是否能改善聲音沙啞

11 PICO檢索示範 – 關鍵字 (初級班) P I C O gastroesophageal reflux PPI
non-drug therapies OR placebos OR… O hoarseness

12 PICO檢索示範 – 關鍵字 (中級班) P I C O non-drug therapies OR placebos OR…
gastroesophageal reflux OR GERD OR GER OR GORD OR GOR OR esophageal reflux OR gastro-esophageal reflux OR gastro-oesophageal reflux I PPI OR PPIs OR proton pump inhibitor OR proton pumps OR Esomeprazole OR Lansoprazole OR Omeprazole OR Pantoprazole OR Rabeprazole OR Nexium OR Prevacid OR Prilosec OR Protonix OR Aciphex C non-drug therapies OR placebos OR… O hoarseness Gastroesophageal 關鍵字(同義詞、MeSH Term)的擬定，可參考上層EBM資料庫、Textbook、藥學資料庫、相關文獻 底線字表示為MeSH Term

13 Clinical Evidence: Search
GERD “body weight”

14 Clinical Evidence: Result
針對此臨床問題之各種介入之益害

15 Clinical Evidence: Result

16 ACP PIER: Search Search: 會搜尋整個Stat!Ref平台電子書
Search This Title: 指ACP PIER GERD hoarseness

17 ACP PIER: Result: Therapy

18 ACP PIER: Result: Therapy
level of evidence 此表列出PPI常用藥物名稱 對於非專科者可參考 reference level of evidence 連到PubMed

19 Gastroesophageal Reflux Gastroesophageal Reflux
authors articles 自由詞彙 vs 控制詞彙 檢索機制 translation Gastroesophageal Reflux 系統控制使用者和作者用語一致 使用者要設法和作者心意相通 控制詞彙派 Controlled Vocabulary 自由詞彙派 Free Text Standard (MeSH) database Medline 較大型或精緻的書目資料庫 通常同時有這兩種機制 自由詞彙派 Free text (例: summaries型資料庫、Google) 原理 User所輸入關鍵字會直接比對原始篇名、摘要、作者 (、內文)等欄位若吻合，文章就會被找出 優 user檢索過程較簡單 適用控制詞彙未提供的概念。如新名詞；或形容用語，如initial treatment 缺 語義容易模糊 要儘可能列舉同義詞 可能要列舉狹義詞 ======================================================= 控制詞彙派 Controlled vocabulary (例: MeSH: Medical Subject Headings) 索引專家預先給每篇文章分類主題(控制詞彙) User所輸入關鍵字會被嘗試轉譯成控制詞彙 若1與2吻合，文章就會被找出 解決同義字問題 可彈性檢索廣/狹義詞 使用得宜可提高精確率與回收率 user要”習慣”’才會用 新概念不適用 用語容易受限不彈性 Gastroesophageal Reflux translation GERD user queries reference:

20 MeSH: Medical Subject Headings
使用者輸入用語也不盡相同 每篇文章表達用語不同

21 PubMed: Interface & Functions
檢索及功能區塊 進階功能與服務 此PubMed網址和馬偕圖書館電子館藏有建立連結，可以把此網址加入我的最愛

22 PubMed: Search (初級班) gastroesophageal reflux AND PPI AND hoarseness

23 PubMed: Search Strategy (中級班)
Clinical Queries 限定期刊 修正PICO I O PICO 彈性組合 P I P I O O I P 初級PICO (快速法)

24 Demo: P Demo gastroesophageal reflux OR GERD OR GER OR GORD OR GOR OR esophageal reflux OR gastro-esophageal reflux OR gastro-oesophageal reflux 輸入P關鍵字 gastroesophageal reflux OR GERD OR GER OR GORD OR GOR OR esophageal reflux OR gastro-esophageal reflux OR gastro-oesophageal reflux

25 Demo P關鍵字的檢索結果

26 Demo PPI OR PPIs OR proton pump inhibitor OR proton pumps OR Esomeprazole OR Lansoprazole OR Omeprazole OR Pantoprazole OR Rabeprazole OR Nexium OR Prevacid OR Prilosec OR Protonix OR Aciphex 輸入I 關鍵字 PPI OR PPIs OR proton pump inhibitor OR proton pumps OR Esomeprazole OR Lansoprazole OR Omeprazole OR Pantoprazole OR Rabeprazole OR Nexium OR Prevacid OR Prilosec OR Protonix OR Aciphex

27 Demo hoarseness 輸入O 關鍵字 hoarseness

28 Demo #2 AND #3 AND #4 開始組合檢索

29 Demo 組合檢索結果

30 PubMed: P+I+C+O 彈性組合 (#2 ~ #7 )
I O P I P I O O I P P: gastroesophageal reflux OR GERD OR GER OR GORD OR GOR OR esophageal reflux OR gastro-esophageal reflux OR gastro-oesophageal reflux I: PPI OR PPIs OR proton pump inhibitor OR proton pumps OR Esomeprazole OR Lansoprazole OR Omeprazole OR Pantoprazole OR Rabeprazole OR Nexium OR Prevacid OR Prilosec OR Protonix OR Aciphex O: hoarseness 避免某個面向檢索結果很低，影響整體檢索結果 檢索結果低時，易修正檢索策略 方便後續彈性組合檢索 PICO何者重要? 取決於臨床問題特性、檢索者目的和時間、文獻需求質量

31 Search #2 AND #3 AND (#4 OR atypical)
PubMed: 透過線索修正關鍵詞 (#8) 文章乙: 摘要與篇名: 都未提到hoarseness 只有提到atypical manifestations 找到一篇文章甲：摘要中提到 hoarseness是GERD的atypical symptom 文章乙: 內文: 卻有hoarseness的敘述 因為有時候關鍵詞不一定會直接表現在摘要中 Search #2 AND #3 AND (#4 OR atypical)

32 PubMed: 限定期刊ACP, Cochrane (#9)
#6 AND("ACP Journal Club"[Jour] OR acp

33 PubMed: Systematic Reviews (#10)
Tip: 為何使用#6來篩選Systematic Reviews，而非#8或其他 Answer: (1) 因為#8文獻量太少，再做Systematic Reviews的篩選一定沒剩幾筆 (2) Outcome: 有提到hoarseness(Outcome)的文獻，不一定會將hoarseness這個詞表現在一篇文章的篇名、摘要，也未必有被分派到MeSH Term，故不容易被檢索出來；尤其一篇Systematic Review所評讀的文獻範圍通常很廣、分析項目很多(如各種Symptoms)，故內文也許會有hoarseness的分析，但不會表現在上述書目欄位中。 (3)可以試看看使用#8來篩選Systematic Reviews ，將會找不到下面幾篇重要文章。 #6 Tip: 為何使用#6(3108筆)來篩選Systematic Reviews，而非#8(161筆)或其他 (1) 因為#8文獻量太少，再做Systematic Reviews的篩選一定沒剩幾筆 (2) 有提到hoarseness(Outcome)的文獻，不一定會將hoarseness詞彙表現在一篇文章的篇名、摘要，也未必有被分派到MeSH Term，故不容易被檢索出來；尤其一篇SR所評讀的文獻範圍通常很廣、分析項目很多(如各種Symptoms)，故內文也許會有hoarseness的分析，但不會表現在上述項目中。 (3)可以試看看使用#8來篩選Systematic Reviews ，將會找不到下面幾篇重要文章。

34 PubMed: Result: Systematic Review

35 PubMed: Clinical Study (#11~#12)
#8 品質要有保障 文章盡量找齊 therapy/narrow: 篩選出RCTs therapy/broad: 篩選出Clinical Trials

36 PubMed: Result: RCT 選擇therapy/narrow後自動最佳化篩選策略 36/65

37 PubMed: Search Strategy (中級班)
Clinical Queries 限定期刊 修正PICO I O PICO 彈性組合 P I P I O O I P 初級PICO (快速法)

38 PubMed: Limit 謹慎: 使用Limits後， “In process” 、“supplied by publisher”、“非Medline”的文獻，將被排除～ 因為此機制是針對已被Medline做過索引程序的書目所設計        (要視臨床問題特性、檢索者時間和文獻需求質量調整)

39 PubMed: History 可以在此輸入#數字、關鍵字、布林邏輯運算元等做組合檢索 看此筆檢索結果 點#數字彈跳選項

40 PubMed: Details 系統的最終的檢索策略 系統的轉譯過程 使用者輸入關鍵字 常見欄位名稱
[MeSH Terms]: 醫學主題標題詞 [TIAB]: Title篇名與Abstract摘要欄位 [Text Word]: 所有文字欄位，含Title、Abstract 、MeSH terms、Publication Types、Substance Names、Personal Name [All Fileds]: 所有欄位 [SB]：Subset，特定子集資料庫 系統的最終的檢索策略 系統的轉譯過程 使用者輸入關鍵字

41 PubMed: Details 讓系統轉譯正確技巧
盡可能輸入全名: PPI vs. proton pump inhibitor 每個關鍵字搜尋後檢查Details，再適當修正 必要時才查詢MeSH Database確認用語 系統如何轉譯 關鍵字轉譯時除了自動比對MeSH，同時也檢索Free Text(篇名、摘要)等欄位 若比對不到MeSH，自動檢索Free Text欄位 自動包含(explode)所有狹義詞 關鍵字加了雙引號 “ ” 或 星號 * 就不會被比對MeSH

42 PubMed: Display: Citation
研究設計 主題 Tip: 可參考一篇關鍵書目的MeSH Terms 修正PICO關鍵詞，如"proton pumps" 年齡層 研究設計 主題 性別

43 沒有最完美標準的檢索公式 要視 臨床問題特性 檢索者目的和時間 文獻需求質和量 來靈活調整檢索策略 搜尋不必一次到位 隨時都可以再修正 