實證醫學之嚴格評讀 嘉義基督教醫院 整形外科 李孝貞

4 每年的 醫學雜誌

醫學資料庫的種類  Secondary sources （證據評鑑資料庫） Cochrane database of systematic reviews Best Evidence, ACPJC, EBM Review, Bandolier (article review) Clinical Evidence (EB guideline or EB textbook) uptodate, MD consult  Primary sources （原始文獻資料庫） 中華民國期刊論文, Medline, PubMed, CINAHL, ….  教科書, 網路電子書

The Evidence Pyramid Hierarchy of studies

Grade of Recommendation Level of Evidence Therapy [A]1a Systemic review of RCTs 1b Single RCT 1c ‘ All-or-none ’ [B]2a Systemic review of cohort studies 2b Cohort study or poor RCT 2c ‘ Outcomes ’ research 3a Systemic review of case-control studies 3b Case-control study [C]4 Case series [D]5 Expert opinion, physiology, bench research

Read the “key”  Levels of Recommendation (USPSTF) A – Highest – Strongly recommended (PAP smears) B – Recommended (Mammograms age 40+) C – no recommendation for or against (too close a balance between harm/benefit) (osteoporosis screening below age 60) D – Recommend AGAINST I – insufficient evidence to make any recommendation for or against (Prostate cancer screening)

RCT (Randomized Control Trial) Lung cancer study  隨機取一群人，隨機分二組。一組每天至少抽煙 一包共 10 年；一組不抽煙。若干年後統計兩組肺 癌的發生率。

Cohort study 世代研究 Lung cancer study  找兩組人，一組有抽煙習慣，每天至少抽煙一包 共 10 年，另一組不抽煙。若干年後統計兩組肺癌 的發生率。

Case control study Lung cancer study 找兩組人  一組有 lung cancer ，分析其抽煙史 ( 每天至少抽煙 一包共 10 年 ) 或不抽煙。  一組沒有 lung cancer ，分析其抽煙史 ( 每天至少抽 煙一包共 10 年 ) 或不抽煙。

Case series Lung cancer study  找一組無 lung cancer 無抽煙的人，每天至少抽煙 一包共 10 年，若干年後得 lung cancer 的前後對照。

臨床問題的類別  Therapy select treatments that do more good than harm, worth the efforts and costs of using them  Harm / Etiology identify causes of disease (including iatrogenic forms)  Diagnosis (tests) select and interpret diagnostic tests  Prognosis estimate the patient's likely clinical course over time and anticipate likely complications of disease

依性質選最佳的研究方法 Different study design has different level of evidence, the best quality study design for each question: Frequency - Prevalence (case control), Incidence (cohort) Etiology / Harm - cohort Diagnosis – case control Prognosis - cohort Treatment / Intervention - RCT

實證醫學五步驟 步驟一： 形成出一個可回答的臨床問題 步驟二： 搜尋最佳證據 步驟三： 嚴格評讀證據之： (a) 效度 (b) 重要性（效益大小） (c) 臨床適用性 步驟四： 將臨床專業與病人價值觀相結合 步驟五： 評估執行效果及效用

步驟三：嚴格評讀證據 : a) 效度 b) 重要性 c) 臨床適用性 V Validity (Reliability) 效度 / 信度 Can we believe it ? Is it valid? ( 研究方法的探討 ) I Importance (Impact) 重要性 We believe it ! But does it matter? Is it important? ( 研究結果的分析 ) P Practice (Applicability) 臨床適用性 If we believe it - does it apply to our patients? Is it applicable? ( 如何在臨床運用 )

(RAM-bo) 各種型式的問題都包含以下三個共同議題 (RAM-bo) ： (Representative) 1. 研究族群是否具有代表性 (Representative) ？ （隨機選擇 (random selection)/ 連貫性 / 起始點病人 群），或者，如果是比較性的，組別間是否可以比 較？（隨機分派 (random allocation)/ 調整） (Ascertainment/follow-up) 2. 是否有足夠的確認和追蹤 (Ascertainment/follow-up) ？ （反應率 / 追蹤 / 確認＞ 80% ） (Measurement) (blinded)(objective) 3. 結果的估計值 (Measurement) 是否公正？恰當？ （使用盲法 (blinded) 或客觀的 (objective) 估計） 嚴格評讀證據 — 效度

“ 該治療性研究結果是可信的嗎 ? ” R  病人的治療分派是否為隨機？ 隨機方式是否恰當？實驗開始前，實驗組及 對照組是否相似、可比較？ (R) A  病人追蹤是否夠久、夠完整？所有病人是否 依其原先分派組別作分析？ (A) M  病人及醫師是否對治療不知情 (blind) ？實驗 組及對照組是否被同等對待？ (M)

Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial. van der Aalst CM, van den Bergh KA, Willemsen MC, de Koning HJ, van Klaveren RJ. Department of Public Health/Pulmonology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands. c. Thorax Jul;65(7): Abstract BACKGROUND Lung cancer screening may provide a new opportunity for attempts to quit among smokers or might delay smoking cessation, but studies to date failed to provide evidence for this. This study investigated the effect of lung cancer screening on smoking abstinence in male smokers participating in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial).

METHODS: In the NELSON trial, 50- to 75-year-old participants at high risk for developing lung cancer were randomised to either lung cancer screening or no screening. Smoking behaviour was evaluated in two random samples of male smokers in the screen (n=641) and control arm (n=643) before (T0) and 2 years after randomisation (T1). In addition, the data were also analysed by intention-to-treat (ITT) analysis, as recommended in smoking cessation intervention trials, although non-response in screening trials can also be due to reasons other than continued smoking.

請看結果段 (Results section) 中所描述的主要結果。 效果有多大？多重要？ 統計意義要看信賴區間及 P 值； 臨床意義則要看效果的估計值： 效果的相對估計值：相對危險 (relative risk) 、相對危險性降低度 (relative risk reduction) 、勝算比 (odds ratio) ）代表生物學上的影 響。 效果的絕對估計值：絕對危險性降低度 (absolute risk reduction) 、益 一需治數 (NNT,number needed to treat) 則代表在臨床上對病人的 影響。 嚴格評讀證據 — 重要性 效益大小（ Impact-size of the benefit ）

Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial. van der Aalst CM, van den Bergh KA, Willemsen MC, de Koning HJ, van Klaveren RJ. Department of Public Health/Pulmonology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands. c. Thorax Jul;65(7): RESULTS: Almost 17% (16.6%) of the trial participants quit smoking, which is higher than the 3-7% found in the general adult population. However, screening was associated with a lower prolonged abstinence rate (14.5%) compared with no screening (19.1%) (OR 1.40, 95% CI 1.01 to 1.92; p<0.05). No stastistically significant difference was found after performing an ITT analysis.

嚴格評讀證據 — 臨床適用性 If we believe it, does it apply to our patient?  Can it be applied to my patient? 病患差異  Can it be done here? 風土 ( 可運用的資源 )  How do patient values affect the decision? 民情 ( 病患的偏好 )

If the treatment can work? 有效 ~ 同樣的治療應用在不同的病患族群是否有 不同的反應 ? ~ 我們的病人與研究中的病人是否非常不同， 以致於無法應用這個研究結果？ 嚴格評讀證據 — 臨床適用性 Biologic Issues

If the treatment will work? 可行 ~ 這個治療適用於我們的診療環境嗎？ ~ 病患配合度 ? ~ 醫療提供者 ( 醫事人員、醫療單位、保險制度 ) 的配合度與能力 ? 嚴格評讀證據 — 重要性 Social and Economic Issues

How efficient the treatment will be? ~ 我們的病人是否有其他共病狀況可能改變 治療的結果 ? 影響有多大 ? ~ 病人可能從治療中得到什麼好處或壞處？ 經由治療而減少的不良後果是否比不治療 有明顯的差別 ? 嚴格評讀證據 — 重要性 Epidemiologic Issues

Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial. van der Aalst CM, van den Bergh KA, Willemsen MC, de Koning HJ, van Klaveren RJ. Department of Public Health/Pulmonology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands. c. Thorax Jul;65(7): CONCLUSIONS: This study showed that all trial participants were inclined to stop smoking more than average, which suggests that screening is a teachable moment to improve smoking behaviour. In those who underwent screening the smoking abstinence rate was significantly lower than for the control group, although the difference was modest. After ITT analysis this difference was no longer observed.

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