# 臨床證據的明日之星 Network Meta-analysis

## Presentation on theme: "臨床證據的明日之星 Network Meta-analysis"— Presentation transcript:

NMA 臨床證據的明日之星 Network Meta-analysis 陳弘洲醫師

Meta-analysis研究的優缺點 優點 缺點 證據等級高 不用臨床試驗 研究時間短 研究經費低 入門稍難 選題不易 競爭者眾

Introduction of Network Meta-analysis

What is Network Meta-analysis?

Meta-analysis= 找出兩位選手所有對戰紀錄加以分析 Network Meta-analysis= 世界網球排名

Meta-analysis的盲點 假設有ABC三種治療某疾病藥物, 想知道A與C誰較佳 找出共有10篇A vs C的RCTs
Meta-analysis結果顯示療效A > C, 故A較佳 如果… 另有20篇RCTs顯示A<<B, 另30篇RCTs顯示C>>B 故C>>B>>A A與C究竟誰療效較佳???

*Adapted by CTL from Bucher 1997, Song 2003, Glenny 2005
A versus C *Adapted by CTL from Bucher 1997, Song 2003, Glenny 2005

A versus C 單位統一 Conscious data用Standard Mean Differences
(SMD, 指統一用standard deviation當單位) Dichotomous data多用Relative Risk (RR) AC差 = (權重)d x(直接 AC差) + (權重)I x(間接 AC差)  d AC = W d x d AC d+ W I x d AC I

N 越大weight越大 SD越大weight 越小

Cipriani et al. Lancet 2009 Feb 28;373(9665):746-58

Cipriani et al. Lancet 2009 Feb 28;373(9665):746-58

Cipriani et al. Lancet 2009 Feb 28;373(9665):746-58

"plantar fasci*" or "plantar heel*" or "plantar foot" or "heel pain" or "painful heel*" or "hindfoot pain" or "painful hindfoot “ 如找dyslipidemia: dyslipid* or hyperlipid* or lipid or cholesterol or lipoprotein or triglyceride or TC or TG or HDL or LDL

Krogh et al. The American Journal of Sports Medicine 2012

Characteristics of the selected trials.
Study (Year) Patients n, (Feet n) Comparison (No. of Patients Assigned to Each Treatment Arm) Followup peroid Outcomes Measure Incl/Excl Criteria Avg Age, y Avg Disease Duration Babcock, 2005 27 patients (43 feet) Botulinum toxin A (BOTOX) 70u, 0.7mL (n = 22 feet) vs saline 0.7mL (n = 21 feet). One injection at baseline 3,8wk VAS, Maryland Foot Score, Pain relief VAS, pressure algometry Incl: adult, clinical diagnosis of PF, duration < 6mo, failure of conventional treatment. Excl: open wound of the foot or heel, history of foot surgery or fracture, or history of chronic narcotic use, other differential diagnosis 44 N/A Ball, 2013 65 Methylprednisolone acetate 20mg, 1mL, US-guided injection (n=22), palpation- guided injection (n=22) vs 0.9% saline 1mL, US-guided injection (n=21). One injection at baseline 6,12wk VAS, heel tenderness index, plantar fascia thickness Incl: clinical diagnosis of PF, failure of conventional treatment > 8wk. Excl: diagnosis of inflammatory arthritis, prior surgery or trauma to the heel, previous steroid injection. 49 6mo Crawford, 1999 106 Prednisolone acetate 25mg, 1mL + 2% Lignocaine 1mL (n=27) vs Prednisolone acetate 25mg, 1mL + 2% Lignocaine 1mL + tibial nerve block (n=26) vs 2% Lignocaine 2mL (n=27) vs 2% Lignocaine 2mL + tibial nerve block (n=26). One injection at baseline 1, 3,6mo VAS Incl: clinical diagnosis of PF. Excl: age < 18y/o, previous steroid injection within 6 mo. 57 Diaz-Llopis, 2012 56 Botulinum toxin A (BOTOX) 70u, 0.7mL (n = 28) vs Betamethasone 12mg, 2mL, + 1% Mepivacaine 0.5mL (n = 28). One injection at baseline, 2nd cross-over injection optional at 1mo with failed treatment. Final Botulinum toxin A (n=34) vs Betamethasone (n=22) 1,6mo FHSQ Excl: other differential diagnosis, previous injection within 6mo 54

Database collection Study A vs B f/u Outcome Measure Group A n Pre SD
Post Post-Pre Group B Zelen 2013 0 vs 6 8 wk FACES Pain Scores Saline 13 8 1.6 4.6 1.2 mDHACM 15 8.6 0.7 Peterlein 2012 0 vs 2 18wk VAS in rest 16 -1.7 3.75 BTX 17 -1.55 3.38 Kim 2014 8 vs 9 28wk FFI-pain PRP 9 60.4 14.7 33.7 23.4 Prolotherapy 11 56.5 14 41.1 21.4 Huang 2010 3mo 25 5.4 0.6 5.2 1 5.9 0.9 2 Ball 2013 0 vs 3 12wk VAS 18 56 27.9 53.8 33.8 Corticosteroid 62 19.2 28.4 24.9 Crawford 1999 4 vs 5 6mo Corticosteroid+Local anesthesia 5.6 2.3 2.4 2.6 Local anesthesia 5.5 2.1 3.3 2.7 Diaz-Llopis 2012 2 vs 3 1mo FHSQ-pain 28 -29.1 19.5 -63.3 21.9 -34.2 21.1 -31.6 21.0 -53.7 31.2 -22.12 27.4 Elizondo-Rodriguez 2013 19 7.1 1.75 1.1 1.5 7.7 1.32 3.8 1.15 Guner 2013 3 vs 7 12mo 30 7.97 1.37 3.17 2.31 NSAID 31 8.26 1.41 2.94 2.04 Kalaci 2009 (A) 3 vs 5 7.24 2.22 0.96 1.24 6.72 1.74 3.4 2.88 Kalaci 2009 (B) 1 vs 3 ABI 6.84 2.27 3.53 3.06 6.96 2.71 1.52 2.14 Kiter 2006 7.6 1.3 1.8 7.28 2.57 2.9 Lee 2007 7.3 3.6 6.9 1.7 3 McMillan 2012 41 -35.8 20.4 -59.7 25.4 -36.8 19.9 -65.4 27.7 Omar, 2012 3 vs 8 6wk 8.8 6.5 8.2 Tiwari, 2013 6.03 0.85 2.8 0.76 0.45

Krogh et al. The American Journal of Sports Medicine 2012
Injection Therapies in Treating Lateral Epicondylitis Krogh et al. The American Journal of Sports Medicine 2012

From Oxford Center for Evidenced-Based Medicine. http://www.cebm.net
Critical Appraisal of Meta-analysis Validity Were the criteria for inclusion of studies appropriate? 文章的收錄條件是否適當？ Was the search for eligible studies thorough? 搜尋的進行是否夠全面？ Was the validity of the included studies assessed? 是否有收錄的文章進行效度分析? Were the assessments of the studies reproducible? 對文章的分析是否具有再現性? From Oxford Center for Evidenced-Based Medicine.

Critical Appraisal of Meta-analysis
Importance What are the overall results of the review? 此篇綜論的總結果為何? Were the results similar from study to study? 各文章間的結果是否相似? How precise were the results? 實驗結果是否夠精確? From Oxford Center for Evidenced-Based Medicine.

Critical Appraisal of Indirect Evidence
Transitivity: 間接證據是否真能轉換成直接證據? 病人族群、治療方法、實驗設計是否相似 Consistency: 間接證據與直接證據結果是否相似? 結果間的異質性(heterogeneity)如何? 如有Bias應加以探討並做sensitivity analysis 適時去除掉不正確之證據

Chen HC123, Lin SH4, Huang YM5, Hou WH 46
NMA研究實例 Injection Therapies in Treating Plantar Fasciitis: A Network Meta-analysis of Randomized Controlled Trials Chen HC123, Lin SH4, Huang YM5, Hou WH 46 1Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, Taipei 2College of Medicine, Taipei Medical University, Taipei 3Center for Evidence-Based Health Care, Shuang Ho Hospital, Taipei Medical University, Taipei 4Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei 5Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei 6College of Nursing, Taipei Medical University, Taipei

Plantar Fasciitis (足底筋膜炎)

Injection Therapies 直接注射於足底筋膜上 常見注射物： 價格差異大 效果何者較佳仍未有定論

Goal of our study 針對現有文獻做完整的搜尋以找出所有治療足底筋膜炎的RCT

Methods Databases: Pubmed, Cochrane Liberary, Scopus, CINAHL
Keywords: "plantar fasci*" or "plantar heel*" or "plantar foot" or "heel pain" or "painful heel*" or "hindfoot pain" or "painful hindfoot“ Outcome: pain related score (primary), complications (secondary) Quality assessment: Cochrane risk of bias assessment tool 52

Results 53

Figure 1 54

Table 1: Characteristics of the selected trials
Data items of Table 1 Number of participants Treatments compared Follow-up period Outcome measures Percentages of female participants Average ages of participants Average disease duration of participants. 55

Table 1: Characteristics of the selected trials (1)
56

Table 1: Characteristics of the selected trials (2)
57

Figure 2: Network of included comparisons
58

Table 2: Quality assessment
59

Table 3: Comparisons of the pain reduction over the 8 injectants
60

Figure 3: Consistency: compare Network (direct+ indirect) with direct Meta

Table 4: Pain score estimate in every treatment
Rank Injectants SMD (95% credible interval) 1 mDHACM -6.09 ( to 3.43) 2 Platelet-Rich Plasma -3.77 ( to 5.27) 3 Prolotherapy -3.29 ( to 6.09) 4 Botulium Toxin -2.47 ( to 6.41) 5 NSAID -2.34 (-11.5 to 6.86) 6 Corticosteroid -1.80 ( to 7.03) 7 Autologous Blood -1.76 ( to 7.21) 8 Placebo -0.89 (-9.72 to 7.89) 62

Figure 4: Forest plot Injectants vs Placebo

Figure 5: Ranking

Network Meta-analysis優點與缺點