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1 291 Vol. 35, pp , 2007 EBM : EBM EBM RCT Evidence based medicine; EBM evidence EBM Randomized Controlled trial; RCT RCT Table 1 EBM MED- LINE The Cochrane Library The Cochrane Library EBM 7

2 292 Table 1. Evidence Level Agency for Health Care Policy and Research, Figure 1. Proportion of meta-analysis; result of a PubMed search. Only articles for human in English were counted. PubMed http: entrez Figure

3 EBM EBM EBM PICO patient intervention comparison outcome 2 MEDLINE The Cochrane Library Table 2 2 1, 2 9

4 294 Table 2. Methods of Meta-analysis The Quality of Reporting of Metaanalyses QUOROM 3 D PubMed D RCT Medical Subject Headings Mesh randomized controlled trial controlled clinical trial women hip fractures vitamin D D 4, 5, 6 1 : 60 2 : RCT 3 : : D 1 400IU 5 : 12 6 : 7 : D D QUOROM 5 RCT 7, 8, 9, 10, 11 Figure 2 5 RCT Table 3 General variance-based method 1 D 95 Chaphy, Chaphy, Trivedi, Porthouse, Jackson, D Chapy, Chaphy, , Trivedi,

5 EBM potentially relevant RCTs identified and screened for retrieval 9 excluded 5 review/meta-analysis 3 focused on specific patients 1 conducted in the same population 15 RCTs retrieved for more detailed evaluation 1 excluded 1 non-rct 14 potentially appropriate RCTs to be included in meta-analysis 9 excluded 2 did not have hip fracture outcomes 6 did not separate men and women 1 mean age 60 years 5 RCTs included in meta-analysis Figure 2. QUOROM flow diagram. Table 3. Randomized Controlled Trials on the E#ect of the E#ect of Oral Vitamin D3 Supplementation on Hip Fracture in Elderly Women. 11

6 296 Table 4. Relative Risks for Oral Vitamin D3 Supplementation Preventing Hip Fractures in Elderly Women. General variance-based method was used for meta-analysis. Figure 3. Relative risks for oral vitamin D3 supplementation preventing hip fractures in elderly women; result of a meta-analysis. General variance-based method was used for meta-analysis , Porthouse, , Jackson, Chaphy, , Chaphy, , Trivedi, , Porthouse, Jackson, Chaphy, , Chaphy, , Trivedi, , Porthouse , Jackson ln ln 95 ln RCT 5 Qln ln 2 Q 1.10 Q 4 1 c 2 Q 5 5 RCT Table 4 Figure 3 RCT RCT 1 12

7 EBM DerSimonian-Laird method D EBM D 1 400IU 800IU 12, 13 publication bias English bias, database bias, citation bias, multiple publication bias publication bias EBM 1 EBM Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Lancet 1999; 354: Avenell A, Gillespie WJ, Gillespie LD, O Connell DL. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis, Cochrane Database Syst Rev 2005; 3: CD Bischof-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293: Jackson C, Gaugris S, Sen SS, Hosking D. The e#ect of cholecalciferol vitamin D3 on the risk of fall and fracture: a meta-analysis. QJM 2007; 13

8 : Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. E#ect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 1994; 308: Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk; the Decalyos II study. Osteoporos Int 2002; 13: Trivedi DP, Doll R, Khaw KT. E#ect of four monthly oral vitamin D3 cholecalciferol supplementation on fractures and Mortality in men and women living in the community: randomized double blind controlled trial. BMJ 2003; 326: Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Pu#er S, Sutcli#e A, Watt I, Torgerson DJ. Randomised controlled trial of calcium and supplementation with cholecalciferol vitamin D3 for prevention of fractures in primary care. BMJ 2005; 330: Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski- Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D. Calcium plus vitamin D supplementation and the risk of fractures, N Engl J Med 2006; 354: Egger M, Smith GD. Bias in location and selection of studies, BMJ 1998; 316: Egger M, Ebrahim S, Smith GD. Where now for meta-analysis? Int J Epidemiol. 2002; 31:

9 EBM 299 Abstract Evidence-based medicine and Meta-analysis Machi Suka and Katsumi Yoshida A meta-analysis is a review of all relevant studies on a specific topic which includes statistical accountability of interstudy variability. Thousands of meta-analyses are published in the medical literature each year. The results from meta-analyses contribute to promoting evidence-based medicine. This paper gives an overview of meta-analysis and describes methods, merits, and limitations. The retrieval and selection of studies must be performed carefully to reduce the risk of biases. Department of Preventive Medicine, St. Marianna University School of Medicine 15

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