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ACKNOWLEDGEMENTS

META-ANALYSIS: AN OVERVIEW WITH APPLICATION TO PHYSICAL ACTIVITY by George A. Kelley, DA, FACSM, Professor, Dept. of Community Medicine/Director, Meta-Analytic Research Group, West Virginia University, Morgantown, WV E-mail: gkelley@hsc.wvu.edu. ACKNOWLEDGEMENTS.

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ACKNOWLEDGEMENTS

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  1. META-ANALYSIS: AN OVERVIEW WITH APPLICATION TO PHYSICAL ACTIVITYbyGeorge A. Kelley, DA, FACSM, Professor, Dept. of Community Medicine/Director, Meta-Analytic Research Group, West Virginia University, Morgantown, WV E-mail: gkelley@hsc.wvu.edu

  2. ACKNOWLEDGEMENTS • Kristi Kelley, M.Ed. – West Virginia University • Russell L. Moore – University of Colorado • Zung Vu Tran, Ph.D. – Colorado Prevention Center • James Hagberg, Ph.D. – University of Maryland @ College Park • Doug Seals, Ph.D. – University of Colorado @ Boulder • Christine Snow, Ph.D. – Oregon State University • Charlotte Sanborn, Ph.D. – Texas Woman’s University • William Haskell, Ph.D. – Stanford University

  3. Objectives • List and describe the 9 levels of the evidence-based pyramid • List and describe the 2 types of systematic reviews • List and describe the 3 main things to consider when appraising a systematic review • List and describe the 4 methodological steps for conducting a meta-analysis

  4. Topics • Evidence-Based Medicine • Overview of Systematic Reviews • Application of Systematic Review

  5. I. Evidence-Based Pyramid Source: SUNY Downstate Medical Center. Medical Research Library of Brooklyn. Evidence Based Medicine Course. A Guide to Research Methods: The Evidence Pyramid: http://servers.medlib.hscbklyn.edu/ebmdos/2100.htm

  6. A. Advantages II. Overview of Systematic Reviews • Study question specific & narrow • Data collection comprehensive & specific • Study selection based on uniformly applied criteria

  7. B. Types of Systematic Reviews Notes: Quantitative is meta-analysis; SM, Summary means, IPD, individual patient data; *, IPD meta-analysis best but often difficult to obtain IPD from investigators (Sources: Kelley GA, Kelley KS, Tran ZV. Retrieval of individual patient data for an exercise meta-analysis. Am J Med Sports 2002;4:350-4; Duval S, Vazquez G, Baker WL, Jacobs DR. The Collaborative Study of Obesity and Diabetes in Adults (CODA) project meta-analysis design and description of participating studies. Obesity Reviews 2007;8:263-76).

  8. Number of Citations from a PubMed Search using Keyword “meta-analysis” (Accessed 09/01/07)

  9. C. Importance • Need to use a systematic approach for synthesizing information • Proliferation of information in today's society (Evidence-based medicine notebook. On the need for evidence-based medicine. Evidence Based Medicine 1995;1:5-6)

  10. D. Appraisal of Systematic Reviews • Validity of trial methodology • Magnitude and precision of treatment effects • Application of the results to your patient or population Source: Akobeng AK. Understanding systematic reviews and meta-analysis. Arch Dis Child 90(8); 845-848, 2005.

  11. III. Application of Systematic Review (Summary Means Meta-Analysis) Kelley GA, Kelley KS, Tran ZV. Walking and non-HDL-C in adults: A meta-analysis of randomized controlled trials. Prev Cardiol8(2);102-107, 2005. Funded by the National Institutes of Health, National Heart, Lung, and Blood Institute (NIH-R01-HL 069802), G.A. Kelley, Principal Investigator

  12. Rationale for study • Non-high density lipoprotein cholesterol best predictor of CVD (Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B in the Prediction of Coronary Heart Disease in Men. Circulation 2005;112(22)33:75-83) • Physical activity recommended for improving lipids/lipoproteins(National Cholesterol Education Program; National Heart Lung and Blood Institute; National Institutes of Health. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. NIH Publication No. 02-5215, September 2002)

  13. Walking most common form of physical activity in US (Eyler AA, Brownson RC, Bacak SJ, Housemann RA. The epidemiology of walking for physical activity in the United States. Med Sci Sports Exerc 2003;35(9)1529-36) • RCTs have not reported the effects of walking on non-HDL-C

  14. B. Methods 1. Data Sources • Computer searches (Medline, Embase, Sport Discus, Current Contents, Dissertation Abstracts) • Cross-referencing from previous review articles/original studies • Expert to review reference list (W. Haskell, personal communication)

  15. 2. Study Selection • Randomized controlled trials • Walking program for > 8 weeks • Adult humans > 18 years of age • English-language only • Published & unpublished (1955 to 2003) • TC and HDL-C assessed

  16. 3. Data Abstraction • Coding sheet (more than 200 items/study) • Major variables coded: study, subject, & training program characteristics, primary & secondary outcomes • Dual-coding, independent of each other • Every item reviewed for accuracy

  17. 4. Statistical Analysis • Overall results (primary/secondary outcomes) • Changes in pre to post differences in walking and control groups • Each outcome weighted by the inverse of the variance • Multilevel model (two-stage) with a random effects component & 95% CIs for pooled outcomes(Dersimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88) dj = γ0 + uj + ej

  18. Heterogeneity using the Q statistic and p < 0.10(Cochran WG. The combination of estimates from different experiments. Biometrics 1954;10:101-29) • Inconsistency as I2 = 100% x (Q - df)/Q(Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J 2003;327:557-60) • Study quality – (0 to 5 scale)(Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials Is blinding necessary? Control Clin Trials 1996;17:1-12) • Publication bias – Trim & Fill(Duval S, Tweedie R. Trim and fill a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;5:64:55-63)

  19. Categorical Analysis – Multilevel (two-stage) random effects ANOVA-like models for meta-analysis at p < 0.01 • Multilevel model (two-stage) with covariate & random effects component (p < 0.01) dj = γ0 + γ1W1j + uj + ej

  20. C. RESULTSTable 1. Study characteristics

  21. Table 2. Initial characteristics of subjects. N, number of groups reporting data; M + SD, mean + standard deviation; BMI, body mass index; VO2max, maximum oxygen consumption; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high density lipoprotein cholesterol, calculated as total cholesterol minus high-density lipoprotein cholesterol .

  22. Table 3. Walking program characteristics Notes: N, number of groups; M + SD, mean + standard deviation; Compliance, percentage of exercise sessions attended.

  23. Table 4. Primary and secondary outcomes. N, number of outcomes; BMI, body mass index; VO2max, maximum oxygen consumption; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high density lipoprotein cholesterol (total cholesterol minus high-density lipoprotein cholesterol); CI, Confidence interval; *, significantly different from zero (0).

  24. Table 5. Relative Changes in Outcomes

  25. Categorical and Regression Analysis • Changes in BMI and changes in Non-HDL-C (r = 0.46, p = 0.004)

  26. D. CONCLUSIONS 1. Walking is associated with clinically important reductions in non-HDL-C in adult humans. Pedersen TR, Olsson AG, Faergeman O, Kjekshus J, Wedel H, Berg K, Wilhelmsen L, Haghfelt T, Thorgeirsson G, Pyorala K, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 1998;97(15):1453-60.

  27. E. Limitations Availability of data Because of multiple tests, significant regression results could be due to the play of chance Efficacious but not known if effective

  28. THANK YOU FOR LISTENING Crooked River, Idaho

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