Evidence-Based Practice in the Culture of Health Care

2. The Culture of Health Care Evidence-Based Practice Lecture f This material (Comp 2 Unit 5) was developed by Oregon Health & Science University, funded by the Department of Health and Human Services, Office of the National Coordinator for Health Information Technology under Award Number IU24OC000015. This material was updated in 2016 by Bellevue College under Award Number 90WT0002. This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.

3. Evidence-Based PracticeLearning Objectives • Define the key tenets of evidence-based medicine (EBM) and its role in the culture of health care (Lectures a, b). • Construct answerable clinical questions and critically appraise evidence answering them (Lecture b). • Explain how EBM can be applied to intervention studies, including the phrasing of answerable questions, finding evidence to answer them, and applying them to given clinical situations (Lecture c). • Describe how EBM can be applied to the other key clinical questions of diagnosis, harm, and prognosis (Lectures d, e). • Discuss the benefits and limitations to summarizing evidence (Lecture f). • Describe how EBM is used in clinical settings through clinical practice guidelines and decision analysis (Lecture g).

4. Summarizing Evidence • For many tests and treatments, there are multiple studies such that one study does not tell the whole story • As such, there is a growing trend toward “systematic reviews” or “evidence reports” to bring together all the evidence on a treatment or test • Per the Haynes 4S model (Haynes, 2001), syntheses bring together primary data, whereas synopses make the data available to users in highly digested form • Summarizing the evidence presents many methodological challenges (Helfand, Morton, Guallar, & Mulrow, 2005)

5. Steps in Creating a Systematic Review(Guyatt, Rennie, Meade, & Cook, 2008) • Define the question—Population, intervention, comparison, outcome(s) • Conduct literature search—Define information sources and searching strategy • Apply inclusion and exclusion criteria for articles retrieved, and measure reproducibility • Abstract appropriate data • Conduct analysis—Determine method of pooling, explore heterogeneity, and assess for publication and other bias

6. Types of Analysis in a Systematic Review • Meta-analysis, which combines results of multiple similar studies, is often used • Systematic review ≠ meta-analysis • Studies may be too heterogeneous in terms of patient characteristics, settings, or other factors, e.g., telemedicine outcomes and diagnosis (Hersh et al., 2001, 2002; Hersh, Hickam, et al., 2006) • When meta-analysis is done, summary measures employed usually include odds ratio or weighted mean difference

7. Usual Meta-Analysis Summary Statistics • Odds ratio (OR) • Used for binary events, e.g., death, complication, recurrence • Usually configured such that OR < 1 indicates treatment benefit • If confidence interval (CI) does not cross OR = 1 line, then results are statistically significant • Can calculate number needed to treat (NNT) from OR • Weighted mean difference (WMD) • Used for numeric events, e.g., measurements • Usually configured such that WMD < 0 indicates treatment benefit • If CI does not cross WMD = 0 line, then results are statistically significant

8. Systematic Reviews of Treatment of Cardiac Risk Factors • A series of meta-analyses found benefits for lowering cholesterol (Law, Wald, & Rudnicka, 2003), blood pressure (Law, Wald, Morris, & Jordan, 2003), and homocysteine (Wald, Law, & Morris, 2002) • Led to proposal for development of a “polypill” (six medications: statin, three blood pressure–lowering drugs in half standard dose, beta blocker, folic acid, and aspirin) that could potentially reduce cardiovascular disease by 80% (Wald & Law, 2003; Wald, 2012; Yusuf, 2012) • Though a “polymeal” may be natural, safer, and tastier, with wine, fish, dark chocolate, fruits and vegetables, garlic, and almonds (Franco, et al., 2004) • Initial clinical trial in India found lowering of blood pressure and cholesterol. Subsequent study confirmed the findings. (Yusuf et al., 2009; Yusuf, 2012)

9. The Cochrane Collaboration(Levin, 2001) • “An international collaboration with the aim of preparing and maintaining systematic reviews of the effects of health care interventions” (Hersch, 2008) • Largest producers of systematic reviews, limited to interventions • http://www.cochrane.org • Celebrated its 20th anniversary in 2013 (Grimshaw, 2013)

10. Cochrane Database of Systematic Reviews (CDSR) “It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomized controlled trials.” —Archie Cochrane, 1972 • CDSR embodies Cochrane’s vision • About 2,000 reviews done but many more needed to cover medicine comprehensively

11. Elements of Cochrane Reviews • Statement of clinical problem or question • Sources of evidence • Literature search • Non-experimental data if included • Inclusion and exclusion criteria • Results in tabular and graphical form • Conclusions • Date of last update • Last substantive update or significant new evidence • Example of report: “A discussion of approaches to knowledge synthesis” (Hartling, 2014)

12. Other Sources of Summarized Evidence • Syntheses found in: • CDSR: http://www.cochrane.org • PubMed Health: http://www.ncbi.nlm.nih.gov/pubmedhealth • Synopses • Clinical Evidence: “Evidence formulary” • InfoPOEMS: “Patient-Oriented Evidence that Matters” • Physician’s Information and Education Resource (PIER) from the American College of Physicians

13. Limitations of Systematic Reviews • Not everyone accepts use of meta-analysis; Feinstein (1995) calls it “statistical alchemy” • Meta-analyses on same topic sometimes reach different conclusions due to methodologic differences (Hopayian, 2001) • “Truth” determined by meta-analysis has the shortest “half-life” of all knowledge (Poynard et al., 2002) • Effect of publication bias may be exacerbated in systematic reviews (Dickersin, 1997; Dwan, 2013)

14. Evidence-Based PracticeSummary - Lecture f • For many tests and treatments, there are multiple studies such that one study does not give the complete picture • This has led to the production of “systematic reviews” or “evidence reports” to bring together all the evidence on a treatment or test • Per the Haynes 4S model, syntheses bring primary data together, whereas synopses make it available to users in highly summarized form

15. Evidence-Based PracticeReferences – Lecture f References Bello, A., Wiebe, N., Garg, A., & Tonelli, M. (2015). Evidence-based decision-making 2: Systematic reviews and meta-analysis. Clinical Epidemiology: Practice and Methods, 397-416. Cipriani, A., Higgins, J. P., Geddes, J. R., & Salanti, G. (2013). Conceptual and technical challenges in network meta-analysis. Annals of internal medicine, 159(2), 130-137. Dickersin, K. (1997). How important is publication bias? A synthesis of available data. AIDS Education and Prevention, 9, 15–21. Dwan, K., Gamble, C., Williamson, P. R., & Kirkham, J. J. (2013). Systematic review of the empirical evidence of study publication bias and outcome reporting bias—an updated review. PloS one, 8(7), e66844. Retrieved from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066844 Feinstein, A. (1995). Meta-analysis: Statistical alchemy for the 21st century. Journal of Clinical Epidemiology, 48, 71–79. Franco, O., Bonneux, L., deLaet, C., Peeters, A., Steyerberg, E., & Mackenbach, J. (2004). The polymeal: A more natural, safer, and probably tastier (than the polypill) strategy to reduce cardiovascular disease by more than 75%. British Medical Journal, 329, 1147–1150. Grimshaw, J., Craig, J., Tovey, D., & Wilson, M. (2013). The Cochrane Collaboration 20 years in. Canadian Medical Association Journal, 185(13), 1117-1118. Retrieved from http://www.cmaj.ca/content/185/13/1117.full.pdf+html

16. Evidence-Based PracticeReferences – Lecture f Continued References Guyatt, G., Rennie, D., Meade, M., & Cook, D. (2014). Users’ guides to the medical literature: A manual for evidence-based clinical practice, 3rd ed. New York: McGraw-Hill. Hartling, L., Vandermeer, B., & Fernandes, R. M. (2014). Systematic reviews, overviews of reviews and comparative effectiveness reviews: a discussion of approaches to knowledge synthesis. Evidence‐Based Child Health: A Cochrane Review Journal, 9(2), 486-494.Haynes, R. (2001). Of studies, syntheses, synopses, and systems: The “4S” evolution of services for finding current best evidence. ACP Journal Club, 134, A11–A13. Helfand, M., Morton, S., Guallar, E., & Mulrow, C. (2005). Challenges of summarizing better information for better health: The evidence-based practice center experience. Annals of Internal Medicine, 142(12, Part 2). Hersh, W., Helfand, M., Wallace, J., Kraemer, D., Patterson, P., Shapiro, S., & Greenlick, M. (2001). Clinical outcomes resulting from telemedicine interventions: a systematic review. BMC Medical Informatics and Decision Making, 1, 5. Retrieved from http://www.biomedcentral.com/1472-6947/1/5 Hersh, W., Helfand, M., Wallace, J., Kraemer, D., Patterson, P., Shapiro, S., & Greenlick, M. (2002). A systematic review of the efficacy of telemedicine for making diagnostic and management decisions. Journal of Telemedicine and Telecare, 8, 197-209. Hersh, W., Hickam, D., Severance, S., Dana, T., Krages, K., & Helfand, M. (2006). Diagnosis, access, and outcomes: update of a systematic review on telemedicine services. Journal of Telemedicine & Telecare, 12(Supp 2), 3-31.

17. Evidence-Based PracticeReferences – Lecture f Continued 2 References Hopayian, K. (2001). The need for caution in interpreting high quality systematic reviews. British Medical Journal, 323, 681-684. Law, M., Wald, N., Morris, J., & Jordan, R. (2003). Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. British Medical Journal, 326, 1427–1431. Law, M., Wald, N., & Rudnicka, A. (2003). Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. British Medical Journal, 326, 1423–1427. Levin, A. (2001). The Cochrane collaboration. Annals of Internal Medicine, 135, 309–312. McKenzie, J. E., Beller, E. M., & Forbes, A. B. (2016). Introduction to systematic reviews and meta‐analysis. Respirology, 21(4), 626-637. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/resp.12783/epdf Poynard, T., Munteanu, M., Ratziu, V., Benhamou, Y., Martino, V. D., Taieb, J., & Opolon, P. (2002). Truth survival in clinical research: An evidence-based requiem? Annals of Internal Medicine, 136, 888–895. Thom, S., Poulter, N., Field, J., Patel, A., Prabhakaran, D., Stanton, A., ... & Bompoint, S. (2013). Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA, 310(9), 918-929. Retrieved from http://jama.jamanetwork.com/article.aspx?articleID=1734704

18. Evidence-Based PracticeReferences – Lecture f Continued 3 References Uman, L. S. (2011). Systematic reviews and meta-analyses. Journal of the Canadian Academy of Child and Adolescent Psychiatry, 20(1), 57. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024725/pdf/ccap20_1p57.pdf Wald, D., Law, M., & Morris, J. (2002). Homocysteine and cardiovascular disease: Evidence on causality from a meta-analysis. British Medical Journal, 325, 1202–1206. Wald, N., & Law, M. (2003). A strategy to reduce cardiovascular disease by more than 80%. British Medical Journal, 326, 1419–1423. Wald, D. S., Morris, J. K., & Wald, N. J. (2012). Randomized polypill crossover trial in people aged 50 and over. PLoS One, 7(7), e41297. Yusuf, S., Pais, P., Afzal, R., Xavier, D., Teo, K., Eikelboom, J., Sigamani, A., ... Indian Polycap Study (TIPS). (2009). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): A phase II, double-blind, randomised trial. Lancet, 373, 1341–1351. Yusuf, S., Pais, P., Sigamani, A., Xavier, D., Afzal, R., Gao, P., & Teo, K. K. (2012). Comparison of Risk Factor Reduction and Tolerability of a Full-Dose Polypill (With Potassium) Versus Low-Dose Polypill (Polycap) in Individuals at High Risk of Cardiovascular Diseases The Second Indian Polycap Study (TIPS-2) Investigators. Circulation: Cardiovascular Quality and Outcomes,5(4), 463-471.

19. Evidence-Based PracticeReferences – Lecture f Continued 4 References Yusuf, S., Pais, P., Afzal, R., Xavier, D., Teo, K., Eikelboom, J., Sigamani, A., ... Indian Polycap Study (TIPS). (2009). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): A phase II, double-blind, randomised trial. Lancet, 373, 1341–1351. Yusuf, S., Pais, P., Sigamani, A., Xavier, D., Afzal, R., Gao, P., & Teo, K. K. (2012). Comparison of Risk Factor Reduction and Tolerability of a Full-Dose Polypill (With Potassium) Versus Low-Dose Polypill (Polycap) in Individuals at High Risk of Cardiovascular Diseases The Second Indian Polycap Study (TIPS-2) Investigators. Circulation: Cardiovascular Quality and Outcomes,5(4), 463-471.

20. The Culture of Health CareEvidence-Based PracticeLecture f This material was developed by Oregon Health & Science University, funded by the Department of Health and Human Services, Office of the National Coordinator for Health Information Technology under Award Number IU24OC000015. This material was updated in 2016 by Bellevue College under Award Number 90WT0002.