Evidence Based Practice Lecture 6

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 Practice
Learning 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).
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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)
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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
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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
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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
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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)
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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)
9

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
10

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) 11

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
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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)
13

14. Evidence-Based Practice
Summary - 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
14

15. Evidence-Based Practice
References – 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
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16. Evidence-Based Practice
References – 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.
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17. Evidence-Based Practice
References – 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
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18. Evidence-Based Practice
References – 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.
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19. Evidence-Based Practice
References – 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.
19

20. The Culture of Health Care
Evidence-Based Practice
Lecture 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.
20