Evidence-Based Practice Lecture 3

2. The Culture of Health care
Evidence-Based Practice
Lecture c
This material (Comp2 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 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).
3

4. Using EBM to Assess Questions
about Interventions
• Questions concerning benefit of a clinical
intervention to treat or prevent disease
• Can include drug therapy, diet therapy,
surgery, alternative medicine, and so on
• Best evidence comes from a randomized
controlled trial (RCT) or meta-analysis of
RCTs
– Patients similar in all regards with exception
of intervention applied
4

5. Why Are RCTs the Best Evidence
for Interventions?
• Reduction in bias
– Vitamin C to prevent the common cold (Douglas, Chalker,
& Treacy, 2000; Hemila, 2013)
– Women’s Health Initiative (Writing Group for the Women's
Health Initiative Investigators, 2002; Chlebowski et al.,
2015)
• Emphasis on clinical end-points and patient-oriented
outcomes
– Cardiac Arrhythmia Suppression Trial (Epstein et al., 1993)
• “New” treatments are not necessarily better
– In radiation oncology, trials of new treatments are as likely
as not to be successful (Soares et al., 2005)
5

6. Other Issues for RCTs
• Quality of study inversely related to magnitude of
treatment effect (Moher et al., 1998)
• Lower-quality (e.g., non-RCT) studies more
likely to be later “overturned” (Ioannidis, 2005;
Lehrer, 2010; Prasad, 2011; Savović,2012)
• But well-designed observational studies may be
just as good (Benson & Hartz, 2000; Dehabreh,
2012; Kovesdy, 2012)
6

7. History of RCTs
• James Lind (1717–1794), British naval doctor
and surgeon, demonstrated that lemons and
oranges improved health of sailors with scurvy
over those who did not receive them
(Lindemann, 1999)
• First true RCT performed in UK in 1940s,
demonstrating superiority of streptomycin over
placebo for tuberculosis (Streptomycin in
Tuberculosis Trials Committee, 1948)
7

8. How Do We Critically Appraise an
Intervention Study?
• Remember the questions to be asked of
any study
– Are the results valid?
– What are the results?
– Can the results be applied to patient care?
8

9. Questions to Ask about a Study
on Intervention
• Are the results valid?
– Did experimental and control groups begin the
study with a similar prognosis?
o Were patients randomized?
o Was randomization concealed (blinded or
masked)?
o Were patients analyzed in the groups to which they
were randomized?
o Were patients in treatment and control groups
similar with respect to known prognosis?
9

10. Questions to Ask about a Study
on Intervention Continued
• Are the results valid? Did experimental
and control groups retain a similar
prognosis after the study started?
o Were patients aware of group allocation?
o Were clinicians aware of group allocation?
o Were assessors aware of group allocation?
o Was follow-up complete?
10

11. Questions to Ask about a Study
on Intervention Continued 2
• What are the results?
– How large was the treatment effect?
o What was the relative risk reduction?
o What was the absolute risk reduction?
– How precise was the estimate of treatment effect?
o Were the confidence intervals or p-values stated?
• Can the results be applied to patient care?
– Were the study participants similar to my patient?
– Were all clinically important outcomes considered?
– Are the likely treatment benefits worth the potential
harm and costs?
11

12. Examples of RCTs
• Women’s Health Initiative (WHI)
– Previous non-RCT studies suggested women who used
postmenopausal hormone replacement therapy (HRT) at
any time had lower mortality overall and from heart
disease
o In general, RCTs and observational studies had yielded conflicting
results
– WHI study was RCT that “settled the issue” (Writing Group
for the Women's Health Initiative Investigators, 2002;
Lowe, 2002), showing no benefit and possible harm from
increased risk of breast cancer and cardiovascular disease
o Observational studies found to be confounded by non-similarities
between users and non-users (Humphrey, Chan, & Sox, 2002)
12

13. Examples of RCTs Continued
• Eradication of H. pylori to prevent
recurrence of gastric cancer (Fukase et
al., 2008)
• H. pylori is bacteria associated with peptic
ulcer disease
• When eradicated with antibiotics in
patients with cancer of stomach,
recurrence of cancer is less likely to occur
– Relative risk reduction = 66%
13

14. Evidence-Based Practice
Summary – Lecture c
• Most common type of question in EBM is
about intervention, sometimes called
treatment or therapy
• Best evidence for intervention is the RCT
or a systematic review of multiple RCTs on
a given topic
14

15. Evidence-Based Practice
References – Lecture c
References
Benson, K., & Hartz, A. (2000). A comparison of observational studies and randomized, controlled
trials. New England Journal of Medicine, 342, 1878–1886.
Berlin, J. (2014). Meta-analysis as evidence: Building a better pyramid. JAMA 312(6):603–606.
Chlebowski, R. T., Rohan, T. E., Manson, J. E., Aragaki, A. K., Kaunitz, A., et al. (2015). Breast cancer
after use of estrogen plus progestin and estrogen alone: Analyses of data from 2 women’s health
initiative randomized clinical trials. JAMA Oncology, 1 (3), 296–305.
Dahabreh, I. J., Sheldrick, R. C., Paulus, J. K., Chung, M., Varvarigou, V., et al. (2012). Do
observational studies using propensity score methods agree with randomized trials? A systematic
comparison of studies on acute coronary syndromes. European Heart Journal, 33 (15), 1893–
1901.
Douglas, R., Chalker, E., & Treacy, B. (2000). Vitamin C for preventing and treating the common cold.
Cochrane Database of Systematic Reviews, 2, CD000980.
Epstein, A., Hallstrom, A. P., Rogers, W. J., Liebson, P. R., Seals, A. A. et al. (1993). Mortality following
ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial
infarction. The original design concept of the Cardiac Arrhythmia Suppression Trial (CAST).
JAMA, 270, 2451–2455.
Fukase, K., Kato, M., Kikuchi, S., Inoue, K., Uemura, N., et al. (2008). Effect of eradication of
Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of
early gastric cancer: An open-label, randomised controlled trial. Lancet, 372, 392–397.
15

16. Evidence-Based Practice
References – Lecture c Continued
References
Hemila, H., & Chalker, E. (2013). Vitamin C for preventing and treating the common cold. Cochrane
Database Syst Rev, 1. Art. No.: CD000980.
Humphrey, L., Chan, B., & Sox, H. (2002). Postmenopausal hormone replacement therapy and the
primary prevention of cardiovascular disease. Annals of Internal Medicine, 137, 273–284.
Ioannidis, J. (2005). Contradicted and initially stronger effects in highly cited clinical research. JAMA,
294, 218–228.
Kovesdy, C. P., & Kalantar-Zadeh, K. (2012). Observational studies versus randomized controlled
trials: Avenues to causal inference in nephrology. Advances in Chronic Kidney Disease, 19 (1),
11–18.
Krog, A. H., Sahba, M., Pettersen, E. M., Sandven, I., Thorsby, P. M., Jørgensen, J. J., ... & Kazmi, S.
S. (2016). Comparison of the acute-phase response after laparoscopic versus open
aortobifemoral bypass surgery: a substudy of a randomized controlled trial. Vascular Health and
Risk Management, 12, 371. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045228/pdf/vhrm-12-371.pdf
Lehrer, J. (2010). The truth wears off. The New Yorker, 13 (52), 229. Retrieved from
http://jackmccallum.com/The%20Truth%20Wears%20Off--Scientific%20Method%20Error.pdf
Lindemann, M. (1999). Medicine and society in early modern Europe. Cambridge, UK: Cambridge
University Press.
Lowe, J. (2002). Estrogen plus progestin increased coronary heart disease and breast cancer events
in postmenopausal women. ACP Journal Club, 137, 41.
16

17. Evidence-Based Practice
References – Lecture c Continued 2
References
Moher, D., Pham, B., Jones, A., Cook, D. J., Jadad, A. R., et al. (1998). Does quality of reports of
randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet, 352,
609–613.
Prasad, V., Gall, V., & Cifu, A. (2011). The frequency of medical reversal. Archives of Internal
Medicine, 171 (18), 1675–1676. Retrieved from
http://archinte.jamanetwork.com/article.aspx?articleid=1105961
Santangeli, P., Muser, D., Maeda, S., Filtz, A., Zado, E. S., et al. (2016, Mar. 4). Comparative
effectiveness of antiarrhythmic drugs and catheter ablation for the prevention of recurrent
ventricular tachycardia in patients with implantable cardioverter-defibrillators: A systematic review
and meta-analysis of randomized controlled trials. Heart Rhythm.
Savović, J., Jones, H. E., Altman, D. G., Harris, R. J., Jüni, P., et al. (2012). Influence of reported study
design characteristics on intervention effect estimates from randomized, controlled trials. Annals
of Internal Medicine, 157 (6), 429–438
Soares, H. P., Kumar, A., Daniels, S., Swann, S., Cantor, A., et al. (2005). Evaluation of new
treatments in radiation oncology: Are they better than standard treatments? JAMA, 293, 970–978.
Streptomycin in Tuberculosis Trials Committee. (1948). Streptomycin treatment of pulmonary
tuberculosis. British Medical Journal, 30, 769–782.
Writing Group for the Women’s Health Initiative Investigators. (2002). Risks and benefits of estrogen
plus progestin in healthy postmenopausal women—Principal results from the Women’s Health
Initiative randomized controlled trial. JAMA, 288, 321–333.
17

18. The Culture of Health Care
Evidence-Based Practice
Lecture c
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.
18