The Culture of Health care

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 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 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. 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

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)

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)

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)

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?

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? • Were patients randomized? • Was randomization concealed (blinded or masked)? • Were patients analyzed in the groups to which they were randomized? • Were patients in treatment and control groups similar with respect to known prognosis?

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? • Were patients aware of group allocation? • Were clinicians aware of group allocation? • Were assessors aware of group allocation? • Was follow-up complete?

11. Questions to Ask about a Study on Intervention Continued 2 • What are the results? • How large was the treatment effect? • What was the relative risk reduction? • What was the absolute risk reduction? • How precise was the estimate of treatment effect? • 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?

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 • 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 • Observational studies found to be confounded by non-similarities between users and non-users (Humphrey, Chan, & Sox, 2002)

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%

14. Evidence-Based PracticeSummary – 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

15. Evidence-Based PracticeReferences – 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.

16. Evidence-Based PracticeReferences – 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.

17. Evidence-Based PracticeReferences – Lecture c Continued2 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.

18. The Culture of Health CareEvidence-Based PracticeLecture 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.