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2. The Culture of Health care
Evidence-Based Practice
Welcome to The Culture of Health Care: Evidence-Based Practice. This is Lecture c.
The component, The Culture of Health Care, addresses job expectations in health care settings. It discusses how care is organized within a practice setting, privacy laws, and professional and ethical issues encountered in the workplace.
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 IU24OC 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

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).
By the end of this unit, Evidence-Based Practice, students will be able to:
Define the key tenets of evidence-based medicine (EBM) and its role in the culture of health care.
Construct answerable clinical questions and critically appraise evidence answering them.
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.
Describe how EBM can be applied to key clinical questions of diagnosis, harm, and prognosis.
Discuss the benefits and limitations to summarizing evidence.
Describe how EBM is used in clinical settings through clinical practice guidelines and decision analysis.

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
This lecture discusses interventions and how they are assessed in evidence-based medicine. Questions about interventions address treatment or therapy as well as the other ways we intervene to improve health and eliminate disease.
When evidence-based medicine is used to assess questions about interventions, the concern is about the benefit of a clinical intervention to treat or prevent disease. This assessment approach can be applied to any intervention, such as drug therapy, diet therapy, surgery, and complementary and alternative medicine. The best evidence for assessing an intervention comes from a randomized controlled trial (RCT) [R-C-T] or, even better, from a meta-analysis of multiple RCTs. A key aspect of an RCT is that patients are similar in all regards with the exception of the intervention applied. This condition is the ideal; however, it’s important to carefully assess this aspect when appraising a study because the ideal conditions are not always present.

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)
RCTs provide the best evidence for interventions because they allow us to reduce bias when participants don’t know what treatment they are getting. For example, most of you probably know someone who touts the benefits of vitamin C in preventing the common cold. Maybe even you do. We all know people who say that since they started taking vitamin C, they never get colds. However, the reality is that there have been more than thirty RCTs that have assessed this intervention. When you eliminate the bias to people knowing whether they are taking either vitamin C or a placebo, there is no difference in the number of colds that people get.
Another example is the Women’s Health Initiative. Prior to this study by Chlebowski and colleagues, there was strong belief that postmenopausal estrogen replacement therapy was beneficial for women—that it reduced heart disease and cognitive deficits. However, this belief was overturned by this very well designed RCT.
Another benefit for RCTs is that they tend to focus on clinical endpoints and patient-oriented outcomes, or at least they should. In the 1980s, it was common to prescribe lidocaine [lie-duh- keyn] whenever a patient had a myocardial infarction in the belief that suppressing cardiac rhythm abnormalities would prevent complications such as fatal ventricular fibrillation [fahy- bruh-ley-shuhn]. However, the Cardiac Arrhythmia [uh-rith-mee-uh] Suppression Trial, which randomized people to lidocaine and no lidocaine, showed that not only was there no benefit for lidocaine, but it was actually dangerous, bringing a quick end to that practice.
There’s a common view that any new intervention is better than the old. One researcher looked at radiation oncology trials and noticed that new treatments were just as likely as not to be successful. Just because something new is introduced doesn’t mean we can’t test it out. However, testing needs to be done in an RCT to demonstrate whether the new approach really is better.

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)
There have been other interesting findings about RCTs over the years. One is that there seems to be an inverse relationship between the quality of the study and the magnitude of the treatment effect—the better the design of the study, the lower the treatment effect, or the benefit, of the treatment. We’ll see how this is actually measured in a moment. It has also been found that evidence of lower quality, particularly non-randomized controlled trials, is more likely to be later overturned than is good, high-quality evidence. However, it should be noted that well-designed observational studies in which you don’t randomize and control people may be just as good as an RCT if the observational studies are well designed and well carried out.

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)
RCTs have a fascinating history. It is often said that the first RCT was performed by Dr. James Lind, who was a British naval doctor and surgeon in the 1700s. He performed experiments in which he gave citrus fruits, particularly lemons and oranges, to some sailors and didn’t give citrus fruits to others. He noticed, unequivocally, that the sailors who were administered citrus fruits did not develop scurvy, which we now know is caused by vitamin C deficiency. Those who did not get the citrus fruits were much more likely to develop scurvy.
The first true RCT was performed in the United Kingdom in the 1940s. The trial looked at the treatments for tuberculosis and compared streptomycin [strep-tuh-mahy-sin], an early antibiotic for tuberculosis, with a placebo—this study demonstrated clear superiority for the antibiotic.

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?
How do we critically appraise a study about an intervention? In the previous lecture, we discussed three questions that we ask of any study:
Are the results of the study valid?
What do the results show?
Can the results be applied to patient care? (Or, in the case of a clinician, Can the results be applied to my patient?)

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?
To determine whether results are valid, we ask if the experimental and control groups began the study with a similar prognosis: Were the patient groups identical? Were the patients then randomized into the control or experimental treatment? Was the randomization concealed from the clinician—that is, did the clinician have absolutely no role in the randomization? (If the clinician can bias the randomization, then the clinician will bias the trial.) Were the patients analyzed in the groups to which they were randomized (sometimes called intent-to-treat analysis)? Were the patients in the treatment and control groups similar with respect to the known prognosis? Sometimes the randomization does not work, and we end up with somewhat different groups, which raises concerns about the validity of the RCT.

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?
There are more questions to ask about the validity of the results. In particular, did the experimental control groups retain a similar prognosis after the study started? Were the participants aware of what group they were allocated to? Did the clinicians or the assessors (the people judging the output of the study) know which participants were assigned to which group? In some studies, the participants know what group they are in. And in a study of, for example, a particular surgery, the clinicians obviously know which participants are in which group. But we want to make sure that the randomization process works and that the assessors, to the best extent possible, are not aware of the group allocation. We also need to know that the follow-up was complete, that a large proportion of patients were not lost to follow-up.

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?
Once we are confident that the study is valid, we can look at the results. There are two major issues to consider. First, how large was the treatment effect, or how beneficial was it (if indeed it was beneficial)? Next, how precise was the estimate of treatment effect? With the treatment effect, we ask about both the relative risk reduction and the absolute risk reduction. For the precision of the treatment effect, we basically need to know whether it is statistically significant, so we need to know the confidence in our roles, or the p values for the experiments.
Once we know the treatment effect, we can ask whether the results can be applied to patient care. Were the study participants similar to my patient? If they weren’t, then there may be some issues about the generalizability of the results. Were all the clinically important outcomes considered? Even though there is always a primary outcome in a study, did the researchers look at other outcomes as well so that we can assess the larger perspective of the intervention benefit? And then, are the likely treatment benefits worth the potential harm and costs? We’ll see that RCTs do not always do a good job of accounting for adverse effects, but we must analyze the reports of adverse effects so that we can balance the benefits and harms.

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)
Let’s look at some examples of RCTs. A number of well-known RCTs come from the Women’s Health Initiative, or WHI [W-H-I]. Before the publication of the WHI RCTs, there were many previous non-randomized controlled studies that suggested women who at any time had used postmenopausal hormone replacement therapy, or HRT [H-R-T], which is an estrogen and/or progesterone regimen after menopause, had lower mortality overall and lower mortality from heart disease. In general, RCTs and observational studies had yielded conflicting results. The original WHI study was the RCT that “settled the issue,” showing that HRT provided not only no benefit but also possible harm from increased risk of breast cancer and cardiovascular disease. Further analysis of the previous observational studies found that they were confounded by non-similarities among users and non-users. For example, women of higher socioeconomic status, who were in general healthier, were more likely to use HRT. When these differences were controlled for, the benefit of HRT was no longer seen.

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%
An example of an RCT showing benefit for an intervention comes from a study of whether eradication of Helicobacter pylori [hel-i-koh-back-ter pie-lor-ee] bacteria from the stomach of individuals with gastric cancer (cancer in the stomach) reduces recurrence of the disease. This eradication was done with a combination of antibiotics and resulted in a relative risk reduction of sixty-six percent, or a two-thirds reduction, in the number of cases of recurrence.

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
This concludes Lecture c of Evidence-Based Practice. In summary, the most common type of question in EBM is about intervention, sometimes called treatment or therapy. The best evidence for intervention is the RCT, or a systematic review of multiple RCTs on a given topic.

15. Evidence-Based Practice References – Lecture c
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, CD
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.
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16. Evidence-Based Practice References – Lecture c Continued
Hemila, H., & Chalker, E. (2013). Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev, 1. Art. No.: CD
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, Retrieved from
Lehrer, J. (2010). The truth wears off. The New Yorker, 13 (52), Retrieved from
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.
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17. Evidence-Based Practice References – Lecture c Continued 2
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
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.
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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 IU24OC This material was updated in 2016 by Bellevue College under Award Number 90WT0002.
No audio.
Health IT Workforce Curriculum Version 4.0