1. Medical Literature: Reading, Interpreting, and Writing Muhammad Mamdani, PharmD, MA, MPH Director, Applied Health Research Centre LKSKI of St. Michael’s Hospital Associate Professor – University of Toronto Adjunct Faculty – King Saud University February 2010

3. Clinical Research: Basic Purpose and Context

5. Perception: Reality vs Belief

6. Variability in Perceptions

8. The Evolving Nature of Research

10. But How Do I Know About the Quality and Validity of the Study?

12. The Medical Research Spectrum (Sung, JAMA, 2003)

13. The Medical Research Spectrum (Sung, JAMA, 2003)

14. Basic Clinical Research Methodology

15. Comparative Clinical Research: A Simplistic Overview (Melot, CCM, 2009)

17. Randomized Clinical Trial: Design (Melot, CCM, 2009)

18. Validity and Biases in Clinical Trials (Melot, CCM, 2009)

24. How Do I Know Which Study Design is Best? Oxford Centre for Evidence-Based Medicine, 2002 Level of Evidence Study Type Level 1 RCTs Level 2 Cohort Studies Level 3 Case-Control Studies Level 4 Case Series Level 5 Expert Opinion

25. Analytical Aspects

28. Measures of Association: An Example Total n = 40,000 N per study group = 20,000 Absolute Risks AR (Placebo) = 0.5% AR (Treatment) = 0.15% ARR = 0. 5% - 0.15% = 0.35% NNT = 1/0.35% = 296 Relative Risks RR = 0.15% / 0.5% = 0.30 RRR = 1/RR = 70% OR (CC: Logistic Regression) HR (Cohort: Cox PH Models) Placebo Treatment MI 100 30 No MI 19900 19970

30. Literature Evaluation Tools

32. Consort Statement

33. STROBE

34. Group Activity: Pitt et al

36. Pitt et al: Study Overview

39. RALES - Results Outcome Absolute Risk Relative Risk Death Pl=46% Spir=35% p<0.001 0.70 (0.60-0.82) Readmission for HF Pl=36% Spir=26% p<0.001 0.65 (0.54-0.77) Serious Hyperkalemia Pl=1.2% Spir=1.7% p=0.42 NS

40. What Happened in Actual Practice? Juurlink et al, NEJM, 2004

41. Spironolactone Prescription Uptake 1994-2001 RALES

42. Hospital Admission Associated with  K + RALES

43. Admission Associated with  K + Ending in Death RALES

44. What about the expected benefits?

45. Readmission for Heart Failure RALES

46. All-Cause Mortality RALES

47. What Happened???

49. What’s the Problem?

52. Bozkurt et al J Am Coll Cardiol 2003;41:211-4 Criteria Bozkurt et al (n=104) RALES (n=822) NHYA (% patients) I II III IV Undocumented 4.5% 4.5% 15.3% 10.3% 65.4% 0% 0.5% 72% 27% 0% % Patients with LVEF < 35% 54.8% 100% % Patients with renal insufficiency at baseline 30.7% Excluded Use of beta-blockers 34.6% 11%

56. Where Does Evidence Fit Into the Decision-Making Process? BELIEFS BEHAVIOUR Evidence Personal Values / Experience Societal Values ‘ Other’ Factors

57. Clinical Research: Writing a Scientific Manuscript

58. What Do Journal Editors Look For? What will maximize the journal’s IMPACT FACTOR? Characteristic Implications Clinical Relevance Research question should be relevant: Ask other clinicians about question’s clinical importance Originality Research question should ideally be unique: Perform a PubMed search Clarity Research question should be simple Study design should be well explained with ONE primary endpoint Before beginning study – know which 4 or 5 figures and/or tables will be produced; make mock figures/tables Know your audience: simple language Good Science Assemble a team: study lead, methodologist, statistician, clinician, at least one senior researcher Must have good design, sufficient sample size, and analysis plan Brevity Keep the manuscript short: 2,000 – 3,000 words Consider different formats: brief reports, research letters

59. Fogg, BJ, et al, What makes Websites Credible? Stanford Persuasive Technology Lab

60. Author Photo Results believable trustworthy competent credible unbiased expert COMPOSITE casual photo no photo formal photo Fogg, BJ, et al, What makes Websites Credible? Stanford Persuasive Technology Lab

65. Research and Communications: An Example