1. Landmark Trials: Recommendations for Interpretation and Presentation Julianna Burzynski, PharmD, BCOP, BCPS Heme/Onc Clinical Pharmacy Specialist 11/29/07

2. Article Criteria 1. Significantly impacted our understanding as pharmacists and our approach to patient care 2. If 2 articles are presented each must be presented in less than 30 minutes 3. Succinctly present and summarize some have read the paper some have read the paper some have not read paper some have not read paper

3. Hierarchy of Evidence-Based Medicine (EBM) Resources

4. Presentation Format Handout Handout PowerPoint Slides PowerPoint Slides The article alone The article alone Guide audience thru material Guide audience thru material Identify page and paragraph Identify page and paragraph Case based with a clinical question Case based with a clinical question e.g. Internal Medicine Clinical Decision Making Journal Club e.g. Internal Medicine Clinical Decision Making Journal Club

5. Article Presentation Background / Introduction Background / Introduction Study Rationale Study Rationale Objective / hypothesis / endpoints Objective / hypothesis / endpoints Methods Methods Study Results Study Results Author Conclusions Author Conclusions Study Critique Study Critique Application to Clinical Practice Application to Clinical Practice

6. Background / Introduction 1. Describe who this will impact 2. Depict current standard of care Reference and describe Reference and describe Clinical trial that defines practice Clinical trial that defines practice Evidence based guidelines or position statement Evidence based guidelines or position statement ASCO, ASH, NCCN, ASHP ASCO, ASH, NCCN, ASHP

7. Study Rationale Why was the study necessary? Why was the study necessary? Study Objective Study Objective 1. Hypothesis 2. Primary endpoint 3. Secondary endpoints

8. Methods Inclusion Inclusion Are they appropriate / applicable? Are they appropriate / applicable? Exclusion Exclusion Are appropriate / applicable? Are appropriate / applicable? Intervention Intervention Is it appropriate? Is it appropriate? Dose Dose Duration of follow-up Duration of follow-up Method of measurement Method of measurement Is it supported by earlier studies or literature? Is it supported by earlier studies or literature?

9. Statistics a priori power analysis a priori power analysis   risk you are willing to take that you say there is no difference when one exists risk you are willing to take that you say there is no difference when one exists   risk you are willing to take that difference is due to chance risk you are willing to take that difference is due to chance   anticipated difference Does this match with prior results? Does this match with prior results?

10. Fire alarm analogy to statistics

11. Statistics Were the tests appropriate for the type of data analyzed Were the tests appropriate for the type of data analyzed Nominal, ordinal, continuous Nominal, ordinal, continuous Parametric, non-parametric Parametric, non-parametric Samples Samples Independent or related Independent or related 2 or > 3 2 or > 3 Number of confounders Number of confounders

12. Study Results Describe who was included Describe who was included N = XX N = XX Number of patients screened, enrolled, included in analysis Number of patients screened, enrolled, included in analysis Lost to follow-up? Lost to follow-up? Assessed in their assigned treatment group? Assessed in their assigned treatment group? Primary endpoint Primary endpoint Secondary endpoints Secondary endpoints

13. Study Results Were all results reported? Were all results reported? Were descriptive statistics presented? Were descriptive statistics presented? Relative risk or odds ratio Relative risk or odds ratio Confidence interval Confidence interval Relative and absolute risk reduction Relative and absolute risk reduction Number needed to treat or harm Number needed to treat or harm

14. Author Conclusions Their application to practice Their application to practice

15. General Considerations Conflict of interest Conflict of interest Informed consent / IRB approval Informed consent / IRB approval Funding source Funding source Journal reputation Journal reputation Peer - reviewed Peer - reviewed Validity Validity Bias Bias Confounding variable Confounding variable

16. Validity Does the study measure what it was intended to measure? Does the study measure what it was intended to measure? Does it represent an unbiased estimate of underlying truth? Does it represent an unbiased estimate of underlying truth? Internal Validity Internal Validity Reproducible Reproducible External Validity External Validity Generalizable Generalizable

17. Bias Allocation Allocation Channeling Channeling Classification Classification Compliance Compliance Detection Detection Information Information Interviewer Interviewer Measurement Measurement Observer Observer Recall Recall Selection Selection A systematic tendency to produce an outcome that differs from the underlying truth

18. Confounding Variable Related to the outcome of interest Related to the outcome of interest May  the likelihood of the outcome May  the likelihood of the outcome Unequally distributed in groups Unequally distributed in groups Not usually a concern in RCT Not usually a concern in RCT

19. Application to Clinical Practice Describe how this changes or fits in to current clinical practice Describe how this changes or fits in to current clinical practice Make a recommendation for or against treatment of the patient population studied based on your review Make a recommendation for or against treatment of the patient population studied based on your review

21. Resources Dr. Guyatt Dr. Guyatt Plummer Library Plummer Library R 118.6 118.6.U83.U83 2002x 2002x

22. 3 Questions to Ask 1. Are the results valid? 2. What are the results? 3. How can I apply the results to patient care? Gyatt, G, Rennie D (ed). Users’ Guides to the Medical Literature. Chicago: American Medical Association. 2002.

23. 3 Questions to Ask 1. Are the results valid? Did the groups begin w/ similar prognosis/risk factors Did the groups begin w/ similar prognosis/risk factors Were they randomized? Were they randomized? Was it blinded or masked? Was it blinded or masked? Were they analyzed as ITT? Were they analyzed as ITT? Was follow-up complete? Was follow-up complete?

24. 3 Questions to Ask 2. What are the results? How large was the treatment effect? How large was the treatment effect? How precise was the estimate of treatment effect? How precise was the estimate of treatment effect?

25. 3 Questions to Ask 3. How can I apply the results to patient care? Were the study patients similar to mine? Were the study patients similar to mine? Were all clinically important outcomes considered? Were all clinically important outcomes considered? Are the likely treatment benefits worth the potential harm & costs? Are the likely treatment benefits worth the potential harm & costs?

26. Internet Resources for EBM U of Toronto U of Toronto U of Toronto U of Toronto BMJ BMJ BMJ U of Utah U of Utah U of Utah U of Utah

27. Study Design PICO Participants Participants How were patients selected? How were patients selected? Exposure Exposure Intervention definition Intervention definition How / when / by whom administered How / when / by whom administered Comparison Comparison Control intervention definition Control intervention definition How / when / by whom administered How / when / by whom administered Outcome Outcome Definition of 1° & 2° outcome Definition of 1° & 2° outcome How / when / by whom assessed? How / when / by whom assessed?

28. Resources Dr. Gehlbach Dr. Gehlbach Plummer Library Plummer Library R 118.6 118.6.G43.G43 2006 2006