Research Rotation Part II

1. Research Rotation Part II B Kanna MD, MPH, FACP Associate Program Director of Internal Medicine Associate Director of Graduate Medical Education for Research

2. Section I Critique of A randomized controlled clinical trial

3. Validity • the best available approximation to the truth of a given proposition, inference, or conclusion • Accurate & reproducible Person 2 Person 1

4. Checking Validity • Conclusion Validity: • In this study, is there a relationship between the two variables? • Internal Validity: • Assuming that there is a relationship in this study, is the relationship a causal one? • Construct Validity: • Assuming that there is a causal relationship in this study, did we implement the program we intended to implement and did we measure the outcome we wanted to measure? • External Validity: • Assuming that there is a causal relationship in this study between the constructs of the cause and the effect, can we generalize this effect to other persons, places or times? http://www.socialresearchmethods.net/kb/introval.php

5. Random Error Sample 2 Universe of subjects Sample 1 CHANCE Sample 3 CHANCE

6. Checking Internal validity Universe of subjects Sample 2 Confounding Rx Outcome Sample 3 Bias

7. Applying this to a study/observation Day 1 Red pill Sx improves Day 2 Red pill Sx improves Day 3 Red pill Sx improves

8. THREE THINGS TO REMEMBER! • CHANCE – RANDOM ERROR • BIAS – SYSTEMATIC ERROR • CONFOUNDING – ADDITIONAL FACTORS

9. How to apply these concepts during the critique of RCT • Learn the general steps in a study design • Choose a topic • Define a hypothesis • Select patients • Sample size • Randomization • Treatment • Follow-up • Collection of data • Analysis • Interpretation • Conclusion • Generalize findings

11. Section II Selected topics

12. Study designs • Observational • Case control • Cohort • Cross sectional • Interventional • Randomized • Non-randomized

13. Number needed to Rx and harm • NNT = 1/ Absolute risk reduction • Rx = 0.9% • Placebo = 3.2% • ARR = 5.0- 2.5 = 2.3% • NNT = 1/ 0.023 = 45 • NNH = 1 / Absolute risk of adverse events

14. Sensitivity, Specificity & Post test probability

15. How to design & start a study • Step 1: Select a topic • Step 2: Choose a mentor and guide • Step 3: Define topic • Step 4: Search literature • Step 5: Define problem • Step 6: Collect back ground information • Step 7: Study Methods Study design; Sample selection; Sample size; Inclusion & Exclusion criteria Follow-up; Measurements; Endpoints; Statistical methods;, P value, CI, Test of significance Confounding factors, Stratification, Regression Results, Discussion , Limitations • Step 8: IRB application along with aggregate data request • Step 9: IRB approval • Step 10: Start project (Revise protocol if needed and apply for IRB modifications)

16. How to write an IRB protocol Simplified Guide for residents • 1. Title page Title; Authors; Contact information of primary authors; Department • 2. Summary of the protocol • 3. Introduction Problem definition; Magnitude; Need for study • 4. Background Physiologic principles; Cause and effect; Hypothesis • 5. Methods Study design; Sample selection; Inclusion & Exclusion criteria; Sample size Data collection (tool); Follow-up( If applicable) ; Measurements ( if applicable); Endpoints • 6. Statistical methods Testing hypothesis; P value; CI; Tests of significance; Others analyses (e.g. subgroups) • 7. Confounding & Bias Confounding ; Stratification; Regression; Methods used to Limit Bias • 8. Confidentiality and Privacy • 9. Consent/Waiver ( see Lincoln IRB consent procedures) • 10. Reporting of results • 11. Significance or Implications of the study • 12. References • 13. Tables, Figures and legends