1. Gil Harari Statistical considerations in clinical trials www.medistat.co.il

2. Elephants, Diamonds & Biostatistics ???

3. Analyses Variables Primary Efficacy Variables Secondary Efficacy Variables Safety Variable Adverse Events. Physical examinations. Laboratory measurements. Reasons for discontinuation.

4. Statistical considerations in biomedical studies

5. Is risk factor X associated with disease Y? From the sample, we compute an estimate of the effect of X on Y (e.g., risk ratio if cohort study): - Is the effect real? Did chance play a role?

6. Why worry about chance? Population Sampling variability… - you only get to pick one sample!

7. Interpreting the results Population Selection of subjects Inference Make inferences from data collected using laws of probability and statistics - tests of significance (p-value) - confidence intervals

8. How do we determine if an association is significant? Significance is in context of “Statistical” significance –p-Value –Treatment Effect –Confidence Interval 8

9. Subjects for Discussion 1.What is a p-Value? 2.Sample Size Calculation 3.Clinical Significance Versus Statistical Significance

10. Basic Principles of Statistical Analysis Significance Tests Difference Between Treatments Is it by chance? Apply a significance test

11. Sample Size Calculations

12. Sample Size Calculation

13. Based on: 1. Study Design 2. Treatment Effect (Effect Size) (δ) 3. Type I error (α), Type II error (β) 4. Power of the study (1-β)

14. Clinical significance Versus Statistical Significance CR TA % Improvement 43% 65% Clinical SignificanceStatistical Significance P=0.17 P=0.03 TB CR 52% 41% N = 15N = 60

15. תודה