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Bonferroni: Friend or Foe? Multiple Testing in Cardiovascular Medicine Dhruv S. Kazi, MD, MSc AHA Cardiovascular Outcomes Research Fellow Stanford University.

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Presentation on theme: "Bonferroni: Friend or Foe? Multiple Testing in Cardiovascular Medicine Dhruv S. Kazi, MD, MSc AHA Cardiovascular Outcomes Research Fellow Stanford University."— Presentation transcript:

1 Bonferroni: Friend or Foe? Multiple Testing in Cardiovascular Medicine Dhruv S. Kazi, MD, MSc AHA Cardiovascular Outcomes Research Fellow Stanford University

2 “Off hand, I’d say you’re suffering from an arrow through your head, but just to play it safe, let’s get an echo.”

3 Death from Cardiovascular Causes, Nonfatal Myocardial Infarction, or Stroke = 9 billion dollars Yusuf, S, et al. N Engl J Med 2001;345: CURE

4 Liver Clopidogrel Cytochrome P450-dependent oxidation Binds to P2Y12 Receptor on Platelets Ticagrelor Binds to P2Y12 Receptor on Platelets CYP2C19

5 Potential Strategies  Clopidogrel  Ticagrelor Which one would you want?

6 Cannon, CP, et al. Lancet 2010; 375: Primary Efficacy Endpoint in the PLATO-Invasive RCT

7 Cannon, CP, et al. Lancet 2010; 375:

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12 Methods  Cohort: 100,000 patients who present with ACS and undergo PCI, age at entry – 65 years  Analytic Horizon: Lifetime  Perspective: “Ideal Insurer”  Interventions – DAPT 12 months from last ACS or PCI, whichever is later – Aspirin monotherapy for life thereafter

13 Possible Explanations?

14  True Difference  Chance Finding  Fraud?

15 The Multiple-Look Problem Number of analyses Cumulative prob of a positive association

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17 So how do you get around this? Traditionally, “don’t run multiple subgroups” unless: -The analyses are pre-specified -The analyses are biologically plausible And if you must, conduct rigorous statistical adjustment!

18 Bonferroni Adjustment  Conservative  Assumes independence  1-(1- α ) 1/n ~ α/n  But does this make sense? BMJ April 18; 316(7139): 1236–1238.

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20 How Do We Proceed? (Do you still want the drug?)  Multiple testing is problematic (even if pre-specified)  The challenges of a priori hypotheses

21 Conclusions  Multiple testing is a complicated question: with real clinical consequences  Statistical adjustment is a necessary but imperfect solution Trial and Error. Kaul S, et al. J Am Coll Cardiol 2010;55:415–27

22 Conclusion The p value is no substitute for a brain.

23 Thank You!


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