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Bonferroni: Friend or Foe? Bonferroni: Friend or Foe?

Bonferroni: Friend or Foe? - PowerPoint Presentation

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Bonferroni: Friend or Foe? - PPT Presentation

Multiple Testing in Cardiovascular Medicine Dhruv S Kazi MD MSc AHA Cardiovascular Outcomes Research Fellow Stanford University kazistanfordedu Off hand Id say youre suffering from an arrow through your head but just to play it safe lets get an echo ID: 739772

analyses multiple stanford cardiovascular multiple analyses cardiovascular stanford 2010 kazi testing adjustment platelets ticagrelor binds pre cannon lancet 375

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Slide1

Bonferroni: Friend or Foe?Multiple Testing in Cardiovascular Medicine

Dhruv S. Kazi, MD, MSc

AHA Cardiovascular Outcomes Research Fellow

Stanford University

kazi@stanford.eduSlide2

“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.”Slide3

Death from Cardiovascular Causes,

Nonfatal Myocardial Infarction, or Stroke

= 9 billion dollars

Yusuf, S, et al. N Engl J Med 2001;345:494-502

CURESlide4

Liver

Clopidogrel

Cytochrome P450-dependent oxidation

Binds to P2Y12 Receptor on Platelets

Ticagrelor

Binds to P2Y12 Receptor on Platelets

CYP2C19Slide5

Potential StrategiesClopidogrel

Ticagrelor

Which one would you want?Slide6

Cannon, CP, et al. Lancet 2010; 375: 283-93.

Primary Efficacy Endpoint in the PLATO-Invasive RCTSlide7

Cannon, CP, et al. Lancet 2010; 375: 283-93.Slide8
Slide9
Slide10
Slide11
Slide12

MethodsCohort: 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 thereafterSlide13

Possible Explanations?Slide14

Possible Explanations?True Difference

Chance Finding

Fraud?Slide15

The Multiple-Look Problem

Number of analyses

Cumulative

prob

of

a positive associationSlide16
Slide17

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!Slide18

Bonferroni Adjustment ConservativeAssumes independence1-(1-

α

)

1/n

~

α/n

But does this make sense? BMJ. 1998 April 18; 316(7139): 1236–1238.Slide19
Slide20

How Do We Proceed? (Do you still want the drug?)

Multiple testing is problematic (even if pre-specified)

The challenges of a priori hypothesesSlide21

ConclusionsMultiple testing is a complicated question: with real clinical consequencesStatistical adjustment is a necessary but imperfect solution

Trial and Error. Kaul S, et al. J Am Coll Cardiol 2010;55:415–27Slide22

ConclusionThe p value is no substitute for a brain. Slide23

Thank You!

kazi@stanford.edu