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Someone seeks help to analyze

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Statisticians have a « marketing » problem

Two complementary professions

Statistician

A multidisciplinary profession

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biostatistician?

Development cost per new drug > 1 BN $Development cost per new drug > 1 BN $Surrogate endpoints

Evaluation of surrogate endpoints

i (i = 1,N)i (i = 1,N)

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Is pathological response a surrogate for survival?

Is pathological response a surrogate for survival?

R²trial = 0.03

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Surrogate endpoints

Surrogate endpoints

Surrogate endpoints

Central statistical monitoring

Statisticianscientist?

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CSM compares each site with all others

data Cen

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1234

1 2 3 4 5 6 7 85

1 2 3 4 5 6 7 861 2 3 4 5 6 7 87

1 2 3 4 5 6 7 8

1 2 3 4 5 6 7 89

1 2 3 4 5 6 7 810

1 2 3 4 5 6 7 811

1 2 3 4 5 6 7 8

1 2 3 4 5 6 7 8

1 2 3 4 5 6 7 8

1 2 3 4 5 6 7 8

1 2 3 4 5 6 7 8812

(ST) P-value matrix

Example: 3 centers with highly atypical data

Operating characteristics

Machine learning helps create « signals »Machine Learningstatisticaltests

P-valuematrix

Site
scoresIdentify
dataquality
signals

Classifysignals asSuggestActions

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50 trials~ 107 tests

P-values are tagged for « signals »50 trials~ 107 tests

P-values are grouped into « signals »Random Forests
Modularity optimization
Graph partitioning

Features

Gradient Boosted Trees

Test typeP-valueP-value rank
Center score
Center rank
Nr patients
Domain name*
Variable name
Observed
Expected

CluePoints for quality control

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Features
Test typeP-valueP-value rank
Center score
Center rank
Nr patients
Domain name*
Variable name
Observed
Expected

S1S2

S3

CluePoints for « detective » work

Generalized pairwise comparisons

Statistician

simply researcher?

Current analyses of randomized clinical trials

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Randomized clinical trial

Pairwise comparisonsMann-Whitney form of the Wilcoxon test

Any single outcome measure

Binary outcome measure

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Continuous outcome measure

Time to event outcome measure

Several prioritized outcome measures

Thresholds of clinical relevance

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Benefit / risk analyses

The net treatment benefit

Survival benefit of erlotinib

Toxicities of erlotinib

Worst grade

Erlotinib group (n=282)

Placebo group (n=280)

Grade 148 (17%)69 (24.6%)

Grade 2118 (41.8%)

89 (31.8%)

Grade 372 (25.5%)

47 (16.8%)

related AE51

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Grade 429%
11 (3.9%)

19%

Grade 54 (1.4%)

3 (1.1%)6 (2.1%)52

Prioritized outcomes: OS and worst toxicity

Personalized medicine

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BENEFIT - Biostatistical Estimation of Net Effects
For Individualization of Therapy

Personalized medicine

Acknowledgments

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