Jessica A. Behrle, Senior Principal Biostatistician

at Janssen R&DJohnson & Johnson

My

http://thisisstatistics.org/Why Study Statistics

My career path to Stats

LOVED MATH

Exposure to StatsResearch Experience for Undergraduates

Co-op

More Stats

What Do I Do?

• Statisticians are doing “detective work- numerical detective work - or counting detective work - or graphical detective work… “ by John Tukey (famous statistician)

What are my Duties?

• Determine the questions or problems to be addressed and the data needed to answer them

• Determine methods for finding or collecting data• Design ways to collect data • Analyze and interpret data• Report conclusions from their analyses

What Skills Are Important?

Quantitative

Problem Solving

Computer

Communication People

Nonclinical Statistics

• Support– Preclinical/Discovery– Manufacturing

• Consultant• Teach

Lead Target Safety Phase I Phase II Phase III Post Marketing

Preclinical Clinical

10

Rat’s Eye

Retina

Special Acknowledgements to the creator: Ray Heslip , SIDD

Number of Photoreceptors (i.e., Thickness) was measured at locations across

the retina.

11

Temporal to NasalT4 T3 T2 T1 N1 N2 N3 N4

Superior ToInferior

S4

S3 12 10 10 11 11 11 10 11

S2 10 12 17 24 14 10 10 6

S1 11 10 10 11 10 10 17 13

I1 11 10 10 10 10 19 9 11

I2 12 12 13 13 15 22 11 10

I3 10 20 11 11 11 12 10 13

I4

Ex. # Photoreceptor Cells by Quadrant (i.e., Thickness)

TEMPORAL/SUPERIOR

(TS)

NASAL/SUPERIOR

(NS)

TEMPORAL/INFERIOR

(TI)NASAL/INFERIOR

(NI)

12

Treatments

Group Name

N Strain of Rat

Surgery Location

Low dose 12 Dys Sub-retinal

Mid dose 12 Dys Sub-retinal

High dose 11* Dys Sub-retinal

WT 12 WT NA

Untreated 12 Dys NA

Sham 11* Dys Sub-retinal

Histology was obtained from 4 rats on day 30, 4 rats on day 60, and 4 rats on day 90.

*Histology was obtained from only 3 rats on day 30.

13

Stat Methods of 1st Analysis

· where― is Grand Mean― Trti is Treatment Effect; i=high, mid, low, Sham, Untreated, and Wild Type (WT)

― Dayj is Day Effect; j=30, 60, and 90

― Quadrantk is Quadrant Effect; k=TS, NS, TI, and NI

― Ratl is Random Effect for Rat; l=rat id#

― ijkl is residual error

· Pairwise comparisons of treatments

· =0.05

ijklkjikj

kijilkji

QuadrantDayTrtQuadrantDay

QuadrantTrtDayTrtRatQuadrantDayTrtThickness

log

· Average thickness computed per quadrant and then modeled

14

Observed Thicknesses

15

Results of 1st Analysis

· High dose ↑ Untreated― 78.2 ± 12.5%

· Mid dose ↑ Untreated― 73.9 ± 11.9%

· Low dose ↑ Untreated― 57.3 ± 10.7%

· No overall significant difference is detected between the 3 doses.

― Largest diff High vs Low: 13.3 ± 7.9% (p-value=0.081)

· Each dose has significant ↓ compared to WT.

Overall

16

Quadrant Results: Doses vs. Untreated

· Day 90 · Day 60

TS ↑

TI ↑ NI ↑smallest

NS ↑

Arrows indicate statistically significant difference

TS ↑

TI ↑

NS

NI

Some of Statistical Analyses involved in Manufacturing

• Design - DOE• Comparability• Estimate Shelf-Life• Set Specifications

Lead Target Safety Phase I Phase II Phase III Post Marketing

Preclinical Clinical

Manufacture

Purification

http://www.buildingbiologics.com/manufacturing-biologics.html

Purification DOEsColor Map On Correlations

X1

X2

X3

X4

X5

X6

X1*X

2X1

*X3

X1*X

4X1

*X5

X1*X

6X2

*X3

X2*X

4X2

*X5

X2*X

6X3

*X4

X3*X

5X3

*X6

X4*X

5X4

*X6

X5*X

6

|r|0

1

|r|0

1

X1

X2

X3

X4

X5

X6

X1*X

2X1

*X3

X1*X

4X1

*X5

X1*X

6X2

*X3

X2*X

4X2

*X5

X2*X

6X3

*X4

X3*X

5X3

*X6

X4*X

5X4

*X6

X5*X

6

Difference between 2 sites

• Manufacturing a product in NA and EU• Question to address: Is there a difference in

the manufacturing process in these 2 regions?• Collect the data from the 2 regions.

– 20 measurements from each region– Measurement has values from 0 – 100 (↑ good)

• Combine, Understand and Show

JMP Data Table

• Consulting Courses• Save your text books (you may need them

later)• Learn how statistics can be used in fields that

interest you• Internships/Co-ops

ADVICE

My

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