On Being a Statistician:Normality not Required

Presented to Mr. Kunkle’s Statistics Class

By Robert Capen

About me

I have a Ph.D. in Statistics from the University of Florida

I have worked in industry since 1991I have been at Merck since 1995

What got me interested in Statistics?

I really liked the fact that statistics was an applied science It wasn’t just mathematical theory but also

required creative thinking, critical evaluation and good people/listening skills

I am a skeptic at heart and statistics gave me a valuable set of tools to evaluate the conclusions others drew from the data they collected or analyses they performed

What careers are out there for Statisticians?

PharmaceuticalFinancialInsuranceIndustrialAcademiaGovernmentConsulting

What careers are out there for Statisticians?

Statistician: Navarro Research and Engineering Navarro Research and Engineering, Inc. is a premier

contractor for the Department of Energy (DOE) and the National Nuclear Security Administration

Pricing Statistician: Grainger Position Description: Responsible for providing input to the

development and execution of Grainger’s price delivery strategy across GIS Brand segments.

Intern-Statistician: Flextronics International Headquartered in Singapore, Flextronics is a leading

Electronics Manufacturing Services (EMS) provider focused on delivering complete design, engineering and manufacturing services to automotive, computing, consumer, industrial, infrastructure, etc.

Go to www.monster.com or “Hot Jobs” on Yahoo and search under “statistician”

What careers are out there for Statisticians?

R&D Statistician – Materials: Corning Incorporated Corning is the world leader in specialty glass and ceramics.

We create and make keystone components that enable high-technology systems for consumer electronics, mobile emissions control, telecommunications and life sciences.

Statistician: Cetero Research Cetero Research is a leading provider of early clinical,

bioanalytical and specialty Phase II-IV research services to the bioanalytical, generic and pharma industries.

Statistician: WPS Health Insurance WPS Health Insurance is a large not-for-profit company that

has been in business for over 60 years. We offer health benefit plans to employer groups and individuals, administer Medicare benefits and serve U.S. military families world wide.

What education do you need to become a statistician?

A Bachelors degree is the absolute minimumWhile you can find jobs requiring only a B.S.

degree, you really should get a post grad. Degree (M.S. or Ph.D.)

At Merck, you cannot be hired as a statistician unless you have at least a Masters degree.

What can I expect if I pursue a degree in Statistics?

There will be a lot of (advanced) math Learning at least one major statistical computing

package is a must SAS, S-Plus, R, Minitab, JMP, etc Learning a computing language like Fortran or C++ can also

be useful If you have a keen interest in applying statistics to real

problems, then look for universities that encourage you to take science or engineering courses as electives and/or offers you the chance to work in a consulting lab.

A technical writing course is also very useful

Rough salary ranges for starting Statisticians

B.S.:$40,000 - $60,000M.S.: $60,000 - $90,000Ph.D.: $90,000 - $120,000

www.amstat.org/careers

Statisticians at Merck

All statisticians in R & D are part of BARDS (Biostatistics and Research Decision Sciences)

BARDS

Early Development

Statistics

Late Development

Statistics

Scientific Programming

EpidemiologyHealth

Economic Statistics

Statisticians at Merck

Early Development

Statistics

Biometrics Research

Nonclinical Statistics

Early Clinical Development

Statistics

Investigative Research

Personnel: - 9-Ph.D., 8-MS Statisticians - Senior Secretary - Stat Programmer - 3 Full-Time Consultants

Statisticians at Merck

Nonclinical Statistics (NCS) is responsible for providing experimental design and data analysis support to product and analytical development throughout MRL. We work together with research scientists and engineers to evaluate and implement efficient and effective experimental strategies, employ or guide our colleagues in the use of appropriate statistical methodologies to answer their research and development questions, and develop novel statistical methods to address previously unmet needs. 

Why Study Statistics?

“Statistics is the Technology of the Scientific Method” – I. J. Good

Scientific Research

Statistics

Caveat Emptor!

But like all technology, it has to be used wisely…

Ann Landers survey

“A few weeks ago, a young married couple wrote to say they were undecided as whether or not to have a family. They asked me to solicit opinions from parents of young children as well as older couples whose families were grown. ‘Was it worth it?’ they wanted to know. ‘Were the rewards enough to make up for the grief?’ The question, as I put it to my readers, was this: ‘If you had it to do over again, would you have children?’ Well, dear friends, the responses were staggering. Much to my surprise, 70 per cent of those who responded [~10,000] said ‘no.’” Does this seem right? What could explain this result?

Ann Landers survey

This is an example of a biased statistic because the sample (even though it was very large) cannot be considered as being randomly drawn from the population.  Why?

A national (scientific) survey asked the same question of 1373 randomly selected respondents, 91% responded “yes.”

Is this example still relevant today?

Are 16-year-olds safe drivers?

The following statistics suggest that 16-year-olds are safer drivers than people in their twenties, and that octogenarians are very safe.  Is this true?

* This example comes from econoclass.com

Are 16-year-olds safe drivers?

No.  As the following graph shows, the reason 16-year-old and octogenarians appear to be safe drivers is that they don't drive nearly as much as people in other age groups. 

Moral: Think about the Data!

What do I do at Merck?

Assay ValidationRisk AssessmentTechnology transferProcess DevelopmentProduct Stability AssessmentSpecification SettingOut-of-Specification InvestigationsAnd a lot more

What do I do at Merck?

All of this work utilizes many of the basic statistical methods/calculations you have been exposed to Average, Standard Deviation, Percentages,

Probability, Normal and t-distributions, Confidence Intervals, Hypothesis Tests, etc,

And some you haven’t Regression, Variance Component Analysis, Mixed

Models, Equivalence Testing, 2 and F-Distributions, Outliers, Bayesian Methods, etc.

I function as part of a team consisting of chemists, biologists, engineers, and others.

Assay Validation

Potency: a measure of the activity of a drug in a biological system

Example: GARDASIL® Potency AssayMeasured as the antigen concentration or

antigen mass/unit volume in a biological matrix – Very critical to get good potency information on the lots we manufacture!

About GARDASIL®

About 30 types of HPV are known as genital HPV since they affect the genital area HPV Types 16 and 18 cause 70% of cervical cancer cases HPV Types 6 and 11 cause 90% of genital warts cases

GARDASIL® is a vaccine (injection/shot) that is used for girls and women 9 through 26 years of age to help protect against various diseases caused by Human Papillomavirus (HPV). It is also used for boys and men 9 through 26 years of age to help protect against genital warts

Target VLP Concentrations: Type 6: 20 µg VLP/mL Type 11: 40 µg VLP/mL Type 16: 40 µg VLP/mL Type 18: 20 µg VLP/mL

VLP stands for “virus like particles, which are non-infectious components of the virus that strongly activate the

immune response

Assay Validation Parameters

Accuracy Linearity Specificity Precision Repeatability Ruggedness Robustness LOD/LOQ Range

Bias

Variability

Sensitivity

Risk Assessment

Product: 15-Valency Vaccine Assays: Relative IC50 (rIC50) – One Assay

per Valency.Relative IC50 Assay

00.20.40.60.8

11.21.4

0.00001 0.0001 0.001 0.01 0.1 1 10 100Concentration

Ass

ay R

ead

ing Unknown

Standard

Horizontal Distance Represents the

Log(rIC50)

Risk Assessment

Current Procedure for Testing a Lot:Perform 3 assay runs per valency (Geometrically) average the 3 rIC50s

Laboratory Issues:Resource intensive – 3×15 = 45 runs per lotTakes 1 – 2 weeks to do all testing

Proposal:Only perform 2 runs and (geometrically)

average the corresponding rIC50s

Risk Assessment

Statistical Issues:1. What do you think? Hint: think standard

error2. Hard one! Obscure Hint: think lottery

winner

Risk Assessment

Questions:What is the risk that a “good” lot will fail at

release if only 2 runs are performed?What is the risk that a stable lot will fail at

least one time point during stability testing?Accounting for statistical multiplicity

What risk is acceptable?How should I address these questions?

Always Ask Questions!

A psychologist wishes to determine whether genetics (nature) or environment (nurture) plays the dominant role in terms of athleticism and intelligence. She has come to you for advice on how to design and analyze the study. What questions might you ask of her?

What do some People think about Statisticians?

Torture numbers, and they'll confess to anything.  - Gregg Easterbrook (American Author)

A statistician is a professional who diligently analyzes data and then carefully draws confusions about them. – Anonymous.

If your experiment needs statistics, you ought to have done a better experiment. – Ernest Rutherford (Chemist/Physicist)

What do Statisticians think about Statisticians?

Ethical Guidelines for Statistical Practice: American Statistical Association Prepared by the Committee on Professional Ethics Approved by the Board of Directors, August 7, 1999

Statement:Because society depends on sound statistical

practice, all practitioners of statistics, whatever their training and occupation, have social obligations to perform their work in a professional, competent, and ethical manner...

www.amstat.org/committees/ethics

In other words…

It is commonly believed that anyone who tabulates numbers is a statistician. This is like believing that anyone who owns a scalpel is a surgeon. - Robert Hooke. (How to Tell the Liars from the Statisticians)

Thank you!