1. What I do with Statistics Presented to Mr. Kunkle’s Statistics Class By Robert Capen

2. About me I have a Ph.D. in Statistics from the University of Florida I have worked in industry since 1991 I have been at Merck since 1995

3. What got me interested in Stats? 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

4. A useful definition of Statistics “Statistics is the Technology of the Scientific Method” – I. J. Good Scientific Research Statistics

5. A useful definition of Statistics But like all technology, it has to be used wisely…

6. 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?

7. 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.”

8. 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

9. 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.

10. Monte Hall – Let’s make a deal! Three curtains to choose from. Behind one of them is a new car, behind the other two are “zonks.” Monte knows where the car is. You pick curtain #1, Monte opens up curtain #3 and shows you a zonk. He then asks if you want to stay with curtain #1 or switch to curtain #2? What should you do?

11. What education do you need to become a statistician? A Bachelors degree is the absolute minimum While 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.

12. What can I expect if I pursue a degree in Statistics? There will be a lot of math 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

13. What do I do at Merck? Assay Validation Technology transfer Process Development Specification Setting Out-of-Specification Investigations And a lot more

14. 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,

15. GARDASIL (Human Papillomavirus) 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). GARDASIL is also used for boys and men 9 through 26 years of age to help protect against genital warts

16. Gardasil Potency Potency: a measure of the activity of a drug in a biological system Measured as the antigen concentration or antigen mass/unit volume in a biological matrix GARDASIL 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 activates the immune response

17. Validation parameters Accuracy Linearity Specificity Precision Repeatability Ruggedness Robustness LOD/LOQ Range Bias Variability Sensitivity

18. Validation parameters - Bias Accuracy – does the assay generate “true” values? Linearity – does the assay generate results that are directly proportional to the amount of analyte in the sample? Specificity – does the assay measure the target analyte and no other substance in the sample specimen?

19. Validation parameters - Variability Precision & Repeatability – Measures the amount of random scatter in the data under typical (Precision) & ideal (Repeatability) scenarios Ruggedness & Robustness – quantifies the degree of influence due to uncontrollable (“noise”) parameters (Ruggedness) and controllable parameters (Robustness)

20. Validation parameters - Sensitivity LOD – Limit of Detection: Smallest concentration that can be detected LOQ – Limit of Quantitation: Smallest concentration that can be detected accurately and precisely LOD ≤ LOQ Range: lower and upper concentrations within which the assay produces accurate, specific, linear and precise results.

21. Example - Specificity

22. Example – Precision & Repeatability

23. Example - Ruggedness

25. Validation summary Collaboration with laboratory scientists to develop validation protocol Contains pre-established acceptance criteria Conforms to regulatory guidance Summary results provided to clients written in plain language Technical details provided in comprehensive statistical report Confidence intervals, preliminary screening of data for outliers, derivation of criteria for judging the validity of an assay run, statistical calculations, etc.)

26. Some quotes containing pearls of wisdom Torture numbers, and they'll confess to anything. - Gregg Easterbrook (American author) If your experiment needs statistics, you ought to have done a better experiment. –Ernest Rutherford (chemist/physicist) Thank you!