1. Statistics and Statistical Careers in Clinical Trials Joseph Massaro Department of Biostatistics Boston University School of Public Health jmm@bu.edu

2. Clinical Trial Clinical trials: Trials to evaluate the effectiveness and safety of medications or medical devices by monitoring their effects on large groups of people (www.medterms.com).www.medterms.com

3. Lipitor (Atorvastatin) Effect on MI/Death (from www.drugs.com/pro/lipitor.html)www.drugs.com/pro/lipitor.html

4. Example of a Clinical Trial Question on Advanced Placement Exam FDA will recommend a new cholesterol drug if there is sufficient evidence it reduces cholesterol >10 mg/dl more than placebo, on average, over 6 weeks. Let μ E, μ P = true mean 6-week cholesterol reduction (mg/dl) for the experimental and placebo, respectively.

5. Example of a Clinical Trial Question on Advanced Placement Exam FDA will recommend a new cholesterol drug if there is sufficient evidence it reduces cholesterol >10 mg/dl more than placebo, on average, over 6 weeks. Let μ E, μ P = true mean 6-week cholesterol reduction (mg/dl) for the experimental and placebo, respectively. – A. What is the null and alternative hypothesis of interest?

6. Example of a Clinical Trial Question on Advanced Placement Exam FDA will recommend a new cholesterol drug if there is sufficient evidence it reduces cholesterol >10 mg/dl more than placebo, on average, over 6 weeks. Let μ E, μ P = true mean 6-week cholesterol reduction (mg/dl) for the experimental and placebo, respectively. – A. What is the null and alternative hypothesis of interest? H 0 : μ E - μ P ≤ 10 vs. H 1 : μ E - μ P > 10

7. Example of a Clinical Trial Question on Advanced Placement Exam FDA will recommend a new cholesterol drug if there is sufficient evidence it reduces cholesterol >10 mg/dl more than placebo, on average, over 6 weeks. Let μ E, μ P = true mean 6-week cholesterol reduction (mg/dl) for the experimental and placebo, respectively. – B. 200 people were in the clinical trial: 100 received experimental and 100 received control. The sponsor performed a paired t-test to test H 0. Is this appropriate?

8. Example of a Clinical Trial Question on Advanced Placement Exam FDA will recommend a new cholesterol drug if there is sufficient evidence it reduces cholesterol >10 mg/dl more than placebo, on average, over 6 weeks. Let μ E, μ P = true mean 6-week cholesterol reduction (mg/dl) for the experimental and placebo, respectively. – B. 200 people were in the clinical trial: 100 received experimental and 100 received control. The sponsor performed a paired t-test to test H 0. Is this appropriate? No: the two groups are independent.

9. Degrees and Careers To pursue a career in clinical trials, stat/biostat degrees to first consider are: – Bachelors (undergraduate) – Masters of Public Health (“concentration” in biostatistics) – Masters in Statistics/Biostatistics – Ph.D. in Statistics/Biostatistics

10. Degrees and Careers Bachelors – Gets your “foot in door” – entry level jobs – To advance career as a clinical trials biostatistician, strongly consider graduate degree – Bachelors in stats/biostats not necessarily required to pursue graduate degree in stats/biostats Mathematics Biology Need at least 2 semesters of Calculus and Linear Algebra

11. Degrees and Careers Masters of Public Health (MPH) – MPH usually very applied curriculum (little statistical theory) – Again, gets your “foot in door” as clinical trial biostatistician Probably can handle 50-75% of clinical trial analyses – To advance career as a clinical trial biostatistician, consider Masters or Ph.D. in statistics/biostatistics – Other clinical trial opportunities with MPH: Require knowledge of statistics but not necessarily performing statistical analysis – Statistical Programmer – Data Manager – Trial Manager

12. Degrees and Careers Masters in Statistics/Biostatistics – Applications and underlying theory – Often more than adequate to have a successful biostatistical career in clinical trials Design clinical trials Develop statistical plan for clinical trials Carry out analysis – If “upper management” is a goal, consider Ph.D.

13. Degrees and Careers Ph.D. in Statistics/Biostatistics – More applications/more advanced theory – Similar biostatistical opportunities as Master’s, but perhaps for more complex studies. Also, present (and “defend”) designs and analysis results to regulatory agencies – Often required for upper management/supervisory positions

14. Intangibles Be a good “team” member – ability to work with others Ability/willingness to investigate and learn Starting out: willingness to do “entry level” tasks – EVERY task has an opportunity to learn – While in graduate school I performed data entry for two years I learned in that time about how data is collected and managed for a clinical trial – Proofread clinical trial reports/manuscripts – Double-check computer output (quality control)

15. Don’t Ignore Other Disciplines in Undergraduate Career E.g., Clinical trial statisticians need to be good writers (grammar, conciseness) – Manuscript writing for journals – Reports for FDA