Masters of Arts in Biology

1. Masters of Arts in Biology December 5th, 2012 Elizabeth O. Harrington, Ph.D. Associate Dean, Office of Graduate & Postdoctoral Studies Division of Biology & Medicine

2. Masters of Arts in Biology • Established in 1993 via contractual agreement. • Accredited by Connecticut Department of Education. • Course offering is a section of an existing Brown University course.

3. Masters of Arts in Biology • “The quality of student performance required is at least as rigorous as for the Master of Arts degree within any Graduate Program in the Division. The basic difference is to make it easier for a student to obtain breadth in Biology in more than one graduate area by not imposing strict requirements for specific courses.” • http://brown.edu/scs/adult/pfizer/

4. Masters of Arts in BiologyObjectives • Provide graduate instruction within the biological sciences for Pfizer colleagues and contractors who wish to extend their knowledge in discrete areas relating to their employment and/or interests. • Provide a broad-based and rigorous Master of Arts training in biological sciences.

5. Masters of Arts in BiologyExperiences Over 160 M.A. in Biology awarded.

6. Masters of Arts in BiologyExperiences Some have gone on to higher degrees….

7. Masters of Arts in BiologyOverview • Open to Pfizer contractors and colleagues. • Only one prerequisite required: • A Bachelors degree in any field. • All courses held on-site at Pfizer-Groton campus and available via WebEx.

8. Masters of Arts in BiologyOverview • Pfizer employees and contractors register as Special Students via Office of Continuing Studies; • Standard Brown tuition fees apply. • Students apply to Graduate School for the M.A. program after successful completion of two courses. • Pfizer reimburses colleagues only who pass with grade of a ‘C’ or better.

9. Masters of Arts in BiologyProgram Requirements • 8 graduate courses: • 2 of 8 courses in “core” subjects • cell biology, • biochemistry, • genetics, • pharmacology; • 6 of 8 courses with grade of ‘B’ or better. • Passing final paper or proposal “culminating experience” on topic approved by Assoc Dean, Graduate & Postdoctoral Studies.

10. Masters of Arts in BiologyProgram Requirements: Culminating Experience • As a culminating experience for the Master of Arts in Biology Program, there are two options: • an NIH style research proposal based on an original hypothesis or • a final paper which, based on the course work taken by the student, represents an original in-depth analysis and literature review of a problem in modern biology.

11. Masters of Arts in BiologyProgram Requirements: Culminating Experience • Research proposal (written as though you were preparing a NIH RO1 application) will include: • project summary/abstract, • specific aims, • research strategy, • literature cited. • Final paper (10-15 pgs, excluding figures and references) will include: • introduction, • discussion, • conclusion, • literature cited.

12. Masters of Arts in BiologyProgram Requirements: Culminating Experience • Topics must be discussed with, and approved by the Associate Dean for Graduate and Postdoctoral Studies. • The final project may be undertaken following completion of 7 courses, but must be completed no later than one semester following completion of the 8th course.

13. Masters of Arts in Biology Program Requirements: Culminating Experience • Both projects are designed to demonstrate the student's ability to master and integrate the knowledge gained in the prior course work and to apply that knowledge to a specific problem in modern biology.

14. Masters of Arts in BiologyProgram Requirements • No courses can be transferred from another institution. • Must be actively employed as a colleague or contractor at Pfizer. • Pfizer M.A. students may take courses toward the degree on Brown University campus with permission of instructor and Assoc. Dean of Graduate and Postdoctoral Studies.

15. Masters of Arts in BiologyProgram Requirements • Once accepted by the Graduate School, the students are expected to enroll in courses continuously each semester; • with the exception of the summer term. • If not, a request for a Leave of Absence (LOA) must be submitted one month prior to the start of the term via the Graduate School to avoid billing. • Only one LOA is permissible during the course of study.

16. Masters of Arts in BiologyApplication Requirements • Successful completion of two Brown University graduate courses (B or better). • Undergraduate transcript with date of degree. • Letter of recommendation from Supervisor at Pfizer. • 1-2 pg. Colleague Statement • No GRE requirement or application fee!

17. Masters of Arts in BiologyUpcoming Courses • Fall 2011: Environmental Health & Disease • Spring 2012: Drug and Gene Delivery • Fall 2012: Advance Biochemistry • Core course • Spring 2013: Introduction to Epidemiologic Research Methods • Fall 2013: Virology

18. Masters of Arts in BiologyPrevious Courses • Advanced Biochemistry, • Advanced Microbiology, • Cancer Biology, • Cell Biology, • Developmental Biology, • Drug Delivery, • Human Physiology, • Virology

19. Beth Triche, Ph.D. Primary Instructor David Dore, PharmD, Ph.D. Co-Instructor Introduction to Epidemiologic Research Methods

20. Epidemiology • Descriptive epidemiology • Causal intuition v. causal inference • Why epidemiology? • Formalizes methods for understanding when we can make causal inferences from data that doesn’t contain outcomes under both conditions • Changing recommendations • Thalidomide v. Bendectin • Estrogen for Stroke Trial • Personalized medicine A few years ago, they said we should use HRT, and now they say it will hurt us?

21. Required readings Traditional epi Texts: • MoysesSzklo and F. Javier Nieto. Epidemiology: Beyond the Basics, 2nd ed., Boston: Jones & Bartlett Publishers, 2007. • Miguel Hernan and James M. Robins. Causal Inference. Unpublished text. • Other journal articles and selected chapters from additional texts Contemporary epi

22. Aims • Understand some of the differences in studies that may explain differences in findings • Compare and contrast alternative explanations for observed associations • Random Error • Bias • Confounding

23. Aims • Be able to use the principles of epidemiology to design a study to address a given research question • Identify potential strengths and limitations of alternative designs • Identify potential issues of data availability, quality and resources required

24. Course Objectives • Develop strong foundation in traditional and contemporary epidemiologic methods • Apply key terms and topics including measures of disease occurrence, association, bias, causation, effect modification, and random error • Understand differences between confounding, effect measure modification, interaction, and mediation • Perform and interpret basic epidemiologic calculations • Understand and apply study designs, including strengths, weaknesses, and principal uses of each design • Measurement issues (conceptual v. operational definitions) • Identify basic strategies to improve study accuracy and efficiency (e.g., matching, stratification)

25. Course Objectives • Understand issues specific to pharmacoepidemiologic studies • Define what pharmacoepidemiology is, including basic principles and terminology common to these studies • Cite advantages and disadvantages of common data sources in pharmacoepidemiology • Understand the difficulty of confounding in pharmacoepidemiologic studies • Understand the role of passive and active safety surveillance in pharmacoepidemiology

26. An Example

27. The Signal • 2006, Denker and Dimarco: Single case report of presumed acute pancreatitis on the 5th day of exenatide therapy1 • 2008, Ahmad and Swann: FDA officers report on 30 exenatide-associated cases of acute pancreatitis noting potential biological plausibility, citing the drug’s derivation from Gila monster venom2 • Venom hypothesis subsequently refuted by the manufactuer3 1Diabetes Care. 2006;29(2):471. 2N Engl J Med. 2008;358(18):1970-1 3N Engl J Med. 2008;358(18):1971-2

28. ChartReviews Hospital Inpatient Surveys ClinicalMeasures TissueSamples Data Elements in the Normative Health Information Database NHI • Member identifier • Prescribing physician • Drug dispensed (NDC) • Quantity and date dispensed • Drug strength • Days supply • Dollar amounts • Member identifier • Physician or Facility identifier • Procedures (CPT-4, revenue codes, ICD-9) • Diagnosis (ICD-9-CM, DRG) • Admission and discharge dates • Date and place of service • Dollar amounts • Member Identifier • Plan • Gender • Age • Dates of Eligibility • Member identifier • Lab Test Name • Result • Member identifier • Income • Net Worth • Education • Race & Ethnicity • Life Stage • Life Style Indicators AdministrativeData PharmacyClaimsData Physician andFacility ClaimsData Lab TestResults Data Consumer Elements Unique Dataset Per-Project Data

29. New User Cohort Design • Enrollment Period: September 1, 2004 to December 31, 2007 • Follow-up Through: March 31, 2008 Observation Period 2.5 years 9-month continuous health plan enrollment baseline period No pancreatitis history, No prior dispensing of same drug (or drug class) Exenatide Other Antidiabetic drugs* *Includes initiators of metformin, thiazolidinediones, insulins, sulfonylureas, non-sulfonylurea secretagogues, sitagliptin, pramlintide, and α-glucosidase inhibitors Dore DD, et al. Diabetes Obes Metab. 2011 Feb 14. doi: 10.1111/j.1463-1326.2011.01376.x.

30. Formation of Study Cohorts Normative Health Information Database (6/1/2005 to 12/31/2007) At least one dispensing exenatide N = 37,097 At least one dispensing other antidiabetic drug N = 620,799 Removed 263,954 patients without continuous enrollment prior to comparator dispensing Removed 11,226 patients without continuous enrollment prior to exenatide dispensing Continuous Enrollment N = 25,871 Continuous Enrollment N = 356,845 Removed 120,229 patients with a dispensing of comparator in the baseline period Removed 0 patients with a dispensing of exenatide in the baseline period No dispensing of exenatide 9 mos prior N = 25,871 No dispensing of comparator 9 mos prior N = 236,616 Removed 2,080 patients with a baseline diagnosis of pancreatic disease Removed 152 patients with a baseline diagnosis of pancreatic disease Eligible for exenatide initiator cohort N = 25,719 Eligible for comparator initiator cohort N = 234,536 Dore DD, et al. Diabetes Obes Metab. 2011 Feb 14. doi: 10.1111/j.1463-1326.2011.01376.x.

31. A Clinical Definition Sudden inflammation of the pancreas characterized by severe abdominal pain, nausea, vomiting, and food intolerance Caused by gallstones, alcohol abuse, rapid weight loss among other factors Identification of Acute Pancreatitis in the Claims Data Acute pancreatitis cases were identified based on the presence of the relevant diagnosis code (ICD-9) on claims from an ER or hospitalization visit Acute pancreatitis: 577.0 ICD-9 code in any position define possible events Acute Pancreatitis Outcomes

32. Selection of Providers for Medical Record Acquisition (Data Combined from Several Patients)

34. Primary Results‡ Dore DD, et al. Diabetes ObesMetab. 2011 Feb 14. doi: 10.1111/j.1463-1326.2011.01376.x.

35. Virology Peter R. Shank, Ph.D. Professor of Medical Science

36. Course Goals • To gain understanding of molecular mechanisms of viral pathogenesis. • We will begin with a general introduction to the field of virology and then focuses on the biology of specific viruses that are associated with human disease. • Lectures will include material from the current literature. • At the end of the course you should have an understanding of the major viral pathogens of man and some of the treatments used to prevent viral diseases.

37. Evaluation • There will be two examinations • A midterm on 10/16/13. • Worth 100 points. • A final on 12/18/13. • Worth 150 points. • There will be 10 on-line quizzes based on the lectures and readings. • Each worth 10 points.

38. Guest lecturers • Prof. Walter Atwood • Prof. Andrew Campbell

39. Guest lecturers • Prof. Thais Salizar Mather • Prof. Richard Bungiro

40. Why is this Man Smiling?

41. Some said: • He thought there was something other than flu vaccine in the syringe…… • Actually he was so happy that he was going to get to teach virology again at Pfizer!

42. Who is this?

43. Craig Mellow • Nobel Laureate • 2006 for Physiology and Medicine • Brown graduate • Class 1982 B.S. • Ph.D. • Harvard 1990 • When did he take Virology (BioMed156)? • Spring of 1981 • How did he do? • He received an “A”

44. Sir F. Macfarlane BurnetFormer Director of the Walter and Eliza Hall Institute

45. Sir F. Macfarlane BurnetFormer Director of the Walter and Eliza Hall Institute • An Australian virologist/immunologist • Shared the 1960 Nobel prize for Medicine and Physiology. • Made several seminal discoveries in the 1930’s • including that there were multiple distinct strains of polio virus not just one.

46. Sir F. Macfarlane BurnetFormer Director of the Walter and Eliza Hall Institute • Natural History of Infectious Disease (published in 1962) • In the Introduction to the 3rd edition, wrote: • “…the late 20th century would be witness to the virtual elimination of infectious disease as a significant factor in social life”. • (To write about infectious disease)… "is almost to write of something that has passed into history.“ • He was wrong……

47. 2010 UNAIDS data • Infected 33.4M • New infections ca. 2.7M (2.4-2.9M) • Deaths ca. 1.8M (1.6-1.9M) • Ca. 12M AIDS orphans in Africa • US ca. 56,000 new infections • Overall 60M infections with 25M deaths

48. Effect of HIV on life expectancy

49. We’re doing better but have a ways to go!

50. Questions?