1. Research Activities at The Boston Collaborative Drug Surveillance Program; Boston University School of Public Health Susan Jick Professor of Epidemiology Director of the Boston Collaborative Drug Surveillance Program

2. Primary Objectives of the BCDSP  Post-marketing drug safety studies  Disease epidemiology to support drug safety concerns  Expertise in large electronic databases

3. What kinds of safety Questions Get Asked?  Generally interested in rare or uncommon adverse events  Difficult to study using clinical trials  Difficult to collect information on large enough patient populations  Case-control  Cohort  Large databases have made it possible to study large cohorts of drug users  We can now study drugs in relation to rare outcomes

4. Early Post-Marketing Safety  What is post-marketing safety?  Generally observational research on marketed drugs  Prior to the 1960’s there were no formal drug safety studies  All data prior to the late 1970’s was collected by hand  First use of automated data was initiated around 1978  Group Health Cooperative  Around 300,000 members

6. This is where I came in  I first started working with data from GHC in the early 1980’s  While getting my MPH at BU SPH  Later went on to get my doctorate at BU  Started teaching the Drug Epidemiology class while getting my doctorate  And the rest is history….

7. Later Developments  Other resources became available in the 1980’s  Research capabilities increased dramatically  Large cohorts of drug exposed persons could be identified  Rare events could be studied  Databases with covariate information became available

8. The Clinical Practice Research Datalink  Started in 1988  Data on millions of patients  Became available to the public in the 2000’s  GP data from the UK  All diagnoses  Drugs  Clinical details  Patient characteristics

10. Great Potential  Research capabilities have increased dramatically because of available data  Our research has changed correspondingly  So has the potential for error and poor research  Understanding research methods and data resource has never been more important

12. What are the big challenges?

13. Major methodologic concerns  Confounding  By age, sex, calendar time, geography  And by indication  Appropriate and accurate exposure information and definition  Poor quality data  Data errors  Need for validation  Is information complete?  Ability to test assumptions

14. Examples of Drug Safety Studies at the BCDSP  MMR vaccine and autism  Oral contraceptives and venous thromboembolism  Vioxx and MI  Accutane and depression  Hormone replacement and breast cancer  Antidepressant drugs and suicide

15. What could go wrong?  What is confounding by indication?  People take drugs for a reason  Is that reason, or indication for use, associated with the outcome of interest?  In antidepressant users can you evaluate whether or not the drug increases the risk of depression?  How do we control for it?  Can one always control for it?

16. A glimpse of our research