Databases or Registries? Points to Consider

1. Databases or Registries? Points to Consider Mary Lou Skovron, DrPH Group Director, Global Epidemiology Bristol-Myers Squibb FDA/Industry Statistics Workshop September 29, 2006

2. Overview • Claims databases • Types • Advantages • Limitations • Registries • Types • Advantages • Limitations • Examples • Conclusions

3. Claims Databases

4. Claims DatabasesTypes • Open-Plan eg UHC, PharMetrics • Pharmacy-based • Practice-based • Hospital-based • HMO, eg Kaiser-Permanente • Government eg Medicare, Medicaid

5. Claims Databases:Advantages • Already exist, accruing patient information…useful when a relatively quick answer is needed • Potentially large populations from which to draw treated patient and comparison samples…statistical power not usually an issue • May include subgroups not included in clinical trials…expand knowledge

6. Claims Databases:Limitations • ICD-9 coding… potential for misclassification • Limited sensitivity/specificity • Coding affected by reimbursement • Short ‘residence’ in the database • Clinical, lab, imaging data not usually present • Rare events in rare diseases require huge “electronic” populations to identify adequate numbers treated • May not represent important sub-populations • Surveillance bias and channeling bias • Inpatient drug exposures not usually recorded

7. Claims Databases: Application • Acute events (short-term events) • Events that come to medical attention, eg CVA • Validated algorithm to identify indication and event of interest OR medical record review to verify events • Statistical approaches for confounders (eg propensity scores, instrumental variables, risk factor scores, multivariate analyses)

8. Registries

9. Registries • “A systematic collection of defined events or product exposures in a defined patient population for a defined period of time”1 • “A registry per se is not a study. It is an organized collection of data in humans within a particular disease group or other special group…”2 1Arlett P, Moseley J, Seligman PJ p 119 in Pharmacoepidemiology Fourth Edition, Strom BL, ed 2005 2 CIOMS V Section II.h.

10. Registries:Types • Drug/Device Registry: Includes subjects receiving the drug or device regardless of indication • Disease Registry: Includes patients with the disease regardless of drug or device exposure

11. Registries:Strengths • Richer data than in electronic databases: Patient SES, history, treatment, clinical data can be collected • Define encounter frequency and follow-up duration • Event ascertainment does not depend on ICD-9 coding • Can address additional questions in the data

12. Registries:Limitations • Accrual can be slow if insufficient sites engaged • Generalizability must be established • Practical limits on number of patients followed

13. Registries:Application • Long-term outcomes • Rare diseases • Potential confounders important • Multiple objectives

14. Usefulness of Registries • Characteristics of patients in the target population for the new drug • Clinical course of the disease • Treatment patterns, health care utilization • Frequency of adverse events

15. Registry Lifecycle • Early: Describe patient demographics, clinical characteristics, practice patterns (usually cross-sectional analyses); incidence of AEs with short lag times • Intermediate: Analyze relationships pf patient characteristics, treatment with outcomes; incidence of less common AEs, AEs with longer lag times; assess risk factors for AE incidence • Advanced: Evaluate changes in practice patterns; impact on outcomes and AE incidence; assess rare AE incidence

16. Registry Quality • DeCIDE Network currently developing a reference document on developing, conducting and evaluating registries • Sponsored by AHRQ • Document in draft, Outline available on the web • Report currently in draft

17. Examples

18. Example:Cox-2 Inhibitors and Cardiac Events • Cox-2 use frequent in population • Primary care drug • Cardiac events not rare in target population • Short-term (< 2 years) events • Clinical history important

19. One SolutionCox-2 Inhibitors and Cardiac Events • Claims database analysis1 • Advantages: • Data already accrued when study need identified • Large population • Limitation offset • Multivariate regression to control confounding • Verified cardiac events by chart review • Remaining limitations • Under-represented > 65 yo 1Velentgas P et al 2006

20. Key Feature of the Solution • Numbers readily available: • Exposure: ~ 425,000 eligible subjects available for study • at least one dispensing of the 5 study medications during preceding 18-month period • first dispensing after minimum of six months without any of the medications • Endpoint: ~ 725 confirmed MI/ACS • Verification of endpoints • Medial record review applying accepted criteria

21. Example:Thrombolytics And Bleeding • Important focus: subpopulations eg ethnicity, gender, age • Short-term event • Benefit and risk • Hospital-based treatment

22. SolutionThrombolytics and Bleeding • Registry approach: National Registry of Myocardial Infarctions • Salient strengths: • Clinical and lab data ascertained • Data from medical records • Limitation Offset • Validated completeness against another data source • Large number of hospitals to assure adequate subpopulations • Remaining limitations • Short-term data cannot answer long-term questions

23. Key Feature of the Solution • Large number of hospitals participate order to gather data on~200,000 MIs per year • Rich patient, clinical, treatment and outcome information • Answered the question about safety in subgroups under-represented in the clinical trials • In its > 10 year lifecycle has contributed to broad understanding and improvement of medical practice • External investigators can propose research; external advisory group reviews and approves all research

24. Example: Safety of Orencia®, a New Biological for RA • Short-term (infections) and longer-term (NHL and other malignancies) events • Low general population prevalence of RA candidates for biologics treatment • RA a specialty-treated disorder • Proactive approach

25. Solution: Complementary Approaches • Claims database study in UHC data • Event validation • Large pool of potential comparators • Population treatment patterns • Infections, other possible short-term events • Registry building on the independently conducted National databank for Rheumatic Diseases • Large pool of participating rheumatologists • 5,000 Orencia® initiators comparison to >=15,000 initiators/switchers of other treatments • Patient self-report and event verification • Enrollment and retention enhancements • Short and long-term events

26. Key Features of the Solution • External scientific advisory group • Individual protocols • Statistical analysis plans • Interpretation of results including approaches to integration

27. Conclusions

28. Conclusions • One size does not fit all: evaluate options • Registries: a useful alternative to electronic databases • Consider complementary approaches

29. Useful References • Strom BL, ed; Pharmacoepidemiology 4th Edition; UK; John Wiley and Sons Ltd;2005 • AHRQ DeCIDE Network upcoming publication • http://effectivehealthcare.ahrq.gov/decide/

30. Thank You