1. 1 Drug Utilization for Immediate- and Modified Release Opioids in the U.S. Gianna C. Rigoni, Pharm.D., M.S. Epidemiologist Division of Surveillance, Research & Communication Support Office of Drug Safety, FDA September 9, 2003

2. 2 Drug Utilization Data Sources Outpatient Data –IMS Health, National Prescription Audit Plus  (NPA Plus  ) –IMS Health, National Disease and Therapeutic Index  (NDTI  ) Inpatient Data –Premier, Inc., Perspective Rx View 

3. 3 Outpatient Drug Utilization

4. 4 National Prescription Audit (NPA Plus  ) Measures the “retail outflow” of prescriptions from pharmacies to consumers Includes: chain, independent, mass merchandisers, food stores with pharmacies, mail-order *, and long- term care * pharmacies The number of dispensed prescriptions is obtained from a sample of approximately 22,000 pharmacies in the U.S. and is projected nationally * Excluded from this analysis

5. 5 Total Prescriptions Dispensed * Annually for Selected Opioids, 1998 - 2002 Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

6. 6 Total Prescriptions Dispensed * Annually for Immediate-Release Opioids, 1998 - 2002 (WITH Hydrocodone & Oxycodone Combination Products) Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

7. 7 Total Prescriptions Dispensed* Annually for Selected Immediate-Release Opioids, 1998 - 2002 (WITHOUT Hydrocodone & Oxycodone Combination Products) Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

8. 8 Total Prescriptions Dispensed * Annually for Modified-Release Opioids & Methadone, 1998 - 2002

9. 9 Top MD Specialties * Prescribing Immediate-Release Opioids, 1998 vs. 2002 (WITH Hydrocodone & Oxycodone Combination Products) MD Specialty% Prescriptions FAMILY PRACTICE14.6% DENTISTRY12.2% INTERNAL MEDICINE12.2% ORTHOPEDIC SURGERY10.2% OSTEOPATHIC MEDICINE7.8% EMERGENCY MEDICINE6.1% GENERAL SURGERY3.6% OBSTETRICS/GYNECOLOGY3.2% ALL OTHERS30.2% 1998 2002 MD Specialty% Prescriptions DENTISTRY15.5% FAMILY PRACTICE13.0% ORTHOPEDIC SURGERY11.5% INTERNAL MEDICINE11.1% OSTEOPATHIC MEDICINE6.7% EMERGENCY MEDICINE5.5% GENERAL SURGERY4.2% OBSTETRICS/GYNECOLOGY3.5% ALL OTHERS28.9% Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

10. 10 Top MD Specialties * Prescribing Selected Immediate-Release Opioids, 1998 vs. 2002 (WITHOUT Hydrocodone & Oxycodone Combination Products) 1998 2002 MD Specialty% Prescriptions HEM/ONC/NEOPLASTIC23.4% INTERNAL MEDICINE17.9% FAMILY PRACTICE12.6% ANESTHESIOLOGY7.9% OSTEOPATHIC MEDICINE6.5% ORTHOPEDIC SURGERY2.6% NEUROLOGY2.1% PHYSICAL MED & REHAB2.0% ALL OTHERS24.8% MD Specialty% Prescriptions INTERNAL MEDICINE15.2% ANESTHESIOLOGY14.6% FAMILY PRACTICE13.1% HEM/ONC/NEOPLASTIC10.8% OSTEOPATHIC MEDICINE8.9% PHYSICAL MED & REHAB5.4% ORTHOPEDIC SURGERY3.5% NEUROLOGY2.6% ALL OTHERS25.9% Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

11. 11 Top MD Specialties * Prescribing Modified-Release Opioids & Methadone, 1998 vs. 2002 MD Specialty% Prescriptions FAMILY PRACTICE17.1% INTERNAL MEDICINE16.7% ANESTHESIOLOGY16.4% OSTEOPATHIC MEDICINE10.3% PHYSICAL MEDICINE & REHAB6.3% HEM/ONC/NEOPLASTIC6.2% ALL OTHERS27.1% 19982002 MD Specialty% Prescriptions INTERNAL MEDICINE17.5% ANESTHESIOLOGY14.5% FAMILY PRACTICE13.9% HEM/ONC/NEOPLASTIC13.9% OSTEOPATHIC MEDICINE8.4% PHYSICAL MEDICINE & REHAB3.4% ALL OTHERS28.2% Source: IMS Health, National Prescription Audit Plus TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003.

12. 12 National Disease and Therapeutic Index (NDTI  ) Collects data on drug products and indications mentioned during office-based physician visits Provides descriptive information on profiles and trends of diagnoses, patients, and treatment patterns occurring in office-based practice Data are gathered from a panel of 2,000-3,000 office-based physicians in the U.S. and projected nationally

13. 13 Indications * Associated with Immediate-Release Opioids, 1998 vs. 2002 (WITH Hydrocodone & Oxycodone Combination Products) * Source: IMS Health, National Disease and Therapeutic Index TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003. Surgical Procedures include post-op exams Musculoskeletal Pain includes back pain, myalgias, osteoarthritis, rheumatoid arthritis, etc. Other Pain includes migraine, headache, calculi, fractures, dental pain, complications of pregnancy, etc.

14. 14 Indications * Associated with Selected Immediate-Release Opioids, 1998 vs. 2002 (WITHOUT Hydrocodone & Oxycodone Combination Products) * Source: IMS Health, National Disease and Therapeutic Index TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003. Surgical Procedures include post-op exams Musculoskeletal Pain includes back pain, myalgias, osteoarthritis, rheumatoid arthritis, etc. Other Pain includes migraine, headache, calculi, fractures, dental pain, complications of pregnancy, etc.

15. 15 Indications * Associated with Modified- Release Opioids & Methadone, 1998 vs. 2002 * Source: IMS Health, National Disease and Therapeutic Index TM, Year 1998 to 2002, Excluding Long-Term Care & Mail Order Channels, Data Extracted August 2003. Surgical Procedures include post-op exams Musculoskeletal Pain includes back pain, myalgias, osteoarthritis, rheumatoid arthritis, etc. Other Pain includes migraine, headache, calculi, fractures, dental pain, complications of pregnancy, etc.

16. 16 Inpatient Drug Utilization

17. 17 Premier Perspective Rx View  Information on inpatient use of drugs from approximately 400 acute, short-stay, non-federal hospitals belonging to Premier GPO Includes demographic and pharmacy billing information, as well as diagnoses and procedures for every discharge from 2000 - 2002 –No linkages between procedures and drugs –We can only identify if a billing for a drug and a procedure occurred on the same day Patients with a discharge diagnosis associated with any type of cancer were excluded from this analysis

18. 18 % of All Surgical Procedures * Associated with a Modified- Release Opioid Billed the Day of or Day After Surgery * Source: Premier, Inc., Perspective Rx View TM, Excludes Discharge Diagnoses of Neoplasms, Extracted August 2003. N = 39,896 SurgeriesN = 59,966 SurgeriesN = 62,516 Surgeries

19. 19 % of the Top 3 Surgical Procedures * Associated with a Modified-Release Opioid Billed the Day of or Day After Surgery * Source: Premier, Inc., Perspective Rx View TM, Excludes Discharge Diagnoses of Neoplasms, Extracted August 2003. N = 277 HospitalsN = 402 HospitalsN = 406 Hospitals

20. 20 Limitations Outpatient Drug Use Data –Data on dispensed prescriptions include prescriptions filled in the retail pharmacy setting only Mail order pharmacy, long-term care & methadone maintenance clinics are not included –Data on indications for opiate use reflect office-based physicians’ prescribing based on a small sample of physicians Inpatient Drug Use Data –Billing of medications/procedures as proxy for actual clinical care may be imprecise –Represents only patients admitted in to the hospital that have a surgical procedure

21. 21 Conclusions Use of opioids appears to be increasing in outpatient settings and is widespread in inpatient settings Primary care providers continue to be the leading prescribers of opioids in the outpatient setting Indications for the outpatient use of opioids –Immediate-release opioids (WITHOUT hydrocodone & oxycodone combination products) Other PainCancer-Related Pain –Modified-release opioids Cancer-Related PainMusculoskeletal Pain Post-operative indications for the inpatient use of opioids –Apparent substantial use of modified-release opioids for post-op musculoskeletal procedures Modified-release oxycodone constitutes most of this use