Researched Abuse, Diversion, and Addiction-Related Surveillance Sidney H. Schnoll, M.D., Ph.D.

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Researched Abuse, Diversion, andAddiction-Relate
d Surveillance Sidney H. Schnoll, M.D., Ph.D.
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RADARS System Need for Surveillance System

• Increasing reports of abuse and diversion of
  OxyContin
• Lack of data to support or refute media reports
• National data sets (DAWN, NHSDA) reporting
  increasing problems with prescription opioids

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Narcotic Analgesics ED Mentions as a Percent of
Total Drug Abuse Mentions
Drug Abuse Warning Network (DAWN), 1995-2002
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National Household Survey of Drug Abuse Any
Lifetime Use of Hydromorphone
Lifetime Drug Use Behaviors 1999 2000 2001
Nonmedical Use of Multiple (2 or more) Prescription Analgesics (not hydromorphone) 88.6 93.1 93.3
Use of Cocaine 95.4 87.7 92.2
Use of Heroin 64.2 55.5 54.8
Use of Cocaine or Heroin 95.4 88.8 94.0
Nonmedical Use of Multiple Analgesics AND Cocaine or Heroin 84.1 84.2 88.2
Needle Use 53.4 57.7 65.2
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RADARS System Need for Surveillance System

• National data sets reported data 18-24 months
  after collection
• Those abusing and diverting were not necessarily
  patients
• Traditional drug safety/pharmacovigilance not the
  answer
• Needed rapid implementation

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RADARS System Design Considerations

• Develop advisory board of experts in addiction,
  drug policy, law enforcement and epidemiology
• Use existing models if possible, i.e. tramadol
  independent steering committee
• Expand and use different models as needed
• Keep pipeline in mind

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RADARS System External Advisory Board (EAB)

• Edgar Adams, Ph.D. Harris Interactive
• Cmdr. John Burke NADDI
• Theodore Cicero, Ph.D. Washington Univ.
• Richard Dart, M.D. Rocky Mountain PCC
• Danna Droz, R.Ph., J.D. NASCSA
• Ann Geller, M.D. Columbia University
• James Inciardi, Ph.D. Univ. of Delaware
• Herbert Kleber, M.D. Columbia University
• Alvaro Muñoz, Ph.D. Johns Hopkins Univ.
• Mark Parrino, M.P.A. AATOD
• Edward Senay, M.D. Univ. of Chicago
• George Woody, M.D. Univ. of Pennsylvania

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RADARS System Goals

• Prospectively study the nature and extent of
  abuse of scheduled prescription opioid
  medications
• Suggest interventions to reduce diversion and
  abuse that are related to problems identified

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The RADARS System Drugs

• buprenorphine
• fentanyl
• hydrocodone
• hydromorphone
• methadone
• morphine
• oxycodone

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RADARS System Levels of Activity
Signal Detection
Relative Rate Determination
Signal Verification
Other Purdue Signals
Focused Studies
Interventions
Outcomes
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Signal Detection Components Rationale

• Serves as an early warning system
• Timely collection (quarterly)
• Geographically sensitive (3-digit ZIP code)
• Calculation of local rates
• Useful for monitoring newly approved drugs

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Our Early Detection System in Action
The RADARS System Signal Detection Studies began
picking up abuse and diversion of generic
OxyContin one week after launch.
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Signal Detection Studies

• Funded by Purdue Pharma L.P.
• Studies conducted at major research organizations
  and universities under direction of Principal
  Investigators
• Data independently housed
• Data reports presented to the EAB and Purdue on a
  quarterly basis

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Denominator Candidates
Pros Cons
Population Readily available Uniform exposure assumed
Prescriptions filled Readily available Easily understood One Rx ? One person no adjustment for dosage strength, days of therapy, quantity, acute vs. chronic use
Kg distributed Readily available Easily understood No adjustment for potency rate for high potency drugs will be over-estimated
Delivery units Provides closer estimate to drug available than prescriptions alone No adjustment for dosage strength
Patients dispensed medications Provides estimate of those benefiting from medication Based on projected figures that have high error rate in low population areas
6. Dosage units Used by DEA and familiar to regulatory agencies Bases calculation on injectable dosages of buprenorphine and fentanyl, assumes incorrect minimum dosage strength for oxycodone
7. Minimum divertible dosage units Modifies DEA approach to correct for dosage units and delivery type Harder to understand, not intuitive New metric
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Comparison of Abuse Rates Using Different
Denominators
Rates based on median rate of abuse according to
denominator total exposure using Poison Control
Center data from 1Q03
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Median National Rates by Signal Detection Study
in ZIP Codes with Greater Than 100 Patients
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5 Highest Rates of Abuse for Oxycodone
Extended-Release and the Corresponding 3 Digit
Zip Codes
Quarter 3 Digit Zip Codes state (Numerator, Denominator) 3 Digit Zip Codes state (Numerator, Denominator) 3 Digit Zip Codes state (Numerator, Denominator) 3 Digit Zip Codes state (Numerator, Denominator) 3 Digit Zip Codes state (Numerator, Denominator)
2002Q4 048 ME (1, 48.83) 246 VA (2, 263.20) 597 MT (2, 266.59) 403 KY (2, 327.43) 811 CO (1, 227.23)
2003Q1 408 KY (3, 71.07) 412 KY (2, 59.73) 416 KY (2, 98.10) 415 KY (2, 144.75) 426 KY (1, 110.31)
2003Q2 413 KY (1, 20.41) 408 KY (2, 61.23) 050 VT (1, 89.83) 229 VA (5, 511.45) 426 KY (1, 103.35)
2003Q3 418 KY (1, 20.99) 413 KY (1, 22.33) 408 KY (2, 59.83) 415KY (2, 116.54) 409 KY (4, 241.57)
2003Q4 413 KY (2, 19.01) 412 KY (2, 35.64) 256 WV (4, 80.08) 408 KY (2, 47.13) 409 KY (6, 228.90)
2004Q1 412 KY (2, 10.50) 408 KY (4, 42.82) 413 KY (1, 11.72) 248 WV (3, 37.17) 418 KY (1, 19.80)
2004Q2 048 ME (2, 33.05) 268 WV (1, 31.79) 246 VA (6, 206.75) 247 WV (4, 158.07) 808 CO (1, 45.17)
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Drug Evaluation Network System(DENS)Thomas
McLellan, PhD, Principal InvestigatorTRI
University of Pennsylvania

• Rationale
• Collect data on abuse of prescription drugs by
  those entering drug abuse treatment programs and
  track trends over time
• Objectives
• Gather data on prescription drug abuse in
  admissions to treatment programs
• Track trends in prescription drugs abused over
  time
• DENS has lost federal funding no further data
  will be collected. TRI is not interested in
  collecting data for individual companies

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Law Enforcement Drug DiversionJames Inciardi,
PhD, Principal InvestigatorUniversity of Delaware

• Rationale
• Monitor diversion of RADARS System Drugs
  compared to other drugs in a specific geographic
  locale
• Objectives
• Monitor the extent of diversion from a national
  convenience sample of police diversion units
• Identify signal sites for these drugs over time
• Identify epicenters of diversion (3-digit zip
  code locations where a signal is detected gt 1Q
  per year)
•  

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Key Informant NetworkTheodore Cicero, PhD,
Principal InvestigatorWashington University

• Rationale
• Monitor an extensive network of specialists to
  proactively seek out documented cases of abuse
• Objectives
• Use key informants to proactively count the cases
  of abuse addiction to RADARS System Drugs in
  specific geographic locations
• Monitor the number of cases of abuse and
  addiction of the RADARS System Drugs over time

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Poison Control Centers (PCCs)Richard Dart, MD,
PhD, Principal InvestigatorUniversity of Colorado

• Rationale
• Monitor calls to PCCs regarding abuse of RADARS
  System Drugs
• Objectives
• Prospectively monitor exposure and information
  calls
• Monitor the changes in these calls over time

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Opioid Abuse in Methadone Treatment
EnrolleesMark Parrino, MPA and Andrew Rosenblum,
Ph.D.,Principal Investigators, AATOD and NDRI

• Rationale
• Collect admission data on new enrollees at 75
  MTPs regarding abuse and addiction involving
  RADARS System Drugs
• Objectives
• Monitor drugs used by new admissions
• Monitor need for pain medication
• Monitor trends over time

Pilot study completed February 2005. Full study
implemented March 2005.
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Field ResearchStructured Interview Process

• Law Enforcement
• Drug Treatment Center
• Physician
• Pharmacist
• Other
• Indian Health Services
• Hospital
• Board of Pharmacy
• State Agencies

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Limitations and Concerns

• Not 100 coverage for all studies
• Not all sites report each quarter
• No universally accepted method defined for
  calculating rates/denominator issues
• Potential double counting
• No access to raw data
• Adverse event reporting

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Researched Abuse, Diversion, andAddiction-Relate
d Surveillance