Diversion, misuse and trafficking of methadone and buprenorphine

Global Addiction Conference Richard C. Dart, MD, PhD Professor, University of Colorado

Prescription Opioid Deaths are Rising Internationally

United Kingdom Drug Related Deaths 2001 - 2011

Source: RADARS® System, Denver Health and Hospitals What is the RADARS® System?

• History – 2006, Denver Health and Hospital Authority (DHHA) – Multiple pharmaceutical subscribers – Independent program – Denver Public Safety Net Hospital for 150 years – State sanctioned independent authority • Conflict of Interest Statement – None, other than running system for DHHA as noted above.

3 RADARS System Scientific Advisory Board

Principal Investigators Substance Abuse Experts • Theodore J. Cicero, PhD • Herbert D. Kleber, MD Washington University at St. Louis Columbia University

• Richard C. Dart, MD, PhD • Sidney Schnoll, MD, PhD Denver Health and Hospital Authority Pinney Associates

• Hilary Surratt, PhD • George E. Woody, MD Nova Southeastern University University of Pennsylvania

• Mark W. Parrino, MPA Epidemiology/Biostatistics American Association for the • Edgar Adams, ScD Treatment of Opioid Dependence Covance

Law Enforcement • Nabarun Dasgupta, MPH • John Burke Founder – Epidemico National Association of Drug Diversion Investigators • Alvaro Muñoz, PhD Johns Hopkins University 4

Challenges of Prescription Drug Abuse Surveillance

• Clandestine behavior • Geographical variability • Changes rapidly • Multiple age groups • Product specificity – 15 active pharmaceutial ingredients (API) • Opioids: Hydrocodone, oxycodone, hydromorphone, oxymorphone, morphine, fentanyl, tapentadol, tramadol, buprenorphine, methadone • Stimulants – Dozens of specific products (OxyContin, Opana, Suboxone, Subutex, etc.) RADARS System Mosaic

53 Poison Drug Criminal Justice Centers 280 investigator Acute Events Transactions 46 States 50 states

Entering OTP Entering SKIP 125 practices Treatment 73 programs Treatment 33 states 50 states

College Survey New StreetRx.com 2000 students Illicit Market Initiates Users/Buyers 50 States Price 50 states RADARS® System Process A Tale of Two Denominators

Drug Poison College OTP SKIP Diversion Center Survey

Numerators compiled by each program

POPULATION RATE = Event Count by Area Population

• Disease burden on population • Does not account for drug availability

UNIQUE RECIPIENTS OF Event Count by Area DISPENSED DRUG (URDD) RATE =URDD

• URDD = Number of unique people filling prescription for drug (refills excluded)

7 TRENDS IN PRESCRIPTION OPIOID ABUSE IN THE UNITED STATES

8 Overall Opioid Abuse Trends in United States Population Rates, 2002-2012

10

Population Rate 5

0 2002 2007 2012 0.8 Availability Rate 0.6 (URDD) 0.4 0.2 0 2002 2007 2012 Poison Center Drug Diversion SKIP OTP 9 RADARS System Opioid Abuse Trends URDD Rates (Ranked Highest-Lowest) 2012

Rank Poison Center Opioid Survey of Key Drug Treatment Informant Pts Diversion

1 Methadone Oxymorphone Oxymorphone Oxymorphone

2 Oxymorphone Methadone Hydromorphone Hydromorphone

3 Buprenorphine Hydromorphone Methadone Methadone

4 Hydromorphone Buprenorphine Buprenorphine Buprenorphine

5 Morphine Morphine Morphine Morphine

6 Fentanyl Fentanyl Fentanyl Oxycodone

7 Tramadol Tapentadol Tapentadol Fentanyl

8 Oxycodone Oxycodone Oxycodone Hydrocodone

9 Tapentadol Hydrocodone Hydrocodone Tramadol

10 Hydrocodone Tramadol Tramadol Tapentadol 10 BUPRENORPHINE AND METHADONE ABUSE IN THE US How Many Patients Fill a Prescription for Methadone? Unique Recipients of dispensed drug (URDD) 2009Q1 - 2012Q4

Methadone

Combination Buprenorphine Tablets SI Buprenorphine Tablets Combination Buprenorphine Film 20091 20092 20093 20094 20101 20102 20103 20104 20111 20112 20113 20114 20121 20122 20123 20124 Buprenorphine Data Comparison RADARS System & CESAR Fax

RADARS System Drug Diversion Program Diversion Reports 2002 - 2012 1200

1000

800

600 Total Buprenorphine Total Methadone 400 Diversion reports Diversion 200

0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 13 CESAR = Center for Substance Abuse Research Opioid Treatment Program Past 30 Day Endorsements, 2009-2012

1.4 Population Rate Methadone high, but decreasing 1.2

1 Bup-Single Ingredient 100,000 Increasing 0.8

0.6 Bup-Naloxone Film Strip increasing slightly 0.4

0.2 Bup-Naloxone Combination Population rate rate Population Decreasing Slightly 0 9 Availability Rate 8 (URDD) Bup-Single Ingredient Highest, 7 Increased, Flat 6 5 Methadone Decreasing 4 3 Bup-Naloxone Combination 2

URDD rate perURDD 1,000 rate Lower, Flat 1 0 Bup-Naloxone Film Strip Lowest, Decreasing 20091 20092 20093 20094 20101 20102 20103 20104 20111 20112 20113 20114 20121 20122 20123 20124 Survey of Key Informant Patients Past 30 Day Endorsements, 2009-2012 0.7 Population Rate Methadone high, but 0.6 decreasing 0.5 Bup-Single Ingredient 0.4 per 100,000

Increasing 0.3 Bup-Naloxone Combination 0.2 Increasing Flat

Population Population 0.1 Bup-Naloxone Film Strip 0 Increasing slightly 7 6 Availability Rate (URDD) Bup-Single Ingredient 5 Increasing Dramatically 4 3 Methadone Slight Decrease 2 Bup-Naloxone Combination URDD rate perURDD 1,000 rate 1 Increasing 0 Bup-Naloxone Film Strip low, flat 20091 20092 20093 20094 20101 20102 20103 20104 20111 20112 20113 20114 20121 20122 20123 20124 RADARS System Drug Diversion Cases 2009-2012

0.25 Methadone high, but Population Rate decreasing slightly 0.2 Bup-Naloxone Combination 0.15 Decreasing Slightly

0.1 Bup-Naloxone Film Strip Increasing 0.05 Bup-Single Ingredient 100,000 per rate Population

0 Increasing 2.5 Availability Rate (URDD) Bup-Naloxone Combination 2 Increasing Greatly 1.5 Bup-Single Ingredient 1 Increasing Greatly

URDD rate per 1,000URDD rate 0.5 Methadone Slight Decrease

0 Bup-Naloxone Film Strip increasing slightly 20091 20092 20093 20094 20101 20102 20103 20104 20111 20112 20113 20114 20121 20122 20123 20124 StreetRx www.streetrx.com • Population – Any person in US with access to the internet • Definition/Type of Cases – Utilize crowdsourcing methodology to calculate average price of specific prescription drug in particular location – Validated by DD • Coverage – All 50 states

17 Comparison of StreetRx, RADARS System Drug Diversion and Silk Road

Dasgupta, Suratt, et al, manuscript submitted 18 Death Cases in Poison Center Program All Ages, 2009Q1 - 2012Q4

50 45 40 Total Methadone 35 30 Total Combination 25 Buprenorphine Tablets 20 Total Single Ingredient 15 Buprenorphine Tablets 10 Total Buprenorphine 5 Oral Films 0 2009 2010 2011 2012 Death Cases in Poison Center Program Ages under 12 years, 2009Q1 - 2012Q4

4

Total Methadone

3

Total Combination Buprenorphine Tablets 2

Total Single Ingredient Buprenorphine Tablets 1

Total Buprenorphine Oral Films 0 2009 2010 2011 2012 Poison Center Program Intentional Abuse Exposures of Opana ER 1st Quarter 2009 through 3rd Quarter 2012 0.8 Total 0.7 Oxymorphone Introduction of 0.6

OxyContin ORF

0.5

0.4 Pre ADF

0.3

Rate per Rate 1,000 URDD Post ADF 0.2

0.1

0

21 Year/Quarter Conclusions

• Prescription opioid abuse in the US may be plateauing, but still causes 16,000 deaths per year • Methadone – Endorsements in treatment programs decreasing – More deaths than any other opioid – But most deaths involve pills (treatment of pain) • Buprenorphine – Abuse is increasing quickly perhaps due to generic availability • Single-ingredient “Subutex” • Combination tablet (Bup-naloxone; “Suboxone”) – Exceptional safety in all groups – Abuse of buprenorphine strip has been very low – Why is the price of buprenorphine so high?

Thank you!