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Trends of Opioid Misuse and Diversion: Lessons from the
United States31 October 2012
Richard C. Dart, MD, PhD
Director – Rocky Mountain Poison and Drug Center
Professor - University of Colorado, Department of Emergency Medicine
1
Unintentional Drug Death
2
The Prescription Drug Abuse Epidemic
010002000300040005000600070008000
'99 '00 '01 '02 '03 '04
Year
Num
ber o
f dea
ths
prescription opioidcocaineheroin
Other specified drugs, 16.1%
Meth / amphet., 6.4%Heroin, 7.7%
Cocaine, 25.1%
Benzo./antidepress, 6.5%
Other opioid painkillers, 22.0%
Methadone, 16.2%
0%
20%
40%
60%
80%
100%
Paulozzi, CDC www.deadiversion.usdoj.gov/arcos/retail_drug_summary/index.html
40% of OpioidAnalgesicDeaths
Moving Forward: USA
• Pharmaceutical strategies– Improve physical tamper resistance (i.e. OxyContin®, Exalgo®)– Incorporate deterrent (i.e. Suboxone®, Embeda®)
• Regulatory strategies– REMS: FDA Approval of Extended Release (ER) & Long Acting
(LA) opioid Risk Evaluation Mitigation Strategy (REMS) in July 2012; other class-wide REMS in draft
– Prescription Monitoring Programs (PMP) across US
• Measuring impact of these strategies– RADARS® System Data Trending– Mosaic approach
4
Prescription Opioid Misuse & Diversion
5
• United States Experience– Deaths from opioid abuse have surpassed deaths caused by
motor vehicle accidents– Abuse deterrent formulations– Increasing availability of generic products– Toll of accidental pediatric exposures
• Outline of Presentation– RADARS® System Methodology & General Results– Trends with abuse deterrent formulations & market changes– Medical outcomes following pediatric exposures– Lessons learned
What is the RADARS® System?
• History– 2001, created by Purdue Pharma– 2006, Denver Health and Hospital Authority
• Multiple pharmaceutical subscribers• Independent program• Denver Public Safety Net Hospital for 150 years• State sanctioned independent authority
• Purpose– Measure rates of misuse, abuse and diversion of
prescription drugs
6
Drug Diversion
Criminal Justice 280 investigator 50 states
StreetRxwww.streetrx.com
Users/BuyersCrowdsourcing 50 states
College Survey
2000 students 50 States 3x each year
Survey of Key Informants’
Patients (SKIP)
Patients in Tx125 practices50 states
Poison Center
Acute Events51 Centers 47 States
Opioid Tx Program (OTP)
Patients in Tx73 programs 33 states
Mosaic Approach to Surveillance
7
RADARS® System ProcessA Tale of Two Denominators
8
POPULATION RATE = Counts by SystemUS Population
• Disease burden on whole population• Does not account for drug availability
UNIQUE RECIPIENTS OF Counts by SystemDISPENSED DRUG (URDD) RATE URDD
• Number of unique people filling prescription for drug (refills excluded)
=
RADARS System Opioid AbusePopulation Rate (Ranked Highest-Lowest)
2011Rank Poison Center Opioid
TreatmentSurvey of Key Informant Pts
Drug Diversion
College Survey
1 Hydrocodone Oxycodone Hydrocodone Oxycodone Hydrocodone
2 Oxycodone Hydrocodone Oxycodone Hydrocodone Oxycodone
3 Tramadol Methadone Morphine Morphine Morphine
4 Methadone Morphine Hydromorphone Buprenorphine Tramadol
5 Morphine Hydromorphone Methadone Methadone Fentanyl
6 Buprenorphine Buprenorphine Buprenorphine Hydromorphone Methadone
7 Fentanyl Fentanyl Fentanyl Tramadol Buprenorphine
8 Hydromorphone Tramadol Tramadol Fentanyl Hydromorphone
9
RADARS System Opioid AbuseURDD Rates (Ranked Highest-Lowest)
2011
10
Rank Poison Center Opioid Treatment
Survey of Key Informant Pts
Drug Diversion
College Survey
1 Methadone Methadone Hydromorphone Methadone Methadone
2 Buprenorphine Hydromorphone Methadone Hydromorphone Hydromorphone
3 Morphine Morphine Morphine Buprenorphine Morphine
4 Hydromorphone Buprenorphine Buprenorphine Morphine Fentanyl
5 Fentanyl Fentanyl Fentanyl Oxycodone Buprenorphine
6 Tramadol Oxycodone Oxycodone Fentanyl Oxycodone
7 Oxycodone Hydrocodone Hydrocodone Hydrocodone Hydrocodone
8 Hydrocodone Tramadol Tramadol Tramadol Tramadol
11
RADARS System Opioid Abuse TrendsRates by Program, 2002-2012
0
2
4
6
8
10
12
2002
Q1
2002
Q3
2003
Q1
2003
Q3
2004
Q1
2004
Q3
2005
Q1
2005
Q3
2006
Q1
2006
Q3
2007
Q1
2007
Q3
2008
Q1
2008
Q3
2009
Q1
2009
Q3
2010
Q1
2010
Q3
2011
Q1
2011
Q3
Drug Diversion Poison CenterOpioid Treatment SKIP
2002 2012
Population
0
0.2
0.4
0.6
0.820
02Q1
2002
Q3
2003
Q1
2003
Q3
2004
Q1
2004
Q3
2005
Q1
2005
Q3
2006
Q1
2006
Q3
2007
Q1
2007
Q3
2008
Q1
2008
Q3
2009
Q1
2009
Q3
2010
Q1
2010
Q3
2011
Q1
2011
Q3
Drug Diversion Poison CenterOpioid Treatment SKIP
URDD
2002 2012
RADARS System Opioid Abuse TrendsPoison Center Program Intentional Exposures
2003 - 2011
0
0.5
1
1.5
2
2.5
01/2003
02/2003
03/2003
04/2003
01/2004
02/2004
03/2004
04/2004
01/2005
02/2005
03/2005
04/2005
01/2006
02/2006
03/2006
04/2006
01/2007
02/2007
03/2007
04/2007
01/2008
02/2008
03/2008
04/2008
01/2009
02/2009
03/2009
04/2009
01/2010
02/2010
03/2010
04/2010
Rat
e pe
r 1,0
00 U
RD
D
Quarter/Year
BuprenorphineFentanylHydrocodoneHydromorphoneMethadoneMorphineOxycodoneOxymorphone
2002 2011
US CDC* Mortality Data
13
MME = morphine milligram equivalent; RR = rate ratio; CI = confidence interval. *Centers for Disease Control and Prevention† Counts for each opioid might not sum to the total shown for all deaths because some deaths involved more than one opioid. CDC, July 2012. Morbidity and Mortality Weekly Report. Vital Signs: Risk for Overdose from Methadone Used for Pain Relief — United States, 1999–2010.
Opioid No. Death rate/100kg MME
RR (95% CI)
All deaths
Single drug deaths
All deaths
Single drug deaths
All deaths
Single drug deaths
All deaths Single drug deaths
Buprenorphine 20 2 0.8 0.1 0.02 0.01 0.01–0.04 0.00–0.03
Fentanyl 364 99 7.7 2.1 0.28 0.26 0.25–0.32 0.21–0.33
Hydrocodone 550 42 14.3 1.1 0.42 0.11 0.38–0.47 0.08–0.16
Hydromorphone 74 4 9.1 0.5 0.27 0.05 0.21–0.34 0.02–0.14
Morphine 824 153 20.2 3.8 0.64 0.41 0.58–0.70 0.34–0.50
Oxycodone 1,097 150 8.7 1.2 0.26 0.12 0.24–0.28 0.10–0.
Methadone 1,034 298 33.6 9.7 1.00 1.00 referent referent
Total† 3,294 748 10.4 2.4
Drug-related deaths involving opioids, by type of opioid — Drug Abuse Warning Network Medical Examiner System, 13 states, 2009
13
CDC: 2009 Mortality Data Rank
14
MME = morphine milligram equivalent URDD = unique recipient of dispensed drug
Rank CDCDeath rate/100kg MME
1 methadone2 morphine3 hydrocodone4 hydromorphone5 oxycodone6 fentanyl7 buprenorphine
RADARS System vs CDC2009 Mortality Data Rank
15
Rank PC ProgramRate/1,000 URDD
CDCDeath rate/100kg MME
1 methadone methadone2 morphine morphine3 fentanyl hydrocodone4 buprenorphine hydromorphone5 hydromorphone oxycodone6 oxycodone fentanyl7 hydrocodone buprenorphine
MME = morphine milligram equivalent URDD = unique recipient of dispensed drug
Spearman rank correlation is fairly strong (p=0.052) in the ranks of the two estimates..
Abuse Deterrent FormulationsEffective Innovation or Marketing Gambit?
OxyContin Suboxone
OxyContin® URDD Rate
Before ReformulationAfter Reformulation
00.51
1.52
Cases/1000
URD
DDrug Diversion
00.050.10.150.20.250.3
Expo
sures/10
00 URD
D Poison Center
Drug ∆(%)OxyContin -52.9%Other Opioids -16.8%
Drug ∆(%)OxyContin -31.3%Other Opioids -10.0%
17
URDD: Unique recipients of dispensed drug
OxyContin® URDD Rate
Before ReformulationAfter Reformulation
0
0.5
1
1.5En
dorsem
ents/1000 URD
D Survey of Key Informant Patients
01234
Endo
rsem
ents/1000 URD
D Opioid Treatment Program Drug ∆(%)OxyContin -14.8%Other Opioids -11.6%
Drug ∆(%)OxyContin -9.4%Other Opioids 7.6%
18
URDD: Unique recipients of dispensed drug
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
20101 20102 20103 20104 20111
Route of OxyContin AbuseSurvey Key Informant Pts, 2008 - 2011
OxyContin OP Formulation
Released
Swallowed
Other Routes
0
0.5
1
1.5
2
2.5
01/200202/200203/200204/200201/200302/200303/200304/200301/200402/200403/200404/200401/200502/200503/200504/200501/200602/200603/200604/200601/200702/200703/200704/200701/200802/200803/200804/200801/200902/200903/200904/200901/201002/201003/201004/2010
Rat
e pe
r 100
,000
Pop
ulat
ion Oxycodone
IR Oxycodone
OxyContin
Increase in Oxycodone Population Rate is Driven by IR Formulation
Drug Diversion
-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.301/200302/200303/200304/200301/200402/200403/200404/200401/200502/200503/200504/200501/200602/200603/200604/200601/200702/200703/200704/200701/200802/200803/200804/200801/200902/200903/200904/200901/201002/201003/201004/2010
Rat
e pe
r 100
,000
Pop
ulat
ion
Quarter/Year
Oxycodone
IR Oxycodone
OxyContin
2002 2011
Poison Centers2002 2011
• Data support that reformulated OxyContin is tamper and abuse deterrent – Poison Center abuse, Drug Diversion and Opioid Treatment
Program cases have decreased– OxyContin rates decreased at a much higher percentage than
other opioids over the same time period– Decrease in both Population and URDD rates suggests
reduction in both availability and desirability
• New formulation still is abused– SKIP data show minimal effect
• Abuse of other drugs increasing– Net effect?
Reformulated OxyContin Conclusions
21URDD: Unique recipients of dispensed drug; SKIP: Survey of key informants’ patients
Availability of Buprenorphine has ExpandedUnique Recipient of Dispensed Drug (URDD)
2006Q1
2006Q2
2006Q3
2006Q4
2007Q1
2007Q2
2007Q3
2007Q4
2008Q1
2008Q2
2008Q3
2008Q4
2009Q1
2009Q2
2009Q3
2009Q4
2010Q1
2010Q2
2010Q3
2010Q4
2011Q1
2011Q2
2011Q3
2011Q4
2012Q1
URD
D
Suboxone Tablets
Suboxone Oral Film
Total SIBuprenorphineTotal Buprenorphine
2006 2012
22
Buprenorphine Rates Poison Center, Drug Diversion Programs
Population Rate (2006 – 2012)
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
Popu
lation
Rate pe
r 100
,000
Suboxone TabletsSuboxone Oral FilmTotal SI buprenorphineTotal buprenorphineNot otherwise specified buprenorphine
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
Popu
latio
n Ra
te per 100
,000
Suboxone TabletsSuboxone Oral FilmTotal SI buprenorphineTotal buprenorphineNot otherwise specified buprenorphine
Poison Center Drug Diversion
2006 2012 2006 2012
23
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
URD
D ra
te per 1,000
Total buprenorphineSI buprenorphine tabletsSuboxone® tabletsSuboxone® oral film
2010 20120.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
Popu
latio
n rate per 100,000
Total buprenorphineSI buprenorphine tabletsNot otherwise specified buprenorphineSuboxone® tabletsSuboxone® oral film
2010 2012
Opioid Treatment ProgramPopulation v. URDD Rate 2010 Q1 - 2012 Q1
24
25
Survey Key Informants’ PatientsPopulation v. URDD Rate, 2010 Q1 - 2012 Q1
0.00
0.10
0.20
0.30
0.40
0.50
0.60
Popu
latio
n rate per 100,000
Total buprenorphineSI buprenorphine tabletsNot otherwise specified buprenorphineSuboxone® tabletsSuboxone® oral film
2010 20120.00
1.00
2.00
3.00
4.00
5.00
6.00
URD
D ra
te per 1,000
Total buprenorphineSI buprenorphine tabletsSuboxone® tabletsSuboxone® oral film
2010 2012
25
RADARS® SystemPoison Center Program –
Exposure Rates and Medical Outcomes in Children
26
Poison Center ProgramUnintentional General, Population and URDD Rates
Children 0-12 Years (2009 Q4 – 2012Q1)
27
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Rate per 100,000
Pop
ulation
Single ingredient buprenoprhineSuboxoneSuboxone Oral Film
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
Rate per 1,000
URD
D
Single ingredient buprenoprhineSuboxoneSuboxone Oral Film
28
Buprenorphine Conclusions
• Has availability of buprenorphine expanded?– Dramatic increase in people filling a prescription
(URDD)– Marked increase of misuse and abuse in all systems
• Is Suboxone an abuse deterrent formulation? – Yes, endorsements are falling and lower than single
ingredient in most programs• Misuse and abuse of buprenorphine in high risk
populations (OTP and SKIP)– Total endorsements rising quickly– Single ingredient is generally preferred
29URDD: Unique recipients of dispensed drug; OTP: Opioid treatment program; SKIP: Survey of key informants’ patients 29
StreetRx.com
30
StreetRx (www.streetrx.com/canada)
31
Search: Ontario
Street Price QuotientOxyContin® Reformulation Analysis
32
RADARS® SystemIntervention
Assessments
33
Operation UNITE
• Launched in 2003 to address prescription opioid abuse in Kentucky
• Three-pronged intervention – Education– Enforcement– Treatment
Rise in Abuse Less inOperation UNITE Region
-50
0
50
100
150
200
The RADARS® System Poison Center ProgramIntentional Abuse Population Rates – All Opioids
2nd Quarter 2006 to 4th Quarter 2011Percent Change from Baseline
Rise in Abuse is Attenuatedin States with PDMPs
• States without a PDMP– Poison Center cases: Increase 1.9% per quarter*– Opioid Treatment Program: Increase 4.9% per quarter
• States with a PDMP– Poison center cases increase at 0.2% per quarter– Opioid Treatment Program: Increase 2.6% per quarter
* All increases are percent increases per quarter, exponential, adjusted for population and unique recipients of a dispensed drug (URDD)
Reifler LZ, Droz D, Bailey JE, Schnoll SH, Fant R, Dart RC, Bucher-Bartelson BB. Do prescription monitoring programs impact state trends in opioid abuse / misuse? Pain Med 2012; 13:434-42.
• Important to employ mosaic approach– No one data source is perfect– Different sources answer different questions– Triangulation and validation of external data sources
• Initial evidence supports that abuse deterrent formulations reduce abuse of those products– Dependent upon how drug is misused– Important to monitor consequence of “squeezing the
balloon”• Policy implications
– Should formulations with higher abuse remain on market?
Summary
37
