1. CDC: Epi to Policy April 22, 2013 Atlanta, GA CONSIDERATIONS ON THE USE OF PRESCRIPTION MONITORING PROGRAMS BY PRESCRIBERS, PHARMACISTS, & PUBLIC HEALTH DEPARTMENTS The Warren Alpert Medical School of Brown University Traci C. Green, PhD, MSc Director of Public Health Research & Methodology, Inflexxion, Inc. Assistant Professor of Emergency Medicine & Epidemiology The Warren Alpert School of Medicine at Brown University, Rhode Island Hospital

2. DISCLOSURES: TRACI C. GREEN  The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:  Employment at Inflexxion, Inc.,  Funding: CDC National Center for Injury Prevention and Control, 5R21CE001846-02 and 1R21CE002165-01; National Institute on Drug Abuse, 1R21DA029201-02A1

3. INFLEXXION AT A GLANCE Founded in 1989 – over 85 employees Science based programs in the areas of:  Pharmaceutical Risk Management  Pain treatment, self-management, & education  Prescription drug abuse  Substance abuse/behavioral health evaluation & treatment  College student health Over $80 million over the last 18 years in US National Institutes of Health (NIH) research support

4. NAVIPPRO PROGRAM

5. AIMS  To present a conceptual model of PMP use & overdose risk  To contrast PMP use between two states, Connecticut and Rhode Island, with different PMP accessibility  To report data on use of PMPs in medical, pharmacy practice, including responses to suspected diversion or “doctor shopping”  To reflect how overdose is represented in PMP materials & resources, contrast with PMP use laws

6. BACKGROUND  DRUG POISONING (overdose) is the leading cause of adult injury death in Rhode Island (RI), Connecticut (CT) and 28 other states  More fatal drug poisonings involve PRESCRIPTION OPIOIDS than other illicit drugs. Two-thirds of RI and CT overdoses involve prescription opioids  PRESCRIPTION MONITORING PROGRAMS (PMPs) can influence risks associated with abuseable medications, exist in 49 states  PRESCRIBERS & PHARMACISTS are on the “front lines” of the prescription opioid abuse epidemic  Motivated to use PMPs to detect diversion, help reduce “dr. shopping” (Fass 2011; Ulbrich 2010)  Limited data exist on effects of PMP use on MEDICAL, PHARMACY PRACTICE

7.  “DR. SHOPPING”: indicator of addiction, help seeking, overdose risk (Hall et al., 2008; Martyres et al.,2004)  Multiple comorbidities, histories of trauma, interpersonal violence, PTSD  Coprescribed other CNS depressants  Higher prevalence of substance use disorder (SUD)  Greater likelihood of complex pain condition(s)  More often opioid therapy, multiple opioids, multiple providers  Housing stability/residence  Denial of medications may contribute to poor health outcomes: initiation, illicit use, riskier use, overdose (Fibbi et al, 2012) COMPLICATED DATA, COMPLICATED PATIENTS

8. WHERE ARE OVERDOSES HIGHEST?

9. PAINKILLERS SOLD BY STATE PER 10,000 PEOPLE (2010)

10. Risk Factors for Unintentional Opioid Poisoning  Change in TOLERANCE  using ALONE, by oneself  MIXING opioids with other central nervous system depressing substances (alcohol, benzodiazepines)  ILLNESS  (Sporer 2007, Binswanger 2007, Green 2012)

11. EFFECTS ON OVERDOSE RISK Drugs prescribed, #, type, dose Risk reduction counseling Abuse detected Drugs dispensed (licit) Detect abuse, Doctor shopping/ diversion (illicit) Inappropriate prescription (errors) Closing narcotics investigations Diversion, rogue prescribers, pill mill detection Law enforcement intelligence PMP Pharmacists Prescribers Law Enforcement Public health/ Safety dept. Target public health measures Trend Awareness Disciplinary actions

12.  RARx Study-PMP as public health tool in Rx opioid overdose risk reduction  Online survey of prescribers, pharmacists in RI, CT  Data linkage, spatial analysis, case-control  12 week rapid assessment and response on nonmedical prescription opioid use & overdose, July-August 2011  3 non-urban sites, 2 New England states  Community advisory boards in both states  195 key informant interviews with systems, interactors, community informants (opioid users, dealers, chronic pain patients, families of overdose survivors)  PMPU Study—local health impacts of PMP use  Local PMP use effects on Supply, Demand, Harm  Data linkage: street drug price, initiation of heroin, nonmedical use, circulating medications  7 states: 5 with active PMPs, 2009-2012 analysis  Survey of PMPs on overdose-specific programming, framing TWO STUDIES

13. Controlled substance data from licensed pharmacies, electronically uploaded, securely stored in a central database CT  Maintained by Dept of Consumer Protection, Drug Control Division  Operational since July 2008  Registered health profs licensed to prescribe/dispense controlled substances  Schedule II-V prescriptions  Electronic queries, patient report generated in seconds  Health professional queries outnumber law enforcement queries RI  Maintained by Dept of Health, Board of Pharmacy  Cannot be directly accessed or queried by health profs  Inquiries made indirectly by phone, email, fax, mail  Schedule II and III medications  Patient report receipt may take hours to weeks  Law enforcement, investigative queries outnumber health prof queries RARX: CT & RI PMP

16.  Anonymous surveys emailed to CT, RI licensed prescribers, pharmacists  Items from literature, PMP staff input  Current SA/MH practices, counsel on overdose risk, Rx opioid storage+disposal, PMP use, barriers to PMP use, addressing dr. shopping/diversion  Data collected March-August 2011; 3 reminder emails  Respondents: PMP registered users, prescribers (n=1385), pharmacists (n=306)  Analyses  By state pharmacy practice, PMP use; PMP user comparisons on responses to suspected dr. shopping/diversion RARX PMP SURVEYS: METHODS

18. RARX PMP SURVEY FINDINGS: PRESCRIBERS  Most use PMP reports to screen for abuse, complement patient care  Primary means of diagnosing drug abuse is “professional judgment”  When concerned about “dr. shopping”/diversion, PMP users significantly more likely than non-users to:  Screen for drug abuse, conduct urine screens, refer to another provider, refer to substance abuse treatment  Revisit pain treatment agreements  Less likely to do nothing (ignore it)  Fewer calls to law enforcement to intervene  Little patient counseling on overdose, risk factors  Indirect not direct influence on overdose risk Green et al., How Does Use of a Prescription Monitoring Program Change Medical Practice? Pain Medicine July 2012

19. DIRECT & INDIRECT EFFECTS ON OVERDOSE RISK Drugs prescribed, #, type, dose Risk reduction counseling Abuse detected Drugs dispensed (licit) Detect abuse, Doctor shopping/ diversion (illicit) Inappropriate prescription (errors) Closing narcotics investigations Diversion, rogue prescribers, pill mill detection Law enforcement intelligence PMP Pharmacists Prescribers Law Enforcement Public health/ Safety dept. Target public health measures Trend Awareness Disciplinary actions Overdose risk identified, counseled Initiate/refer to drug treatment

21. RARX RESULTS: PHARMACIST PMP USE Lack of awareness No/limited internet access Report delay Employer doesn’t require it Employer doesn’t permit it

22.  Screening for abuse  Professional judgment (80%-90%), PMP report (CT: 79%, RI: 22%), ask directly  No differences by state or PMP use on patient counseling topics on prescribed Rx opioids  Coingestion risks  Addiction  Unauthorized dose escalations  Sharing medications  Overdose symptoms  Disposal  Storage  Nothing/does not counsel patient (12%-20%) RARX RESULTS: PMPS CHANGING PHARMACY PRACTICE?

23. Detecting “dr. shopping”  Similar % RI & CT pharmacists used insurance rejection (77.9%), professional judgment (73.1%), and verifying the prescription and prescriber (68.6%)  check PMP (CT: 67%, RI: 7%, p<0.001) Views of PMP: helps reduce diversion, prescription opioid abuse in their state, in their practice  PMP users in CT had most positive view of PMP effects  CT pharmacists had more positive view of PMP than RI pharmacists RARX RESULTS: PMP USE CHANGING PHARMACY PRACTICE?

24. Responses to suspected diversion/“dr shopping” Typical PMP user actions vs. typical non-user actions (ref) aOR [95% CI] Contact the patient’s physician(s) (if known)0.86 [0.21, 3.47] Discuss the concerns with the patient0.48 [0.25, 0.92] Refer the patient back to provider1.50 [0.79, 2.86] Refuse to fill the prescription0.63 [0.30, 1.30] State out of stock of the drug0.27 [0.12, 0.60] Counsel the patient on potential overdose risk 0.59 [0.27, 1.27] Refer the patient to substance abuse treatment 1.29 [0.25, 6.53] Ask the patient to leave the pharmacy0.46 [0.17, 1.29] Notify law enforcement0.81 [0.33, 2.01]

25. DIRECT & INDIRECT EFFECTS ON OVERDOSE RISK Drugs prescribed, #, type, dose Risk reduction counseling Abuse detected Drugs dispensed (licit) Detect abuse, Doctor shopping/ diversion (illicit) Inappropriate prescription (errors) Closing narcotics investigations Diversion, rogue prescribers, pill mill detection Law enforcement intelligence PMP Pharmacists Prescribers Law Enforcement Public health/ Safety dept. Target public health measures Trend Awareness Disciplinary actions Overdose risk identified, counseled Initiate/refer to drug treatment Overdose risk identified, counseled

26.  Compared Emergency provider (EP) prescribing decisions before, after review of PMP data (Baehren et al., 2010)  Changed prescribing behavior for 41% (of 179 cases): 61% fewer/no opioids, 39% more opioids than originally planned  Online survey of EPs, presented index, suspicious patient cases (Grover et al, 2012)  Fair-moderate agreement on patient drug seeking based on high # of prescribers or high # of prescriptions (PMP-like data)  No differences attendings vs. residents: PMP use not clinical differences  Compared EP impression of “drug seeking behavior”: clinical evaluation vs actual PMP data (Weiner et al., under review)  544 patients, 38 providers, 2 EDs, patients with pain complaint  Only Fair agreement (k=.3), low PPV= 41.2%  Prescribing plan change for 9.5% at discharge: 3% no opioids, 6.5% opioids previously unplanned  Predictors of EP suspicion vs. PMP cutoff underscore emphasis placed on clinical impression PMP USE IN THE EMERGENCY DEPARTMENT

27. How do PMPs talk about overdose? What tools are available to PMP users to reduce the risk of fatal overdose? How do states with mandatory PMP use/registration laws differ? December 2012-March 2013, systematically reviewed PMP websites 44 states w/active PMPs, 3 w/enacted PMP legislation, inactive programs Specific mentions/materials on site pages Searched: “overdose”, “death”, “poisoning”, “naloxone”, “narcan” Content: practical instructions, program goals, mission statement, regulations, training materials, informational pamphlets, FAQs Mentions coded for thematic similarities, location on website FRAMING THE PROBLEM: PMP & OVERDOSE MENTIONS PRELIMINARY FINDINGS

28. PMP WEBSITE CONTENT

29. OD mentionsOD related provider tools Mandatory usage & registration laws (n=3) KY, MA, TN 00 Mandatory usage only (n=9) CO, DE, LA, NY, NC, NV, OH, OK, WV 30 Home page: "To reduce morbidity and mortality from unintentional drug overdoses” Link to legislation: "to address the problems of widespread drug abuse and the resulting overdose deaths” PMP WEBSITE CONTENT BY USE LAWS

30. www.ncdhhs.gov/MHDDS AS/controlledsubstance/

31. PMP WEBSITE CONTENT BY USE LAWS OD mentionsOD related provider tools Mandatory usage & registration laws (n=3) KY, MA, TN 00 Mandatory usage only (n=9) CO, DE, LA, NY, NC, NV, OH, OK, WV 30 Mandatory registration only (n=5) AZ, ME, NH, NM, UT 31 UT regulation: for every acute hospital poisoning/overdose involving a prescribed controlled substance, law mandates notification of practitioners who may have prescribed controlled substance to patient, send PMP & hospital report to prescriber Intent: encourage discussions with patient related to poisoning/overdose, advise on future prevention, make decisions regarding future prescriptions written for patient

32.  Naloxone is an opioid overdose antidote & is standard treatment in the pre-hospital setting  Community-wide distribution of naloxone is associated with overdose mortality reductions of 27-46%  188+ community based programs, trained 50,000+, with 10,000+ reversals  Naloxone only available by prescription  Law is a key driver of accessibility to naloxone  Encourage prescribing/appropriate use of naloxone  Provide limited immunity if call 911 in overdose  NM (2001), NY, IL, WA, CA, RI, CT, MA PMP USE & NALOXONE LAWS PMP users Naloxone prescribers PMP users Naloxone prescribers

33. www.orpdmp.com

34. Prescribers: How to change, sustain PMP use to directly & indirectly reduce overdose risk? Pharmacists: Why avoidance of talking with patient about PMP report? How to improve this situation, expand therapeutic use of PMP patient report in the pharmacy? EPs: How to promote efficient, therapeutic use of PMP in ED setting? Public health/safety: How can the PMP/data be used to directly reduce, raise awareness of overdose risk? How can we better coordinate use of available tools? DISCUSSION

35. CDCONDCPFDA PRIMARY PREVENTION Use PMPs, insurance to combat “dr. shopping” Tracking, monitoring: operational PMPs, inter-state data sharing Legislation/enforcement of pill mill laws, Rx fraud Target “unscrupulous” health professionals, pill mills, “dr shopping” EBM, CMEs to improve safer prescribing *complex pain, pain-SA hx Mandatory education for controlled substance prescribers Class-wide REMS, voluntary provider education Patients, parents education Medication “take-backs” / drop boxes ADFs SECONDARY & TERTIARY PREVENTION Distribution of naloxone to laypersons, 1 st responders Distribution of naloxone to laypersons MAT: suboxone, methadone RECOMMENDATIONS

37. Thank you! tgreen@inflexxion.com traci.c.green@gmail.com

38. REFERENCES Surveillance-related  TC Green, R Black, JM Grimes-Serrano, SH Budman, SF Butler. Typologies of Prescription Opioid Use in a Large Sample of Adults Assessed for Substance Abuse Treatment. PLoS ONE (6(11): e27244). http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027244 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027244  SF Butler, SH Budman, A Licari, TA Cassidy, K Lioy, J Dickinson, JS Brownstein, JC Benneyan, TC Green, N Katz. National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO™): A real-time, product-specific, public health surveillance system for monitoring prescription drug abuse. Pharmacoepidemiology and Drug Safety 2008.  JS Brownstein, TC Green, T Cassidy, SF Butler. Geographic Information Systems and Pharmacoepidemiology: Using spatial cluster detection to monitor local patterns of prescription opioid abuse. Pharmacoepidemiology and Drug Safety 2010; 19(6):627-37. Nonmedical Use of Prescription opioids: Trends  TC Green, EF Donnelly. Preventable death: Accidental drug overdose in Rhode Island. Medicine & Health Rhode Island. 2011; 24(11): 341-343.  M Yokell, TC Green, S Bowman, M McKenzie, JD Rich. Opioid overdose prevention and naloxone distribution in Rhode Island. Medicine & Health Rhode Island. 2011; 94 (8): 240-242.  TC Green, LE Grau, HW Carver, M Kinzly, R Heimer. Epidemiologic and geographic trends in fatal opioid intoxications in Connecticut, USA: 1997-2007. Drug and Alcohol Dependence 2011 Jun 1;115(3):221-8.

39. RARx  TC Green, MR Mann, SE Bowman, N Zaller, X Soto, J Gadea, C Cordy, P Kelly, PD Friedmann. How does use of a prescription monitoring program change pharmacy practice? Journal of the American Pharmacy Association (in press)  N Zaller, MA Yokell, TC Green. Pharmacists’ and injection drug users’ attitudes toward take-home naloxone: challenges and opportunities. Substance Use and Misuse (in press).  TC Green, SE Bowman, M Ray, N Zaller, R Heimer, P Case. Collaboration or coercion? Partnering to Divert Prescription Opioid Medications. Journal of Urban Health (in press)  TC Green, SE Bowman, N Zaller,M Ray, P Case, R Heimer. Barriers to medical provider support for prescription naloxone as overdose antidote for lay responders. Substance Use and Misuse (in press)  TC Green, MR Mann, SE Bowman, N Zaller, X Soto, J Gadea, C Cordy, P Kelly, PD Friedmann. How does use of a prescription monitoring program change medical practice? Pain Medicine (e-pub 2012 Jul 30.)  TC Green, N Zaller, S Bowman, JD Rich, PD Friedmann. Revisiting Paulozzi et al.’s “Prescription Drug Monitoring Programs and Death Rates from Drug Overdose”. Letter. Pain Medicine 2011; 12 (6): 982-985.  M Yokell, N Zaller, TC Green, M McKenzie, J Rich. Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose. Journal of Opioid Management. January/February 2012; 63-66.

40. Naloxone & Good Samaritan law-related  Davis, Corey S., Webb, Damika and Burris, Scott C., Changing Law from Barrier to Facilitator of Opioid Overdose Prevention (April 17, 2013). Available at SSRN: http://ssrn.com/abstract=2252624  C. Banta-Green, “Washington’s 911 Good Samaritan Overdose Law: Initial Evaluation Results,” November 2011, available at (last visited January 8, 2013).  N. Dasgupta, C. Sanford, S. Albert, and F. Brason, “Opioid Drug Overdose: A Prescription for Harm and Potential for Prevention,” American Journal of Lifestyle Medicine 4, no. 1 (2010): 32-37, at 34.  A. Walley et al., “Opioid Overdose Prevention with Intranasal Naloxone among People Who Take Methadone,” Journal of Substance Abuse Treatment 44, no. 2 (2013):241- 247.  TC Green, LE Grau, R Heimer. Distinguishing signs of opioid overdose and indication for naloxone: An evaluation of six overdose training and naloxone distribution programs in the United States. Addiction 2008.  “Naloxone OD Prevention Laws Map,” available at  Centers for Disease Control and Prevention, “Community-Based Opioid Overdose Prevention Programs Providing Naloxone – United States, 2010,” Morbidity and Mortality Weekly Report 61, no. 6 (2012): 101-105.  A. Walley et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysisBMJ 2013;346:f174 doi: 10.1136/bmj.f174 (Published 31 January 2013). http://www.bmj.com/content/346/bmj.f174.pdf%2Bhtml http://www.bmj.com/content/346/bmj.f174.pdf%2Bhtml