1. Access to Controlled Medicines Willem Scholten, PharmD, MPA Team Leader, Access to Controlled Medicines, World Health Organization, Geneva, Switzerland TECHNICAL BRIEFING SEMINAR Geneva, 29 October – 2 November 2012

2. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 2 |2 | Overview The global pain management crisis Causes of the problem Working methods for improvement –Including WHO Policy guidelines

3. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 3 |3 | Uses of Controlled Medicines –Ergometrine and ephedrine: emergency obstetrics –Benzodiazepines: anxiolytics, hypnotics, antiepileptics –Phenobarbital: antiepileptic –Opioid analgesics: e. g. morphine moderate and severe pain –Long-acting opioid agonists: methadone, buprenorphine treatment of opioid dependence

4. Is there a crisis?

5. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 5 |5 | Inequality 93.8% of all (licit) morphine consumption by 21.8% of the world population (INCB 2010, Data for 2009) 4.7 billion people live in countries where medical opioid consumption is near to zero (on a total world population of 6.5 billion) (Seya et al. 2011, Data for 2006)

6. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 6 |6 | Other Controlled Medicines Opioid analgesics best documented. Also access problems with other controlled medicines Opioid agonist treatment of opioid dependence: –World-wide coverage: 8% of patients only Phenobarbital – 80% of epilepsy patients in Africa have no access Ketamine !!!!!!!!!!! –Upcoming surgery/anaesthesia crisis world-wide

7. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 7 |7 | Consumption increase Global consumption of strong opioids rose from – 1.82 mg/capita of Morphine Equivalents (1980) to –59.66 mg / capita (2009) (Pain & Policy Studies Group, University of Wisconsin) Increase is faster since the introduction of the Three- Step Ladder of Cancer Pain Relief (WHO, 1986) Most of increase in industrialized countries

8. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 8 |8 | Patients affected (world wide, annually) Cancer pain patients untreated5.4 million HIV pain patients untreated1 million Lethal injuries0.8 million Surgery8-40 million

9. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 9 |9 | Adequacy Consumption of Opioid Analgesics (2007) from: Seya MJ et al, J Pain & Pall Care Pharmacother 2011;25:6-18

10. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 10 | Adequacy of Consumption Measure (ACM) ≥1 Adequate 0.3 – 1 Moderate 0.1 – 0.3 Low 0.03 – 0.1 Very Low < 0.03 "No" consumption Logarithmic scale!!!

11. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 11 | Adequacy as a function of development Data for 2006

12. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 12 | Method for ACM Based on –Consumption of all strong opioids (INCB statistics 2006) –Morbidity (HIV, cancer, lethal injuries) –Benchmark: average of Top-20 Human Develop Index Method for calculating long term needs  Long term targets for countries –Unsuitable for accurate calculation of short term needs A first comparison between the consumption of and the need for opioid analgesics at country, regional and global levels Seya MJ et al, J Pain and Pall Care Pharmacother, 2011;25:6-18

13. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 13 | ACM Benchmark No generally accepted Good per Capita Consumption Level Assumption: most developed countries are near to "good"  Average of " Top–x " from Human Development Index (HDI) can be used as benchmark –Choice of x is arbitrary – but major impact on outcome!

14. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 14 | Adequacy of opioid consumption ( x million people)* WorldWPROSEAROEUROEMROAMROAFRO 4640012903350Adequate 252250228000Moderate 2551280127000Low 45779094772061Very low 4718151172283400304503No cons. 433222266449270No data 658017631721887540895774Total * Number of people living in countries where opioid consumption is …

15. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 15 | Global need to treat all pain Current global consumption of strong opioids: 213 000 kg morphine equivalents (2006) Needed to treat all pain adequately: 1 292 000 kg morphine equivalents Seya MJ et al., J of Pain and Palliative Care Pharmacotherapy; 2011;25:6-18

16. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 16 | Validation? For the Netherlands: ACM: 51 % (Seya et al.) 43% of chronic non-cancer pain patients report not to receive pain treatment 79% of patients believe their pain is inadequately treated Bekkering GE et al, Epidemiology of chronic pain and its treatment in the Netherlands. The Netherlands J of Med. 2011; 69(3): 141 – 152 (Systematic review) Studies for other European countries on their way; this will allow validation of ACM-method

17. Treatment of opioid dependence

18. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 18 | Availability of MMT/BMT

19. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 19 | References BM Mathers, Degenhardt L, Ali H et al,. HIV Prevention, treatment, and care services for people who inject drugs; a systematic revie of global, regional, and national coverage.The Lancet 2010; 375: 1014 – 28. BM Mathers, Degenhardt L, Phillips B et al. Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review. The Lancet (www.thelancet.com) Published online September 24, 2008 DOI:10.1016/S0140-6736(08)61311-2

20. Why do people do this one to another?

21. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 21 | Because they have… Excessive fear for dependence Excessive fear for diversion Neglected and ignored medical needs

22. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 22 | Why do these barriers exist and what are they? One century of drug control –23 January 1912, The Hague: first Opium Convention Focus has been on prevention of –abuse, –dependence and –crime related to trafficking Medical and scientific supply "forgotten"

23. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 23 | Preamble Single Convention Single Convention on Narcotic Drugs (1961; as amended) Recognizing that the medical use of narcotic drugs continues to be indispensable for the relief of pain and suffering and that adequate provision must be made to ensure the availability of narcotic drugs for such purposes …

24. Barriers frequently encountered

25. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 25 | Categories of barriers Legislation and Policy Knowledge Attitudes –Health-Care Professionals –General Public Economic

26. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 26 | Legislative barriers Inappropriate laws and regulations –Rules often not preventing abuse, dependence and diversion –Rules often a barrier for medical access Limitations on prescriptions and administration –Duration –Maximum dosage –Administration of medicines restricted Special prescription forms Limitation of outlets Limitations on who is allowed to prescribe –Special licensing in spite of medical degree

27. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 27 | Policy barriers Access to controlled medicines not included in national policy plans –National Pharmaceutical Policy Plan –National Cancer Control Plan –National HIV/AIDS Plan Investigation/prosecution of prescribers –Investigation of those who subscribe at an adequate level Too much red tape –Speed of licensing procedures

28. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 28 | Knowledge barriers Medical Schools –Many do not teach opioid analgesia Physicians –Fear for dependence –Unfamiliarity with prescribing and dosing –Prescribing obsolete medicines (pethidine=meperidine still in use) –Unfamiliarity with pain assessment –Learned "not to treat symptoms, but disease"

29. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 29 | Attitude barriers Patient and family –Association morphine  impending death –Conviction that suffering chastens Health-care and other professionals –Continuing use of obsolete or counter-productive terminology –Seniors not allowing juniors to introduce new techniques

30. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 30 | Economical and procurement barriers General issues as for other medicines e.g. –Insurance and affordability –Distribution problems In some countries Separate distribution systems for controlled medicines

31. How to Beat the Global Pain Management Crisis?

32. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 32 | Improving access Suggested steps Policy analysis Legal analysis (external lawyer, trained on the issue) National policy on improving access National one-day symposia for awareness raising

33. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 33 | Working methods (1) Preferrably: working group that includes –authorities –representatives of relevant health-care professionals Pharmacists, GPs, PC, oncology, surgery…. (pain everywhere!) Treatment of opioid dependence Veterinarians? –patient representatives

34. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 34 | Working methods (2) Full analysis of barriers Policy planning –Priority setting Implementation Evaluate, set new priorities and adjust policy plan etc…

35. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 35 | Tools WHO Policy guidelines WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illness Published 2012 on-line (free) and in print Other WHO pain guidelines to follow –Persisting Pain in Adults –Acute Pain

36. WHO Policy Guidelines

37. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 37 | WHO Policy Guidelines English, French and Spanish in print form In print form: US$ 25.– (US$ 17.50 for developing countries) On-line: 15 languages available free of charge online http://www.who.int/medicines/areas/quality _safety/guide_nocp_sanend/en/index.html Ensuring Balance in National Policies on Controlled Substances, Guidance for accessibility and availability of controlled medicines (Geneva 2011)

38. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 38 | Policy principle Based on Principle of Balance: Obligation of governments to establish a system of drug control that – ensures the adequate availability of controlled substances for medical and scientific purposes – while simultaneously preventing abuse, diversion and trafficking 21 Guidelines and Country Check List

39. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 39 | 21 Guidelines Topics Content of drug control legislation and policy (2 GLs) Authorities and their role in the system (4 GLs) Policy planning for availability and accessibility (4 GLs) Healthcare professionals (4 GLs) Estimates and statistics (3 GLs) Procurement (3 GLs) Other (1 GL)

40. WHO Pain Treatment Guidelines

41. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 41 | Ground breaking guidelines Cancer Pain Relief (1986) –2nd Edition: 1996 WHO Cancer Pain and Palliative Care in Children (1998)

42. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 42 | Cancer Pain Relief (in children) Systematic approach: –"By the ladder" –"By the clock" –"By the appropriate route" –"By the individual" Three Step Analgesic Ladder No maximum dose on morphine –"The right dose is the dose that works" Obsolete now for some recommended opioids –E.g. levorphanol, pethidine Not evidence-based / no transparency

43. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 43 | WHO Pain Treatment Guidelines Series WHO Treatment Guidelines on Persisting Pain in Children with Medical Illnesses –On-line since February 2012 –In print: next week! Persisting Pain in Adults (in progress) –Scoping document online available Acute Pain (Planned)

44. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 44 | Persisting Pain in Children Package

45. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 45 | Persisting Pain in Children Package Printed version will be available as a package: Guidelines and brochures Wall chart Dosage card 2 Pain measurement schales (FPS-R and VAS)

46. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 46 | Contents (1) Principles –All moderate and severe pain in children should always be addressed. 19 clinical recommendations –Two-step approach 4 health system recommendations Most evidence levels assessed "low" and "very low"  Research agenda –Evidence Based Child Health 6: 1017-1020 (2011)

47. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 47 | Contents (2) Chapter 1. Introduction. Chapter 2. Classification of pain in children Chapter 3. Evaluation of persisting pain in the paediatric population Chapter 4. Pharmacological treatment strategies Chapter 5. Improving access to pain relief in health systems

48. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 48 | Contents (3) Annex 1. Clinical recommendations Annex 2. Evidence retrieval and appraisal Annex 3. Research agenda Annex 4. Health system interventions recommendation Annex 5. Opioid analgesics and international conventions

49. Conclusion

50. Access to Controlled Medicines | TECHNICAL BRIEFING SEMINAR Geneva, 31 Oct 2012 50 | Conclusion Potentially 4.7 billion people affected Medical opioid consumption needs to go up 6 times Policies needed to identify and overcome barriers Concerted action by health-care professionals of all specialties and policy makers required Tools include WHO policy and treatment guidelines

51. Willem Scholten, PharmD, MPA Team Leader, Access to Controlled Medicines, World Health Organization, Geneva, Switzerland wk.scholten@ bluewin.ch Access to Controlled Medicines