Pain Management Updates and Issues

1. Pain Management Updates and Issues Robert Twillman, PhD The University of Kansas Medical Center

2. Pain is a major public health issue • 80% of patients present for health care because of pain • Chronic pain affects 30-40% of the population • Over 40% of hospital patients report poor pain control • Unrelieved pain costs our economy over $100 billion each year

3. Prescription Opioid Abuse is a Public Health Issue • 2007 National Survey on Drug Use and Health(NSDUH): • 33.5 million Americans had used a pain reliever non-medically at least once in their lifetimes (13% increase from 2002)

4. Sources of Abused Drugs, NSDUH 2007 “Other” includes “Wrote Fake Prescription”, “Stole from Doctor’s Office/Clinic/Hospital/Pharmacy”, and “Some Other Way”

5. Sources of Abused Drugs, NSDUH 2007 “Other” includes “Wrote Fake Prescription”, “Stole from Doctor’s Office/Clinic/Hospital/Pharmacy”, and “Some Other Way”

6. NSDUH Data Are Unreliable • Definition of “nonmedical use” is problematic • Asking about source of drug is problematic • High social desirability factor • Asking your research subject where he got his drug is affected by this • Asking your research subject where his source got the drug is tremendously unreliable

7. Prescription Opioid Abuse is a Public Health Issue • 2002 Drug Abuse Warning Network data (DAWN; ED visits): • 108,320 for opioid analgesics (153% increase from 1995) • 2006 Treatment Episode Data Set (TEDS): • Non-heroin opioids were primary drug of abuse for 74,750 patients entering substance abuse treatment nationwide (550% increase from 1996)

8. Drug Treatment Admissions, Non-Heroin Opioids as Primary Drug 450% Increase over 10 years

9. Recent Survey • Teen-agers now say it is easier to get prescription drugs than it is to get beer

10. Sources of Diverted Prescription Opioids • Supply chain thefts • Internet pharmacies • Thefts from patients • “Purchases” from patients • Prescription forgery • Illegal prescribing practices • Prescribing to individuals who deceive prescribers

11. Measuring and Controlling Drug Diversion • Due to the nature of the problem, measuring the extent of drug diversion is extremely difficult • Pharmacy thefts can be tracked, as can prescriptions • Most other sources are virtually impossible to examine • Can drug abuse statistics be used as a surrogate? Are all abused drugs diverted?

12. HCP-Related Reasons for Inadequate Pain Management • Survey of 1177 Oncologists: • Inadequate Pain Assessment (79%) • Patient Reluctance to Report Pain (62%) • Patient Reluctance to Take Opioids (62%) • MD Reluctance to Prescribe Opioids (61%)

13. Why are physicians anxious about managing chronic pain with opioids? • Uncertainty related to assessment • Concern about detrimental side effects • Unfamiliarity with opioids, adjuvants • Fear of addiction • Fear of lawsuits • Fear of regulatory scrutiny

14. Means of Improving Pain Management • Changes to policies and standards • Education of providers and patients • Development of practice guidelines • Monitoring and continuous quality improvement

15. Patient-Related Reasons forInadequate Pain Management • Fear of addiction • Fear of side effects • Expectations are low • MD might have to choose which to treat--disease or pain • Fear of distracting the doctor • Complaining about pain might annoy the doctor

16. What We Hear From Patients • Many have difficulty finding physicians who will treat their pain adequately • A few report problems with pharmacies filling prescriptions for pain medications • Some have difficulty getting insurance companies and Medicaid to pay for pain treatment • Many have (incorrectly) been told they either are addicted or at high risk for addiction

17. National Pain Policy Issues

18. Current Issues • Federal legislation • National Pain Care Policy Act • Methadone Treatment and Protection Act • FDA activities • Propoxyphene • Acetaminophen recommendations • REMS for long-acting opioids

19. Current Issues • DEA activities • ePrescribing • Disposal of Controlled Substances • American Geriatric Society pain treatment guidelines

20. National Pain Care Policy Act • Originally introduced in early 2000s • In last session of Congress • Passed House near end of session • Stalled in Senate HELP Committee • Current session • Passed House quickly • Stalled in Senate HELP Committee • Now amended to health care reform bills in both houses

21. National Pain Care Policy Act • Background • Pain affects about 80% of people presenting for health care • Pain research funding at NIH represents 0.1% of all NIH grant funding • There are 23 review groups to evaluate pain-related grants, which must compete against very unlike grant applications • Ongoing significant deficits in healthcare provider education related to pain management

22. National Pain Care Policy Act • Provisions • IOM to convene a Conference on Pain ($500K appropriated) • Director of NIH encouraged to expand, through Pain Consortium, an aggressive program of basic and clinical research • Pain Consortium to issue yearly recommendations on research initiatives • NIH to establish Interagency Pain Research Coordinating Committee

23. National Pain Care Policy Act • Secretary of HHS is to establish grant program for education and training in pain care ($5M annually appropriated) • Secretary shall establish and implement a national pain care education outreach and awareness campaign (focused on consumers; $2M appropriated for FY 2010, $4M for FY 2011 and FY2012)

24. Methadone Treatment and Protection Act • Introduced by Senator Rockefeller (D-WV) on 3/31/09 • Referred to Senate HELP Committee

25. Methadone Treatment and Protection Act • Background • Methadone is a highly effective, very inexpensive long-acting opioid analgesic • It is difficult to use because of its pharmacological properties • It has a long half-life (up to 100 hours for some of its metabolites) • Does not produce significant euphoria • Effects of dose change not completely seen for about 4 days

26. Methadone Treatment and Protection Act • Methadone uses • Methadone maintenance for opioid addicts • Intended to prevent withdrawal, curb cravings • Administered daily at clinics • Typically a life-long treatment • Management of pain • Very low doses may be very effective • Administered 2-4 times per day • May be stopped if pain is no longer present

27. Methadone Treatment and Protection Act • 1998-2006: Prescriptions increased 700% • In 2005, there were 4462 methadone-related deaths, up by 468% since 1999 • Other poisoning deaths increased by 66% over same period • Rate of methadone deaths in 15 to 24-year-olds increased 11-fold, and may be underreported

28. Methadone Treatment and Protection Act • Bill calls for: • Consumer education campaign ($15M each year FY2010-2014) • Practitioner education (funded through portion of DEA registration renewal fees) • No use of 40 mg diskette doses outside of maintenance programs • Secretary of HHS to establish Controlled Substances Clinical Standards Commission

29. Methadone Treatment and Protection Act • Bill calls for: • Funding of 1995 National All-Schedules Prescription Electronic Reporting (NASPER) program at $25M per year for FY2010-2014 • Improved reporting standards for methadone-related deaths

30. Food and Drug Administration Activities

31. Propoxyphene • Propoxyphene is an opioid analgesic • Research suggests it is may be only marginally effective, if at all, in treating pain • It has a long-lived metabolite that irritates the nervous system and causes heart rhythm disturbances • Found in Davron, Darvocet; marketed since 1957 • Pain guidelines recommend not to use this drug

32. Propoxyphene • FDA was asked to review drug because: • Insufficient evidence to suggest it is an effective analgesic • It was withdrawn from the UK market because of the risk of deliberate and accidental overdose • It is cardiotoxic and has narrow therapeutic index • It is widely prescribed, especially in elderly, and is associated with a large number of deaths

33. Propoxyphene • FDA advisory committee voted 14-12 to recommend withdrawal from the market • FDA decided to keep drug on the market • “Benefits outweigh risks” • Manufacturer required to do safety studies • FDA to work with other agencies to conduct additional studies

34. Acetaminophen • Active ingredient in Tylenol • Found in a multitude of over-the-counter medications • Also found in some prescription medications, combined with opioids • High acute doses can cause fulminant liver failure and death • High chronic doses can cause chronic liver failure

35. Acetaminophen • Frequently, problems arise because patients are prescribed medications containing acetaminophen while also taking OTC acetaminophen • FDA decided to review this medication to see if there were ways to improve its safety • Advisory panel meeting was held June 29-30 • Votes taken on a number of questions

36. Acetaminophen • Question: Do you recommend current maximum dose be allowed? • Strong yes: 11 • Yes: 10 • No: 16 • Question: Should max single dose be 650 mg? • Strong yes: 12 • Yes: 12 • No: 13

37. Acetaminophen • Question: If current doses of OTC products are lowered, should current maximum dose (2 X 500 mg) be switched to prescription-only? • Strong yes: 8 • Yes: 18 • No: 11

38. Acetaminophen • Question: Do you recommend pack size limits for OTC products? • Strong yes: 2 • Yes: 15 • No: 20 • Question: Should OTC combination products be eliminated? • Strong yes: 2 • Yes: 11 • No: 24

39. Acetaminophen • Question: Should only one concentration of OTC liquid be available? • Strong yes: 19 • Yes: 17 • No: 1 • Question: Should prescription combination products be eliminated? • Strong yes: 10 • Yes: 10 • No: 17

40. Acetaminophen • Question: Should all prescription combination products be blister-packed? • Strong yes: 5 • Yes: 22 • No: 10 • Question: Should there be a boxed warning on prescription combination products? • Strong yes: 25 • Yes: 11 • No: 1

41. Opioid Risk Evaluation and Mitigation Systems (REMS) • The FDA Amendments Act of 2007 gave FDA authority to require that drugs and biological products have a REMS to insure that the benefits of drug or product outweigh the risks • FDA has been requiring this more often • Now considering applying this to long-acting opioids

42. Why a REMS for Long-Acting Opioids? • Perception is that there have been massive increases in abuse of these medications • Perception is that there have been many overdose deaths due to this abuse • Considerable pressure being exerted by Congress to do something about this

43. What Might a REMS for Long-Acting Opioids Look Like? • Might require registration of prescribers, pharmacies, and patients • Might require specific education for prescribers and pharmacists • Might restrict outlets for medications • Might require ongoing evaluation of effects of REMS

44. Why is This a Concern? • Research shows that any barrier to prescribing opioids results in significant decrease it their use, regardless of the appropriateness of that use • Example: Triplicate prescription forms • Provides an easy way for providers to “opt out” of prescribing • People with pain already have major issues in accessing appropriate care • The chilling effect of REMS may worsen this

45. What Has FDA Done So Far? • Series of meetings with Pharma and pain advocacy groups • Series of public meetings • Many discussions individually with pharma companies • Threatened to withdraw all opioids from the market • Established a REMS for a new short-acting opioid analgesic

46. Onsolis REMS • Onsolis is a BEMA (bioerodable mucoadhesive) product containing fentanyl • Adheres to inside of cheek and dissolves, releasing fentanyl into the bloodstream • Works very rapidly and does not require the patient to swallow • Occupies a niche in pain management that is similar to two existing drugs, Actiq and Fentora

47. Onsolis REMS On July 16, 2009, FDA approved Onsolis to manage breakthrough pain in cancer patients, with a REMS

48. Onsolis REMS • REMS requires: • Prescribers, pharmacies, and patients must register with the manufacturer • Registration program will provide educational materials to prescribers and pharmacies • Patients will receive a counseling phone call prior to dispensing • Only participating pharmacies will fill prescriptions, which must be mailed to patients’ homes • Boxed warning: no use for migraine, dental pain, postoperative pain, or in patients not using opioids continuously

49. Onsolis REMS • FDA says this REMS is specifically tailored to Onsolis and should not be viewed as a model for long-acting opioids • Still, it contains many of the elements discussed for long-acting opioids • Evaluation of effects of this REMS is not mentioned in the press release

50. DEA: ePrescribing • DEA has undertaken a rule-making process designed to allow for the electronic transmission of prescriptions from prescriber to pharmacy • Proposed rule first issued June 27, 2008