Opioid Use: What are the technological, clinical, ethical, and regulatory issues? Michael Von Korff Group Health Research Institute

Population Prevalence (%) of Chronic Opioid Therapy Group Health Cooperative & Kaiser N California Chronic Opioid Therapy: 90 days & > 10 Rx fills and/or > 120 days supply Persons with cancer excluded Over 8 million U.S. adults now receive COT for Chronic Non-Cancer Pain receiving over 85% of the morphine equivalents dispensed for acute or chronic pain Boudreau et al, Pharmacoepi Drug Safety, 2009

Increased diversion, abuse of prescription opioids and opioid-related emergency room visits were evident in drug abuse surveillance systems by the late 1990’s Early Warning of Opioid-Related Problems Through Community Surveillance Community-based surveys of COT patients find widely varying risks of addiction (4 to 26%). Risks of serious opioid misuse among COT patients are more common than addiction COT patients on higher doses receive a large share of all opioids dispensed for acute or chronic pain on a population basis: |  60% goes to patients receiving a daily dose of 50 + mg. MED  40% goes to patients receiving a daily dose of mg. MED

Source: CDC Unintentional Drug Overdose Deaths By Specific Drug Type, United States, Prescription Opioid 1999= 4,041 Drug Overdose Deaths 2006 = 13,755

Opioid Overdose Risk by Average Daily Dose of Medically Prescribed Opioids Opioid Overdose Hazard Ratio (& rate per year) Average Daily Opioid Dose in Morphine Equivalents 1.8 % 0.7 % 0.3 % 0.2 % 9-fold increase in risk relative to low-dose patients (non-fatal and fatal overdose ascertained from health plan records) Dunn et al., Annals Int Med, 2010 ** ns ** p<0.05

Opioid-Related Overdose Mortality: Odds Ratios by Dose Bohnert et al., JAMA, 2011 ** ns Gomes et al., Arch Int Med, 2011 ** p<0.05

Concurrent Opioid & CNS Depressant Use by Substance Abuse History NO SUBSTANCE ABUSE HX SUBSTANCE ABUSE Hx (N=1180) (N=675) Concurrent Concurrent Concurrent Concurrent Alcohol Use Sedative Use Alcohol Use Sedative Use 12.5 % 28.8 % 11.9 % 39.6 % Concurrent sedative use = Taking sedative-hypnotics on more than half the days in the past 90. Concurrent alcohol use = Having two drinks or more within two hours before or after taking opiate medicine (in past 2 weeks) COT patients using opioids every day in the past 2 weeks Saunders et al., paper under review Both = 3.1 %

Fracture Risk by Average Daily Dose of Medically Prescribed Opioids: Persons Age 60+ Fracture Hazard Ratio (& rate per year) Average Daily Opioid Dose in Morphine Equivalents 10.0 % 7.0 % 5.7 % 3.8 % 2-fold increase in risk relative to non-users (Fractures ascertained from health plan records) Saunders et al., JGIM, % were hip or pelvis fractures 37 % were hospitalized within 2 days of fracture 24 % were admitted to a nursing home or PCF within 1 month of fracture

Substance abuse Overdose Serious fractures Myocardial Infarction Neuroendocrine dysfunction Exacerbation of sleep apnea Immunosuppressive effects Serious fecal impaction Dry mouth causing dental problems Potentially Serious Adverse Effects of COT Inadequately Studied

Use of Opioids to Manage Chronic Non-Cancer Pain: Where do the Best Interests of Patients and Society Lie? Compassionate, evidence-based treatment of chronic pain Patient safety: “Do No Harm” Societal rights to control drugs that are abused