Testimony of Sidney Wolfe, M.D. Health Research Group of Public Citizen FDA Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products Advisory Committees Opioid Risk Mitigation: May 4, 2016 (I have no financial conflict of interest)

Is the rest of the world wrong, but the U.S. right about massive opioid use? Is it any wonder that the CDC has found “In 2014, more than 14,000 people [in the U.S.] died from overdoses involving prescription opioids.” According to the UN-associated International Narcotics Control Board’s 2015 report, Narcotic Drugs (also source for data on the next slide), the U.S. leads the world’s 168 countries in the consumption of defined daily doses (DDD) of all schedule II opioids per million people per day: 50,142 such doses/million population per day, more than one daily dose for every 20 people in the U.S. Narcotic Drugs: Publication of INCB, 2015: Table XIV.1.a

DDD of total Schedule II Opioids (average for ) for 168 Countries U.S. 50,142 DDD/million people/day (1 of 20) With average ‘11-’14 U.S. Population 314 million, average # of U.S opioid doses per day= 15.7 million for entire population, though most don’t use opioids Canada 30,540 DDD/million people/day Germany 26, <25,000 all other EU countries (< 1 of 40) 141 < 5,000 (< 1 of 200) 129 < 2,500 (< 1 of 400) Narcotic Drugs: Publication of INCB, 2015: Table XIV.1.a

International Changes in average total annual DDD: to Worldwide: increase of 4.33 billion, from 3.01 in ‘01-’03, to 7.35 billion total DDD/year in U.S. : Increase of 2.74 billion, from 2.27 to 5.02 billion Thus, the interim increase in US opioid prescribing is larger than the combined increases in the entire rest of the world, making up 63% of the entire 10- year world-wide increase. Berterame, et al. Lancet 2016; 387: 1644–56

Age-Standardized Rates of Cancer (Cancer ASR) Berterame, et al. Lancet 2016; 387: 1644–56

Conclusions from previous study “Much of increased usage that has occurred in high-income countries is probably partly due to long-term prescribing for non-cancer pain.” “..the absence of real growth in use in most of the world shows a continuing absence of provision of these essential medicines.” Berterame, et al. Lancet 2016; 387: 1644–56

July 2010 AC Meeting: Industry-Proposed Opioid REMS “the individual components of the REMS are insufficient to address the misuse and abuse of ER opioid analgesics.” (25/35 agreed) Members “stressed the need for appropriate and adequate legislation to further the collaboration with other federal agencies since voluntary training and education efforts have not worked.” “the failure can be put at the feet of the continued role of the drug companies in providing education about pain management...many people around this table were concerned that the educational message was biased by the role of industry.”

Experiment to test physician choices as a function of patient requests With increasing DTC advertising, even though not for opioids, patients are more likely to request other drugs as well, having been generally “activated” by such advertising. 198 primary care physicians in six states were shown videos of patients presenting with sciatica, either passively requesting pain relief or actively requesting oxycodone. McKinlay et al. Med Care April ; 52(4): 294–299

Effect of nature of patients’ pain med request-- presenting with sciatica-- on physicians’ choices of analgesic McKinlay et al. Med Care April ; 52(4): 294–299

Conclusions Key decision-makers in the unacceptable U.S epidemic of opioid misprescribing, abuse and death are physicians, too often influenced by opioid industry- funded “education” and promotion. Whereas many prescribers are appropriately cautious, not contributing to the epidemic, too many are a complicit cause. If opioids were no more dangerous than other drugs, why do they require a narcotics license to prescribe? What more needs to be done? Mandatory training and testing to get a narcotics license, with as little opioid industry involvement as possible. Legislation is needed.