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DATE IMPORTED:December 22, 2017Cataldo Ambulance medics John Gardner (L) and David Farmer care for a man in his 40's who was found unresponsive after overdosing on an opioid in the Boston suburb of Salem, Massachusetts, August 9, 2017. The victim received a total of 12mg of naloxone. Nurses at the hospital recognised the man, saying he was brought in the day before after overdosing. REUTERS/Brian Snyder
Up Front

Evidence for addressing the opioid epidemic: Rounding out the picture



Colleen Barry

Fred & Julie Soper Professor - Johns Hopkins University

Richard Frank

Margaret T. Morris Professor of Health Economics in the Department of Health Care Policy - Harvard Medical School

Drug overdoses killed over 70,000 people in 2017 and about two-thirds of those deaths were attributable to opioid overdoses. The opioid epidemic has enlisted researchers from economics, drug policy, sociology, statistics and public health among others to establish what works in addressing the staggering toll of the epidemic. Evidence based on research designs that offer strong causal inferences are essential. Federal, state and local governments have mobilized resources aimed at reducing the misuse of prescription opioids, stemming the flow and lethality of illicit opioids, preventing deaths from overdoses and expanding the availability of effective treatments. Because the severity of the epidemic demands immediate action even in the absence of complete evidence, policymakers are making bets based on available information. These open up opportunities to learn and to adjust strategies based on evaluation results. In this paper, we assemble evidence from a broad range of disciplines that touch on strategies to stem the opioid crisis. Specifically, we address two concerns. The first is that rigorous evidence on the impact of interventions aimed at attenuating the social costs of opioid misuse is produced by a variety of scholars from fields beyond economics and those contributions have been overlooked in recent reviews.[1] The second is that without incorporating an understanding of the diseases and the institutional contexts, rigorous research designs will yield misleading evidence. In assembling the evidence we review below, we focus primarily on results from evaluations that use quasi-experimental research designs and more clinical studies that used controlled randomized experiments. In some cases we refer to modeling studies, and they are identified as such.

Curbing Supply of Illicit Drugs: Illicit opioids are consumer goods and supply control policies seek to disrupt the illegal markets. The existing evidence shows that enforcement of drug laws serves to increase the price of opioids like heroin[2], and those higher prices result in reduced harms.[3] The evidence also indicates that incarceration of people involved in illicit drug markets is highly inefficient. There is some evidence that shows that intervening to disrupt the input of chemicals used in the production of synthetic illicit drugs can be effective.[4] This offers a basis for efforts to disrupt the flow of input chemicals for fentanyl that accounts for nearly all the recent growth in opioid deaths.

Altering Access and Relative Prices: By reducing the potential for diversion of prescription opioids through strong monitoring,[5] taking actions to raise the price of drugs like heroin and by promoting “abuse deterrent” formulations, policymakers try to affect both the supply and demand of opioids subject to misuse. Some studies suggest that there can be unintended consequences when a subset of a family of opioid products is targeted for intervention. Recent analyses highlight the substantial substitutability across opioid products (legal and illicit).[6] For example, the introduction of abuse deterrent Oxycontin has been shown to increase the demand for heroin.[7] The expanded availability of relatively lower priced fentanyl has increased the use of that drug and the lethality of opioids.[8] In contrast, crackdowns on so-called ‘pill mills’ significantly reduced misuse of prescription opioids. Evidence for the impact on heroin is mixed. One study showed a very small increase in the use of illicit drugs, like heroin.[9]  Another study reported a decline in heroin overdose mortality.[10] The implication is that the net impact is context and delivery channel specific.

Identifying Safer Alternatives for Managing Chronic Pain: Overprescribing of opioids for treating chronic non-cancer pain has been a main driver of the opioid crisis. Thus, encouraging non-opioid pain treatment alternatives may reduce the excessive prescribing of opioids and their misuse and overdose. A recent review[11] identified medical cannabis laws as offering a promising alternative to pain control, based on two policy evaluations.[12],[13] Those two studies and other similar work[14],[15],[16],[17] have limitations that should introduce caution in seeing medical cannabis as a good bet for reducing overdoses or improving pain management.[18] The studies used correlations from general population samples to study a hypothesized substitution of cannabis for opioids among only those with chronic non-cancer pain diagnoses.[19] The basic clinical evidence does not support optimism about the proposed mechanism. A 2017 National Academy of Medicine report[20] concluded that there were some potential clinical benefits of cannabis for pain, but a 2018 Cochrane review[21] found no high quality clinical studies on the topic. In addition, medical cannabis laws were enacted amid a flurry of state policy activity aimed at curbing the epidemic, and existing studies have not teased apart these policy effects.  Beyond cannabis, the National Institutes of Health is investing in developing non-addictive pain medicines[22] and emerging evidence supports other promising approaches, including non-pharmacological, non-opioid analgesic, interventional and neural-stimulation, and biofeedback treatments.[23]

Expanding Evidence-Based Treatment: Prior work assessing the evidence on policy levers to combat the opioid crisis[24] paid insufficient attention to the critical role of medication treatment for opioid use disorder (OUD).  A large experimental evidence base indicates that FDA-approved medications to treat OUD—methadone, buprenorphine, and extended release naltrexone—are effective and save lives.[25],[26],[27],[28],[29],[30],[31] Yet, most people who could benefit from these medications do not get them. Paying attention to the barriers to medication treatment is important for designing responses to the epidemic.  Only 36 percent of specialty substance use disorder treatment facilities in the U.S. provided any of the FDA-approved medications in 2016, up from 20 percent in 2007, and rates of offering methadone (~10 percent) were unchanged over these ten years.[32] Only six percent provided all three medications. Offering a choice of medications is critical to patient-centered care, because each medication has different attributes that matter for different patients. Options to address the large treatment gap include removing regulatory barriers in general medical settings by allowing prescribing of methadone in primary care[33] and strengthening incentives for physicians and other professionals to become buprenorphine-waivered and build sizable patient panels.

Research points to other promising avenues to close treatment gaps. Medicaid is the single most important insurance source covering an estimated four in 10 nonelderly adults with OUD,[34] and research is emerging on the impact of Medicaid expansion in 36 states and in Washington, DC on increasing insured rates,[35] improving medication treatment rates[36] and reducing crime[37] among individuals with OUD.  Medicaid expansion has also created unprecedented opportunities for improving treatment for individuals with OUD returning to the community following incarceration, a period which is at high risk of drug overdose mortality.[38] Only one in 20 people referred through the judicial system to specialty treatment for OUD receive methadone or buprenorphine.[39] Medication is rarely offered in corrections settings, but research indicates that forced methadone withdrawal upon arrest lowers the likelihood of resuming methadone following release,[40] and funding medication treatment during incarceration reduces mortality after release.[41]

Encouraging Harm Reduction: Harm reduction refers to interventions to minimize the negative health, social, and economic consequences of drug use for people unable or unwilling to stop using drugs. Such interventions include naloxone distribution, syringe services, safe consumption sites, and anonymous fentanyl testing, among others. Naloxone is a quick-acting medication to reverse the respiratory effects of overdose. One working paper cited in a recent review[42] concluded that naloxone distribution policies may increase mortality by keeping drug users alive (mechanically correct) to continue using and by reducing the consequences of opioid misuse, thereby encouraging it. We have described our concerns with the quality of the evidence in that paper elsewhere.[43] Perhaps most revealing is that quasi-experimental studies that actually measured the use of naloxone (as opposed to internet searches) have produced contradictory evidence showing net decreases in mortality. [44],[45],[46],[47], [48],[49] Modeling exercises[50] based on evidence reviews and observations of practice suggest that these policies save lives and should be part of a comprehensive policy response.

A robust clinical literature and abundant learning from program implementation  including reviews by the World Health Organization and the United Nations supports the notion that syringe services programs, which provide sterile equipment to injection drug users, are safe and reduce blood-borne infections,[51], [52],[53],[54] and can save money in averted treatment costs.[55],[56] An unpublished economics working paper, the only syringe services citation referenced in a recent review,[57] found evidence of a large decrease in HIV diagnoses and increased rates of opioid-related mortality and hospital admissions in counties that introduced new syringe services programs relative to counties with existing programs.  Given the broader literature,  we would argue that it is jumping the gun to argue that the net effects of syringe services programs are welfare reducing on the basis of this one study.

Safe consumption sites (SCSs) where individuals can use pre-obtained drugs under medical supervision are operating in Canada and Western Europe, but not legally sanctioned in any jurisdiction in the U.S. Published[58],[59],[60],[61] and unpublished[62],[63] systematic reviews have assessed effects in non-U.S. sites on overdoses, crime and injection material disposal. No randomized controlled trials have been published, and we agree with the bottom line of the recent RAND review[64] that scientific evidence is limited in the number of high quality studies and locations studied. We also agree with the RAND assessment that estimating the overall effect of SCSs on overdoses is challenging and that published studies are from a time period and locations where the heroin supply was not adulterated with fentanyl, making the analyses somewhat less relevant to the current state of the U.S. epidemic. Likewise, research is just emerging assessing drug testing technologies (i.e., test strips versus machine detection) and demand for fentanyl testing among drug users.[65] This early work reveals a high degree of motivation among drug users to avoid (rather than seek) fentanyl and to modify drug consumption behavior if fentanyl is identified. Fentanyl testing could also improve real-time public health surveillance. We view pilot efforts to advance and study safe consumption sites and fentanyl testing as warranted given the scale of the crisis.

Conclusion. Useful evidence and evaluations relevant to addressing the opioid crisis comes from many quarters. Strong methods are important for making good policy bets, but so too, is understanding basic facts about diseases, the ways in which they are treated, how programs and policies work on the ground and how hard identification of causal mechanisms can be even for clever researchers.

Our aim in this discussion was to contribute to an expanded appreciation of what is known and what is less certain about key policy parameters for making policy to end the opioid crisis. Having participated in policymaking about the opioid epidemic, we have come to appreciate the considerable levels of uncertainty that even well designed studies carry, because they are often context specific, operate in dynamic environments where revelation of mechanisms can be less clear to those designing policies, and affect people’s lives more than skilled and enthusiastic researchers often like to believe. For those reasons, triangulation across multiple sources of evidence, appreciation of policy contexts, and common sense must come together to advance evidence-informed policy.


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[4] Cunningham JK, LM Liu, R Callaghan; Impact of U.S. and Canadian Precursor Chemical Regulation on Methamphetamine Purity in the United States, Addiction 104:441-453, 2009

[5] Numerous studies of Prescription Drug Monitoring Programs have been published in a variety of outlets. Several from the economics literature were cited by Doleac and colleagues in the recent Brookings review. Also, see for example, Meara E, Horwitz JR, Powell W et al. State Legal Restrictions and Prescription-Opioid Use among Disabled Adults. 2016 Jul 7;375(1):44-53; Patrick SW, Fry CE, Buntin MB.  Implementation Of Prescription Drug Monitoring Programs Associated With Reductions In Opioid-Related Death Rates. Health Affairs. 2016 Jul 1;35(7):1324-32; Bao Y, Pan Y, Taylor A, et al. Prescription drug monitoring programs are associated with sustained reductions in opioid prescribing by physicians. Health Affairs. 2016;35(6):1045-1051; Wen H, Schackman BR, Aden B, Bao Y. States with prescription drug monitoring mandates saw a reduction in opioids prescribed to Medicaid enrollees. Health Affairs. 2017;36(4):733-741; Haffajee RL, Mellow MM, Zhang F, Zaslavsky AM, Larochelle MR, Wharam Jf (2018).  Four states with robust prescription drug monitoring programs reduced opioid dosages.  Health Affairs.  2018.  37(6): 964-974.

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[11] Doleac and colleagues.

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The authors did not receive any financial support from any firm or person for this article or from any firm or person with a financial or political interest in this article. They are currently not an officer, director, or board member of any organization with an interest in this article.

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