Historical Context

Opioids have been used for medicinal and recreational purposes for millennia. While the use of opioids for treatment of acute severe pain has generally been accepted, their use for managing chronic noncancer pain has been controversial since the 19th century, with the popular view shifting over the decades between broad acceptance and a more restrictive perspective (Rosenblum et al., 2009). The tension between the desire to make opioids available to those who may benefit from them and the recognition that opioids are addictive drugs with societal consequences began with medical developments that occurred during the 1800s (Booth, 1986; Musto, 1999; Rosenblum et al., 2009). These developments included the extraction of morphine from opium in 1803 and the development of the hypodermic needle (which can be used to inject morphine to relieve neuralgic pain) in the 1850s (Rosenblum et al., 2009). Morphine was used widely for pain management during the American Civil War, and many soldiers developed OUD. With few effective alternatives, moreover, many medical professionals used morphine to treat chronic pain conditions. This and the nonmedical use of opioids were major drivers of an opioid addiction epidemic that took place in the latter 19th century (Courtwright, 2015).

By the late 1800s, scientists were starting to recognize the problem of OUD, and a policy response began to emerge. What is thought to be the first accurate and comprehensive description of addiction to morphine was produced in 1877. In hopes of developing a less addictive alternative to morphine, heroin (diacetylmorphine) was synthesized in 1874 (although it was later found to be more potent than morphine) (Rosenblum et al., 2009). Medical professionals became increasingly critical of the use of opioids to treat pain and lobbied successfully for state and local laws to control the sale of opioids and other narcotics. Consumption of medicinal opioids declined as a result (Courtwright, 2015).

Reform efforts continued in the early 20th century. The Harrison Narcotics Act, enacted by Congress in 1914, required persons who imported, produced, sold, or dispensed opium-based drugs (as well as coca-based drugs) to register, pay a tax, and keep detailed records that officials could use in enforcing laws to restrict opioid transactions to legitimate medical channels. This act had the effect of criminalizing the use of opium for nonmedical purposes (Courtwright, 2015; Hoffman, 2016).³ The use of heroin for medicinal and other purposes was specifically banned by the Heroin Act, enacted by Congress in 1924.

The consensus among medical professionals for most of the 20th century was that opioids should not be used for the management of chronic pain because of the lack of evidence regarding their effectiveness for this type of pain and the risk of OUD (Rosenblum et al., 2009). Research aimed at developing new and potentially less addictive opioids continued, however, and Percocet and Vicodin—which combined semisynthetic opioids with acetaminophen—became available in the 1970s for relief of moderate to moderately severe pain. These and most other prescription opioids are now regulated under the Controlled Substances Act (CSA) of 1970 as Schedule II drugs—those with a “high potential for abuse which may lead to severe psychological or physical dependence” (DEA, 2017b).⁴

Liberalization of Prescribing in 1990s

Medical practice in the United States began to shift markedly toward more liberal use of opioids for chronic noncancer pain following the development and marketing of new formulations of opioid drugs in the 1990s (Compton and Volkow, 2006; Rosenblum et al., 2009). As noted earlier, in 1995 the FDA approved OxyContin (oxycodone controlled-release), which allowed dosing every 12 instead of every 4 to 6 hours (FDA, 2017c). The drug's manufacturer (Purdue Pharma) marketed it aggressively to providers and patients in the years following its release to the market in 1996. Purdue claimed in some of its promotional materials that the risk of addiction to the drug was small (Van Zee, 2009).

Around the same time, there was growing recognition in the medical community that many individuals with chronic pain were being treated inadequately (Pokrovnichka, 2008). In 1996, the American Academy of Pain Medicine and American Pain Society issued a joint consensus statement titled The Use of Opioids for the Treatment of Chronic Pain, describing potential benefits of using opioids for management of chronic (including noncancer) pain (Haddox et al., 1997; Hoffman, 2016). Advocates representing the interests of pain patients suggested that pain be considered a “fifth vital sign” in an effort to improve pain assessment and treatment (Campbell, 1996), and some health care organizations incorporated this concept into guidelines and clinical practice (Mularski et al., 2006). There were also concerted efforts by pain specialists to persuade state medical boards and state legislatures to remove legal impediments to medically accepted pain treatment (Hoffman, 2016).⁵ This shift in professional understanding was accompanied by a public campaign to call public and professional attention to the prevalence of pain and its seriousness as a public health problem.

Congress declared 2001–2011 the “Decade of Pain Control and Research” (Brennan, 2015). The 2010 Patient Protection and Affordable Care Act (ACA) directed the U.S. Department of Health and Human Services (HHS) to work with the IOM to increase recognition of pain as a public health problem (IOM, 2011). In response, HHS, through the National Institutes of Health (NIH), commissioned an IOM committee to review the science on pain and recommend actions to advance the field. The resulting report, Relieving Pain in America, provided a blueprint for “transforming the way pain is understood, assessed, treated, and prevented” (IOM, 2011, p. 2).

In the context of Purdue's substantial promotional expenditures and these changing professional attitudes, sales of OxyContin rose from $48 million in 1996 to more than $1 billion by 2000 (Van Zee, 2009). Sales of prescription opioids are estimated to have quadrupled between 1999 and 2010 (CDC, 2011), driven in part by OxyContin during the early portion of this period (GAO, 2003). However, problems began to emerge around 2000, with reports of widespread diversion, tampering, and misuse of OxyContin (Cicero et al., 2005; GAO, 2003; Hoffman, 2016). In response, the FDA changed the OxyContin label in 2001 “to add and strengthen warnings about the drug's potential for abuse and misuse” and in 2003 issued a warning letter to the manufacturer regarding promotional materials that omitted and minimized the drug's safety risks (FDA, 2017c).⁶ The U.S. Drug Enforcement Administration (DEA) prosecuted many physicians for illegal distribution of OxyContin (Hoffman, 2016).⁷

Nonetheless, sales of prescription opioids continued to increase (Pan, 2016). Data from the National Prescription Audit show that the number of opioid prescriptions dispensed from U.S. outpatient retail pharmacies for all approved and marketed ER/LA and some of the most common IR opioid analgesics grew from 148 million in 2005 to 206 million by 2011. Opioid dispensing during this period was driven primarily by IR opioids (which work quickly and often are prescribed for short-term, intermittent, or “breakthrough” pain) rather than ER/LA opioids such as OxyContin (see Figure 1-1).⁸ Sales of OxyContin increased from just over $1 billion in 2000 to $1.84 billion in 2003 and then declined in the wake of the FDA actions described above until 2006, after which there was another increase in sales until 2010 (Public Citizen, 2007).

FIGURE 1-1

Nationally estimated number of prescriptions dispensed for extended-release/long-acting (ER/LA) and selected immediate-release (IR) opioid analgesics (oral solids and transdermal products) from U.S. outpatient retail pharmacies, 2005–2015. *ER/LA (more...)

Public Health Consequences

During the years coinciding with the growth in opioid prescribing, the United States experienced an increase in deaths from opioid overdose and in admissions to treatment associated with opioid use. According to CDC data, there was a 1.9-fold increase in the total number of deaths from prescription opioids (excluding nonmethadone synthetics) between 1999 and 2011 (see Figure 1-2). While the number of overdose deaths from prescription opioids remained relatively stable between 2011 and 2015, overdose deaths from illicit opioids (e.g., heroin and synthetic opioids such as fentanyl) continued to increase, related in part to a growing number of people with OUD in connection with prescription opioids. Overdose deaths from illicit opioids increased rather steadily during 1999 to 2015, growing 6.4-fold over that period (see Figure 1-2). Poisoning, driven largely by opioids, became the leading cause of death due to injury in the United States in 2008, surpassing motor vehicle crashes (Warner et al., 2011). The annual incidence of hospitalization for prescription opioid poisoning among children and adolescents aged 1–19 increased 165 percent (from 1.4 to 3.7 per 100,000) between 1997 and 2012 (Gaither et al., 2016). Between 2003 and 2013, the proportion of admissions to treatment associated primarily with nonheroin opioid use and heroin use increased from 3 to 9 percent and 15 to 19 percent, respectively (SAMHSA, 2015).

FIGURE 1-2

Number of overdose deaths from prescription and illicit opioids, United States, 1999–2015. SOURCE: NCHS, 2016.

International Context

Historically, the United States has consumed a large majority of the world's supply of opioid drugs. An older figure that continues to be cited is that approximately 80 percent of the world's supply of opioid drugs is consumed in the United States (Manchikanti and Singh, 2008). According to another estimate, 90 percent of the world's supply of morphine, fentanyl, and oxycodone was used in the United States, Canada, Australia, and New Zealand in 2009, and in that same year, the United States consumed 83 and 99 percent of the world's oxycodone and hydrocodone, respectively (Hauser et al., 2016). Based on available data (UNODC, 2017), other countries, including Mexico and countries in Central and South America, Africa, and Asia, appear to have a considerably lower prevalence of past-year use of both prescription and illicit opioids, although this does not necessarily mean that these countries are free of problems related to opioids.

Consumption of opioid drugs has increased globally since the 1980s. Data indicate that in more recent decades, increases in consumption have been highest in the United States and to a lesser extent in other industrialized nations. For example, during 2000–2010, opioid consumption increased 400 percent in the United States, compared with 65 percent in Great Britain and 37 percent in Germany (Hauser et al., 2014). In Australia, where the prevalence of opioid use also is high, opioid dispensing increased nearly four-fold between 1990 and 2014 (from 4.6 to 17.4 defined daily doses/1,000 population/day) (Karanges et al., 2016). Spain saw a 14-fold increase in opioid daily doses between 1992 and 2006 (Garcia del Pozo et al., 2008).

The responses in countries experiencing high rates of opioid misuse, OUD, and opioid overdose have varied. Some are noteworthy for their public health orientation. In the Canadian province of British Columbia (Canada has the second highest rate of opioid consumption after the United States), harm reduction strategies implemented to reduce opioid overdose included making the opioid overdose reversal drug naloxone available outside of pharmacies without a prescription and opening supervised injection facilities (SIFs) (British Columbia was the first region in North America to open a SIF, in 2003) (Voon, 2016). The British Columbia Ministry of Health also issued guidelines for the clinical management of OUD to foster improved linkage to medically supervised treatment (Dunlap and Cifu, 2016). SIFs, which have been found to be associated with reductions in syringe sharing and overdose fatality (Kerr et al., 2005; Marshall et al., 2011), are operating as well in several other countries that have experienced significant opioid misuse problems, including Spain, Australia, and Germany, and are now being considered in the United States.

Some countries have reduced criminalization of drug use, with positive results. Portugal, while not having opioid-related problems at the levels seen in other countries, became the first country to decriminalize the possession and use of drugs in 2001, making these violations administrative as opposed to criminal offenses (Greenwald, 2009). Individuals who are addicted to heroin or other drugs are offered access to treatment, which is widely available through health centers, hospitals, and pharmacies, as well as to needle exchange and other services. Since these changes were implemented, the country has seen more people enter treatment, and HIV transmission rates have declined among injection drug users (EMCDDA, 2016).

The United States' response to the opioid epidemic also has taken on an increasingly public health focus. Examples include efforts to make OUD treatment, naloxone, syringe exchange, and other services more widely available, and the promulgation of guidelines for prescribers that emphasize greater caution in opioid prescribing and recommend referral to evidence-based treatment for patients with OUD. As discussed in this report, these strategies are at various stages of implementation and evaluation.

Statutory Context

Opioid regulation lies at the intersection of two federal statutes, each with its roots in the early 20th century. The first is the Food, Drug, and Cosmetic Act (FDCA), a successor to the groundbreaking Pure Food and Drug Act of 1906, which now requires manufacturers of medical drugs and devices to prove that they are safe and effective for their intended uses before they may be marketed to consumers. The second applicable statute is the CSA, enacted in 1970 as a successor to the Harrison Narcotics Act of 1914, mentioned above. The CSA was designed to provide an overarching framework for tight federal regulation, including both public health oversight and aggressive enforcement, for all drugs with “potential for abuse,” whether or not intended for medical use. Previously, those functions had operated relatively autonomously, with drug development and prescription control under the FDA, and enforcement responsibility originally lodged in the U.S. Department of the Treasury and later transferred to the U.S. Department of Justice (Spillane, 2004). Enforcement duties under the CSA are now exercised by the DEA, but the CSA also retains a significant role for HHS, usually acting through the FDA, in the regulation of controlled substances with medical uses.

The CSA created tiered levels of control and reporting responsibilities based on the potential danger posed by a given drug, and established a structure for coordinating regulatory and enforcement action (Spillane, 2004). The act also was designed to create a “big tent” for all drugs that might be subject to misuse and to explicitly subject such drugs as barbiturates and amphetamines to the same control as narcotics. Each controlled substance is assigned to a specific schedule. Schedule I substances are strictly limited and may be used only in some highly controlled research contexts, if at all. Schedule II substances are subject to production quotas and registry requirements for importers and exporters. Drugs assigned to the lower schedules are subject to progressively diminished levels of control. A controlled substance may be prescribed only for a “legitimate medical purpose” by a practitioner licensed by the DEA “acting in the usual course of his professional practice.” The CSA gives the DEA the power to revoke licensure when a physician is determined to have violated that standard, and offending practitioners may be subject to criminal prosecution.

The primary focus of the CSA was ambiguous from the outset: the Nixon administration saw it principally as a way to control street use of illicit drugs, while its congressional sponsors saw it as a vehicle for limiting overproduction and overprescription of legally marketed drugs based on balancing the dangers of abuse against the health benefits of legitimate medical use (Spillane and McAllister, 2003, p. S8). To its congressional sponsors, the CSA represented a key step in the direction of a national public health approach to drug abuse and addiction. The second step, taken in the Drug Abuse Office and Treatment Act of 1972, established a Special Action Office for Drug Abuse Prevention in the White House and enacted sweeping federal protection of the confidentiality of SUD treatment records that continues to serve as a centerpiece of national policy.

The DEA was created in 1973 to carry out the U.S. Department of Justice's responsibility for enforcing the CSA (Senate Committee on Government Operations, 1973, pp. 5–6). It was believed that making one agency accountable would “maximize coordination between Federal investigation and prosecution efforts.” The new agency was to draw on Federal Bureau of Investigation expertise with organized crime, and to provide a single focal point for enforcement with state, local, and international authorities (Senate Committee on Government Operations, 1973, pp. 5–6). The DEA enforces both the criminal and noncriminal regulatory requirements of the CSA, but it does so as a law enforcement agency; it is not designed to function as a public health agency, nor does it pretend to be one (DEA, 2017a).

Over the four and a half decades since its passage, the CSA has been amended many times, usually to increase law enforcement authority. The Comprehensive Crime Control Act of 1984 and the Anti-Drug Abuse Acts of 1986 and 1988 added provisions to deal with synthetic compounds and new enforcement mechanisms, such as forfeiture provisions, and introduced mandatory minimum sentences. The Illicit Drug Anti-Proliferation Act of 2003 amended the CSA to deal with MDMA (3,4-methylenedioxy-methamphetamine, or ecstasy) and other club drugs. The Ryan-Haight Act of 2008 amended the CSA to regulate online pharmacy distribution. The Secure and Responsible Drug Disposal Act of 2010 requires the DEA to establish programs for voluntary disposal of controlled substances that are no longer required by patients. And the Synthetic Drug Abuse Prevention Act of 2012 not only mandated restrictive scheduling for various synthetic drugs but also streamlined the scheduling process so that newly approved drugs could enter the market more quickly.

Among the many important issues that have surfaced during the opioid crisis are whether the public health goals of the CSA envisioned by its architects have been achieved, and whether regulatory activities carried out by the FDA and the DEA under the FDCA and the CSA have been suitably coordinated and harmonized. One issue of particular interest in the context of this report is surveillance. As a key component of its public health aims, the CSA mandated the collection of epidemiologic data on use and abuse of the drugs controlled by the act and on other substances that might warrant control. The first such effort, the Drug Abuse Warning Network (DAWN), created in 1972 and discontinued in 2011, revealed a problem that continues to this day: it is difficult to break down the data by specific drug products (Mansbach et al., 2010; Spillane, 2004), which is essential to determining the nature and level of misuse for specific substances. The discontinuation of DAWN in 2011 left a substantial gap in the nation's capacity to monitor, anticipate, and respond to the opioid epidemic as it unfolded.

Recent Federal Policy Initiatives

As noted above, the IOM's 2011 report Relieving Pain in America highlighted the public health significance of pain and the need for fundamental changes in pain policy and practice (IOM, 2011). The report details the landscape of pain in the United States of that time, including such key factors as its overall prevalence; its personal, economic, and social consequences; and the significant shortcomings of prevailing treatment approaches. The report also describes the status of some of the available pain treatment approaches, including pharmacologic options, injection-based interventions, surgery, rehabilitative strategies, psychological therapies, and complementary modalities. The report presents highlights of then-current knowledge about pain mechanisms and the impact of interacting comorbid conditions such as depression, anxiety, and SUD, as well as areas in which knowledge was critically lacking. While the report ably describes the contemporary state of the art, however, important advances have since occurred on many fronts.

One element of this committee's charge was to “provide an update on the state of the science of pain research, care, and education since the 2011 report and characterize the evolving role of opioid analgesics in pain management,” a task that the committee carries out in several chapters of this report. The subsections below summarize three major federal policy activities related to pain management and opioids that have taken place since the 2011 report was published and that provide additional context for the present study: the ongoing formulation of a National Pain Strategy, promulgation of a guideline for opioid prescribing under the auspices of the CDC, and ONDCP's development of a comprehensive plan for managing the opioid crisis.

Ethical Context

The statement of task for this study (see Box 1-1) directed the committee to recommend policy actions by the FDA and other policy makers that would properly “balance the needs of pain patients and the [societal] need to address opioid misuse.” This deceptively simple statement entails many technical challenges related to measurement quantification that are explored in this report. However, it also exposes a genuine ethical quandary that is fundamental to this entire report: How exactly does a regulator (or this committee) weigh and balance, for any particular regulatory action limiting access to opioids, the otherwise avoidable suffering that patients with pain would experience against the harms, not only to those individuals and their families but also to society, that would be prevented by the restriction? The “societal need to reduce opioid misuse” is particularly challenging in ethical terms because much of the harm to society arising from opioid misuse is attributable to diversion of the prescribed drugs from lawful markets and to the operation of black markets. Are these two sets of needs morally commensurate? Are they convertible to a common metric?

The task is made somewhat easier if one recognizes that the point of contention regarding the use of opioids in serving the “needs of pain patients” focuses almost entirely on treatment of chronic noncancer pain. As long as the quantity prescribed, dispensed, and administered is suitably limited, there is little disagreement about the need for opioids for treatment of patients with acute pain within controlled settings such as hospitals (e.g., the perioperative use of opioids for many types of surgeries), or for treatment of patients with cancer or terminal conditions. The area of dispute concerns long-term use of take-home doses for chronic noncancer pain by people who are not terminally ill.

It is instructive to attempt to operationalize the balancing task at the policy level. On the one hand, the policy maker must quantify or otherwise characterize the aggregate reduction in pain experienced by patients if opioids are prescribed and used for these chronic indications. As discussed in Chapter 2, this is a difficult task because of a lack of data on the effectiveness of opioid therapy for long-term (>1 year) outcomes related to pain, function, and quality of life (Chou et al., 2015; Dowell et al., 2016)—notwithstanding the reported experience of many patients and their providers who believe the drugs are beneficial. On the other hand, policy makers must quantify or otherwise characterize the harms that would not have occurred had prescribing of opioids been more restricted. These harms include death from overdose and other harms to patients who become addicted to opioids in the course of treatment, and importantly, it also includes harms due to the misuse of drugs that have been diverted from lawful channels to people other than the patients to whom the drugs are prescribed.

This policy balance between benefits and harms inevitably involves many uncertain parameters requiring considerable speculation: the numbers of patients with pain who will be affected, the nature and intensity of the pain that will be experienced or mitigated under different sets of assumptions about access to the drugs, and the effect of more or less restrictive regulatory approaches on access to the drugs by persons other than the patients to whom they have been prescribed and the harms that might subsequently occur. Converting all these postulated impacts to a common metric, such as quality-adjusted life years (QALYs), would be one way to proceed, although this approach would require overcoming many technical challenges. Moreover, other outcomes at the societal level might be difficult to quantify, such as the impact of one or another policy on public trust in the medical profession and the health care system. Loss of confidence can arise from perceived overprescribing or perceived underprescribing.

This analytic approach of identifying, quantifying, and balancing relevant outcomes at the societal level is the only way policy makers can think clearly about such a complex issue and make their arguments transparent and open to critical review by others. However, one of the confounding features of the policy discourse on the regulation of opioids and opioid prescribing is that many physicians and patient advocates ground their arguments not in an aggregated balance of benefits and harms at the population level but in the patient-centered ethics of clinical medicine (ethics “at the bedside,” so to speak). When viewed from the perspective of an individual physician and an individual patient seeking treatment for chronic pain, regulations restricting access to opioids may be objectionable because they are perceived as unduly constraining the options available to physicians seeking to alleviate the suffering of each patient under their care. This ethical duty entails making an individualized judgment about each patient's needs, recognizing that the needs of a particular patient may differ from those of the “average” patient experiencing a particular type of pain; that the patient's response to treatment may differ from the “typical” response in relation to both specific risks and potential benefits; and that these effects in any particular case are difficult to quantify, especially when there is so little evidence about long-term use of opioids for chronic noncancer pain. From this perspective, the duty to exercise individualized clinical judgment lies at the heart of the physician–patient relationship. Individualized decision making is all the more important in the context of pain, given its inherently subjective nature, and in the context of the ethical paradigm of shared decision making.

In thinking about the task of balancing the aggregated needs of patients in pain at the societal level and the need to prevent harms associated with misuse of opioid analgesics, the committee was sensitive to the ethical tension between the population perspective of public health and the patient-centered perspective of clinical ethics. The bottom line is that these two perspectives address two different questions. The committee's charge was to answer the societal question: What should the FDA and other government entities do when acting to further society's collective interest? The committee was not charged with asking what physicians and other prescribers should do or what options they should have available for particular clinical indications. This does not imply, however, that the ethics of clinical medicine are irrelevant: the framework used by policy makers in balancing the aggregated needs of patients with pain against society's collective interest in preventing opioid-related harms must be sensitive to the impact of alternative policies on public confidence in the health care system, including trust in the physician–patient relationship.

Study Scope and Emphasis

The breadth of the committee's charge posed several challenges. First, the charge envisioned two fairly distinct tasks—an update of the science of pain research, care, and education since the IOM's 2011 report, including the evolving role of opioids in pain management, and a “new” report summarizing the “state of the science” on the use and misuse of prescription opioids and on approaches for addressing the problem. The committee interpreted its charge as focusing primarily on the misuse of prescribed opioids, the occurrence of OUD, and the associated public health harms, with updates to the 2011 report being limited to those bearing on indications for opioid prescribing, alternatives to opioids for pain management, physician education, and priorities for research.

A second challenge was the multiple audiences for this report. The charge requested that the committee provide advice not only to the FDA but also to other policy makers and stakeholders. The committee understood that the FDA's primary reason for requesting this report was its desire for an expanded framework for review, approval, and monitoring of opioids that would encompass the societal harms resulting from opioid prescribing, and accordingly attempted to develop such a framework. However, the FDA knows it cannot address the opioid problem on its own, and its charge to the committee clearly invited a broader view of the report's intended audience. The committee chose to take this broader view because it was convinced that successful efforts to prevent, ameliorate, and minimize the public health harms associated with use and misuse of prescription opioids will require coordinated action at all levels of government and by a diverse array of stakeholder organizations.

A third challenge was that the committee was charged with addressing a complex, multifaceted problem that can be viewed through many lenses. The approach the committee took to carrying out this charge was shaped by the expertise of the its members and its interpretation of the charge. Accordingly, the committee focused on improving the treatment of pain and on responding to the policy challenges presented by the opioid epidemic. Many other relevant topics could have been included, such as why this epidemic has occurred. However, the committee was not directed to investigate the causes of the prescription opioid problem or to judge how it could have been avoided or ameliorated. Indeed, in its initial conversations with FDA officials, the committee was specifically advised that the purpose of this report was not to place blame for the current state of affairs.

Not surprisingly, however, questions about who bears responsibility for the current situation surfaced repeatedly in the committee's public workshops. Some observers, for example, suggested that the 2011 IOM report underemphasized then-emerging opioid-related harms as it highlighted the prevalence and cost of inadequately treated pain. Other speakers argued that the FDA has not been aggressive enough in its regulatory decisions, while still others directed attention to the systemic failures of the nation's health care system.

Nonetheless, the committee did not aim to assign responsibility for past mistakes. Its task was to review and assess approaches and actions that the FDA and others have taken, and could take, to resolve the problem and prevent such problems from arising in the future. To this end, the committee naturally posits a predictive model concerning what interventions might work. In so doing, it relies on a traditional multifactorial causal model commonly used in public health, encompassing considerations ranging from structural factors to individual susceptibility. Using this approach, certain hypotheses about causes of the epidemic are inescapable. For example, the data presented earlier in this chapter make a prima facie case that heavy promotion of opioid prescribing by drug manufacturers (including misleading claims by some) and substantially increased prescribing by physicians were key contributors to the increase in misuse, OUD, and accompanying harms.

It is also clear, however, that overprescribing was not the sole cause of the problem. While increased opioid prescribing for chronic pain has been a vector of the opioid epidemic, researchers agree that such structural factors as lack of economic opportunity, poor working conditions, and eroded social capital in depressed communities, accompanied by hopelessness and despair, are root causes of the misuse of opioids and other substances and SUD (Carpenter et al., 2016; Compton et al., 2014; Nagelhout et al., 2017). It was beyond the scope of the committee's task to review and offer recommendations for mitigating the effects of these underlying structural determinants of opioid misuse and OUD. Nonetheless, the committee believes it is extremely important to keep these determinants in mind while reading this report, which focuses largely, although not entirely, on the supply side of the equation (increased prescribing of opioids) rather than on the more complex structural and environment factors that contribute to the demand side of the equation.

Report Organization

This report is divided into six chapters. Part I, consisting of Chapters 2 and 3, updates the 2011 IOM report. Chapter 2 describes the scope of the problem of pain in the United States and the state of the science on pain management, with an emphasis on the evolving role of prescription opioids and other forms of treatment in pain management. Areas for future research on pain and its management and on OUD to assist the FDA with the development of a framework for opioid approval and monitoring are discussed in Chapter 3. Part II, consisting of Chapters 4, 5 and 6, characterizes the opioid epidemic and the nation's response to it. Chapter 4 describes the epidemiology of opioid use and misuse, OUD, overdose, and other harms from both prescription and illicit opioids (e.g., heroin). Chapter 5 reviews the evidence regarding the effectiveness of strategies being used to address the opioid epidemic and makes recommendations where indicated. Specific topics covered include regulating the types of products approved for use (e.g., ADFs); restricting legal access to approved drugs; modifying prescribing practices; providing patient education; increasing access to treatment for OUD; and reducing harms from opioid use, such as by providing naloxone to prevent opioid overdose and making clean needles available for injection drug users to reduce transmission of HIV and hepatitis C virus. Finally, based on content presented in earlier chapters, Chapter 6 outlines steps the FDA can take to improve its regulation of opioids, including an approach for improving incorporation of individual and public health risks and benefits into future FDA approval and monitoring of these drugs.