Reviewing the National Academies’ Report on Opioids
Discoveries and Accomplishments; Crimes and Misdemeanors
By far the most important thing to know about the National Academies’ new report Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use is that officials at the Food and Drug Administration (FDA), the sponsor of this study, have yet to indicate whether they will accept its most important recommendation: that the FDA undertake a review of previously approved opioids as an entire class of drugs using a “systems” framework that factors public health and overall efficacy of these drugs into its analysis, rather than follow standard practice of approving new brands on a case-by-case basis.
On one hand, this recommendation should be regarded as conventional, even conservative. We learned from The Los Angeles Times in March 2016 that the FDA approved Oxycontin for 12 hour extended release based upon faulty data. Likewise, numerous accounts describe the aggressive marketing of opioid painkillers to treat chronic pain, none more important than Sam Quinones’ 2015 book, Dreamland. Owing to precedent, as well as to the easier evidentiary burden placed on “reformulated” (as opposed to first-in-class) drugs, opioids are still broadly prescribed for chronic pain, despite a lack of evidence demonstrating that benefits outweigh risks, or that opioid effectiveness endures long enough to be considered an option preferable to other treatments for chronic pain.
In fact, the close-in focus for current FDA opioid approvals leads to absurdities such as the one described in Box 6–1 of the Academies’ report, the “Approval of Zohydro Extended Release” — premised on as single study (conducted on narrow grounds) which found, as the Committee notes parenthetically, that the “overall pains scores of both” the placebo and Zohydro groups “worsened” over the period of study; the trial also saw patients who diverted or hoarded the drug, despite experimental controls to safeguard against these outcomes. Nonetheless, the FDA voted to approve the drug.
In the face of this kind of bizarre commitment to not only perpetuate an initial, careless decision but to carry its logic to an indefensible extreme, it is not surprising that the Committee advises a reassessment. But, on the other hand, it should still be regarded as remarkable, because the National Academies, in general, do not lay the groundwork for volte-face turns in policy debates. Instead their reports typically provide an audit of the political establishment; an expert consensus strong enough to survive critique from special interests, but not necessarily one that endures for the ages. The very process the Academies employs empowers special interests; for example, this report was submitted for review to Penney Cowan of the American Chronic Pain Association, one of a dozen non-profit “front groups” under scrutiny by Senator Claire McCaskill for possible funding from the pharmaceutical industry. Cowan’s superlative credentials notwithstanding, there is no commensurate organized interest skeptical of Pharma — or, in terms of Madison’s Federalist #10, there is no “counter-faction.” Yet the recommendation to review all opioids, including those currently on the market, under a framework that incorporates public health considerations survived intact.
Again, to date, the FDA has issued no indication as to whether they will review all opioids currently on the market, despite the fact that a diverse group of professionals, forced to submit to a process that obliges them to respond to every meritorious counter-argument from industry, found that they should do precisely that.
Other Discoveries & Accomplishments of National Academies’ Report
- The National Academies put forward principles of a “systems framework” to incorporate public health outcomes into approval and other regulatory decisions. The Committee also provides a summary of updates in the science of pain since the 2011 Institute of Medicine report, Relieving Pain in America. Findings of interest to a lay audience include: not only do depression and other related disorders make pain worse, typical depression treatment (SSRIs) can be effective in relieving it. This kind of interplay between mental disorders and the experience of pain helps to shed light on things like poly-substance use as well self-medication, as opposed to casting them as pathologies or weaknesses. Folks actually are in pain — worse than might be expected from a purely physical diagnosis — and they are actually taking things to seek relief.
- Across the board increases in heroin use attracts substantial discussion from the Committee, which notes that:
I’ll return to this second question, but for now let me underscore what is paramount: “A preponderance of evidence suggests that the major increase in prescription opioid use beginning in the late 1990s has served as a gateway to increased heroin use.” It is a relief to me and to many others to see such a definitive statement in print. To put it politely, there has been a lot of motivated reasoning to deny this very connection, and lots of prominent media real estate has been given over to this effort.
- That a powerful pharmaceutical industry supports this “motivated reasoning” makes the Committee’s observations regarding the recent loss of publicly available data sources more alarming. During the Obama administration, the years when the opioid crisis grew to become the worst drug epidemic in US history, four publicly-funded data sources were “phased out.” In their place came proprietary data systems; RADARS, one of the best known, came from Purdue Pharma directly. Pharmaceutical clients use these systems extensively, presumably for risk-monitoring, but in a terse statement the Committee noted that “they have not been widely used by health practitioners and researchers.”
- Finally, in the face of a treatment landscape which I often analogize as the “Wild West,” it’s critical to note that Academies’ review of studies that examine treatment programs found that good results achieved using Medication-Assisted-Treatment (MAT) stand up regardless of whether paired with therapy or not. At this point, the evidence places a burden on those programs not offering MAT as a core component of treatment. Meanwhile, in practice, only a small fraction of those in treatment for Substance Use Disorder receive it. The deficit between the need for MAT and its actual dispensation is one measure of our continued complicity in perpetuating the worst drug crisis in US history.
The Sins of the Report: Commission and Omission
The public discussion regarding the over-exposure of the American public to opioids is not as informed as it could be or should be. Unfortunately, the National Academies’ panel does little to clarify that story, and in fact they seem somewhat confused about it themselves.
I am at a loss to explain why the panel omits any mention of the fact that the Drug Enforcement Agency (DEA) sets Aggregate Production Quotas (APQs) for licit (registered) opioid producers and manufacturers every year. Other aspects of the DEA’s work come in for discussion, and the Committee’s charge encompasses the work of other agencies; indeed, they offer several recommendations which apply to agencies other than the FDA, including the DEA. Production quotas fall within both the purview of their work and the ambit of their discussion.
Yet they go unmentioned by the Committee. Starting in the late 1990s, the DEA dramatically escalated licit production quotas for a number of opioids (oxycodone; hydrocodone; oxymorphone, etc.); those quotas, bumped again in 2012 and returned to pre-2012 levels in 2016, have yet to climb back down. This tells you a lot about the DEA, and government collusion in the over-prescribing of opioids more generally. Most important, at least for this purposes of this Committee, APQs remain an untouched — and poorly understood — lever of controlling supply. That the press has by and large overlooked this “in-the-weeds” component of the story is typical of their superficial gloss (one notable exception is German Lopez at Vox), but there is no excuse for an “in-the-weeds” expert panel to do the same.
This oversight from the Committee joins a number of inexplicable mistakes regarding illicit opioids — namely, heroin and illicit synthetics like fentanyl used to maximize heroin’s potency (and unfortunately, more and more sold on its own). Truly, the absence of Sam Quinones’ Dreamland from the Committee’s report undermines the quality of their work. If Committee members did not want to reference his book on the same tier as peer-reviewed scholarship, they should at least allow his insights to inform their work.
Before mentioning the Committee’s errors of fact and judgment on illicit drugs, I want to own that I am hardly a DEA prize-winning research intern or trusted confidante of the world’s underground markets. My work has been marred by a lazy interest in the inner workings of illicit trade; I like to think this flaw compensates for the many who promote a dubious voyeurism. Be that as it may (or may not), if I can spot the flaws in the Committee’s analysis of illicit supply and distribution, then take my word as unrepentant amateur: they are pretty glaring.
Almost no complexity or nuance is evident in the Committee’s analysis of illicit heroin. But, as Quinones chronicles in detail, heroin production and distribution underwent massive change during the time period under discussion. First, the Committee mistakenly refers to black tar heroin as “traditional” and treats “white powder” as an innovation (4–27); instead, black tar was predominant only west of the Mississippi River, while white powder was common in the east, and more typical of “traditional” cartel product. As Quinones describes, the spread of black tar product using an explosive franchise model of production and distribution opened up new markets; this, in turn, diminishes what the Committee would like to say, and not say, regarding Oxycontin reformulation and the turning point of 2010 (4–23,4–24), because the heroin market was also in great flux. The panel fails to treat illicit traffic as a dynamic industry capable of innovation in the same way as the pharmaceutical industry, but judged by these metrics, cartels are, if anything, superior.
Most telling is this error: “The heroin market was revived in the mid-1990s by a new source of initiation in the form of people whose opioid misuse had started with prescription opioids who transitioned to cheaper, and riskier, black-market opioids” (4–25); the Committee then directs the reader to a figure mapping the feeder-market phenomenon (reproduced below).
Nobody outside the influence orbit of Big Pharma doubts that over-supply and over-prescribing of licit opioids laid the groundwork for new illicit heroin markets; I certainly don’t.
But it is essential to point out that the Figure shown here, and the reality of the feeder market phenomenon, begins well into the new century (2003 is the starting point of the graph.)
Nevertheless the Committee is correct that, starting in the mid-1990s, illicit heroin supply in the United States surged. In fact, every illicit product supply rose dramatically, and the reason was simple: NAFTA. (A brief primer by Ryan Grim can be found here.) Drugs are a trade; anything that fosters trade will result in more, and more potent, illicit drugs. But, like other components of the political and media establishment, the Committee resists this knowledge because its governing logic inevitably leads to fundamental questions regarding the validity of drug prohibition itself, which aligns the incentives in all the wrong directions and emboldens all the wrong tendencies. Rather than ask those questions, as would suit a panel convened to conduct scientific inquiry, the Committee, like others before it, instead chose to perform a political exercise, essentially assigning itself the privilege of critiquing current problems without attention to the deep structures of our status quo that gave rise to and greatly compounded them.
The major drivers of opioid supply — whether official quotas that abet the worst in the pharmaceutical industry, or cartels that exploit the inherent weaknesses of prohibition — are shunted aside by the National Academies. This impoverishes the Committee’s analysis and limits the utility of their recommendations, even those that have nothing to do with opioid supply.
Reducing Over-Supply
The Committee also mishandles the appropriate grounding for an important debate underway right now. An unfortunate narrative has taken hold in the media regarding the opioid crisis — namely, that attempts to regulate or diminish over-supply or over-prescribing of licit opioids drive users to illicit and vastly more dangerous versions of the same drug. This is a contention that greatly favors the desires of the pharmaceutical industry to keep opioid prescribing high and as free from regulatory interference as possible.
The evidence is weak regarding this path of transition; by far, the most obvious and overriding factors steering users from licit opioids to illicit ones are dependency and price. But I think it’s important to note the absurdity of the very premise by examining the constituent components of opioid regulations. For example:
- Prescription Drug Monitoring Programs (PDMPs) track prescribing of opioids, and often other drugs, at a state level; some require a prescriber to check the database prior to prescribing. Is the contention here that tracking prescribing, in the hopes of cutting down on pill-shopping or over-prescribing, drove people to heroin? Absent the over-supply and the over-prescribing of opioids, PDMPs would have no effect in this regard.
- Pill Mill legislation requires that a licensed physician run a pain clinic and/or that such clinics be registered with the state. Is the contention here that regulating pain clinics drove people to heroin? Absent the over-supply and the over-prescribing of opioids, Pill Mill laws would have no effect in this regard.
- The reformulation of a drug to a tamper-resistant product and the rescheduling of hydrocodone (from Schedule III to Schedule II) make manipulation of the product and refills more difficult. Is the contention here that we should continue to make Oxy easy to snort, or that a drug should be allowed mindless refills? Absent the over-supply and the over-prescribing of opioids, these regulatory changes would have no effect in driving people to heroin.
I think the point is well-taken that any potential regulation should account for unintended consequences, but massive over-prescribing and over-supply of opioids should not be treated as a null hypothesis, or an acceptable status quo ante. If you were to transport any or all of these interventions prior to 1995 and a world in which Oxycontin was unknown, not a single one would be responsible for driving people to heroin.
The pharmaceutical industry’s preferred framing — that regulation drives people to heroin — becomes particular damaging in light of recent changes like the CDC guidelines for opioid prescribing (March 2016), and individual state laws limiting the number of days for initial, acute pain prescribing (first implemented in Massachusetts, also in March 2016). Both developments are too new for the Committee to analyze in terms of effects, but the panel does repeat some misrepresentations typical of the mainstream press, and favorable to the industry, regarding the latter. Specifically, the Committee relies on an article by Kate Traynor discussing the Maine law, repeating her assertion that chronic pain prescribing is limited to 30 days.
I have yet to become acquainted with a state law that eliminates or substantially curtails chronic pain opioid prescribing — and unlike the Committee, I’ve actually looked at them. In the case of Maine, the law says that a prescriber must limit a script to a thirty-day supply within a thirty-day period, basically mandating monthly refills if necessary. (Here is a helpful explainer from the Maine Medical Association; the legislation does require certain criteria be met in order to prescribe long-term for Morphine Milligram Equivalents above 100, and this guideline has proven controversial among some long-term chronic pain patients.) NB: It would not have been beyond the Committee’s resources to commission a consultant to collect and analyze all state laws, and it would have been a public service for them to have done so. Misrepresentations of what these laws actually do are rampant.
In the main, state laws are designed to dry up the over-supply of opioids for acute pain, a major feeder of the black market in opioids, and many enjoin (but don’t compel) doctors to be more careful about chronic pain prescribing. The CDC guidelines advise doctors to be more judicious in prescribing for both acute and chronic pain, and recommend Immediate Release (rather than Extended Release, Long-Acting) opioids, which tend to be of a lower overall dose. Some state laws incorporate the recommendations of the CDC by asking doctors to do things like prescribe the “lowest effective IR dose” (New Jersey), delegating the final form of this instruction to the judgment of the prescriber.
Neither the ambition nor the method of execution of any of these laws or regulations is unreasonable. Instead, the pharmaceutical industry’s nonsensical framing holds a metaphorical gun-to-our-heads, demanding that we be held hostage to a world of over-prescribing and over-supply, “or else” …heroin. To be clear, I don’t discount that in today’s world, any given regulation or guideline might be the mechanism or immediate motivation for a user to seek out the illicit market. For that matter, so could losing a particular prescription drug benefit or particular health insurance plan. In some instances, a guideline may be poorly implemented by a prescriber, who may himself be poorly trained in opioid tapering or MAT. In others, a vacuum created by drying up a black market in licit opioids might be filled with another black market product: heroin. But the fault in all this lies not in efforts to reign in over-prescribing and over-supply; it lies with over-prescribing and over-supply itself. We have lots of licit opioids because of pharmaceutical industry malfeasance and government complicity; we have lots of heroin because of the perverse incentives of prohibition and flourishing channels of trade. The industry would like you to focus on one branch of one tree; as a corrective and context for good policy, the Committee should have been adamant about sketching the forest. As the panel noted: “A preponderance of evidence suggests that the major increase in prescription opioid use beginning in the late 1990s has served as a gateway to increased heroin use.” This convergence of evidence should structure the analysis of all subsidiary market changes.
And Finally: Retractions/Corrections Needed
Page 4–29; Incorrect.
See, for example: “After the survey was recalibrated in 2015, the ratio of “misused” painkillers obtained from friends and family fell to 53.7 percent.”
Page 1–7: Incorrect.
HR 7079 prohibited the importation of crude opium for the purposes of manufacturing heroin; heroin itself was not contraband until 1956, and not punishable under criminal statute (rather than taxing authority) until 1970. Until 1956, small amounts of heroin in residual supply continued to be used in medical settings, especially as treatment for cough in particularly difficult circumstances.
