In the late 1990s, the pharmaceutical industry reassured physicians that, with the advent of new formulations, opioids could be safely prescribed with little risk of addiction or abuse to patients who had legitimate pain. The American Pain Society, with funding from the pharmaceutical industry, introduced its “pain as the 5th vital sign” campaign, urging physicians to assess patients’ pain and develop plans to address it. In the years that followed, prescriptions for opioids dramatically increased, at great cost to the U.S. health system and to communities across the country.
The pharmaceutical industry has proposed using so-called abuse-deterrent opioids as an important way to address the opioid epidemic that emerged from the “advances” of the 1990s. This feels like déjà vu all over again — a rush to change prescribing patterns and policy based on little or no solid evidence.
The pharmaceutical industry isn’t alone in its interest in abuse-deterrent products. The Food and Drug Administration has embraced them as one component of a comprehensive opioid action plan. Several public meetings by the FDA have addressed these products, with the suggestion that all opioids should be required to have abuse-deterrent properties. Likewise, lawmakers in some states have passed legislation mandating coverage of abuse-deterrent opioids, with many other states currently debating similar laws.
The term “abuse-deterrent opioid” is a misnomer. These products do not prevent the most common form of opioid abuse — ingesting pills orally in a way that isn’t consistent with the actual prescription. These products do make it more difficult to crush, snort, or inject the underlying opioid. Because of this, some have suggested that these products be referred to as “tamper-resistant.”
Yet these products aren’t truly tamper-resistant, either, because they are subject to manipulation, with instructions easily found in internet forums. With that in mind, what is the real-world evidence that these products might be effective in deterring abuse?
The first abuse-deterrent product, OxyContin, was approved in 2010; nine others have been approved since then. Unfortunately, there is a paucity of evidence documenting the real-world effectiveness of these products for actually lowering abuse. Premarketing studies typically assess the “likeability” of these products among recreational drug users. As we have written in the Health Affairs Blog, there are no prospective randomized clinical trials or rigorous observational studies designed to measure the impact of abuse-deterrent opioids on the incidence of abuse and misuse.
Indeed, real-world evidence has been limited to simple time series that have examined abuse rates before and after the reformulation of OxyContin as an abuse-deterrent product. After OxyContin’s reformulation, the FDA required its maker, Purdue Pharma, to “conduct a post-marketing study to determine the impact of the new formulation on the use and misuse of OxyContin.” The FDA then took the extraordinary step of convening a special advisory committee later that year to consult on the types of studies that Purdue Pharma should conduct. At that meeting, the advisory committee concluded that, because “other [non-abuse-deterrent] products may also be on the market it is not appropriate to limit the evaluation to just the same product historically.” Yet these historical comparisons are all we have to go on.
The Institute for Clinical and Economic Review released a report on Tuesday examining the evidence on abuse-deterrent opioids. ICER rated the net health benefits of OxyContin to be only “comparable or better” than non-abuse-deterrent opioids, due to the clear limitations in the real-world evidence on the drug. The institute was unable to rate the effectiveness of other abuse-deterrent products due to a lack of any real-world evidence.
Even if the evidence isn’t compelling that these products result in lower rates of opioid abuse, why not support them on the possibility that they might help, even if just a little? For the precise reason that the pharmaceutical industry is so interested in mandating the use of these products: They are far more expensive than generic opioids.
We compared the best retail price for three approved abuse-deterrent morphine products — Embeda, MorphaBond, and Arymo ER — against the price of generic extended-release morphine, using the same dose (30 milligrams) and supply (60 pills) for each. The best retail price for the generic morphine is $43.82 for a month’s supply, while the best prices for the other three products range from $567.78 to $1,013.03 for a comparable supply.
A mandate to use abuse-deterrent opioids at an up to twentyfold increase in cost would be staggering to health care systems. For example, the Department of Veterans Affairs spent nearly $100 million in fiscal year 2016 on opioids for 1.2 million patients with at least one opioid prescription. Only 1.9 percent of the opioids dispensed were for an abuse-deterrent product, but they accounted for 37 percent of overall opioid spending. Long-acting abuse deterrent opioids were approximately 10 times the cost of long-acting opioids without abuse-deterrent properties.
Applying a conservative tenfold increase in price for abuse-deterrent opioids would increase the VA’s expenditures for opioids to approximately $1 billion a year, and could represent as much as 20 percent of the entire VA pharmacy budget. Such an increase would also compete against funding of other important opioid use disorder treatments, such as medication-assisted treatment and rehabilitation programs.
While abuse-deterrent opioids have a role in addressing opioid misuse, we caution that any mandate for using these products in all patients would result in huge expenditures and perhaps nudge aside other less expensive and more effective approaches to prevention and treatment of opioid abuse. And some patient advocates have rightfully noted that legitimate pain patients are being asked to pay for the abuse predilection of a small minority of patients looking to get high.
Let’s not repeat the mistakes that got us here in the first place. Better evidence of real-world results are needed before mandating coverage for abuse-deterrent opioids, and payers must retain their ability to make evidence-based, value-driven coverage decisions to optimize the health of the members they serve.
C. Bernie Good, M.D., is a core investigator at the Veterans Affairs Center for Health Equity Research and Promotion and a professor of medicine at the University of Pittsburgh School of Medicine. Chronis Manolis, R.Ph., is the vice president of pharmacy and chief pharmacy officer at the University of Pittsburgh Medical Center Health Plan. William Shrank, M.D., is the chief medical officer of the University of Pittsburgh Medical Center’s Health Plan Division.