By David Heitz
People with substance use disorder have improperly used opioid maintenance therapy for as long as it has been around. So, the U.S. Food and Drug Administration required the medications be made “abuse-deterrent.”
Unfortunately, some people also have found a way to abuse those formulations, too.
For that reason, the federal agency convened a two-day summit this July. Agency policymakers want to better understand why people still are overdosing on opioids every day and dying even when they are taking these medications intended to help them recover.
The first day centered around scientific discussion of abuse-deterrent formulations.
“For example, some make crushing or manipulating the tablet to dissolve in liquid for injection more challenging; others combine the active opioid analgesic ingredient with drugs such as naloxone, which if snorted or injected will block the opioid,” FDA Commissioner Dr. Scott Gottlieb explained in a statement leading up to the meeting.
“This has been an important area of innovation that the FDA continues to support. However, we recognize there is a gap in our understanding of whether these products result in real-world, meaningful increase in the frequency and patterns of opioid misuse and abuse.”1
What they learned during the hearing, which included testimony from top experts in the area of addiction and recovery, is that technological challenges and privacy issues limit the amount of data available for influencing policy.
For example, many in attendance said the federal government needs to know opioid maintenance therapy-related outcomes for specific insurance plans. This is because some people can access opioid maintenance therapy sooner in their course of addiction than others. That could influence probability of success or overdose, they argued.
Data Could Help Prevent Overdoses, but Hard to Get
But representatives from various companies that aggregate such data said getting permissions for that kind of information from payers is challenging. There also are numerous technological hurdles in converting data from various records systems in a way that still allows apples-to-apples comparisons.
During the first day of the session, top scientists who attended the session said deterrent formulations need to go beyond what isn’t working: crush-resistant pills that aren’t effective.
It’s also important to make sure that people addicted to opioids have financial incentive to take opioid maintenance therapy. If street drugs offer the same high at a lower price, the addicted likely will continue to go that route, some pointed out.
On the second day, addiction experts said studies that look at abuse-deterrent opioid maintenance therapy too often only look at those who are high-risk. One pointed out studies are needed that follow a range of people, some considered “at risk” and others not, from the very first day they fill their first prescription.
Another said those who need to pay a monthly health insurance premium likely are not abusing their opioid maintenance therapy.
FDA officials say they need more information about the roots of abuse of opioids, such as behaviors and intent. Most data regarding adverse incidents with abuse-deterrent opioids is coming from hospital overdose data and calls to poison control centers.
Such passive surveillance means the FDA is not getting a real-time handle on the opioid crisis as it develops. Therefore, it’s difficult to prevent deaths.
Current surveys used to gather information on drug abuse are long established. Changing them is not simple, and anything involving expenditures must go through the Office of Management and Budget, FDA officials noted, which is a very long process.
Several panelists from the scientific community debated the merits of using internet-based surveys to try to get the information they need about abuse-deterrent opioids. Positives associated with internet surveys included the ability to swiftly change them and to potentially link them up with other datasets.
Negatives included the small sample size and answers that may offer skewed results. For example, one medical professional noted that if you ask people if they shared their opioid medication given to them after a dental procedure, most probably will say yes. He said that’s because so many people do it – many with no intent to abuse.
One way around the Office of Management and Budget hurdle is for the National Institutes of Health to award grants to organizations wanting to perform the research the FDA wants. For example, the Monitoring the Future received funding this way, an FDA official noted.
While much of the discussion focused on getting to the why of drug abuse, one addiction specialist quickly noted that no two people abuse drugs for the exact same reason.
In fact, drug abuse is often brought on by a co-occurring mental illness. Recent research shows that this applies to people who abuse opioids, too.2
Effective addiction treatment needs to address both issues, addiction and mental illness, at the same time. This greatly increases the chances for a lasting recovery.
What the FDA Is Already Doing to Combat Overdose Deaths
While much of the discussion on day one of the abuse-deterrent opioid summit focused on longer-term solutions, Dr. Douglas Throckmorton pointed out, “We are in the midst of a public health crisis. We need to make sure our decisions are timely and appropriate given the data we have.”3
Throckmorton is deputy director of the center for regulatory programs at the FDA.
“This crisis is, in my view, the toughest public health challenge that we face at the FDA,” Dr. Gottlieb said before the first day of the meeting.4
Gottlieb outlined a three-pronged approached he has asked his colleagues at the FDA to consider when it comes to fighting addiction. The elements of this approach include:
Minimizing the risk of creating new opioid addicts. “We need to make sure that only appropriately indicated patients are prescribed opioids, and that the prescriptions are for durations and doses that properly match the clinical reason for which the drug is being prescribed in the first place.”
To that end, Gottlieb announced the agency will for the first time require manufacturers of immediate-release opioid drugs to fund training on appropriate prescribing for doctors.
This already is being done for extended-release opioids, and Gottlieb said those guidelines will be updated.
“This regulatory tool is needed to ensure that the benefits of how these drugs are prescribed continue to outweigh the risks of misuse, abuse, addiction, overdose and death. It’s time to take direct action to address the close to 200 opioid analgesic prescriptions each year that are for the immediate-release products.”
The guidelines, known as Risk Evaluation and Mitigation Strategy, or REMS, also will require training on basic addiction medicine and opioid disorders. Current REMS educational emphases are on pain management and non-pharmacologic alternatives to treating pain.
And the FDA isn’t stopping at requiring doctors to have the training. Nurses, pharmacists and others who want the training will have it available to them.
Currently, there is no mandate that all providers of opioids take REMS training, but that’s being considered, Gottlieb said.
Clarifying language. “We want to know whether we have the right nomenclature for describing the drug features that are expected to make opioids less prone to abuse,” Gottlieb said. “Among other steps, we’ll be surveying doctors to better assess how they perceive these terms.”
The agency also wants to make sure labeling of abuse-deterrent medications does not convey the idea that the medications are addiction-proof as well because “that is simply not true,” Gottlieb said.
Continue to constantly evaluate the efficacy of opioids against the backdrop of risk, and take action up to and including the call for removal of drugs from the market.
“As we recently did with respect to reformulated Opana ER, when we find that the risks of an opioid outweigh its benefits – including the risks associated with illicit use and deliberate manipulation – we will take action,” Gottlieb said.
The FDA’s Plan for Abuse-Deterrent Opioids Moving Forward
Looking to the future, the FDA updated its action plan page for opioid abuse deterrent therapies after the two-day summit.5 It now calls for the following:
Strengthening post-market requirements. “Because the evidence base to guide the use of opioid medications, particularly in the setting of long-term use, is substantially lacking, the FDA is strengthening the requirements for drug companies to generate post-market data on the long-term impact of using extended-release, long-acting opioids.”
Throckmorton said the FDA already is doing this. “The FDA can require post-market studies, and did,” he explained during the hearing.
Using patient records, death records and insurance claims, this has resulted in the development of algorithms that can predict opioid-related abuse and death by analyzing a person’s medical records.
Expanding access to abuse-deterrent formulations. “The FDA will issue draft guidance with its recommendations for the approval standards for generic abuse-deterrent formulations. Release of this guidance is a high priority, since the availability of less costly generic products should accelerate prescribers’ uptake of abuse-deterrent formulations.”
Expand use of advisory committees. “The FDA will convene an expert advisory committee before approving any New Drug Application for an opioid that does not have abuse deterrent properties.”
Reassessing the risk-benefit approval framework for opioid use and encouraging better treatments, such as over-the-counter availability of naloxone and the development of non-opioid-based pain medications.
For his part, Gottlieb told those gathered for the summit on abuse-deterrent opioid replacement therapy that he understands the impacts that the agency’s bold moves will have on various stakeholders.
But a crisis is a crisis. “We need to confront it like any explosive epidemic,” he said. “But we need to make sure all of our actions are carefully considered with broad stakeholder input, and based on sound science.”
1 Gottlieb, Scott. (2017, June 13). Statement from FDA Commissioner Scott Gottlieb, M.D. — FDA is taking new steps to help assess opioid drugs with abuse-deterrent properties. Retrieved July 13, 2017, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562961.htm
2 Heitz, D. (2017, June). Federal Data Shows Many Misusing Opioids have ‘Serious’ Co-occurring Mental Disorder. Rolling Hills Hospital. Retrieved July 13, 2017, from http://rollinghillshospital.org/federal-data-shows-many-misusing-opioids-serious-co-occurring-mental-disorder/
3 FDA hearing on abuse-deterrent opioids. (2017, July 11). FDA Office, Silver Springs, Maryland. Attended by writer via live webcast.
4 Gottlieb, Scott. (2017, July 10). Statement from FDA Commissioner Scott Gottlieb, M.D. – FDA is taking new steps to help assess opioid drugs with abuse-deterrent properties. Retrieved July 13, 2017, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562961.htm
5 FDA Opioids Action Plan. (2017, July 11). U.S. Food and Drug Administration News. Retrieved July 13, 2017, from https://blogs.fda.gov/fdavoice/index.php/2016/10/fdas-opioids-action-plan-a-midyear-checkup/