A new expert report calls for the Food and Drug Administration to rereview all marketed opioids.

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Expert panel to FDA: time to hold opioids to a new standard

To help bolster its campaign against an epidemic of opioid abuse that now kills about 90 people a day, the U.S. Food and Drug Administration (FDA) last year called for help from an independent advisory panel. The resulting report, released today by the National Academies of Sciences, Engineering, and Medicine, makes some strong prescriptions. Among its assorted recommendations—from supporting state syringe exchange programs to increasing federal funding for neurobiology research—the panel suggests that FDA dramatically expand the types of evidence it requires from companies to show that an opioid is safe and effective, both before and after it gets market approval. The new framework would require companies to provide complex data on a drug’s public health impact—potentially including its ability to ensnare people at high risk of addiction as well as shift the dynamics of the illegal drug market. 

FDA has already made some moves to fight opioid addiction. Last month, it asked drugmaker Endo International to withdraw its long-lasting painkiller Opana ER from the market after finding that the new formulation had led to increases in intravenous abuse. This week, it announced that it would subject a broader range of opioids to its Risk Evaluation and Mitigation Strategy requirement, which includes requiring companies to do more to educate physicians about risks and prescribing practices.

But an even broader overhaul is needed, says public health policy expert Aaron Kesselheim of Harvard University, one of the members of the panel that drafted the new opioid report. He recently spoke with ScienceInsider about the panel’s recommendations. The interview has been edited for brevity and clarity.

Q: What is this report asking FDA to do differently?

A: The traditional model is about looking at the benefits and risks of the drug as it relates to the person who is taking it, and weighing the outcomes versus the side effects. There is a much, much bigger ecosystem that a prescription of an opioid affects. It affects the family, and there’s the possibility of diversion of products, there’s the risk that somebody who takes it will then develop an opioid use disorder that might lead to the transition to other types of opioids or other illicit drugs. Those kinds of considerations are not necessarily relevant in the case of a rheumatoid arthritis drug.

We are asking FDA to adopt a position of what we term “opioid exceptionalism,” where the FDA needs to think about opioids differently from other products … taking a public health approach to drug approvals and to other decisions about postmarket surveillance. That’s based on actions that the FDA has already taken, albeit to a much more limited extent, in other areas.

Q: The report suggests requiring clinical trials that measure a drug’s impact on a household or community—and even its effect on local crime or unemployment. Are there ways to do that?

A: The company and the FDA should be thinking about these issues from square one, whether or not that necessarily requires somehow integrating that into the clinical trial, or modeling it based on available data from comparable opioids. We think that all of that could be reflected on and submitted as part of the evaluation. Maybe in addition to collecting outcomes from the individual patients in the trial, you could collect outcomes from members of that patient’s community. The point is that the traditional model of designing a few-month-long placebo controlled trial of a pain score outcome is not sufficient.

Q: You also recommend that FDA go back and review all the existing opioids on the market for these kinds of public health impacts. Where are those data going to come from?

A: Some of the data are out there in sort of large data sets that are collected as part of health insurance processes. Some of them may be collected by different states through all-payers claims databases [or through] prescription drug monitoring programs. In some cases, there may not be the data available, and we need to figure out how to go out and get that data by looking at experience in particular clinics.

Q: Would this kind of review end up forcing drugs to be withdrawn from the market?

A: Yea, it’s possible it could lead to that, but we need to recognize that these are effective drugs in treating short-term pain in particular, and we need to make sure there is an opportunity for people with pain to have opioids as part of their treatment.

Q: Is the responsibility for running these studies likely to rest with FDA, or with companies?

A: It would probably be both. The FDA has certain data sources that are available to it, but I think it might also require the FDA to request certain reviews or studies done by the companies, and so I think it would be both. Again, it’s something that probably would need to take some time, but there’s no time like the present to get started.