FDA UpFront: Dr. Peter Lurie
FDA UpFront is a periodic feature in which we sit down with the people of FDA and interview them about some of the exciting ways they are fulfilling the Agency’s mission to preserve and protect the public health. This week we talk to Peter Lurie, M.D., M.P.H., Associate Commissioner for Public Health Strategy and Analysis, about the recent article he co-wrote with FDA’s Douglas Throckmorton, M.D., Deputy Center Director for Regulatory Programs and HHS’ Christopher M. Jones, PharmD, MPH, Office of the Assistant Secretary for Planning and Evaluation. The “Research Letter,” titled “Effect of US Drug Enforcement Administration’s rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing
”, appears in the January 25 online edition of JAMA Internal Medicine.
Peter Lurie, M.D., M.P.H., Associate Commissioner for Public Health Strategy and Analysis
Q: Why was this study important?
Dr. Lurie: As you know, there is a major epidemic of opioid abuse in this country and among the tools available to the government is deciding in what Schedule a controlled substance should be placed under the Controlled Substances Act, which is primarily administered by the Drug Enforcement Administration (DEA). Each Schedule comes with various requirements for physical security, recordkeeping, prescription limitations and the like. The schedules go from I to V, with Schedule I being the most restrictive; it is for drugs with high potential for abuse and no “accepted medical use” and therefore aren’t available for prescribing.
Products containing hydrocodone in combination with another pain relief ingredient (usually acetaminophen, the active ingredient in Tylenol) have historically been in Schedule III. Among other things, this Schedule permits verbal refills to be made by prescribers. Hydrocodone in combination with other pain medicines have become one of the most commonly prescribed class of drugs in the United States. Given the concerns over the increased abuse of opioids, DEA asked FDA to assess whether additional restrictions were appropriate, notably an upscheduling to Schedule II. In response, FDA in collaboration with the National Institute on Drug Abuse (NIDA), conducted a medical and scientific evaluation of this question. These recommendations were then sent to the HHS Assistant Secretary for Health, who in turn made a recommendation to the DEA that the product should indeed be placed into the more restrictive Schedule II. DEA agreed and the change in Schedule for these products took effect in October 2014. What we did in this project was to evaluate the impact of that upscheduling on the prescribing of hydrocodone combination products and other opioids.
Q: And what did you find?
Dr. Lurie: As it turns out, hydrocodone combination product prescriptions, and the total number of opioid prescriptions, had been going down slowly in a consistent manner the months and years prior to the enactment of the upscheduling, so we had to adjust for that. But, what we found was, at that moment, in October of 2014 when upscheduling went into effect, there was an immediate and significant drop in the prescribing of hydrocodone combination products over and above what would have been expected based on trends prior to upscheduling, amounting to a drop of approximately 13 percent in the numbers of pills dispensed. Most of that decrease was in refill prescriptions, not in new hydrocodone prescribing -- consistent with an impact that was due to the action that we had taken.
Q: So, when you say “a significant drop,” what are we talking about in terms of a number of pills or prescriptions?
Dr. Lurie: What we saw, again after adjusting for prescribing trends prior to upscheduling, was 21 million fewer hydrocodone combination product prescriptions and 905 million fewer tablets in the year after upscheduling. These are large numbers, representing 17 percent fewer hydrocodone combination product prescriptions and 13 percent fewer tablets. This leaves open the question of whether there was compensatory prescribing of other opioid drugs, and so we looked into that as well. While there was a small increase in non-hydrocodone combination product prescribing, the reduction in hydrocodone significantly exceeded that. Overall, we showed that, after taking into account trends in prescribing prior to upscheduling, there were fourteen million fewer opioid prescriptions and 750 million fewer opioid tablets prescribed in the year following the upscheduling, reductions of 6 percent and 5 percent respectively.
Q: Why is this a good thing? Why should people regard this as something positive?
Dr. Lurie: The nation is facing a tragic opioid epidemic and an intervention that can reduce the amount of prescribing without limiting access to legitimate pain medications is critical from a public health point of view. In this paper, we looked at the part that is related to the amount of prescribing, but additional research will be necessary to look at the access aspect. But, in the part that was the focus of this research, we’ve seen a significant decrease in prescribing.
Q: Anything surprise you with these results?
Dr. Lurie: There are a number of ways in which prescribers could have adapted to upscheduling. They could have written more new prescriptions, they could have written larger prescriptions or they could have prescribed other opioid drugs. The encouraging information here is that, while there is some evidence for some of these, in the overall ecology of opioid use, we had an immediate drop in prescribing that I think was larger than I and some other observers would have expected.
Q: When someone looks at these numbers, they may wonder whether we should assume that a large number of patients who stopped taking opioids didn’t need them in the first place, or that there are now more people in pain who no longer have access to these drugs. Which is it?
Dr. Lurie: That’s just not something we directly looked at. But, you’re right -- in any consideration of opioids you have to consider both facilitating appropriate, legitimate access to the drug on the one hand and minimizing abuse on the other. Most authorities believe there is significant over-prescribing of opioids and so we believe there is a place for reductions in prescribing without leaving pain untreated.
Q: Can you talk about what’s next in terms of this issue?
Dr. Lurie: We do hope to conduct additional research in this area because, as I have said, what we have done so far is show that there was a decrease in prescribing. But that doesn’t tell us which patients were affected or whether these decreases in prescribing will be sustained. And we don’t know whether the action will have an impact on abuse, addiction or overdose. So those are all questions for the future.
Q: But we do know, categorically, that there are fewer prescription opioids out there because of this intervention?
Dr. Lurie: I believe we do, because the changes observed happened in such close association with when the action took effect; because the size of the decrease was significant; and because the great majority of the decrease took place in the refill portion of hydrocodone combination product prescribing, which was exactly the kind of prescribing you would think would be affected by upscheduling.