On March 14, 2017, Bob Twillman, PhD, FAPM and Executive Director of the Academy of Integrative Pain Management, testified at the FDA Hearing on Opana ER. Below is a transcript of his testimony, and you can read the results of the hearing here.
My name is Bob Twillman and I am the Executive Director of the Academy of Integrative Pain Management, formerly the American Academy of Pain Management. The AIPM, for its entire 29-year history, has advocated for a multimodal, multidisciplinary model of pain management, one that uses all available evidence-supported treatments to create a personalized pain care plan for each individual. While this model emphasizes maximizing the use of non-pharmacological treatments, it also recognizes that medications, including opioid analgesics, are critical tools that we need to provide the best care possible. For that reason, we advocate for access to all opioid analgesics that have been proven safe and effective.
Yesterday, we heard a lot of information about oxymorphone products, especially about Opana ER. The available data were sliced and diced just about every possible way imaginable. And, at the end of the day, I was left with these impressions:
- Oxymorphone is unique among opioid analgesics by virtue of its metabolic pathway
- Because of that unique metabolic pathway, Opana may be a crucial option for some patients, whether due to their own unique physical makeup, or due to their concomitant medications
- As is true with all opioid analgesics, Opana is abused by a subset of people. That, I’m afraid, is a fact of life that isn’t going to change for any opioid in my lifetime.
- When PEO was added to the original formulation of Opana ER to create an abuse-deterrent opioid product, its predominant method of abuse changed from inhalation to injection
- A certain subset of individuals injecting a highly-altered version of Opana ER suffer adverse outcomes, including thrombotic microagiopathy, HIV infection, and overdose death. Unfortunately, only one of these, the thrombotic microangiopathy, is nearly unique to Opana ER—the others can, and do, occur regularly in people injecting other prescription and illicit opioids
So, where does all that leave us? It leaves us with a product that was proven effective enough to be allowed onto the market. And it leaves us with a product that was proven safe enough to be allowed onto the market, albeit without the requested label indication for abuse-deterrent properties.
But the reason we are here is that questions have now arisen about whether further regulatory steps, including the potential withdrawal of marketing approval, should be taken based on these reports of adverse events.
And I find myself concerned about the direction we seem to be headed here—concerned that not only might we lose a unique opioid analgesic that can help some patients who aren’t helped by other opioids, but that a trend might develop that could threaten other products currently on the market.
I want to advise the committee to tread lightly, because there is very real potential that your vote later today could establish a precedent that none of us will, in the end, be happy with.
I’m fond of saying that, if you want to get the right answer, you first have to ask the right question. I don’t mind so much if, after a question is posed and answered, sometime later, the answer changes. That is the nature of discovery, of learning, the result of exploration. The question, “Does the sun revolve around the earth” was once answered with a “yes”. Then, Copernicus proposed the heliocentric model, which was later proven by Galileo and others. That’s an example of a post hoc change in the answer to a question. Perfectly acceptable. What bothers me, though, is when the question changes after we have an answer—a post hoc change in the question is unsettling. And I think that’s what’s going on here. When Opana ER (and every other medication approved by FDA) was approved, the question was, “Do the data indicate that this medication is safe when used as directed?” That is the question underlying clinical trial design, and it is the question that every marketed drug has answered successfully.
Now, however, I perceive that the question is changing after the fact—the new question seems to be, “Do the data indicate that this medication is safe, even when it is used other than as directed?”
I often search for analogies to try to help people understand what is going on when we encounter complicated situations like this one. I think I may have one that exemplifies the challenge here. My take on the issue is that, because some subset of our population has chosen to intentionally defeat the safety mechanism built into Opana ER, those individuals have been able to inject its ingredients, and some have suffered harm as a result. Because that has happened, there is at least the possibility that Opana ER could be withdrawn from the market, making it unavailable to those who use it appropriately, safely, and with positive outcomes. It’s almost as if a subset of our population chooses not to wear seat belts while driving pickup trucks, and then suffers harm when involved in a crash, leading authorities to consider removing all pickups from the market. But the analogy goes even further than that—we heard yesterday that half or more of the people abusing Opana ER don’t even have pain—and it seems reasonable to assume that an even greater percentage doesn’t have prescriptions for it when they do abuse it. They shouldn’t even be using the medication. In our pickup truck analogy, I suppose, this equates to an unqualified driver (let’s say it’s a 12-year-old) who decides not to use a seat belt, and then is injured in a crash, threatening the existence of pickup trucks.
At the risk of stretching the analogy beyond the breaking point, let me suggest a solution that automobile manufacturers already have shown us. When it became apparent that even passing mandatory seat belt laws wasn’t sufficient to protect drivers, they began putting airbags into their vehicles—first, in the steering wheel, then in the door, and who knows where else. They designed their cars with crumple zones that absorb the energy of head-on and rear-end collisions. They found additional ways to protect drivers, even those who choose not to wear a seat belt.
It seems to me that, in the case of Opana ER, rather than withdrawing it from the market, the better solution is to figure out why people abuse it in the first place, and to address that behavior. Maybe there should be incentives for innovation, so that new technologies are developed to enhance the abuse deterrence already built into the product. Maybe we need increased access to treatment for substance use disorders—something that the federal government seems to be falling all over itself to provide, these days. And maybe we need some help with improving access to pain treatments that don’t involve opioids—those pesky non-pharmacological treatments that every guideline touts, but that no one seems to know how to actually provide to the patients who need them.
I don’t envy the members of this committee, because they have a challenging discussion and vote coming up later today. But I urge committee members to engage in some metacognition before they start their discussion. Think for a minute or two about what is really going on here, about the true meaning of the questions posed, and about the potential consequences, should you decide that the answer to the overly broad question you will be asked is that the benefits of Opana ER for people using it for a legitimate medical purpose no longer outweigh the risks to people using it for other reasons. Because, based on the evidence presented to you, that most assuredly is the question you’re being asked. And your answer can have serious consequences for millions of people with chronic pain.