In “Personalized Medicine and Responsible Access to Pain Medication” (a white paper based on the Center for Medicine in the Public Interest’s September 2013 Capital Hill conference), Dr. Douglas Throckmorton, CDER’s Deputy Director, for Regulatory Programs and the FDA’s point person on opioids, writes,
We understand that for the millions of Americans experiencing an acute medical need or living with chronic pain, opioids, when prescribed appropriately, can allow patients to manage their pain as well as significantly improve their quality of life. However, we have also become increasingly concerned about the abuse and misuse of opioids. We are challenged with determining how to best balance the need to ensure continued access to patients who need these medications while addressing concerns about abuse and misuse.
FDA must walk a difficult public health tightrope, balancing patient need, medication safety, and (in the case of opioids), the dangers of abuse.
This careful balance is now being called into question by 28 state attorneys general who, in a letter to FDA Commissioner Margaret Hamburg, ask the agency to “reconsider its controversial approval of the powerful new narcotic painkiller known as Zohydro.” The attorneys general are concerned that the medicine lacks “an abuse-limiting formula.”
First let’s consider the rhetoric. Was the approval “controversial?” Well, for starters, the FDA approved the medicine notwithstanding a negative adcomm vote. Is that what makes it “controversial?” No. Adcomm votes are recommendations and the advice (while generally followed by the agency) is in no way binding and there’s plenty of precedent for the FDA going its own way.
No, it’s controversial because the issue of opioid abuse is controversial. And that’s an important difference. Nobody said the FDA’s job was easy.
Noble Prize winner Joshua Lederberg once observed that the failure of regulatory legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to innovation in public health. Lederberg noted that in the absence of such changes, “The precedents affecting the long-term rationale of social policy will be set not on the basis of well-debated principles, but on the accidents of the first advertised examples.” And there isn’t a better perspective-setting proposition when it comes to the issue of Zohydro than that quotation.
Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly referred to as the Precautionary Principle, which, in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should not be allowed into the marketplace. Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated. But precaution is not always safer than the alternatives.
Pierre Trudeau once said, “There’s no place for the state in the bedrooms of the nation.” But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests? The AGs who are petitioning the FDA see abuse and seek to minimize access to opioids as the solution.
That’s a law enforcement solution. They mean well, but are behaving like a bull in a china shop. Arbitrarily limiting choice is not generally associated with the scientific method. Should regulation be shaped by factors other than science? Or should advances in medicine and digital information be used to right size regulation reduce the excessive reductionism that leads to regulatory overreaction and promote resilience rather than ever increasing regulation.
Which brings us to the second objection raised by the “Opioid-28,” that Zohydro lacks “an abuse-limiting formula.”
Per Doug Throckmorton,
Another important step towards the goal of creating safer opioids, and one that is a high public health priority for FDA is to encourage the development of formulations of these drugs that deter their abuse. This relatively new science of abuse deterrence is exciting and evolving and showing encouraging promise. To guide drug development in this new field, we also issued a draft guidance for industry in January, announcing a flexible, adaptive approach to encourage the development of abuse-deterrent opioids. We believe abuse deterrent products have promise to help reduce prescription drug abuse and improve public health.
The FDA has its eye on the prize. But what’s the game for the AGs? They refer to an “epidemic.” That’s a powerful word. But does it qualify in the case of opioids?
According to the CDC in 2008, there were 14,800 opioid overdose deaths. Half of those, the CDC has claimed, involved opioids and other illicit substances, whether it’s cocaine or heroin, or alcohol. They also mentioned that alcohol was involved in many of those deaths but they don’t actually tell us the numbers. So conservatively, half or 7,400 deaths occurred in 2008 from opioid overdose. The same year from CDC’s own statistics, there were 36,500 suicides. There also were 24,000 alcohol-induced deaths and that doesn’t count other related alcohol deaths like drunk driving. The bottom line is that the opioid numbers do not even come up in the CDC’s list of the top 15 causes of death of Americans
It’s important to add to this “epidemic” perspective, the fact that people suffering from chronic pain are under-served by existing therapies. A recent IOM report that was issued in June of 2011 found that 100 million Americans are now living with chronic pain. That’s a third of the U.S. population. Ten million of those have pain so severe that they are disabled by the pain. The report also said that pain costs the U.S. economy about 600 billion dollars a year in lost productivity and healthcare cost.
And the “Opioid 28” wants fewer pain medications on the market?
The vast majority of people who use opioids do so legally and safely. A subset, approximately four percent, use these medications illegally. In fact, from 2010 to 2011, the number of Americans misusing and abusing opioid medications declined from 4.6% to 4.2%.
And the FDA’s decision was “controversial?” Really?
Rather than dealing with the problem of abuse with sledgehammer solutions (such as those proposed by the 28 AGs), we should focus on potential solutions such as:
* The structure and impact of programs such as the recently instituted by CVS initiative (detailed in a recent New England Journal of Medicine perspective piece) where, through the use of “Big Data”, the chain pharmacy identified outlier prescribers and took appropriate and responsible action.
* The role of the 21st century pharmacist in improving drug safety and medication adherence via more proactive and remunerated patient education? How can pharmacists become better integrated beyond Med Guides into the FDA’s Safe Use of Medicines initiative? When will pharmacy synchronization really kick into gear, and how will states help to jump-start these important initiatives?
* Government and legislative initiatives such as the Stop Act (H.R. 486), which focuses on tamper-deterrent formulations and the continued development of those. Also, Senate Bill 1277 (sponsored by Senator Barbara Boxer, D/CA) which would establish a commission to bring all of the stakeholders together to have discussions about how to approach this issue so that law enforcement, providers, patients, and pharma can debate the issues and reach common ground.
* The appropriate role of tamper-resistant technologies. They are part of the solution, but they’re not the whole solution. We need to develop policy options that focus on the prescriber/patient relationship, and a professional assessment of what’s the risk involving this patient. Is the patient is going to tamper with the medication and potentially expose themselves or others to some danger. We have to do a better job (via CME and other methods) of training physicians and other prescribers on how to do these kinds of assessments.
And, most importantly, we need to keep the needs of patients front and center.
There is no expedient to which a man will not go to avoid the labor of thinking.
– Thomas Edison