- Speech by
Leadership RoleCommissioner of Food and Drugs - Food and Drug Administration
Speech by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
National Rx Drug Abuse and Heroin Summit
“In Search of More Rational Prescribing”
(Remarks as prepared for delivery)
In 2015, annual opioid related deaths surpassed the number of Americans killed by the AIDS epidemic at its peak in 1995.
The nation has weathered drug epidemics before. But this crisis is different. It’s more insidious, more pervasive, and more devastating.
The roots of this destructive crisis can be traced to the early 1990s -- when pain became the fifth vital sign, when drugs were developed that were erroneously thought to be less addictive, and when physicians began to prescribe opioids more liberally.
Now the resulting addiction is firmly rooted.
A crisis that began with the lawful prescribing of prescription medicines has evolved into a disaster involving illicit drugs, and increasingly, super-potent forms of illicit fentanyl. So even as medical prescriptions are falling, overdose deaths are rising. Many with addiction have moved on to street drugs, which increasingly have become the low-cost option.
And increasingly, others are starting on opioids by going straight to heroin. At the same time, as we attempt to rationalize prescribing practices that were far too liberal, patients in pain who need opioid analgesics are caught in the cross hairs.
We’re now faced with the urgent need to craft policies that rationalize prescribing, and set a new and more appropriate medical standard for the use of opioids. At the same time, we will take heed that the drugs work, and there will be patients who need these medicines; for example, for the management of severe pain. In some medical circumstances opioids are the only drugs that work for some patients, such as those with metastatic cancer.
I want to talk about some of the strategies FDA is pursuing to address these challenges; to reduce overall exposure to opioids, while preserving access for those patients who will benefit.
In too many cases, addiction still starts with a prescriber’s pen, either directly or indirectly through prescription drugs left over, and acquired or stolen from friends or family members.
The number of prescriptions being written is still too high; both for the immediate release opioids as well as long-acting and extended release. The doses of opioids being prescribed are also high, and we know that the higher the daily dose, the greater the chance of misuse, overdose, and death from opioids.
Those excess pills fill medicine cabinets. Some end up being diverted to illicit markets, and being misused by friends or family members, feeding the river of pills that are coursing through our local communities.
To better understand these trends, FDA is using our Sentinel database and other large datasets available to us to assess opioid analgesic use in surgical and primary care settings. We used refill rates versus initial days supplied to estimate opioid amounts that opioid-naïve patients appear to use for common acute pain conditions.
For surgical conditions, we assessed opioid analgesic use in nearly one million patients. Our preliminary analysis suggested wide variation in apparent opioid analgesic use, ranging from one day of opioid analgesics for some laparoscopic procedures such as cholecystectomy to multiple weeks of opioid analgesics for more invasive procedures such as open-heart surgery.
Our modeling suggested that for many common surgical procedures, just a single day of opioids was sufficient. But that’s not what’s being prescribed based on surveys in the literature.
To give you some examples of what we found: For laparoscopic appendectomy, the literature shows that the mean prescription filled was for 30 tablets. But on average, our analysis estimated that patients might require only one day’s worth of medication.
Similarly, after a laparoscopic cholecystectomy, the literature shows that the mean fill was also for 30 tablets. Our data estimated that, on average, only one day of medication might be required.
However, we also found variation in opioid analgesic use within surgical categories, suggesting differences at the patient level that are important to consider. And, while we found data suggesting that too many doses were dispensed for some common procedures, we also found that there were some procedures – like hip replacement or CABG surgery – where longer durations of opioid analgesic use may be needed. These findings suggest the need for regulatory flexibility even as we consider whether to impose requirements to reduce the morphine milligram equivalents that are prescribed.
Our analysis suggests that the first prescription for many surgical indications could typically be for a lot fewer pills -- maybe just a day or two of medication. But some patients may require more analgesia; making it necessary to provide an efficient way for refills.
We plan to expand our analyses to the Medicare and pediatric populations and release the details of these results to the public. There’s still a lot of data we need to develop to better inform policies. It’s critical that we adopt a better framework for medical prescribing -- one based on reliable evidence.
Because, while the epidemic is shifting from prescription opioids towards street drugs, most new heroin users still report that their addiction began with the misuse of a prescribed opioid. So, rationalizing medical use in lawful settings is still a pivotal goal. This is consistent with the broader goals being pursued by the Department of Health and Human Services and announced recently by the Secretary of Health and Human Services, Alex Azar.
One part of accomplishing this is through education. To reduce unnecessary prescribing, we recently announced that we’re expanding our risk management plans, known as Risk Evaluation and Mitigation Strategies or REMS, to incorporate, for the first time, all opioid analgesics that are intended for use in the outpatient setting, including the immediate-release, or IR drugs.
We’ve also revised the FDA’s Blueprint for Health Care Provider Education, which explains how providers should be educated about pain management in general, and prescribing opioid analgesics specifically. In the case of REMS, our regulatory authorities extend over the sponsors. We require that the manufacturers make this training available to prescribers.
But the current opioid REMS is not a mandate on individual doctors to complete the training. We know that not every prescriber participates in this optional education. Given the scale of the epidemic, it’s time to seriously consider mandatory education. Too many doctors from around my generation were trained in a manner that encouraged prescribing that was far too liberal.
Ideally, it might be most efficient to require training at the time of DEA registration and registration renewal that all prescribers must undergo. One could envision coupling this training with education on treatment of addiction including prescribing of buprenorphine, offered at the same time. This way, all providers who train on the appropriate prescribing of opioids would also be trained on how to diagnose and treat opioid use disorder.
This training could also include information about the appropriate dose and duration of opioid analgesic use for the most common outpatient indications. To reinforce this training, this information could be made easily available at the point of care so practitioners could incorporate more of it into their prescribing decisions.
To prompt these opportunities to improve prescribing, I also want to see if professional societies, working with FDA, could develop evidence-based guidelines on the appropriate dose and duration for some common procedures. FDA could then consider ways to make the findings broadly available. With the appropriate data, I’d like to explore ways to include the findings in drug labeling.
The new evidence would not be relied upon for primary evidence of effectiveness, but rather, on how providers might better use these drugs in the face of significant safety concerns about abuse, in specific examples of acute pain.
If evidence based recommendations on appropriate dose by indication were available, then providers and health systems could adopt these guidelines to make sure prescribing comports more closely with clinical need. This could be preferable to fixed limits on prescribing and dispensing by allowing the dose and duration to be more closely tied to the indication for use.
At the same time, we need to seek better information that we could more easily incorporate into the labels of opioid alternatives; like when an NSAID and acetaminophen combination is a suitable, if not better alternative to an immediate release opioid. Separately, a proposal we’re pursuing to streamline the monograph process that currently governs Over-the counter (OTC) labeling could allow this kind of information to be more easily incorporated into the labels of common OTC pain relievers.
If we’re going to enable doctors to get more control over prescribing and pharmacists more control over dispensing, and give health system intermediaries the tools to help encourage these efforts, we’re going to also need a modern national platform geared to more rational opioid prescribing
Today, we’re asking physicians to embrace rational prescribing practices. But we haven’t given them all the tools they need to drive personalized pain management and addiction treatment programs at the point of care. At the same time that we develop evidence-based guidelines to inform clinical practice, we also need prescribing platforms that make it easier for doctors to adopt these recommendations as part of patient care.
For example, a robust e-prescribing system could streamline access for patients with chronic pain who are appropriately managed on an opioid therapy as the history of safe-use could be documented in the system, allowing greater ease for both patients and their providers. This would allow clinicians and pharmacists to focus their attention on new opioid prescriptions and not on appropriately managed patients with chronic pain.
Electronic prescribing for controlled substances can also decrease fraudulent or stolen prescriptions, resulting in less diversion. It could also be an effective tool to integrate REMS materials for patients, providers, and other members of the healthcare team into the existing provider workflow, and to verify safe-use prescribing conditions have been met.
Perhaps most important, a robust e-prescribing system could embed evidence-based prescribing guidelines into its alert system so that rational prescribing is the default option. Evidence-based recommendations around quantity or dose prescribed could support, notifications that would require the prescriber to provide additional validation before departing from these standards.
While the FDA evaluates drugs based on their potential benefits and risks as demonstrated in clinical trials, we recognize that our vantage point can never capture all the clinical nuance embedded in patient care and a physician’s judgment.
In fact, the current science of addiction and opioid prescribing doesn’t show a single inflection point where the risk of addiction dramatically escalates. There’s a risk of addiction at any dose or duration because addiction has roots not just in pharmacology and biology, but also a patient’s social, emotional, and medical history.
Conversely, there’s no specific opioid analgesic amount required to adequately treat acute pain. The published literature and our own data suggest that the duration of opioid analgesic treatment required to manage acute pain can vary widely by condition.
Without evidence based dosing recommendations at the point of care, to support and inform rational prescribing, we’re at serious risk of both undertreating some patients who could benefit from opioid therapy, and over treating a lot of patients who are then placed at a higher risk of addiction.
That’s why we need a uniform system of electronic prescriptions for controlled substances, supported by evidence-based guidelines, preferably as part of drug labels, and integration of Electronic Health Records and Prescription Drug Monitoring Program (PDMP), as well as data sharing across PDMPs.
There are now proposals for just such a system before Congress. Such a framework could be modeled after the Drug Supply Chain Security Act, enacted as part of the Drug Quality and Security Act of 2013. This Act outlines steps to build an electronic, interoperable system to identify and trace certain prescription drugs as they’re distributed in the United States. In the case of controlled substances, the goal would be focused on tracking individual patient prescriptions and transactions for purposes of ensuring appropriate and rational prescribing of opioids to prevent new addiction, ensure appropriate pain management for patients with severe chronic pain, and to prevent misuse.
The opioid epidemic took root in part because vital information was, and is, siloed across the healthcare system. Fragmentation enabled the opioid epidemic to metastasize at a dreadfully rapid rate. Today, information is still incomplete at the most critical point of intervention: when a patient is in a doctor’s office.
This isn’t about micromanaging physician autonomy, or federalizing the practice of medicine. It’s about giving doctors the tools to practice responsible medicine in the 21st Century.
Finally, while we take steps to rationalize appropriate prescribing, FDA also plays an enforcement role when it comes to the illicit market for diverted opioids and illegal drugs. One of those roles is collaborating with Customs and Border Protection on interdiction work on drugs being shipped through the mail. The Omnibus bill signed into law by the President includes $94 million in new funding for processing drugs and other articles imported or offered for import through International Mail Facilities. A lot of the illicit drugs brought into the U.S., including products laced with lethal doses of fentanyl, are being purchased online and shipped in the mail.
Although the sale of prescription opioids without a valid prescription is illegal, the FDA continues to see these products in the packages we inspect. And we find offers to purchase opioids all over social media and the Internet, including Twitter, Facebook, Instagram, Reddit, Google, Yahoo, and Bing.
In a recent report from the U.S. Senate Permanent Subcommittee on Investigations, Congressional investigators also found that “it was easy to find fentanyl advertised online”, pay for it using cryptocurrency or credit cards, and have it shipped to anywhere in the United States through international mail. Over their three-month long investigation, the investigators posed as first-time purchasers of fentanyl with representatives from six online sellers. The online sellers offered to easily sell fentanyl, and to ship any purchases through the “international arm of the U.S. Postal Service,” and accepted payment in Bitcoin, Western Union, MoneyGram, PayPal, credit cards and even prepaid gift cards. They even offered deeply discounted “flash sales” on their products to entice purchase.
The investigators used payment information to identify more than 500 financial transactions totaling $230,000 linked to 300 individuals in 43 states. The Subcommittee was even able to identify seven individuals who died from fentanyl overdoses after sending money and receiving packages from online sellers.
In a hearing on January 25, Senator Rob Portman, the Subcommittee Chair, said that their investigation found that: “…online sellers were quick to respond, unafraid of getting caught, and ready to make a deal. They offered discounts for bulk purchases and even tried to up-sell us to carfentanil – a powerful synthetic opioid that is so strong it’s used as an elephant tranquilizer. Ordering these drugs was as easy as buying any other product online.”
FDA has investigators conducting some dark web operations. We’ve also had some notable take-downs stemming from this work. The easy availability and online purchase of these products from illegal drug peddlers is rampant and fuels the opioid crisis.
I’m concerned that social media companies, internet service providers (ISP) firms that host websites, and others in the internet ecosystem haven’t been proactive enough in rooting out these illegal offers to distribute opioids from their respective platforms. I think we can work with them to do much more to address this public health danger.
Internet firms simply aren’t taking practical steps to find and remove these illegal opioid listings. There’s ample evidence of narcotics being advertised and sold online. I know that Internet firms are reluctant to cross a threshold; where they could find themselves taking on a broader policing role. But these are insidious threats being propagated on these web platforms. ISPs and social media sites have stepped in to crack down on illegal activities when they’ve been forced to, such as when it comes to the sale of child pornography. And we’ve also seen them step in when some advertising offended their political prerogatives.
But so far, when it comes to opioids, we haven’t seen meaningful, voluntary actions. Yet the magnitude of the public health emergency presented by the opioid crisis requires a change in mindset among Internet companies and the adoption of a more responsible, collective approach to eliminating illegal opioid distribution via the Internet. We want to work collaboratively with these firms to organize this action. We trust that the leaders of these firms share our concerns when it comes to this public health crisis. We hope they’ll join our effort.
To these ends, FDA will soon host a summit meeting with CEOs and other senior representatives of the internet stakeholders, academics, and advocacy groups to identify technology gaps and new solutions – like altering search algorithms to inform potential opioid purchasers to pages offering validated treatment programs, along with information about the potentially fatal risks associated with the illicit online sale of opioids.
We need to work together on shared solutions to address the problem of opioids marketing in the online space, and we need Internet media companies to be our partners in this effort; taking on more social responsibility for implementing those solutions.
We’ll ask stakeholders to join us in a policy commitment to reduce opioid availability on the Internet; and to agree to meet again in a year to review our progress and to share best practices in reducing opioid availability on the Internet. All of us, who bear purview over, and responsibility to, addressing this crisis, must collaborate more closely, and consider stronger action.
Until we do, we risk remaining behind the leading edge of this intractable and evolving crisis involving drugs that make life bearable for some patients, but are lethal for far too many others.