Physicians for Responsible Opioid Prescribing – FDA Petition 2012

An Interview with Andrew Kolodny, MD

Andrew Kolodny, MD, is the Chairman of the Department of Psychiatry at Maimonides Medical Center in Brooklyn, NY. He is also one of the founders of the organization Physicians for Responsible Opioid Prescribing (PROP).

Kevin L. Zacharoff, MD:

Thank you for agreeing to sit for this interview with regarding the recent petition submitted by PROP to the FDA requesting specific actions for changes to opioid analgesic labels. Please share with us the primary goals of the petition.

Andrew Kolodny, MD: Let me start by thanking Dr. Zacharoff and for the opportunity to clarify the purpose of the petition we filed with FDA.The petition’s signers are concerned that opioids are being overprescribed to patients with chronic non-cancer pain (CNCP) and that this practice may be harming more pain patients than it helps. According to the CDC, over-prescribing of opioids is fueling an epidemic of fatal overdose and addiction. One of the primary goals for the petition is to reduce over-prescribing by clinicians who are under the false impression that opioids have been proven safe and effective for treating CNCP.Most experts in the field of pain management agree that evidence is lacking to support long-term use of opioids. Unfortunately, drug companies are permitted to promote opioids as if they’ve been proven safe and effective for long-term use because FDA’s marketing rules are linked to a drug’s label. The existing label on opioid analgesics, which simply states that they’re indicated for “moderate to severe pain” is too broad. It’s a carte blanche for drug makers to promote opioids for just about any condition they want, even for conditions where experts recommend against opioid use.


KZ: What are the specific actions requested in the petition?

AK: The three actions requested are:

  1. To strike the term “moderate” from the indication for non-cancer pain.
  2. To add a maximum daily dose, equivalent to 100 milligrams of morphine for non-cancer pain.
  3. To add a maximum duration of 90 days for continuous (daily) use for non-cancer pain.


KZ: What are the expectations with respect to the FDA’s response to the petition?

AK: Our hope is that the FDA, after their review, will agree that the label should be changed to reflect the limits of scientific evidence supporting long-term and high dose opioid use. Since we don’t know if opioids are safe and effective when used beyond 90 days and when prescribed in excess of a 100mg morphine equivalent dose, we believe the label needs to communicate to the medical community that risks may outweigh benefits when prescribed outside these parameters.Ninety days was selected as the maximum duration of use because the clinical trials that have studied opioids for chronic pain are about 12 weeks long. There are reasons to believe that beyond 90 days, the development of tolerance may result in loss of analgesic effects. There are also reasons to be concerned about safety. With long-term exposure the risk of addiction and other adverse events may increase.


KZ: Are there secondary goals for the petition?

AK: Currently, manufacturers have little incentive to study the long term effects of opioid therapy because they can market the use of opioids for many conditions, and for any daily dose and duration. Our hope is that this petition will actually spur research to clarify the scientific basis for long-term efficacy.Additionally, “non-cancer pain” and “cancer pain” are terms that do not adequately describe the various populations of individuals suffering from pain. The term “non-cancer pain” includes diverse conditions that may respond differently to opioids. And the term “cancer pain” is often considered to be a proxy for end of life care, but with advances in cancer treatments, this is not an accurate construct. More people with cancer are thankfully surviving their disease.With a more narrow indication on opioid labels, there will be an incentive for drug companies to research long-term use of opioids for a variety of conditions because drug companies will sponsor research in an effort to gain new indications.


KZ: What have been some of the concerns you have encountered to the petition?

AK: I think that most of the concerns stem from a belief that we’re asking FDA to impose strict limits on opioid prescribing that would interfere with clinical decision making. That’s not at all true. The petitioners are approaching the FDA as the agency that regulates the manufacture and labeling of food and drugs. FDA does not have the authority to regulate medical practice. We believe that chronic opioid therapy (COT) should become off-label because evidence of benefit is lacking while evidence of serious risks is increasing. But we do not believe that the practice should be prohibited. Several of the petition’s signers prescribe long-term opioids to patients with chronic pain. They would not have signed if it meant that they would be forced to take their patients off of long-term opioids. We are asking for a label that reflects the limited scientific evidence supporting long-term and high dose opioid use. This will in turn curtail the marketing by the manufacturers and decrease over-prescribing by clinicians who are under the false impression that COT is an evidence-based practice.Again, it is very important for people to understand that we are aiming for labeling limits, not clinical or prescribing limits. This initiative has no bearing on a prescriber’s ability and right to practice medicine or to prescribe according to the individualized care and needs of the patient. Clinicians should use their best judgment, which at times may require that a medication is prescribed off-label.There seems to be a lot of misunderstanding with regard to off-label prescribing, and there are perceptions that it is synonymous with deviating from a standard of care, which it is not. FDA has no authority to regulate prescribing. Their job is to ensure labeling that is accurate regarding safety and efficacy.


KZ: July 25, 2012 was the petition submission date, how long does FDA have to respond and what do you anticipate as the response?

AK: The FDA has 180 days to respond to a Citizen’s Petition or a Stay of Action Petition like ours, which would bring us to no later than January 25, 2013. We really have no idea what their response will be, but the possibilities are:

  1. Implement all requests in the petition
  2. Implement the requests in some part
  3. Call for an advisory meeting to have them make recommendations to the FDA on the matter
  4. Respond by issuing a statement that further consideration is needed before any decisions are made.


KZ: What do you see as possible barriers to an approval by the FDA?

AK: If FDA were to implement our requests, drug companies would no longer be permitted to promote long-term use of opioids for CNCP. This would probably reduce prescribing and decrease profits for the manufacturers. Some companies are earning billions of dollars a year from opioid sales so we expect that they’re going to do everything in their power to stop the changes from going through.


KZ: Are there any other concerns regarding clarifying the perspective in addition to what we have covered?

AK: Yes. Concerns have been voiced about malpractice liability for clinicians who prescribe COT if our requested label changes are approved. I think it’s important for people to know that prescribing a drug off-label is not considered malpractice. Many doctors prescribe medications off-label. The courts have ruled that off-label use of prescribed medications can in some cases be the standard of care. In a malpractice suit, doctors are judged on whether or not the deviated from the standard of care. They are not judged by whether or not they prescribed a medication off-label.It is certainly possible that the label changes we’re requesting could result in a more cautious standard of care, particularly with regard to high dose prescribing of opioids. If this happens, it will not be the label change that directly increases liability for high dose prescribers. Rather, it will be a standard of care that moves in the direction of more conservative dosing. There’s some evidence this may already be happening as the message gets out to front-line clinicians that they old-line about “no ceiling dose” for opioids was dangerously incorrect. Practitioners who continue to prescribe very high doses are probably at greater risk today than they were a few years ago.


KZ: If opioids are not preferred for pain care, what do clinicians have as alternatives?

AK: PROP has given much consideration to expanding pain care beyond the use of opioids. There are a plethora of interventions that can help people with chronic pain, including non-opioid analgesics, acupuncture (recently published in one study to have positive effects in chronic pain management in the Archives of Internal Medicine), physical therapy, cognitive behavioral therapy, and other non-medication based approaches. Often the non-medication approaches can be more expensive than medication and it’s not clear that health insurance companies are willing to reimburse for these treatments. We are well aware that the providers, payers and patients often view pills as a low cost “quick fix”. More advocacy is required with health insurers to get them to reimburse for use of non-medication based approaches and for multi-disciplinary pain care.We hope that the change in labeling will open other avenues of caring for persons with pain without the increased use of opioids.


KZ: How will the label change help solve the crisis of unintentional opioid overdose deaths?

AK: We do not believe that the label change alone will solve the crisis. There are many things that need to happen to bring the problem under control. Because many of the overdoses are occurring in people with disease of opioid addiction, one of the most important things we need to do is to provide effective treatment for the millions of Americans who have become addicted. If we don’t provide them with treatment, people will continue to overdose and die. We will also see more people switch to heroin.But the other thing we must do is prevent new people from becoming addicted. Unless we can prevent new people from developing this disease, we will not be able to end the epidemic. We believe that the label change will help prevent new cases of iatrogenic addiction in chronic pain patients who are being overprescribed opioids and in teenagers who are too easily able to find opioids in the medicine chests of their friends and family.To sum up, through this petition effort, we seek to reduce the over-prescribing of opioids that’s harming pain patients and fueling this unprecedented public health crisis.Physician’s for Responsible Opioid Prescribing (PROP)