NCHR Testimony at 2016 FDA Advisory Committee Meeting on Opioid REMS

Thank you for the opportunity to speak today. My name is Dr. Tracy Rupp. I was previously a clinical pharmacist at Duke University Medical Center and am now the Director of Public Health Policy Initiatives at the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from the drug or medical device industry and I have no conflicts of interest.

Our Center strongly supports research and programs to improve the safety and appropriate use of opioids. In 2012, health care providers prescribed enough opioid prescriptions for every adult in the United States to have a bottle of pills;[1] and in 2014, more Americans died of opioid overdose than any other year on record.[2] Amidst a crisis of mounting deaths from opioid overdose, we must re-examine whether REMS for opioids are actually reducing the risks associated with their use.

REMS were developed to enable the FDA to approve drugs with serious risks, like opioids, by providing a mechanism to mitigate those risks. But, as we have heard at this meeting, data from the fourth REMS assessment show that we still don’t know whether opioid REMS are effective at reducing either inappropriate prescribing or opioid overdose.

Since only about 20% of long-acting opioid prescribers have completed the voluntary REMS training and 41% of prescribers are not even aware such training is available, it’s not realistic to expect the program to have a significant impact. Of those who have completed training, the prescriber survey indicates gaps in knowledge about initiation, modification, and discontinuation of opioid therapy.[3] Skill in these areas is critical to safe and appropriate opioid prescribing. It is very disappointing that so few prescribers have been trained and, after repeated REMS assessments, we still don’t know if opioid REMS are effective even when prescribers are trained. For those reasons, we support a mandatory prescriber training program that is linked to a prescriber’s DEA registration and rigorously tested for its ability to mitigate the risks of opioid use.

The less-than-rigorous approach to studying the effect of REMS should not be acceptable to any of us, given the scope of the opioid overdose problem. FDA reviewers pointed out many limitations in the applicant’s patient and provider surveys. For example:

• the prescriber study sample was not randomized or self-controlled with pre- and post-test comparisons;
• self-reported behavior was not validated for either prescribers or patients; and
• we don’t know how the surveyed population compares to the targeted population.

It is also not possible to know whether the REMS training itself is responsible for the observed changes in opioid use, since the changes began prior to the implementation of REMS. We strongly urge the FDA to require a more rigorous evaluation of the REMS training where actual behavior, rather than self-assessed behavior or knowledge, is studied. The study should be a well-controlled longitudinal study with the behavior of prescribers who have taken the training compared to behavior of those who haven’t received training. The study should also be designed to tell us whether the opioids that are prescribed are being prescribed appropriately at the patient level.

We also support expansion of REMS to include immediate-release forms of opioids. Most patients who start taking opioids are initially prescribed immediate-release products. There is some evidence of an increase in the use of some immediate release opioids under some circumstances. For example, drug patterns and prescribing behavior data show that, despite a decrease in overall immediate-release opioid use, the use of immediate-release oxycodone actually increased. Similarly, self-reported non-medical use of short- and long-acting opioids increased among college students in the years since REMS have been required. Effective REMS could potentially help reduce the inappropriate use of immediate release opioids.

Lastly, we urge the FDA to perform its own assessment of the effectiveness of opioid REMS on an ongoing basis and make the data publicly available on the FDA’s website. Currently, REMS assessments are completed by the application holder and reviewed by the FDA. This process cannot ensure that assessments are unbiased, accurate, or rigorous. Given the enormous costs of opioid abuse in terms of human life, quality of life, family tragedies, and lost productivity, we must be certain that REMS assessments are providing unbiased information about the effectiveness of the program. Making the data publicly available would allow stakeholders to perform their own assessment of the program’s effectiveness.

In conclusion, if we want to reduce deaths and addiction due to opioids in the United States, we must demand more from everyone involved. Prescribers must be better informed, REMS assessments must be more rigorous, and the data must be transparent. We all must work together to find more effective solutions to the challenge of opioid abuse.

Thank you for the opportunity to comment today and for consideration of our views.


1. Paulozzi LJ, Mack KA, Hockenberry JM. Vital signs: variation among states in prescribing of opioid pain relievers and benzodiazepines—United States, 2012. MMWR Morb Mortal Wkly Rep 2014;63:563–8.
2. MMWR: Increases in Drug and Opioid Overdose Deaths-United States, 2000-2014: January 1, 2016/64(50); 1378-82.
3. Tables 4-9, 36th month assessment of the ER/LA Opioid Analgesics REMS Assessment Report.