NCHR Testimony of TIRF REMS

Stephanie Fox-Rawlings, National Center for Health Research: August 3, 2018

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our Center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.

Our Center worked with Congress to create the REMS [risk evaluation and mitigation strategy] program in legislation that became law quite a few years ago.  The goal always was to enable FDA to approve effective drugs even if they had worrisome risks. The REMS were intended to lower those risks as much as possible, so that patients taking the drug were most likely to be helped and least likely to be harmed.

A major shortcoming of these risk mitigation strategies has always been ensuring that they are effective in lowering risks.  It is difficult to evaluate the effects of the REMS on prescribers, pharmacists, patients, and others who accidentally or intentionally misuse the drugs.

The data before you today that evaluated these REMS are limited.  However, we commend the efforts of TRIG [TIRF REMS Industry Group] and the FDA to assess these REMS and to improve the data as well as the effectiveness of these REMS. We strongly urge that TRIG implements the FDA recommendations in a timely and complete manner to more fully understand to what extent the REMS are or are not working, so that they can increase the benefit to risk ratio of their products.

The data are especially limited regarding the proportion of prescriptions for cancer pain or other indications.  That is a big problem since this product is only approved for cancer pain.

And, also like the FDA reviewers, we are very concerned about the increased rate of adverse events after implementing REMS.  Even though the reports are voluntary and therefore could be biased, the increase after REMS is very disturbing. The quality of the REMS data are also low because only a subset of potential events are evaluated.  This makes the data very difficult to interpret. However, other sources of data also suggest that there are concerning numbers of therapeutic errors, misuse and exposures with severe consequences.

Congress supported REMS because they were intended to reduce the risk of serious harms, while continuing to make the product available to those who need it. The data indicate that these REMS need improvements. For example:

  • 42% of new users were not opioid-tolerant. That is not the indication, so that means at least 42% are prescribed off label.  This increases the risk for central nervous system and breathing problems.
  • Relatively high proportion of survey respondents did not know the correct indication or that TIRFs need to be stopped if around-the-clock opioid medication is stopped.  They learned this in the training, but could not remember it when surveyed later.

Changes to the REMS should be designed to make them more effective at protecting patients. Changes in REMS should not be aimed primarily at increasing the number of prescriptions.  An increase in prescriptions without ensuring appropriate prescribing, dispensing, use, and disposal increases the risk that more patients will be harmed, and that the drugs will be used accidentally or misused by individuals who were not prescribed the drug.

Bottom line: TIRFs [transmucosal immediate-release fentanyl] provide important options for cancer patients dealing with pain. However, we all know that they carry very serious risks and that’s why we need REMS that protect patients’ these risks.  These REMS are not working as well as the should to protect patients and need to be improved.