November 2, 2020
I’m Dr. Diana Zuckerman, president of the National Center for Health Research. [Next slide] Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. My expertise is based on post-doc training in epidemiology and public health, and as a faculty member and researcher at Vassar, Yale, and Harvard. I’ve also worked at HHS, the U.S. Congress, and the White House, and I’m on the Board of the Alliance for a Stronger FDA, which lobbies for more appropriations for FDA.
I will focus today on 2 issues: Risks vs Benefits and REMS
FDA requires evidence that drugs are safe and effective, defined as having benefits that outweigh the risks for most patients. For all opioids, REMS are crucial to reduce the known risks.
Nausea is terrible and Hydexor reduces it. But it’s my understanding that Hydexor’s efficacy for pain was compared to placebo, not to other less risky pain treatments. Data have shown that non-opioid pain meds can be as effective as opioids.
The REMS proposed today are very impressive. FDA has depended on REMS to reduce the risks of opioids, but they have been ineffective. Just a month ago, the Inspector General of HHS released a scathing report. But FDA had previously criticized opioid REMS 4 years ago.
The IG report focused on whether FDA held sponsors accountable for evaluating REMS and whether there was evidence that REMS were effective.
The IG report criticized the sponsors and the FDA for the lack of data on whether REMS truly work, but 2 of their findings seem especially relevant to this meeting:
- “Some opioid manufacturers engaged in deceptive marketing practices that undermined the REMS’ educational messages regarding risk.”
- “FDA has limited authority to enforce manufacturers’ compliance with their REMS.”
I’ll briefly show results from an evaluation of REMS that FDA provided to this Advisory Committee in 2016.
FDA reported that the analysis of an online REMS training program to ensure correct prescribing of opioids showed:
- 48% of physicians who took the training said they didn’t change their prescribing habits
- Only 49% used the Patient Counseling Document
- Most physicians didn’t know about REMS training
The fundamental issue is whether sponsors have an incentive to follow through on their REMS commitment:
- Better training will reduce prescriptions
- Alternative pain management therapies will reduce prescriptions
- A 2017 Boston Medical Center study found that the FDA Blueprint for Prescriber Education failed to provide prescribers with adequate information
Most physicians didn’t take the training, but what about those that did? The next 4 slides are pie charts that show some key information that the physicians were supposed to learn. The first pie chart shows that 1 in 3 physicians did not learn How to assess patients for opioid treatment.
This shows that 83% did NOT learn what was supposed to be taught about initiating, modifying, or terminating opioid treatment.
This slide shows that one-third did not learn general drug information about opioids.
This last pie chart shows that two-thirds did not learn specific product information.
In summary, there is clear evidence that opioid REMS have not worked in the past, and it is not possible to enforce them. So we encourage you to encourage the FDA to not approve an opioid that has not even been studied for efficacy compared to non-opioid pain meds, given the unproven ability to enforce REMS compliance.
The FDA Advisory Committee members voted 14-7 against Hydexor’s revisions to their previous indication and risk mitigation, and numerous members specifically expressed concern about enforcing the labeling and REMS.