The US Food and Drug Administration (FDA) on Thursday released new draft guidance on its benefit-risk assessment framework for opioids, outlining how the agency plans to compare the effectiveness and safety of new opioids with already approved opioids.
The idea for a comparative approval standard, discussed by former FDA Commissioner Scott Gottlieb
in March before a Senate committee, hinges on the fact that “FDA believes that there should be a premarket demonstration that a new opioid is superior to an already-approved opioid,” Gottlieb said.
The new 7-page draft guidance lays out a series of questions that FDA says it will consider in assessing the effectiveness and safety of a new opioid:
- “Do any comparative efficacy data exist for the drug relative to approved opioid or nonopioid analgesic drugs? Does this analgesic drug offer any advantages relative to available approved analgesic drugs for each indication, with regard to effectiveness or duration of response?
- Do any comparative safety data exist for the drug relative to approved opioid or nonopioid analgesic drugs? Does this analgesic drug offer any other safety advantages or disadvantages relative to available approved analgesic drugs for each indication (e.g., abuse-deterrent properties, less risk of drug-drug interactions)?
- What is the anticipated benefit-risk balance relative to available approved analgesic drugs for each indication? Do any comparative safety data exist for the drug relative to approved opioid or nonopioid analgesic drugs? Does this analgesic drug offer any other safety advantages or disadvantages relative to available approved analgesic drugs for each indication (e.g., less risk of drug-drug interactions)?
- Does the drug have any other advantages over other available approved analgesic 153 drugs (e.g., can be mixed with food)?”
But FDA also notes a major caveat to this plan for comparing the effectiveness and safety of new opioids with older ones, adding that, “While the comparative data described above is helpful in applying the benefit risk framework, superiority to other available treatments is not a requirement for approval under FDA’s drug approval authorities.”
Still, the agency further pledged to evaluate, in addition to effectiveness and safety, the ways in which an opioid positively or negatively affects public health, including the drug’s potential effect on both patients and nonpatients, including members of a patient’s household.
The draft also discusses how and why a class-wide risk evaluation and mitigation strategy (REMS) is necessary for all opioids intended for outpatient use.
In addition to the draft guidance, FDA said in a Federal Register notice
that it will hold a public meeting on 17 September entitled, "Standards for Future Opioid Analgesic Approvals and Incentives for New Therapeutics to Treat Pain and Addiction."
“This public hearing is intended to receive stakeholder input on the approval process for new opioids and how FDA might best consider the existing armamentarium of therapies, among other factors, in reviewing applications for new opioids to treat pain,” FDA said.
The agency is also withdrawing
the 2014 draft guidance, “Analgesic Indications: Developing Drug and Biological Products.”
And FDA plans
to issue additional guidance that will outline appropriate clinical endpoints and clinical trial approaches for the development of non-opioid drugs for use in the treatment of acute and chronic pain.
The release of new FDA guidance also follows the World Health Organization's decision to withdraw
its own guidelines on opioids because they were alleged to be influenced by the pharmaceutical industry.
Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework Guidance for Industry