Yesterday I had the pleasure of attending and participating at the joint meeting of the FDA’s Drug Safety & Risk Management and Anesthetic and Analgesic Drug Products advisory committees.
The topics under discussion were the successes and failures of REMS programs for extended release (ER) and long-acting (LA) opioids. Many important presentations and discussion. Two statements that stood out as directional:
“REMS modifications shouldn’t unduly restrict patient access.” (Doris Auth, REMS Assessment Team Leader, Division of Risk Management, CDER)
“Education is not an event, it is a process.” (Graham McMahon, President & CEO, Accreditation Council for Continuing Medical Education)
In short – it’s important to move forward, weighing the risks and benefits of REMS programs not just for prescribers – but for patient too. Bravo.
I was chosen to offer public testimony, and here’s what I had to say:
To paraphrase Peter Drucker, the information revolution will shift -- from the generation of data, to figuring out the meaning and purpose of the data with the patient’s perspective in mind.
Nowhere is this more pertinent than in the discussion of the future of opioid pain medicine and the role of the FDA – and advancing both the science and regulatory approaches to appropriate pain care management. But cutting the Gordian Knot of what “appropriate” means demands more than current REMS programs. It requires working with the providers of continuing medical education to develop better curricula. It means ever better-validated risk evaluation and mitigation strategies with more thoughtful purpose.
It means enhanced and validated reporting tools for post-marketing surveillance. It means using real world data to provide real world advice. And it means using the tools of the 21st century century such as patient and physician apps.
The FDA can play an important role in working to develop and share (with a broad constituency) validated tools for physicians to use in determining which patients may be more prone to slide into abuse so they can choose their therapeutic recommendations more precisely.
One improvement will be to improve the accessibility of the ER/LA Opioid Analgesics REMS website, so that interested healthcare providers can more easily access accredited REMS-compliant material.
We must also work to continue expanding the to include the extended healthcare team. Education of team members beyond analgesic prescribers is critical for implementation of REMS learnings.
We should revise the FDA Blueprint for Prescriber Education to reflect stakeholder input and feedback
We should link Schedule II and Schedule III Narcotics DEA registration and re-registration to either completion of prescription opioid education or other acknowledgements, such as board certification in pain medicine. We should include IR opioids in the REMS modification discussion. It’s where the overwhelming volume is.
With the data collected from REMS programs, a logical next step is to utilize that real world data to amend product-specific labeling to indicate lessons learned outside of the rarified world of the randomized clinical trial environment to assist physicians in using the right product for the right patient. Real world evidence doesn’t just mean recognizing new risks, but also communicating new benefits learned through patient outcomes. And such evidence is both available and exciting.
Beyond the REMS programs discussed during the course of this meeting, the FDA has required all sponsors of brand name products with approved abuse-deterrent labeling to conduct long-term epidemiological studies to assess their effectiveness in reducing abuse in practice.
And then there’s the thorny question of FDA labeling. Product labeling is the basis for articulating the value proposition of a product. As you are aware, data definition and generation are very much still a work-in-progress – as is their relationship to clinical relevance. No absolute magnitude of effect can be set for establishing product characteristics. And the FDA continues to talk about the ambiguous totality of evidence standard – which really means using their best regulatory judgment.
One crucial question that deserves more conversation is the nature of the evidence used to decide whether or not a given product “works” to reduce abuse in the “real world.” Given the data challenges, it may be almost impossible to ever demonstrate a causal link between a new formulation and an impact on patient abuse – but is that because the product didn’t have an effect or our current measurement methodologies and data systems are inadequate to detect it?
The path forward is unclear. Is real world data reliable and robust enough? Should the FDA define and then assign various statistical weights to comparison and population studies? At the end of the day, the agency can’t only look to REMS for risk mitigation but must also seek out data that supports more aggressive labeling language.
Obviously, more work needs to be done in order to refine optimal data sources, study design, statistical methods, and epidemiologic outcomes of interest to developers, physicians, patients … and regulators. No one group can do it by themselves. We need a more, aggressive, creative, and collegial approach to the pain management ecosystem.
At the end of the meeting, the joint committee recommended mandating continuing education for doctors who prescribe opioids, ignoring American Medical Association calls for such requirements to be voluntary. The committee, which held no formal vote on the issue, also urged FDA to update its education materials by incorporating the new CDC guidelines on opioid prescribing and other material on alternative pain treatments. The committee suggested education be required for doctors seeking DEA registration to prescribe controlled substances.
The committee also urged the agency to update its risk evaluation and mitigation strategy to include shorter-acting opioids, amid criticism from some members that opioid manufacturers have too much influence over the strategy. The committee voted 30-0 to urge FDA to make changes to its entire opioid drug safety program. Some of the advisers said there was little evidence the current safety plan has had any effect, adding that it needed a greater emphasis on the drugs' risks.
The topics under discussion were the successes and failures of REMS programs for extended release (ER) and long-acting (LA) opioids. Many important presentations and discussion. Two statements that stood out as directional:
“REMS modifications shouldn’t unduly restrict patient access.” (Doris Auth, REMS Assessment Team Leader, Division of Risk Management, CDER)
“Education is not an event, it is a process.” (Graham McMahon, President & CEO, Accreditation Council for Continuing Medical Education)
In short – it’s important to move forward, weighing the risks and benefits of REMS programs not just for prescribers – but for patient too. Bravo.
I was chosen to offer public testimony, and here’s what I had to say:
To paraphrase Peter Drucker, the information revolution will shift -- from the generation of data, to figuring out the meaning and purpose of the data with the patient’s perspective in mind.
Nowhere is this more pertinent than in the discussion of the future of opioid pain medicine and the role of the FDA – and advancing both the science and regulatory approaches to appropriate pain care management. But cutting the Gordian Knot of what “appropriate” means demands more than current REMS programs. It requires working with the providers of continuing medical education to develop better curricula. It means ever better-validated risk evaluation and mitigation strategies with more thoughtful purpose.
It means enhanced and validated reporting tools for post-marketing surveillance. It means using real world data to provide real world advice. And it means using the tools of the 21st century century such as patient and physician apps.
The FDA can play an important role in working to develop and share (with a broad constituency) validated tools for physicians to use in determining which patients may be more prone to slide into abuse so they can choose their therapeutic recommendations more precisely.
One improvement will be to improve the accessibility of the ER/LA Opioid Analgesics REMS website, so that interested healthcare providers can more easily access accredited REMS-compliant material.
We must also work to continue expanding the to include the extended healthcare team. Education of team members beyond analgesic prescribers is critical for implementation of REMS learnings.
We should revise the FDA Blueprint for Prescriber Education to reflect stakeholder input and feedback
We should link Schedule II and Schedule III Narcotics DEA registration and re-registration to either completion of prescription opioid education or other acknowledgements, such as board certification in pain medicine. We should include IR opioids in the REMS modification discussion. It’s where the overwhelming volume is.
With the data collected from REMS programs, a logical next step is to utilize that real world data to amend product-specific labeling to indicate lessons learned outside of the rarified world of the randomized clinical trial environment to assist physicians in using the right product for the right patient. Real world evidence doesn’t just mean recognizing new risks, but also communicating new benefits learned through patient outcomes. And such evidence is both available and exciting.
Beyond the REMS programs discussed during the course of this meeting, the FDA has required all sponsors of brand name products with approved abuse-deterrent labeling to conduct long-term epidemiological studies to assess their effectiveness in reducing abuse in practice.
And then there’s the thorny question of FDA labeling. Product labeling is the basis for articulating the value proposition of a product. As you are aware, data definition and generation are very much still a work-in-progress – as is their relationship to clinical relevance. No absolute magnitude of effect can be set for establishing product characteristics. And the FDA continues to talk about the ambiguous totality of evidence standard – which really means using their best regulatory judgment.
One crucial question that deserves more conversation is the nature of the evidence used to decide whether or not a given product “works” to reduce abuse in the “real world.” Given the data challenges, it may be almost impossible to ever demonstrate a causal link between a new formulation and an impact on patient abuse – but is that because the product didn’t have an effect or our current measurement methodologies and data systems are inadequate to detect it?
The path forward is unclear. Is real world data reliable and robust enough? Should the FDA define and then assign various statistical weights to comparison and population studies? At the end of the day, the agency can’t only look to REMS for risk mitigation but must also seek out data that supports more aggressive labeling language.
Obviously, more work needs to be done in order to refine optimal data sources, study design, statistical methods, and epidemiologic outcomes of interest to developers, physicians, patients … and regulators. No one group can do it by themselves. We need a more, aggressive, creative, and collegial approach to the pain management ecosystem.
At the end of the meeting, the joint committee recommended mandating continuing education for doctors who prescribe opioids, ignoring American Medical Association calls for such requirements to be voluntary. The committee, which held no formal vote on the issue, also urged FDA to update its education materials by incorporating the new CDC guidelines on opioid prescribing and other material on alternative pain treatments. The committee suggested education be required for doctors seeking DEA registration to prescribe controlled substances.
The committee also urged the agency to update its risk evaluation and mitigation strategy to include shorter-acting opioids, amid criticism from some members that opioid manufacturers have too much influence over the strategy. The committee voted 30-0 to urge FDA to make changes to its entire opioid drug safety program. Some of the advisers said there was little evidence the current safety plan has had any effect, adding that it needed a greater emphasis on the drugs' risks.
