Yesterday the new Duke-Margolis Center for Health Policy (headed by Mark McClellan), held a conference titled, “Off Label Communication in 2016: Meeting Information Needs through New Policy Options.”
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”
