US finalises advisory panel conflict-of-interest guidelines
This article was originally published in Scrip
The US FDAhas finalised new conflict-of-interest policies for advisory committee members that are stricter than current standards though not as severe as initially proposed.
The new requirements will preclude individuals with "disqualifying financial interests" exceeding $50,000 from participating in panel meetings. If an individual has personal financial interests below the $50,000 limit, the FDA may grant a waiver to participate as a voting or non-voting member or speaker if that person's expertise is deemed essential to the panel meeting.
In deciding whether an individual has essential expertise, the FDA will consider the uniqueness of the expert's qualifications, the difficulty locating a similarly qualified individual without a disqualifying financial interest and the agency's inability to find similar expertise on other panels or among existing consultants.
The guideline, which will take effect for advisory panel meetings starting in December, revises and finalises reforms announced last year that were aimed at improving transparency and public disclosure of conflicts of interest among panellists.
The agency said its review of potential conflicts will be more stringent than both its current policy and the legal requirements in the FDA Amendments Act. There currently is no financial threshold for determining whether an individual can participate and vote in a panel meeting. Under FDAAA, the agency must reduce the number of waivers granted by 25% over five years.
In a March 2007 draft guideline, the agency had proposed allowing only those panel members with no disqualifying financial interests to vote at meetings. Non-voting waivers would have been available for individuals whose financial interests fell below the $50,000 cap. The change from the draft proposal stemmed, in part, from public comments expressing concerns about restricting the pool of potential voting members to those without any financial interests.
no imputed interests
Disqualifying financial interests include grants, stock holdings and contracts with a company that would be affected by a panel's recommendations. However, university grants that are not directly tied to a potential advisory committee member will not count as disqualifying financial interests.
Jill Hartzler Warner, an FDA senior policy advisor and counsellor, said the draft guideline set a $50,000 cap for all potential conflicts of interest, including those imputed to the individual. This would include a situation where an individual is employed by a university that gets a grant from a sponsor company, but the individual does not draw a salary from, or conduct the work under, the grant.
In contrast, the final guideline sets a cap only for personal financial interests, including those of the spouse and minor children. "This change was made in response to public comments that pointed out that financial interests like this – imputed to the individual – can be substantial, but the potential for conflict or even the appearance of conflict is remote," Ms Warner said.
The FDA outlines several scenarios in which it will not issue a waiver even though the potential financial conflict is below $50,000. Waivers will not be granted if an individual or his employer receives a grant or contract from a firm that is sponsoring the product application under review, or a competing product, and the individual is the principal investigator. Similarly, a waiver will be denied if the individual is the head of the department conducting the studies and receives personnel or salary support, has input on the clinical trial design or reviews the study data.
The agency also finalised guidance documents on the public availability of panellists' financial interest information and waivers, submission and public availability of panel meeting briefing materials, and meeting voting procedures. Many of the provisions outlined in these documents – including public posting of briefing materials two business days prior to a meeting and simultaneous, rather than sequential, voting – have already become the norm for drug-related panel meetings.
when to convene
New to the package of advisory committee guidance documents is a draft guideline explaining three factors the FDA will use in deciding whether to hold a meeting. The agency will convene a panel meeting when a matter is of such significant public interest, or so controversial, that it would be highly beneficial to obtain the panel's advice as part of the regulatory decision-making process. The agency also will consider whether a panel could provide a special type of expertise needed for it to fully review an issue.
"In the event that one or more of these factors is met, the matter at issue should generally be referred to an advisory committee," the guidance document says. "Conversely, FDA personnel should generally refrain from referring a matter to an advisory committee if none of the factors is met." Examples where one or more of the factors is frequently satisfied include:
? First-in-class drug or significant new indication
? Novel product or use of new technology
? Product involves a significant diagnostic, therapeutic or preventative advance
? Assessment of the risk/benefit of a product or therapeutic class is likely to be controversial, or it appears the risks and benefits are of similar magnitude, especially where the products have a narrow therapeutic effect
? Significant pre-marketing or postmarketing safety concerns about a class of products
? Significant questions about the use of a product in certain subpopulations
? Significant questions about a study
? FDA staff have significant differences of scientific opinion on a complex matter
? Rx-to-OTC switch.