FDA overrides adcomm opinions a fifth of the time, study finds — but why?
For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.
A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.
Most of the time the FDA opted for a more restrictive stance than the experts. Among the 83 instances of discordance, 75% ended with regulators pushing for tougher decisions for the applicants.
But perhaps the more important question is, in what situations do they disagree?
First, let’s set the scene: The majority of those meetings (63%) involved drugs, 21% were about biologics, and 16% concerned medical devices. The subjects ranged from initial product approvals (72%), supplement indications (21%) to safety actions (7%). And the period covered the tenure of three commissioners, Andrew von Eschenbach, Margaret Hamburg and Robert Califf.
The researchers hypothesized several factors that could predict discordances, including types of actions, degree of consensus among panel members, presence of experts with conflicts of interest, public opinion (as captured by speakers and media coverage), and medical need (using orphan or other statuses as a proxy).
They found that the types of actions mattered — for instance, the FDA was more likely to disagree with experts on safety matters — as did how much the adcomm members agreed with each other. Presence of members with COI to declare, advocates coming to the adcomm meeting, coverage in the New York Times, or special regulatory designations? Not so much.
Here’s their theory:
Although advisory committee members and FDA agency members may be broadly aligned in their goals, issues like the agency’s concerns about its reputation may result in different patterns of decision making. For example, the FDA has an incentive to avoid reversing earlier decisions insofar as those reversals might damage its credibility.
That would explain why regulators are more inclined to maintain an existing product’s availability by taking a less restrictive stance on safety issues, while drawing a firmer line over novel products and new indications.
The findings are in line with literature cited in the paper, which the researchers — Audrey Zhang New York University together with Jason Schwartz and Joseph Ross at Yale — say are less comprehensive but suggest that regulators agree with adcomms 60% to 87% of the time.