New FDA expert panels, such as recent meetings on SSRI use during pregnancy and on hormone replacement therapy during menopause, are drawing criticism for being one-sided. One leader says such panels are designed to reach a specific conclusion.
Earlier this summer, the FDA convened an expert panel to weigh the benefits and risks introduced by selective serotonin reuptake inhibitor use during pregnancy. However, the discussion immediately drew controversy due to the near unanimity of panelists critical of SSRIs, with 9 of the 10 experts presenting information that highlighted the potential risks of using the medication during pregnancy.
The FDA’s expert panels—the first of which took place in May—are a new format for the agency during which an “independent panel of scientific experts” will “review the latest scientific evidence, evaluate potential health risks, explore safer alternatives” and possibly offer recommendations for regulatory action.
Another such panel, held a week prior to the SSRI discussion, focused on menopause and hormone replacement therapy (HRT). As with the SSRI discussion, the panel faced criticism over apparent bias, with an overwhelming majority in favor of removing black box warnings for this type of treatment. Diana Zuckerman, president of the nonprofit National Center for Health Research, was struck by the lack of nuance presented during these panels.
“For SSRIs and for hormone therapy, two of the expert panels where I know the issues the best, these are areas with some nuance—you could have panelists who have a diversity of opinion,” she told BioSpace. “What I was most surprised by is how they didn’t do that. They didn’t want any nuance. It seemed they didn’t want any real difference of opinion.
A Lack of Balance
FDA Commissioner Marty Makary opened the expert panel on SSRIs and pregnancy by highlighting how the U.S. is “losing the broader battle” against mental health issues. Makary stressed the potential of alternative means, such as healthy relationships, communities and natural light exposure, to address the situation, before moving on to list the possible risks that SSRIs pose in pregnancy. His statement did not include any mention of the potential benefits of the drugs or the risks created by not taking them.
Mental health disorders pose significant risks for women in the perinatal period, accounting for 5%–20% of maternal deaths in high-income countries.
In the panel discussion that followed, nine participants highlighted the potential negative impacts of SSRIs on the fetus, including increased risk of congenital malformations, prematurity and low birth weight. Some panelists proposed adding a black box warning to the drugs’ labels for use during pregnancy. Only one participant, Kay Roussos-Ross, director of the perinatal mood disorders program at the University of Florida, covered the risks posed to pregnant women by not taking SSRIs to manage depressive symptoms.
“We should be having these regular discussions and reviewing the safety,” Christine Crawford, associate medical director at the National Alliance on Mental Illness (NAMI), told BioSpace. “I also encourage people to keep in mind that, yes, there are data to suggest there might be some issues related to being on an SSRI for the baby, such as persistent pulmonary hypertension. However,” she cautioned, “The likelihood of that happening is far, far, far less likely than someone becoming suicidal while pregnant, if they don’t take SSRIs or stop taking them.”
Christopher Zahn, chief of clinical practice at the American College of Obstetricians and Gynecologists (ACOG), concurred. In an email to BioSpace, he said that pregnant patients need to understand the risks of taking SSRIs, but added that it is also “critically important” they understand the dangers posed by not treating or under-treating their condition. “This concept is sometimes lost in the current environment around the FDA panel discussions,” Zahn said.
Limited Public Access
The FDA’s advisory committees—which have been in place since the 1970s and consist of an independent panel of experts who advise the agency on scientific, medical and regulatory issues, including the potential approval of new drugs and medical devices—are the closest parallel to the new expert panels.
Steven Grossman, policy and regulatory consultant and author of the FDA Matters blog, observed a difference in the makeup of the two formats. “Although from time to time there are accusations that an advisory committee was tilted to one side—even in those cases, it would be subtle and usually involve questions about one or two people, not almost the entire panel,” he told BioSpace in an email.
Zuckerman added that, in her experience, the panels appear to be less inviting to the public than traditional adcomms. The HRT panel Zuckerman attended was held in a much smaller room than is typical for an advisory committee. She noted that this was despite the fact that another adcomm meeting had just concluded, opening up a much larger space. The smaller room quickly filled up, she recalled, and people were turned away. There was also no opportunity for public comment.
Furthermore, the expert panels offered a shorter window for people to sign up to attend, Zuckerman said—less than a week—when compared with advisory committee meetings, which often have a period of three to five weeks to register.
Zuckerman was unfamiliar with many of the attendees, which she noted was unusual for a field in which she had worked for a number of years. This suggested that the audience, at least partially, was made up of invitees of the panelists, she said.
Confirmation Bias
For Zuckerman, the expert panels seem to be designed both to influence public opinion on the topic and also to send a message to industry: “This is the direction we’re going in. Feel free to push us in that direction.”
When asked about the purpose of the expert panels, a Health and Human Services (HHS) spokesperson told BioSpace in an email that “Commissioner Makary has an interest in ensuring policies reflect the latest gold standard science and protect public health.”
For industry, the results of the recent panels are varied. Removing black box warnings from HRT would be a clear opportunity for industry to benefit from increased sales of such products by reducing safety concerns, Zuckerman said. Conversely, adding a black box warning to SSRIs would likely be detrimental to industry sales—though with many of these products being off-patent, they are no longer especially lucrative.
Grossman suggested that the FDA’s focus on SSRIs could simply be a specific concern for Health Secretary Robert F. Kennedy Jr., Makary or even one of their associates. He added that strong pushback on SSRIs and mental health drugs, in general, has always existed.
If a black box warning were to be added to SSRIs in this context, Crawford said this would pose an even bigger barrier to the adoption of the medication by people with mental health disorders, particularly as pregnancy is a period when people are already likely to be anxious about their health.
“We’ve been through this before when the FDA had the black box warning on SSRIs for young people,” Crawford said. “We saw the number of prescriptions for SSRIs plummet and then rates of depression and suicide went up.”
When asked about how the FDA would interpret the conclusions from the panel, the HHS spokesperson said they would not comment on any potential future policy decisions.
