Trade groups slam DSHEA 2.0 proposal related to adverse events

Editor’s note: This is the third article in a series on proposed reforms to DSHEA by several consumer groups in a recent letter to Congress.

Some consumer advocacy groups want U.S. lawmakers to impose a new requirement that manufacturers of dietary supplements report to FDA all “adverse events” associated with their products.

In a March 10 letter to members of Congress recommending reforms to the Dietary Supplement Health and Education Act of 1994 (DSHEA), the Center for Science in the Public Interest (CSPI), Consumer Federation of America (CFA) and other groups proposed strengthening adverse event reporting through a new requirement in the law.

“Supplement companies should be required to report all adverse events linked to their products by having to report all events, and not merely those that they self-designate to be ‘serious,’” the letter stated.

Under current law, the manufacturer, distributor or packer of a dietary supplement whose name appears on a label must report to FDA all “serious” adverse events associated with their products, such as a death, life-threatening experience or inpatient hospitalization.

Companies also must maintain for six years records of all adverse event reports they have received and make them accessible to FDA during an inspection. Considering dietary supplement firms already need to make these records available during an FDA inspection, “why not give them to FDA” so the agency has “the full picture?” asked Laura MacCleery, policy director of CSPI.

Related:Consumer groups ask Congress for 'DSHEA 2.0'

Providing FDA all adverse event reports associated with dietary supplements would give the agency “a better read on the whole landscape of issues in the supplement marketplace,” MacCleery said in an interview. “We’re just trying to make sure FDA knows what it currently doesn’t know about what’s going on with supplements and that the companies aren’t the gatekeepers here in terms of deciding what information FDA should have.”

The consumer groups’ proposal “makes no sense,” considering the industry’s track record when compared to pharmaceuticals, according to Dan Fabricant, Ph.D., a former FDA official who leads the Natural Products Association (NPA).

“Groups like this never say, ‘Hey, I’m working with a medical establishment to get them to better understand MedWatch or to get them to better understand the system to submit adverse events,’” Fabricant said in an interview. “It’s always, ‘We need everything.’”

No data supports the notion that dietary supplements are a “highly dangerous class of goods that needs more attention,” said Michael McGuffin, president of the American Herbal Products Association (AHPA), in an interview. “If we’re looking at proper application of resources—both industry and agency—please let’s not create a paperwork morass just for the sake of being able to claim more numbers of adverse events associated with vitamins and minerals and herbs. There’s not a problem to be fixed here.”

Related:DSHEA 2.0 proposals leave room for finding common ground

In FY20, FDA received about 3,100 adverse events related to dietary supplements, according to FDA’s recent FY22 budget proposal to Congress. Clinical reviewers in the agency’s Center for Food Safety and Applied Nutrition (CFSAN) analyze the reports to determine if there are any potential safety issues that need to be investigated more thoroughly.

Adverse events in the CFSAN Adverse Event Reporting System (CAERS) feature many limitations and do not reflect the agency’s conclusion whether a product actually caused the adverse event, FDA notes on its CAERS webpage.

Rick Kingston is co-founder of SafetyCall International, which provides adverse event management and regulatory compliance services. Adverse events “don’t demonstrate a cause and effect relationship” but merely identify “a potential safety signal” that must be more deliberately investigated, explained Kingston, who also is SafetyCall’s president of regulatory and scientific affairs.

Kingston doesn’t support the consumer groups’ proposal to require that all adverse events linked to supplements be reported to FDA. He noted adverse events often exclude crucial information, such as an incident narrative detailing the onset and duration of symptoms, ingredients profile of a product and a person’s medical conditions.

“Anybody can report anything,” he said in an interview. “It’s sort of like the hotline for ‘America’s Most Wanted.’ You get 10,000 tips and there’s maybe only a handful that represent something that is actually germane to the investigation, which means that you’ve got a lot of background noise.”

Kingston concluded “throwing in all of the stomachaches and everything else that somebody comes up with into a big database is just not going to be conducive to good post-market surveillance.”

Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), questioned how FDA would process all the adverse events associated with dietary supplements if Congress adopted the consumer groups’ proposal.

“It would overwhelm their systems and it wouldn’t be useful,” he said in an interview. “Every person who complains of a headache or an upset stomach—that’s going to get sent to the agency?”

MacCleery contested the idea that FDA couldn’t meaningfully process all adverse events associated with dietary supplements.

“We live in an era of massive amounts of data that are sorted by intelligent programming,” she said, “and FDA can certainly use tools like that to deal with the influx of new information.”

FDA is boosting its technology capabilities. In its FY21 budget request to Congress a year ago, FDA requested $10.2 million for “Artificial Intelligence and Other Emerging Technologies," including $1.6 million for CFSAN.

Congress in FY21 appropriated $7 million to FDA for the above technologies, according to an FDA spokeswoman. As part of that $7 million, $1.073 million was appropriated to CFSAN, she said. 

In an April 14 conversation with the Alliance for a Stronger FDA (Alliance), FDA’s acting commissioner, Dr. Janet Woodcock, discussed the agency’s use of new technology in post-market surveillance.

“The use of AI in post-market surveillance and signal detection will enhance CFSAN’s ability to detect potential problems associated with CFSAN commodities, including leveraging data to investigate outbreaks and potential issues with chronic, long-term consumption of food constituents and contaminants or long-term use of cosmetics,” Woodcock told the Alliance. “FDA will ultimately utilize this information to enhance the science that supports our guidance to industry for protecting public health.”

Woodcock added using AI “in the post-market space will streamline the review of adverse event reports [AERs] for foods, dietary supplements and cosmetics so that FDA can act more quickly to intervene earlier, including by removing unsafe products from the marketplace.

FDA declined to comment on the consumer groups’ adverse event reporting proposal.

Dr. Pieter Cohen is an associate professor of medicine at Harvard Medical School, whose research on dietary supplements has been widely reported in the mainstream and trade press.

Cohen, one of the signatories to the March 10 letter recommending reforms to DSHEA, said there is room to improve the effectiveness of adverse event reporting for dietary supplements. For example, he noted poison control centers who receive calls related to supplements may not be relaying that information to FDA.

“The system’s broken,” Cohen said in an interview. “How we fix it is a really important question for us to all get our brains around.”

Cohen noted doctors may not consistently ask their patients about the dietary supplements they are taking and consumers may not be volunteering such information—further limiting the adverse events FDA receives that are associated with supplements. He said consumers and doctors need to be better educated so such adverse events that potentially pose serious risks are getting reported to FDA.

“If patients aren’t telling their docs [and] docs aren’t asking, there’s no way the doc is going to connect the dots and call the poison control center or report anything to FDA,” Cohen remarked.

While Kingston of SafetyCall International doesn’t support the consumer groups’ proposal, he favors requiring manufacturers prepare an annual review of their products’ safety—based on all their adverse events—and make the report available upon request from FDA.

Companies selling products, Kingstone added, are “in the best position to conduct that safety review.”

McGuffin of AHPA doesn’t see a reason to fiddle with the adverse event reporting system as it applies to dietary supplements.

“That system that works is identifying ‘signals’ as FDA says, and there aren’t very many of them, and that’s good,” he said. “[If] we move to something like ‘report all adverse events’ or even an annual summary of adverse events, you create background noise. If we had some indication that we were a wildly dangerous class of goods, maybe, but that’s not what the data shows…We may well be the safest class of goods regulated by the Food and Drug Administration.”

When asked to respond to assertions by industry representatives that supplements are among the safest categories of FDA-regulated goods, Cohen of Harvard Medical School suggested stakeholders should do everything they can to limit any harm associated with them.

“These are products that should be safe to use,” the physician said, “and I should have confidence that when I recommend supplements to my patients, they’re going to be safe.”