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How has the COVID-19 pandemic changed the landscape of health claims and clinical trials for dietary supplements? A panel including FTC’s Richard Cleland and industry contract research organizations discussed at the Institute of Food Technologists’ FIRST virtual event.
The COVID-19 pandemic has broadly influenced dietary supplement health claims—not just the claims companies are making but also the scientific studies needed to substantiate any health claims made. At the Institute of Food Technologists’ FIRST virtual event this week, a panel, including FTC’s Richard Cleland and industry contract research organizations (CROs), discussed the changes of the past year and a half.
As expected, health claims regarding immune support and COVID-19 are proliferating the dietary supplement market.
Panelist Kathy Musa-Veloso, senior director of health claims and clinical trials at scientific and regulatory consultant Intertek Health Sciences Inc., provided examples of product claims that regulators would consider explicit claims (directly stated) or implicit claims (alluding to the disease via other elements, including visual) related to the COVID-19 disease that would be considered illegal for dietary supplements.
Express claims including the words SARS-CoV-02 or COVID-19 are not allowed. Neither are claims in which effects on COVID-19 are implied, including claims of “supports immune function” followed by the hashtag #COVID-19 or even an image of the virus, citations of studies assessing the virus, or the word pandemic. References to signs and symptoms of COVID-19 also aren’t allowed, such as “alleviates shortness of breath and inflammation,” or claims about the body’s response to the vector, such as “reduces viral replication.” Finally, a supplement product name should not imply a connection to the disease, such as “CovRx” or “CovAway,” she said.
Such disease-related claims fall outside of the structure-function claims permissible for dietary supplements. And they are already happening. Panelist Richard Cleland, assistant director for the Division of Advertising Practices at the Federal Trade Commission’s Bureau of Consumer Protection, said that since March 2020, FTC has issued nearly 400 COVID-related warning letters, including 130 joint warning letters with FDA. “The good news,” he said, “is that we have had a very high level of compliance easily exceeding 95%.” The agencies take additional enforcement action against companies who don’t respond or who don’t take corrective action.
COVID-19 claims infractions have run the gamut. “Warning letters have been sent for everything from dietary supplements to chiropractic adjustments,” he said. In the supplements space, incidents have included ingredients like colloidal silver, vitamins C and D, zinc and other minerals, echinacea, elderberry, essential oils, and herbal teas. “And,” he added, “we’ve not focused on a particular class of targets, either. Warning letters have gone out to doctors and medical clinics as well as dietary supplement companies,” spas, and naturopaths.
Among some of the more alarming examples of infractions he pointed out was a company claiming that its vitamin D and zinc product "actually works better than…any vaccine.”
The bottom line is that any treatment or prevention claim regarding COVID-19 “requires well-controlled human clinical studies,” Cleland said. Observational studies are not sufficient substantiation, he said, “because, among another reasons, they generally do not rule out confounding factors nor do they address the issue of reverse causation.”
Cleland also called out vitamin D specifically. “With regard to vitamin D, the supporting evidence is mostly observational, and the scanty clinical evidence is inconsistent and flawed,” he stated. “Moreover, the relevant scientific question is not necessarily whether there is an association between vitamin D and the severity of COVID symptoms, but assuming that there is an association, whether supplementation has any effect and, if so, when does it have to be administered to be effective and what dose is effective? These are all questions of which currently there are no answers for.”
Cleland said FTC has also been closely monitoring “the promotion of products containing CBD [cannabidiol] for the treatment of serious life-threatening diseases.” So far, Cleland said, FTC has sent 14 warning letters to companies promoting CBD for COVID-19.
Companies that break the law also now face the wrath of the COVID Consumer Protection Act passed by Congress last December. The first company to be charged under the Act was the supplement company that claimed that its vitamin D and zinc supplement was superior to the COVID-19 vaccine in preventing the disease. The new law imposes a civil penalty of up to $43,792 per violation—meaning that if a company posted an unauthorized claim on the Internet, each post on the Internet would be considered a separate violation, as would each day the post remains live. “So, you could see that the amount of civil penalties could rise very quickly,” Cleland said. In addition, companies receiving warning letters have not only been asked to cease and desist selling the products, but some were required to pay consumer redress and to notify consumers that the product claims were unsubstantiated.
Immune-health claims must also be made carefully, cautioned Musa-Veloso. “The strength of the claim wording depends on the available scientific evidence,” she said. “For claims like ‘boosts/promotes/enhances/improves immune function,’ there must be evidence of a statistically significant improvement in the active group relative to the control group in a clinical endpoint or in a clinical response to the challenge.”
Moreover, she said, “For claims like ‘supports the immune system,’ there must be evidence of a statistically significant improvement in the active group relative to the control group in an in vivo or ex vivo marker.” Not only that, she said, but any changes in a marker must be able to be interpreted, and she cautioned to keep in mind that “there is so much redundancy in the immune system that some changes may be difficult to interpret.”
Moving Forward with Clinical Studies
Companies seeking to adhere to the law and to back their claims with clinical studies faced a new reality thanks to the COVID-19 pandemic. Just as the pandemic has been extremely disruptive to supply chains, raw ingredients, and even packaging suppliers in the industry, the pandemic interrupted clinical research. Fortunately, said panelist Mal Evans, chief scientific officer for contract research organization KGK Science Inc., the scientific community learned how to adapt.
“When the pandemic hit last year, clinical research was not immune to the challenges, uncertainties, and disruptions experienced across the world,” said Evans. “Over one year later, although still facing challenges, nutrition researchers are more agile, innovative, and passionate about the potential of the health and wellness industry. The pandemic does not need to be seen as a barrier and is certainly not an excuse for sloppy science or delaying conduct of clinical research. Instead, it has propelled the industry to a new era, and scientists have been forced to exercise their innovative muscle.”
She further noted that “gold-standard, randomized, double-blind, placebo-controlled clinical trials are still possible and do not have to be compromised” in the COVID environment. So, what’s changed?
Contingencies must be planned for, such as “reasonable” stop points—something FDA has provided guidance on—if a study needs to end earlier than planned. Evans said “decisions must be made on where the design can or cannot be flexible.” On the plus side, there’s also the chance to de-centralize study populations to be more reflective of the general population through the use of virtual clinical trials, or even a hybrid model. For virtual models, Evans advised researchers to account for ways to keep participants engaged and to retain participation.
The possibility that subjects will contract COVID-19, or had COVID-19 or the COVID-19 vaccine previously, also needs to be considered. Previously, Evans said, nutrition researchers primarily needed to consider whether subjects were healthy or vulnerable to a health condition. “Participants with COVID-19, however, represent a new population to study,” she pointed out. “Also, consider that those enrolled in the study may contract COVID-19 during the study and may not even know it.” It’s important to plan ahead for these types of drop-outs, she said.
Planning ahead will smooth the path for clinical trials in the COVID environment. “Contingencies need to be evaluated early in the protocol-development stage,” she advised. “If this is an afterthought, it will require protocol amendments, which can add time and expense.”
In the end, “Despite all these considerations and planning…complications may arise that need careful thought to navigate in order to make the most of your study results,” she said. “So, be ready to pivot. In addition to contingency planning, understanding of statistical guidelines will alert you to any surprises during data analysis. Knowing how to best account for and plan for participant dropout and manage [unexpected] outcomes and endpoints is crucial. The trial may also need to end early. In an unavoidable situation, you will need to critically review what data you have and adjust to maximize its value and what adjustments can be made in the analysis.”
The bottom line is that now is not the time to pull back on clinical studies. “Conducting a clinical trial while others are still hesitating is a great way to keep ahead in a competitive market,” she advised. “The opportunities for the industry are not limited by the pandemic. Claims substantiation through high-quality clinical trials and peer-reviewed publications of results remain attainable goals and provide marketing opportunities."
Being straightforward about any interruptions is also key. "Being transparent with the unplanned changes which happen during the trial is important," Evans said. "Stopping a trial early due to the pandemic does not need to prevent publication of the results.”