The lawsuit filed last year against Monster Beverage Corp. by the parents of a deceased 14-year-old girl highlighted the challenges government regulators face in deciphering the correlation between a reported illness and a dietary supplement.
In that case, which Monster is vigorously defending in a California state court, expert medical opinions are likely to prove vital in determining whether caffeine in energy drinks caused, or contributed to, the death of Anais Fournier, who suffered from a preexisting heart condition. FDA is investigating Fournier's death as part of a broader investigation into the safety of energy drinks.
FDA Unable to Detect Cause of Illnesses
A "serious adverse event," FDA officials caution, does not prove that a product is responsible for an illness. In fact, FDA rarely concludes what caused an illness associated with natural products because the data submitted to the agency contains scant details, according to a 58-page report from the U.S. Government Accountability Office (GAO).
Of the 6,037 adverse event reports (AERs) FDA received through 2011, the agency only established a "certain" relationship between the product and the reported health problem in 3 percent of the cases, the GAO revealed. In 67 percent of the incidents, FDA was unable to determine whether the dietary supplement caused the reported health problem because the AER contained inadequate information.
"Details such as underlying medical conditions and allergies are requested as part of the reporting process, but FDA officials said that there is generally a lot of missing information in both voluntary and mandatory AERs," GAO stated.
Industry is not necessarily to blame, according to Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), the Washington, D.C.-based trade association representing supplement manufacturers and ingredient suppliers.
"Sometimes, the consumer calls in, and they don't want to give you any information," he said. While a supplement firm may ask about a preexisting medical condition and request details on an emergency room visit, "They will tell you, 'It's none of your business,' and hang up. The company can only report what it can get."
For roughly half a decade, Monster and supplement firms have been required under federal law to report deaths, hospitalizations and other incidents that are associated with a product and defined as a "serious adverse events." In a 2006 position statement, several months before the Dietary Supplement and Nonprescription Drug Consumer Protection Act was enacted into law, CRN argued, "AERs provide early warning signals to FDA of potential product problems, like product contamination or adulteration, tampering, bioterrorism and ingredient safety issues."
Those early warning signs may be few and far between. The GAO analysis found it can take several months or years for the agency to detect a trend that would lead to a government demand or request that a dietary supplement firm withdraw a product from the market.
"FDA officials said that most AERs do not initiate or support consumer protection actions," the GAO report stated, "because it is difficult to establish causality based on the limited information in an AER."
The effective date for complying with the law was Dec. 22, 2007, and since it took effect, 257 unique firms have reported mandatory AERs, according to an FDA presentation in May 2013 at VIRGO's SupplySide Marketplace trade show in New York.
Underreporting of AERs Suspected
Government officials suspect underreporting. Although the GAO said an estimated 55,000 dietary supplements were on the market as of 2009 and half of the American population is said to take these diet and nutrient boosters, FDA received 6,307 AERs from 2008 through 2011. By comparison, the food and drug agency received more than 1.8 million AERs that relate to prescription drugs from 2008 through 2010.
Are supplement firms skirting their obligations? "Overall, I would say the industry has a good safety record," said Cara Welch, Ph.D., senior vice president of scientific and regulatory affairs with the Natural Products Association (NPA) in Washington, D.C.
There are some notable exceptions. For instance, in an Oct. 16, 2012, letter to Quincy Bioscience Manufacturing Inc. in Wisconsin, an FDA official alleged the company failed to report such serious adverse events as seizures, strokes and worsening of multiple sclerosis in connection with its Prevagen products. The brain vitamin is touted as a supplement that "can provide a healthier brain, sharper mind and clearer thinking."
Customers who took the vitamin reported the aforementioned medical problems, in addition to chest pain, heart arrhythmias and fainting, according to FDA. At the onset of an FDA inspection, Quincy Bioscience had only reported or investigated two adverse events of the more than 1,000 incidents and product complaints that had been reported to the firm between May 2008 and December 1, 2011, Michael Dutcher, an FDA director in the Minneapolis District, wrote in a warning letter. Dutcher did not specify the number of "serious" incidents that the company failed to report. Mark Underwood, president of Quincy Bioscience, did not respond to an emailed request for comment.
In another case highlighting the AER requirements, the U.S. Department of Justice accused two companies ATF Fitness Products, Manufacturing ATF Dedicated Excellence (MADE) and owner James Vercellottiof failing to report AERs and violating cGMPs (current good manufacturing practices). One AER included an incident in which a person went to the hospital and suffered a mild heart attack.
Last year, a judge signed a consent decree, permanently enjoining the firms from manufacturing or distributing more than 400 dietary supplements until completing measures to comply with the law. As of April 2013, the firms had not been authorized to resume operationsthe terms of the consent decree were still in place, an FDA spokesperson, Tamara Ward, said.
In its analysis of FDA inspection results from fiscal years 2008 through 2012, GAO found that FDA identified 20 problems in connection with AER requirements. In 17 of the 20 cases, the government report observed, FDA discovered the firm did not submit a mandatory AER.
Dedicate Personnel to Review AERs
Mister said a supplement firm should assign a person to regularly monitor AERs, and retaining specialists such as Safety Call International or PROSAR is certainly an option to assist with the reporting requirements.
Safety Call International noted last summer it has observed an increase in the number of supplement firms seeking assistance in evaluating their AER systems.
"Having an effective post-market surveillance system in place is not only important to regulators, it's something that every supplement company's insurance carrier wants to see in place as well," said Rick Kingston, Safety Call International's co-founder and president, in a statement.
Firms that don't outsource AER duties may be more prone to commit another type of oversight under the law: failing to include basic contact information on labels. A government report released last year found that 26 out of 127 labels on dietary supplements didn't contain phone numbers or complete addresses, making it difficult for consumers to reach a company in an emergency. Such neglect is seemingly inexcusable given how simple it is to include contact details.
"Do a label review and make sure you have the information on your label so consumers can contact the company," advised CRN's Mister. "It's a good idea to pick up the phone and dial the number on your label and make sure somebody is answering it."
Internal Analysis of AERs Could Detect Trends
Were it not for the mandatory AER lawthe Dietary Supplement and Nonprescription Drug Consumer Protection ActMonster Beverage may never have reported the death of 14-year-old Anais Fournier. Judy Lin Stefcu, a spokeswoman for the company, said the media actually brought the matter to Monster's attention. After Monster was sued by the girl's parents, it investigated whether, and how, its energy drinks played a role in her death. Although the case remains in the early stages of litigation, a group of medical experts Monster has retained contend the energy-drink maker is not liable for any wrongdoing.
While few reported adverse events result in fatalities and the kind of litigation that could expose a supplement firm to millions of dollars in damages (only 2 percent, or 92, of the 6,037 AERs reported death, according to GAO), supplement firms have ample incentive to evaluate each incident. Welch said it is important to analyze the data for all adverse events associated with a company's products, not just incidents that are required to be reported.
"You need to know what is happening with your product," she said. "If it's not causing serious adverse events but it's causing something that brings customers to the realization that this is an adverse event for them, they are probably not going to be purchasing" the product again.
Periodically reviewing the data might reveal trends or a pattern, such as a bad batch of products in a specific lot number.
"You solve the problem before FDA has to come find it," Mister observed. "That makes you the responsible company."