NEJM Study on Dietary Supplement Adverse Events Deserves Closer ScrutinyOctober 21, 2015
“Bad reactions to dietary supplements are sending thousands of Americans to the ER every year, a new study shows.” That’s the attention-getting lead in a CBS News story dated October 15. It was based on a study report appearing in the New England Journal of Medicine. The NEJM study reported results of surveillance data about ‘dietary supplement-related’ adverse events, collected from 63 emergency departments in the United States between 2004 and 2013. The study casts a wide net to include, among adverse events, unsupervised ingestions by children and incidents where seniors were in the emergency room because of difficulty swallowing their supplements.
The Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA) responded to criticize the study, challenging the method of data selection and the methodology used.
The authors of the NEJM article are CDC and FDA personnel, and the critics express wonder about why the authors used data from emergency room visits and not the adverse reaction reports for dietary supplements that were given to FDA since 2008; it would seem that these adverse reaction reports are exactly on point. The critics also note that data concerning products that are not dietary supplements were included among the reports of ‘related’ adverse dietary supplement events, confounding the application of the study’s data to dietary supplements. The response of CRN and NPA goes on to address and mostly contradict or find a lack of significance for each of the report’s assertions. And the authors of the NEJM article themselves identify weaknesses in the sample size and the statistical information the data can provide.
There is another question about the study that deserves attention. The report says “[c]ases were defined as emergency department visits for problems that the treating clinician explicitly attributed to the use of dietary supplements.” This could and perhaps should be taken to mean that the clinicians actually said the ingested supplement caused the problem. Elsewhere in the report, however, the authors talk only of ‘supplement-related’ events, and some of the charts identify the events as ‘associated with’ supplements. There is good reason for this terminology to raise questions.
Years ago, FDA wanted to take a regulatory action with sulfites for use on foods, and claimed that the administrative record demonstrated that sulfites on foods caused – were ‘associated with’ – deaths. Examination of the record, however, showed that not to be the case. For example, in one instance ‘associated with’ meant that a fellow had eaten at a Mexican restaurant, ingested sulfite-treated food, and died in a motorcycle crash on his way home. In that instance and others in that record, the agency incorrectly treated ‘associated with’ to mean ‘caused.’ So it would be good for there to be a clarification, based on the accepted tenets of toxicology, of the meaning of the words ‘related’ and ‘associated with’ in this study – was there an allegation or actual evidence of causation by a dietary supplement of the adverse events or did the personnel who collected and worked with the emergency room documents make that assumption?
The FDA and others, including the NEJM, have long wished for the agency to have the power to deal with dietary supplements as they do with pharmaceuticals, to have the preclearance authority and the other statutory supervisory powers. Over the years, FDA personnel have consistently remarked upon the dangers they see are created by their lack of such complete authority. This theme is given extensive and generous treatment in the NEJM study. The publicity given to the study report, and the statements given by the authors to the press, are unabashed promotions for FDA to be given the controls that the law currently does not give the agency. In the scheme of things, the dietary supplement industry, absent some heroic effort, cannot expect to be given much attention as it makes its responses.
No matter what the final judgment is for the NEJM study, whether it is sound or truly useful as a basis for social policy, the study has done what was intended, as demonstrated by the call-to-action headline of the CBS story; that is, governmental bodies and the public will be influenced to extend regulatory powers over dietary supplements. Whether that will be sufficient to achieve the regulators’ goal remains to be seen.