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USE OF THE FRAMEWORK IN EVALUATING PROTOTYPE INGREDIENTS

The goal of the monograph development phase was to test the proposed process and learn from it to improve the overall framework. Below, each prototype is described as a case study to illustrate how principles and concepts from the Framework were used to meet the objectives of each step. The triggering signals are indicated as presumed in this illustration as it is not possible to know whether FDA would have initially detected them as signals or not.

Chaparral

Presumed Signals

Concerns expressed about the safety of chaparral by several authoritative sources signaled that chaparral’s safety should be investigated, as did several SN/AEMS1 reports of serious adverse events associated with chaparral use (coma, severe hepatic injury, hepatitis, and kidney failure).2 Authoritative sources included FDA itself which, before the Dietary Supplement and Health Education Act, issued a press release warning of a potential relationship between chaparral use and liver toxicity (FDA, 1992), and the American Herbal Products Association’s Botanical Safety Handbook (McGuffin et al., 1997) notation that Health Canada did not allow chaparral as an orally administered, nonmedicinal ingredient. Possible liver problems were also mentioned in several other secondary sources of information (Foster and Tyler, 1999; NMCD, 2002).

While the use of chaparral may not be widespread, the seriousness of the adverse events and the several authoritative sources citing potential problems, especially liver problems, were considered to be a strong signal requiring the evaluation of the nature of the evidence regarding potential liver and other problems. This is consistent with Chapter 4 guidelines that reports of liver necrosis or acute liver failure be considered in an expedited manner due to their potential for mortality and morbidity.

Initial Review: Considering the Nature of the Evidence

The nature of the case studies and reports to FDA were considered first, as described in Chapter 4. Serious adverse events occurred in individuals

1  

Special Nutritional Adverse Event Monitoring System, as available on FDA’s website.

2  

This chapter is presented as a review of the prototype monographs as case studies. The actual references for statements made are in the full prototype monographs available at www.iom.edu/fnb.



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