Ingredients for the six prototype monographs were selected based on limited knowledge, that is, a signal that a risk might exist. In going through the process, it became apparent that it is important initially to evaluate the signal of concern before investing effort and resources to do an exhaustive integrative evaluation. Thus the initial review step in the process was developed to use the guiding principles and spectrum of concern guidelines in Chapters 4 through 8 to efficiently determine if further investigation is warranted (i.e., to set priorities).
The initial review step in the process describes how a relatively cursory review of information about a particular signal will allow FDA to determine a preliminary level of concern as lower, moderate, or higher. The six ingredients illustrate that considering how the information fits into the spectra of concern described at the end of Chapters 4 through 9 will provide enough context to preliminarily determine how much concern the original signal warrants. The prototype ingredients also illustrate that additional information related to the original signal is also often needed to determine how much concern is warranted. If the signal resulted in a moderate concern level, considering other types of data helped determine whether other signals would also suggest value in conducting an integrative evaluation.
Finally, from a public health as well as a limited resources perspective, it is also appropriate to consider the prevalence of use and use by particularly susceptible populations at this stage in the process. An ingredient such as chaparral would not be as likely to affect as many persons, even if harmful, because of its limited current use. Saw palmetto, on the other hand, is used by a large number of U.S. men, warranting its consideration even if the initial review does not characterize concerns as a higher level.
In summary, no decisions regarding the potential for harm are being made in this step; the evaluation at this point is to decide if sufficient concern has been raised by the signal (and/or consideration of other evidence in the case of an initial moderate concern) to suggest an integrative evaluation is warranted. This step in the process allows FDA to set priorities for determining which dietary supplement ingredients require integrative evaluations and when continued monitoring might be a better use of limited resources.
Among the six prototypes developed for this report, only two remained at a higher level of concern after the initial review (chaparral and melato-