FDA has published its draft Guidance on evidence-based health claims: www.cfsan.fda.gov/~dms/hclmgui5.html. The utility of the Guidance is two-fold: to replace two prior guidance documents and to explain how FDA intends to (re)evaluate scientific evidence supporting qualified health claims and claims of significant scientific agreement (SSA). The Guidance is intended to help producers evaluate the strength of the evidence to support “health” claims; to describe the causal connections among the data; and to assess how the evidence fits within the totality of the evidence describing a substance/disease relationship. Also, “When FDA does (re)evaluate a health claim, it intends to use the scientific evaluation process described in the draft Guidance document.”

  • FDA “intends to focus...on (reports of) human intervention and observational studies because only such studies can provide evidence from which scientific conclusions can be drawn...” Have the studies specified and measured the substance that is the subject of the claim?  21 CFR 101.14(a) (2); (b) (2); and (b) (3) for the meaning of “substance.”  Have the studies appropriately specified and measured the disease or health-related conditions that are the subject of the claim? 21 CFR 101.14(a) (5).

  • The Guidance classifies the various types of studies available: intervention studies: “Randomized controlled trials offer the best assessment of a causal relationship...because they control for known confounders of results;” observational studies, (which) lack cause and effect controls; research synthesis; and animal and in vitro, which cannot be used to draw conclusions between the “substance and disease in humans.”

  • The Guidance gives several examples of “surrogate endpoints of disease risk” and opines that “risk biomarkers...have been shown to be valid predictors...and...may be used in place of clinical measurements.”

  • Human studies are to be closely examined and evaluated to determine what, if any, conclusions about a substance/disease relationship can be made. Studies from which scientific conclusions cannot be drawn about the substance/disease relationship are at this point eliminated from further review and consideration.  The Guidance lists a number of specific questions to be applied against both intervention studies and observational studies. The conclusions from observational studies of dietary intake of whole foods or multiple foods are inherently limited (according to the Guidance) as, “A study based on intake of a specific food or foods provides no information from which scientific conclusions may be drawn for the nutrient itself.”

  • The “methodological quality” of the remaining studies (those which have not been eliminated by one of the earlier determiners) is rated as “high, moderate or low.” Assessment factors include study design, data collection, statistical analysis, outcome measurements and relevance of the characteristics of the study population to the general public.

  • As an end point, the Guidance describes FDA’s intention to evaluate the strength of the totality of the scientific evidence. Factors include:  number of studies and study type; methodological quality rating; study outcome and statistical significance; consistency among other studies and relevance to the total body of scientific evidence; and relevance to the U.S. population. (Studies limited to a population sub-group would only support a limited claim of benefit for that group.)

  • The wording of the claim must reflect the scientific support “with specificity and accuracy.” For SSA claims, “a strong standard that proved a high level of confidence in the validity of the substance/disease relationship” is required, meaning that the “validity of the relationship is not likely to be reversed by new and evolving evidence.”

    The FDA has reaffirmed its regulatory position with regard to “sugar-free” claims in two letters: the first, a Warning Letter to a maker of “sugar-free” assortments; and, the second, a guidance document in the form of a “Dear Manufacturer” letter.

    In the letters, FDA reminds manufacturers that the claim of “sugar-free” (or similar claims) may not be used on or in connection with food products, unless the food meets the requirements of a “low-calorie” or “reduced-calorie” food or is labeled as a food for special dietary usefulness. If the food does not meet these weight-control criteria, the label must include the disclaimer that the food is “not a low-calorie food” or is “not a reduced-calorie food” or is “not for weight control.” The disclaimer must be in proximity to the “sugar-free” claim and be of appropriate type size.

    FDA is concerned that consumers associate a “sugar-free” claim with weight control or caloric reduction, and if the food is not reduced or low, this fact must be conspicuously disclosed. The FDA indicates that its prime focus will be on foods which fail to bear the correct disclaimer.