Fact Sheet on FDA's Draft Guidance for Industry:
Substantiation for Dietary Supplement Claims

The act does not define what constitutes "substantiation" for a claim made for a dietary supplement. For this draft guidance, FDA reviewed regulations, case law, the Federal Trade Commission (FTC) experience with its policy on substantiating claims made for dietary supplements in advertising, as well as recommendations from the Commission on Dietary Supplement Labels.

FDA's approach provides flexibility to manufacturers in the precise amount and type of evidence that constitutes adequate substantiation. Thereby providing a standard for substantiation may also help to preserve consumer confidence in these products.

FTC has typically applied a substantiation standard of "competent and reliable scientific evidence" to claims made for dietary supplements in advertising. FDA intends to apply a standard consistent with FTC's approach.

FDA considers the following factors important in determining whether information would constitute "competent and reliable scientific evidence":

• Does each study or piece of evidence bear a relationship to the specific claim(s)?
• What are the individual study's or evidence's strengths and weaknesses?
• If multiple studies exist, do the studies that have the most reliable methodologies suggest a particular outcome?
• If multiple studies exist, what do most studies suggest or find? Does the totality of the evidence agree with the claim(s)?

The first step in determining what information is needed to substantiate a claim for a dietary supplement is to understand the meaning of the claim and clearly identify each implied and express claim. Understanding the claim's meaning will help identify the appropriate study hypotheses and measureable endpoints, which can be used to ensure that the firm has appropriate studies to substantiate the claim.

Whether studies or evidence have a relationship to the specific claim being made or to the dietary supplement product itself is an important consideration in determining if a claim is substantiated. The following are some threshold questions in determining this relationship:

• Have the studies specified and measured the dietary supplement or dietary ingredient that is subject of the claim?
• Have the studies appropriately specified and measured the nutritional deficiency, structure/function, or general well-being that is the subject of the claim?
• Were the studies based on a population that is similar to that which will be consuming the dietary supplement product?

In deciding whether studies substantiate a claim, an important consideration is the scientific quality of studies. Scientific quality is based on several criteria including study type, study population, study design and conduct (e.g., presence of a placebo control), data collection (e.g., dietary assessment method), statistical analysis, and outcome measures. If the scientific study adequately addressed all or most of the above criteria, it would be considered of high quality. Generally accepted scientific and statistical principles should be used to determine the quality of the studies used as evidence to substantiate a claim.

In determining whether there is adequate evidence to substantiate a claim, firms should consider the strength of the entire body of evidence, including criteria such as quality, quantity (number of various types of studies and sample sizes), consistency, relevance of exposure, and persuasiveness.

Ideally, the evidence used to substantiate a claim agrees with the surrounding body of evidence. Conflicting or inconsistent results raise serious questions as to whether a particular claim is substantiated.

There is no general rule for how many studies, or what combination of types of evidence, is sufficient to support a claim. However, the replication of research results in independently conducted studies adds to the persuasiveness of the evidence.

Although the quality and persuasiveness of individual pieces of evidence are important, each piece should be considered in the context of all available information; that is, the strength of the total body of scientific evidence is the critical factor in assessing whether a claim is substantiated.