Rx for Claim Substantiation (Part I) – The Claims –

A health claim can be made for a food or supplement ingredient provided the claim is substantiated by human clinical data.

By definition, a health claim has two essential components: a substance and a disease or health-related condition. Pursuant to Pearson v. Shalala and Whittaker court decisions in the late 1990s, and most recently by the Task Force Report of 2003, the Food and Drug Administration (FDA) issued the “Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims” in July 2007. The guidance outlines the review process used by the agency in determining whether the scientific evidence meets the significant scientific agreement (SSA) standard or, if not, whether the evidence supports a qualified health claim (QHC).

Additionally, the review process encompasses a regulatory assessment and ensures that the ingredient for which the claim is made meets the “reasonable certainty of no harm” safety standard (as a food additive or GRAS ingredient), but may be marketed as a food ingredient or dietary supplement.

An evidence-based review system is the process through which the rigor of the scientific data supporting a proposed claim of a substance/disease relationship is evaluated. The quality and quantity of the scientific data, overall consistency of the evidence and relevance to the U.S. population or target subgroup are factors that play a role in FDA’s determination of whether there is SSA to support an authorized health claim, or credible evidence to support a QHC. Health claims that meet the SSA standard are authorized by publication of a final rule in the Federal Register, while for QHCs, FDA issues a letter regarding its intent to consider “enforcement discretion.”

Another category of claims allowed in the U.S. are structure/function (S/F) claims, which address the role of a specific substance in maintaining normal, healthy structures, or functions of the body. FDA and the Federal Trade Commission (FTC) have stringent guidelines ensuring that S/F claims do not explicitly or implicitly link the relationship to a disease, or health related condition.

S/F claims are the claims most frequently used by industry to describe the role of a nutrient, or dietary ingredient:

(1) intended to affect normal structure, or function (e.g., ‘calcium builds strong bones’);

(2) characterize the means by which a dietary ingredient acts to maintain such structure or function (e.g., ‘fiber maintains bowel regularity’);

(3) describe general well-being from consumption of a dietary ingredient; or

(4) describe a benefit related to a nutrient deficiency disease (such as vitamin C and scurvy).

It is the manufacturer’s responsibility for ensuring the accuracy and truthfulness of S/F claims, as the claims are not subject to FDA pre-market review and approval. However, these, as are all claims, are subject to FTC enforcement if the claims are publicized in the media. Documentation demonstrating the soundness of clinical evidence for the claim is required in case of an audit. If such claim is used on the label or other forms of advertizing, a “disclaimer” must indicate that the FDA has not evaluated the claim, and that the product is not intended to “diagnose, treat, cure or prevent any disease.” Further, a 30-day notification following commencement of marketing of the product is required by the FDA.

The single, most important component of the scientific evidence necessary for substantiation of a SSA, QHC or S/F claim is the clinical data. A full-scale clinical trial relies on a significant financial investment and time, therefore demanding meticulous and advance planning at the outset. Several factors that need to be considered at that time include, but are not limited to (1) the existence and strength of the safety data, (2) prior evidence of efficacy (in animals and/or humans), and (3) determination of the effect/outcome to be studied.

Where do you start? By specifically addressing (1) the research question, (2) the specific hypothesis, (3) identifying the study population, and (4) determining the length of time for the study.

This is the first of a series of articles addressing the why and the how of human clinical trials for claim substantiation.

The next installment in this series of articles will address the study protocol, the use of inclusion/exclusion criteria and the importance of screening and baseline evaluation in clinical trials.