As of October 2009, 295 health claims had been submitted for approval to the European Food Safety Authority (EFSA)—55 were rejected and 13 were accepted. For manufacturers who submitted dossiers, this was disappointing. However, the claims that have been accepted can serve as a blueprint for successful claim applications in the future.

Designing Appropriate Clinical Trials

In examining the various opinions from EFSA, the main issues in most rejected applications revolve around substantiation, and specifically the clinical trials themselves.

There are a few definite faux pas to avoid in designing clinical studies, which will go a long way toward getting claim applications accepted. First of all, EFSA would like to see substantiation come from human clinical studies. Further, the submitted studies should be randomized and controlled, or even better, randomized, placebo-controlled, double-blinded. The number of study participants must be relevant and should be more than 100. Intervention studies are best, since ex vivo and in vitro studies, as well as animal studies are mainly suitable for proof of mechanism. Multi-center studies are better than studies with just one study center.

Equivalence of study population and target population is another main point. The study population for a trial on a food supplement, if it is to be equivalent to the target population, must by definition be healthy subjects, not patients. The equivalence between study population and target population is especially important in children’s claims, where the age of the children included in the study should conform to the age of the intended target group. Inclusion and exclusion criteria must be defined by providing a detailed description of the decision tree.

For the participants, lifestyle factors such as diet, amount of exercise or habits such as smoking need to be registered. Power calculation must be conducted during the planning of a study. Intention to treat (ITT) analysis must be conducted and information about randomization methods must be included. Last but not least, a suitable control must be implemented.

Health Benefits

The health benefit must be defined; mere deficiency symptoms are not considered sufficient for a health claim. Cross-sectional studies don’t yield sufficient proof for cause and effect relationships. A major stumbling block is the fact that the clinical study must be conducted on the product and not just on its individual ingredient. This is especially true for combination products. The study dosage must be equivalent to the recommended dosage of the product, and its effect must be clinically relevant. In case of risk reduction claims, the measured markers must be accepted risk indicators (e.g., LDL levels for cardiovascular disease).

If the new product is a probiotic, proof must be submitted that the microorganisms are live and viable in the product matrix, and the substantiating study must be conducted on the exact same strain in the final product matrix to be acceptable.

Scientific relevance is another important factor. Claims are not accepted if scientific relevance is not substantiated, which basically means that  “potentially” or  “possibly”  beneficial effects will not be accepted by EFSA. Also, a significant difference does not necessarily mean that a result is biologically significant. At the same time, the entirety of all pertinent data is important for scientific substantiation. The intended daily dosage must be effective, which must be substantiated.

Validity of a clinical study depends on the choice of relevant markers. Wherever possible, endpoint measurements should be done. Not just the quality, but also the quantity of study parameters is important for a valid clinical. The study duration should be adequate and the methods that prove efficacy must be validated, standardized and generally accepted.