One of the biggest challenges in designing efficacy trials for companion animal supplements is aligning on an impactful target result without crossing the line into conducting a clinical trial examining a potential veterinary drug.

For example, the regulatory framework in the United States is centered around a product’s intended use. Products considered to be a pet food or feed ingredient must comply with the Association of Amer¬ican Feed Control Officials (AAFCO) requirements as well as individual state regulatory codes. Only claims related to nutrition, flavor, color, aroma, or technical effect are allowed.  Products intended to prevent, treat, or cure a disease are considered to be drugs and must go through a lengthy and complex approval process through the Food and Drug Administration (FDA).

In between these two sit a somewhat gray area of pet supplements, or non-nutritional products intended to support a specific structure or function of the body. To avoid being regulated as a feed product, nutritional claims cannot be made. To avoid being regulated as a veterinary drug product, drug claims also cannot be made. These products must focus on maintaining the animal’s normal state, which can severely limit the types of studies that can be performed. The European Union has rules similar to the US regarding what claims can be made. The difference is that in the EU, pet supplements must also go through an approval process, whereas in the US, they do not. Enforcement in the EU is carried out at the member state level by competent authorities, with scientific guidance and risk assessment provided by the European Food Safety Authority (EFSA). In addition, the European Pet Food Industry Federation (FEDIAF) issues non-binding but widely adopted codes of good labeling practice, which further interpret EU law and set expectations for acceptable types of claims in pet nutrition.

We often conduct shorter-term studies in kennels or catteries; however, these come with their own limitations. For ethical reasons, we do not induce disease states in pets and therefore avoid invasive procedures. Further, the use of animal patients also carries the risk that the study endpoint is related to disease prevention or cure, which would potentially put the investigational product in a medicinal category. Instead, we often use non-invasive models to introduce controlled, benign challenges. One example is a dietary transition model, in which animals are switched from one complete diet to another, transiently perturbing the gut microbiota and inducing a mild, self-limiting dysbiosis.

Similarly, macronutrient modulation (e.g., short-term changes in fiber type or fat level) can be used to elicit measurable shifts in fermentation patterns or stool characteristics without compromising animal welfare. Other commonly used approaches include palatability or satiety challenges, mild environmental changes (such as altered feeding schedules), or standardized exercise challenges to probe metabolic flexibility. These models allow us to study adaptive physiological responses, such as changes in microbiota composition, metabolite profiles, immune state, or digestive tolerance, under controlled conditions and without causing deliberate harm. Nevertheless, because the induced perturbations are intentionally subtle and reversible, detecting robust and biologically meaningful biomarkers remains challenging, often requiring sensitive analytical methods and carefully powered study designs.

On the other hand, it is possible to conduct more robust clinical trials in veterinary hospitals. These are more expensive and time-consuming, and similar to human clinical trials. A key advantage is that it enables access to pets in a naturally diseased state. Although drug claims cannot be made, pet supplement companies often want to know that a given ingredient is effective.  Pet owners tend to view their pets through a similar lens to infants, and pets pose challenges similar to those in clinical research with infants. Pets often show their symptoms as clinical signs but cannot verbalize what they are feeling. This creates an added challenge as veterinarians must rely in part on pet owners’ judgement. Fortunately, pet owners are often the most attentive observers of their animals’ behavior and wellbeing and are able to provide meaningful insights through questionnaires and daily observations.

It is important that the owner-reported outcomes and veterinary assessments can be integrated to strengthen the study design. Owner reports, based on subjective scales and their deep knowledge of their pets, are invaluable, but they must be balanced with objective clinical measures. These objective assessments, such as blood analyses, physical exams, and unbiased evaluations by trained veterinarians, are crucial. Moreover, it’s vital that both veterinarians and pet owners are blinded to the study treatments. This reduces bias and minimizes the placebo effect, which is very common when owners believe their pet is receiving a potentially beneficial treatment. In the end, both owner and veterinary data should be reported and analyzed in tandem, with each source’s strengths and limitations clearly discussed in the publication. 

In conclusion, research in pet nutrition and health must balance scientific rigor, animal welfare, and strict regulatory constraints that limit claims to supporting benign changes within the animal. As a result, studies rely on non‑invasive designs, mild challenge models, and carefully selected endpoints capable of detecting subtle but meaningful physiological responses. Integrating objective veterinary assessments with structured owner‑reported outcomes strengthens both internal validity and real‑world relevance. When thoughtfully designed, such approaches can generate robust evidence that supports compliant claims while advancing the scientific foundation of functional pet nutrition.

For the future, research should prioritize the identification of sensitive, non‑invasive, validated biomarkers, further standardization of benign challenge models and improved validation of owner‑reported outcomes are areas for improved veterinary supplement research. Further, longer‑term and home‑use study designs may help bridge the gap between controlled trials and real‑world feeding practices.