When a Dietary Supplement is a Drug: Oversight and Design Considerations for Clinical Trials Involving Dietary Supplements
With U.S. sales totaling over $36 billion and over 1,500 open studies registered on the ClinicalTrials.gov database, the dietary supplements industry continues to see an exponential rise within health care and clinical trials landscapes. It is increasingly important, then, that researchers focus on building systematic and safe trials.
In order to best design and execute studies involving dietary supplements, sponsors and investigators should seek to understand how dietary supplements are defined, the circumstances under which they can be considered drugs under FDA oversight, and what resources are available to assist researchers with designing trials so that they comply with existing regulations.
Definition of a Dietary Supplement
A product taken by mouth that is intended to supplement the diet and that contains one or more dietary ingredients.1
“Dietary ingredients” include vitamins, minerals, herbs and other botanicals, amino acids, other dietary substances intended to supplement the diet, and concentrates, metabolites, constituents, extracts, or combinations of the preceding types of ingredients. Dietary supplements are manufactured in many forms—tablets, capsules, softgels, liquids, or powders—examples including ginseng, garlic, fish oils, psyllium, enzymes, or combinations of these.
Is It Subject to FDA Oversight?
Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, the manufacturer is responsible for ensuring that a dietary supplement is safe before it is marketed and that claims made are not false or misleading. Conversely, the FDA is responsible for taking action against any unsafe dietary supplement product after it reaches the market.
Generally, manufacturers do not need to register their products with the FDA or get FDA approval before producing or selling dietary supplements. However, there are scenarios where research involving dietary supplements may need premarket FDA approval because they meet the definition of a drug as utilized in the clinical investigation.
Specifically, if a researcher proposes to study a dietary supplement with the intent of diagnosis, cure, mitigation, treatment, or prevention of disease in humans–as opposed to a supplement marketed to affect any structure or function of the body—the supplement would need to be treated as a drug and would be subject to FDA oversight.
|Mild memory loss associated with aging||Alzheimer's disease or senile dementias in the elderly|
|Changes to bone mass||Prevention of osteoporosis|
|Mild mood changes, cramps, and edema associated with the menstrual cycle||Severe depression associated with the menstrual cycle|
For cases where trials are investigating therapeutic effects or disease claims, the manufacturer or researcher would need to submit an Investigational New Drug (IND) application to the FDA.
Using Available Resources to Ensure Safe and Systematic Research
Given this nuanced and complex regulatory schema, researchers should seek to work with regulatory specialists, medical consultants, and IRBs in order to ensure that any studies utilizing dietary supplements meet research review and compliance standards.
Researchers can expect that these experts deliver wide-ranging assessments about the study, ensuring that substantive information about the dietary supplement(s) meets federal, local, and institutional regulations. Specifically, researchers should expect:
- Recommendations on designing studies to minimize risks and suggestions for appropriately documenting all possible safety and adverse event information regarding each supplement (e.g. types and frequency of occurrence of both common as well as serious side effects), in order to assure research integrity and appropriate informed consent.
- Medical and pharmacological review regarding potential drug and dietary supplement interactions; methods of cultivation and processing (e.g. purity, consistency, potency) of dietary ingredients; and available evidence of any prior use of the dietary supplement in humans and/or animals in previous research studies.
- Comprehensive research ascertaining whether the study and dietary supplement is subject to FDA regulations.
Note: even if studies involving the ingestion of dietary supplements were not subject to FDA oversight, they would still likely be covered under OHRP regulations, and would require review by the IRB. Regulatory advisors can utilize their expertise in this arena to provide accurate, practical, and timely guidance regarding the status of dietary supplements and any submission criteria the trial may involve.
- Guidance on submission of IND exemption inquiries to the FDA for official determinations. For particularly intricate or novel trials, advisors may contact the agency to obtain a written response about whether IND regulations apply.
As the interest and influx of dietary supplements in the market continues to grow, so will the number of clinical trials involving these products. Researchers should maximize their use of established industry experts in order to execute dietary supplement studies in a safe and systematic manner.
1 21 U.S.C. 321(ff)