Concept: Reissuance of a Funding Opportunity Announcement for Dietary Supplement and Natural Product Analytical Method Validation Studies

Project Concept Review

Council Date: May 13, 2022

Program Director: Adam Kuszak, Ph.D.; NIH Office of Dietary Supplements; Division of Program Coordination, Planning, and Strategic Initiatives; Office of the Director

Background

The NIH Office of Dietary Supplements (ODS) mission is to support, conduct, and coordinate scientific research and provide intellectual leadership for the purpose of strengthening the knowledge and understanding of dietary supplements to foster an enhanced quality of life and health for the U.S. population. ODS and the National Center for Complementary and Integrative Health (NCCIH) have shared interests in advancing research on the health effects of natural products and a history of collaboration in cofunding grants and other activities.

The rigor and reproducibility of research on dietary supplement health effects is enhanced thorough characterization of experimental interventions and biological samples. Thorough characterization of a natural product intervention facilitates comparability of different studies and increases the knowledge base for understanding mechanisms of action and biological signatures. Quantitative characterization of the metabolites of natural product interventions is important for identifying biomarkers of exposure and understanding which constituents have biological activities. Initiated in 2011, ODS has supported an Administrative Supplement Funding Opportunity Announcement (FOA) for formal analytical method validation studies to promote advances in the characterization of the ingredients and metabolites of dietary supplements and natural products. NCCIH has been a strong partner in administering this Administrative Supplement since its inception, with a majority of awards having been made to NCCIH-funded investigators. 

Purpose of Proposed Initiative

The validation and dissemination of analytical methods that accurately and reliably characterize dietary ingredients and natural product constituents, or their metabolites, is an important step in enhancing rigor and reproducibility in preclinical and clinical research.

ODS seeks Council clearance for the reissuance and continuation of an Administrative Supplement FOA that supports formal analytical method validation studies for the constituents and/or metabolites of interventions used in dietary supplement and natural product research.

This Administrative Supplement seeks applications for the conduct of formal single-laboratory validation (SLV) studies of analytical methods for the identification and/or quantification of dietary ingredients and/or constituents. ODS is committed to fully funding meritorious applications for this Administrative Supplement. The most recent issuance of the Administrative Supplement was PA-20-252.

Objectives

The analytical method(s) proposed for validation must be used to identify and/or quantify dietary supplement–relevant ingredients or constituents (i.e., active or marker chemical compounds, adulterants, contaminants) or their metabolites in experimental reagents, raw materials, and/or clinical specimens (e.g., urine or plasma samples). Candidate constituents for method validation studies include (but are not limited to) phytochemicals, nutrients, and potentially deleterious substances such as pesticides and mycotoxins.

The analytical method(s) to be the subject of validation studies must have already been developed and be in use by the applicant at the time of the funding request. These methods must be within the scope of the active parent National Institutes of Health award. Awardees are expected to publish the method and results of the validation study in a peer-reviewed journal.

Critical aspects of a formal SLV study of quantitative analytical chemistry methods include (but are not limited to):

1. Determination of the method's applicability, accuracy, precision, uncertainty, repeatability, limit of detection, limit of quantification, linearity, selectivity, and sensitivity.
2. Investigation of each step of the method to determine the extent to which matrix, material, and procedural variables may affect quantitation of the analyte(s).

Critical aspects of a formal SLV study of qualitative methods to identify botanical dietary ingredients include (but are not limited to):

1. Determination of applicability, inclusivity, exclusivity, probability of identification, robustness, reproducibility, and repeatability.
2. Careful consideration of sampling plans to establish representative mixtures of the minimum acceptable concentration of target material and maximum concentration of non-target material (inclusivity and exclusivity panels).
3. Utilization of appropriate statistical approaches to establish the method’s ability to distinguish between target and non-target materials and determine a probability of identification and associated confidence intervals.

Examples of quantitative analytical methods that may be supported by this Administrative Supplement include, but are not limited to, liquid chromatography tandem mass spectroscopy for the identification and quantitation of specific phytochemicals in botanical products, and enzyme-linked immunosorbent assays for the identification and quantitation of specific dietary supplement metabolites in urine. Various quantitative methods (e.g., chromatographic patterns, spectral patterns, genetic sequences) are commonly employed to generate the underlying data, which are subsequently statistically assessed to qualitatively determine the probability of identification for botanical and other natural product experimental reagents.

While it is understood that further method optimization is often required in the course of a validation study, the purpose of this Administrative Supplement is not to support de novo method development or initial optimization of newly developed methods. This Administrative Supplement does not support the development or validation of assays for biological activities affected by dietary supplements or their metabolites, adulterants, or contaminants.