Concept: Office of Dietary Supplements (ODS) Funding Opportunity Announcement (FOA) for Validation Studies of Analytical Methods for Dietary Supplement Constituents
Project Concept Review
Council Date: June 5, 2020
Program Officer: Adam Kuszak, Ph.D.
Reproducibility is essential to the utility and translation of research, and replicable characterization of key experimental resources is an important facet of rigorous research on the health effects of dietary supplements and natural products. Accordingly, NCCIH has in place a longstanding Policy on Natural Product Integrity, and ODS similarly requires grant applicants to demonstrate the identity, composition, purity, and stability of the dietary supplements and natural products used in research. Recent publications continue to point to gaps in reagent/intervention authentication and compositional analysis and emphasize their vital role in research rigor and reproducibility.
An important component of improving natural products research reproducibility through enhanced characterization is demonstrating that the analytical methods used to authenticate and assess key experimental resources are reliable and replicable. Formal studies to validate an analytical method meet this need by determining its accuracy, precision, applicability, and sensitivity, thus creating a strong foundation for improving research rigor and reproducibility. However, relatively few publicly available and validated analytical methods exist for constituents in dietary supplements and natural products, making it difficult to rigorously and quantitatively assess the composition of experimental materials and to conduct replicable studies of the mechanism(s) of action, efficacy, or safety of these inherently complex and variable preparations. It is therefore critical that as analytical methods are developed for natural products their performance be characterized and validated. A major goal of the ODS Analytical Methods and Reference Materials (AMRM) Program is to address this need by promoting the development and validation of methods that can be used to identify and quantify dietary supplement constituents, contaminants, adulterants, and their metabolites in target matrixes.
Reissuance of this FOA will support validation studies and dissemination of analytical methods developed by National Institutes of Health (NIH) grantees. The use of validated methods enhances the reliability and comparability of analytical measurements, and the publication of validated methods strengthens the value and impact of NIH-supported research. NIH-funded grantees often develop or optimize methods for dietary supplements and other natural products in the course of performing research, expanding the analytical toolkit to quantify concentrations of specific chemical constituent(s) of interest or to qualitatively assess the identity (or quality) of natural product materials to be used in research. However, these methods may or may not have been previously published, and the details of the methods or their documented validation may not be available to the broader research community.
This Administrative Supplement FOA seeks applications for the conduct of single-laboratory validation (SLV) studies of analytical methods for the identification and/or quantification of dietary ingredients and/or constituents (e.g., active or marker compounds, adulterants, contaminants), or metabolites thereof, in foods, dietary supplements, their raw source materials, and/or clinical specimens (e.g., urine or plasma).
The strategic goals of ODS and NCCIH share a commitment to advancing research rigor and fostering the development of improved methodologies. This ODS Administrative Supplement FOA for formal SLV studies of quantitative analytical methods builds upon existing NIH awards, enhancing the rigor of NIH-funded basic, translational, and clinical research, and increasing the dissemination of reliable research resources. ODS seeks to continue its partnership with NCCIH in a reissuance of the FOA for Validation Studies of Analytical Methods for Dietary Supplement Constituents. ODS is committed to fully fund meritorious proposals; no budget contributions are requested from NCCIH.
The method(s) to be validated must be in use in the parent award to identify and/or quantify constituents (bioactive and other marker constituents and/or their metabolites, adulterants, or contaminants) in products intended for oral administration in humans, or in biological specimens such as urine, plasma, or tissues. The products under investigation in parent grants may be dietary supplement ingredients or related natural products (including vitamins or other bioactive compounds), or foods, or their raw source materials (e.g., plant biomass). The grantee is expected to publish the validated method and results of the validation study in a peer-reviewed journal.
The 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 NIH award. While it is understood that further method optimization is often required in the course of a validation study (and funding requests should take this into account), the purpose of this supplement is not to support de novo method development or initial optimization of newly developed methods.
To be validated, an analytical method’s performance characteristics are systematically evaluated. Critical aspects of a formal SLV study of a quantitative analytical chemistry method include (but are not limited to):
- Determination of applicability, accuracy, precision, uncertainty, repeatability, limit of detection, limit of quantification, linearity, selectivity, and sensitivity.
- Usage of standard or certified reference materials.
- Determination of the effects of matrix, material, and procedural variables on quantitation.
Critical aspects of a formal SLV study of qualitative methods to identify botanical dietary ingredients include (but are not limited to):
- Determination of applicability, inclusivity, exclusivity, probability of identification, robustness, and repeatability.
- Careful consideration of sampling plans to establish representative preparations.
- Wolsko PM, Solondz DK, Phillips RS, et al. Lack of herbal supplement characterization in published randomized controlled trials. American Journal of Medicine. 2005;118(10):1087-1093.
- Gagnier JJ, Boon H, Rochon P, et al. Recommendations for reporting randomized controlled trials of herbal interventions: explanation and elaboration. Journal of Clinical Epidemiology. 2006;59(11):1134-1149.
- Kellogg JJ, Paine MF, McCune JS, et al. Selection and characterization of botanical natural products for research studies: a NaPDI center recommended approach. Natural Product Reports. 2019;36(8):1196-1221.
- Sorkin BC, Kuszak AJ, Bloss G, et al. Improving natural product research translation: from source to clinical trial. FASEB Journal. 2020;34(1):41-65.