September 7, 2022
PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
Office of Dietary Supplements (ODS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Complementary and Integrative Health (NCCIH)
National Cancer Institute (NCI)
The NIH Office of Dietary Supplements (ODS) within the Office of the Director Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) announces the availability of administrative supplements 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 (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, plasma, tissue).
A major goal of the ODS Analytical Methods and Reference Materials (AMRM) Program is to promote 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. To be validated an analytical method’s performance characteristics such as accuracy, precision, applicability, and sensitivity are systematically evaluated. The use of validated methods enhances the reliability and consistency of analytical measurements, and the dissemination of validated methods strengthens the value and impact of NIH-supported research outcomes.
Only PDs/PIs of an active award from NIH are eligible to apply. Applicants are strongly encouraged to consult the Program Officer and the Grant Management Officer of the parent award to confirm eligibility. Parent awards most appropriate for this NOSI include, but are not limited to, those that involve investigating the mechanisms of action, metabolism, and/or health outcomes of dietary supplement interventions. Parent awards that involve the chemical characterization and/or standardization of dietary supplement interventions are also appropriate.
The parent peer-reviewed NIH-funded grant must have at least 18 months of active grant support remaining from the due date. Proposed project period of the Administrative Supplement cannot extend beyond the project period of the parent award. Awards in a No Cost Extension (NCE) by the time the supplement would be made are ineligible.
The method(s) to be validated must identify and/or quantify constituents (i.e., bioactive and other marker constituents and/or their metabolites, adulterants, or contaminants) in preparations intended for oral administration in humans (e.g., dietary supplement ingredients or products) or in biological specimens (e.g., urine, plasma, tissues).
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, targeted and non-targeted metabolomic investigations of the complex chemical profiles for a natural product, and enzyme-linked immunosorbent assays for the identification and quantitation of specific dietary supplement metabolites in urine.
The method(s) subject to the validation must have already been developed and within the scope of the active parent NIH award. The purpose of this supplement is not to support de novo method development or initial optimization of newly developed methods. Final optimization of a method prior to validation is permissible, and applicants should explain details of further optimization steps and why this is needed for validation.
Multi-laboratory, collaborative validation studies and the validation of assays for biological activities or health outcomes are outside the scope of this NOSI.
Validation Study Expectations
The awardee is expected to publish the validated method and results of the validation study in a peer-reviewed journal, and to cite support by ODS as well as by the IC administering the parent award.
Key aspects of a formal SLV study of a quantitative analytical chemistry method include (but are not limited to):
Determination of the method's applicability, accuracy, precision, uncertainty, repeatability, limit of detection, limit of quantification, linearity, selectivity, and sensitivity.
The use, when possible, of standards or certified reference materials for calibration and characterization of method performance.
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).
Key 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, reproducibility, and repeatability.
Careful consideration of sampling plans to establish representative mixtures of the minimum acceptable concentration of target material and maximum concentration of non-target material (i.e., inclusivity and exclusivity panels).
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.
Proposals are expected to consider the applicable requirements of relevant guidelines for a formal SLV study of their method(s) and analytes of interest, and to describe their planned validation scheme in their proposal.
Several policies, guidelines, and procedures have been established for the design and conduct of validation studies for quantitative analytical methods. For example, formal validation procedures are described by internationally recognized bodies such as AOAC International, the International Standardization Organization (ISO), the International Union of Pure and Applied Chemistry (IUPAC), and the Nordic Committee on Food Analysis (NMKL). Recommendations for the conduct of validation studies and reporting criteria for metabolomic methods have been described in the peer review literature, e.g. Sumner et al., 2007, Metabolomics, 3:211-221; Koek et al., 2011, Metabolomics, 7:307-328; and Jorge, Mata, and Antonio, 2016, Phil. Trans. R. Soc. A., 374.
Applicants are strongly encouraged to review AOAC International's guidelines for the requirements and conduct of a formal SLV study of quantitative chemical methods and qualitative identification methods, which can be found in the 2013 AOAC International Official Methods of Analysis, Appendix K: Guidelines for Dietary Supplements and Botanicals (http://www.eoma.aoac.org/app_k.pdf; accessed 7/8/2022). Additional relevant information can be found in the U.S. FDA’s 2019 Guidelines for the Validation of Chemical Methods in Food, Feed, Cosmetics, and Veterinary Products, 3rd Edition (https://www.fda.gov/media/81810/download; accessed 7/8/2022), and the IUPAC Harmonized Guidelines for Single Laboratory Validation of Methods of Analysis (https://doi.org/10.1351/pac200274050835; accessed 7/8/2022).
For validation studies of quantitative methods for metabolites in biological samples, applicants are strongly encouraged to consult the U.S. Food and Drug Administration's guidance for full validation of bioanalytical methods for human metabolite studies (http://www.fda.gov/downloads/drugs/GuidanceComplianceRegulatoryInformation/guidances/UCM070107.pdf, accessed 7/8/2022). The accuracy, precision, reproducibility, and selectivity of the method for endogenous metabolites and known degradation products should be established for the relevant biological matrix.
Various quantitative methods (e.g., chromatographic patterns, spectral patterns, genetic sequences) are commonly employed to generate the underlying data which are subsequently statistically evaluated to qualitatively determine accuracy and reliability of identification for botanical and other natural product experimental reagents. Applicants interested in validation of qualitative methods for identification are strongly encouraged to review Probability of Identification: A Statistical Model for the Validation of Qualitative Botanical Identification Methods (LaBudde and Harnly, 2012, J. AOAC International, 95(1):273).
Additional guidance and answers to Frequently Asked Questions for Office of Dietary Supplements grant funding can be found at https://ods.od.nih.gov/Research/Funding.aspx.
Application budgets may not exceed a maximum direct cost of $100,000 or the amount of the current award, whichever is lower, not including sub-contract (or consortia) Facilities and Administrative costs. Project budgets may not exceed the yearly budget of the parent award.
Application budget is limited to one year only.
Budget requests should reflect costs that are necessary and reasonable to complete the work described in the application. Applicants are expected to have readily available the materials necessary to complete the proposed work. For example, applications should carefully consider the amount of dietary ingredient/constituent/metabolite or standard material which would be necessary to conduct the validation study, as applications proposing significant new work to generate these materials will be considered with a lower priority.
Earliest start date (depending on submission date) – January 2023; March 2023; July 2023; January 2024; March 2024; July 2024; January 2025; March 2025; July 2025.
Description of circumstances for which administrative supplements are available.
Application and Submission Information
Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.
ODS will conduct administrative evaluations of all applications, considering the criteria below, and will support the most meritorious applications, pending the availability of funds.
Adam J. Kuszak, Ph.D.
Office of Dietary Supplements (ODS)