Notice of Availability of Administrative Supplements (Revisions) to NCCAM Grants for Validation Studies of Analytical Methods for Natural Products

Notice Number: NOT-OD-11-016

Update: The following update relating to this announcement has been issued:

• October 24, 2013 - See Issuance of PA-13-381 Administrative Supplements to NIH Awards for Validation Studies of Analytical Methods for Natural Products (Admin Supp).
• March 11, 2011 Notice of Correction, Update, and Clarification to NOT-OD-11-016. See NOT-OD-11-051.

Release Date: December 1, 2010
Receipt Date: January 31, 2011; March 31, 2011; June 31, 2010 (Now June 30, 2011 per NOT-OD-11-051); October 31, 2011; January 31, 2012; March 30, 2012; June 29, 2012
Earliest Anticipated Start Date: March 11, 2011

Office of Dietary Supplements (ODS)
National Center for Complementary and Alternative Medicine (NCCAM)

The Office of Dietary Supplements (ODS) and the National Center for Complementary and Alternative Medicine (NCCAM) announce an administrative supplement program to provide funds to NCCAM-supported research projects for optimization and validation studies of new analytical methods. These methods must have been developed or be under development during the active parent grant. They must be used to identify and quantify constituents (bioactive and other chemical marker constituents, adulterants, or contaminants) in products intended for oral administration in humans. As test agents they may be investigated in vitro or in vivo. The products may be dietary supplements, foods, and other orally-administered natural products, as well as their raw source materials. Candidates for validation studies may include (but are not limited to): phytochemicals; nutrients; and potentially deleterious substances such as toxic elements, pesticides, and mycotoxins. In addition, metabolites from these orally administered products found in urine, plasma or other tissues may be candidates for validation studies.

BACKGROUND

Very few publicly available and validated analytical methods exist for bioactive constituents in food, dietary supplements, and other orally administered natural products. This makes it difficult to confirm product composition and to conduct adequate clinical studies assessing mechanism, safety, and efficacy. A validated method is a method that has been systematically evaluated for reliability and accuracy. Experimental approaches to demonstrate the validity of a quantitative analytical method include single-laboratory and multiple-laboratory validation studies.

The analytical methods program is the largest component of ODS's Analytical Methods and Reference Materials (AMRM) Program (http://dietary-supplements.info.nih.gov/factsheets/AMRMProgramWebsite.asp). The goal of this program is to develop and validate methods that identify and quantify product constituents and their metabolites. Under this program, the ODS and U.S. Food and Drug Administration have supported AOAC International, an internationally recognized standards setting body, in developing an infrastructure to support methods validation (http://www.aoac.org/dietsupp6/Dietary-Supplement-web-site/DSHomePage2.html). Despite the success of the AMRM program, its progress could be accelerated and could capture the methods developed outside the current program structure which primarily serves regulators and industry. Program expansion to academia, including NCCAM grantees, would better serve the research community.

NCCAM grantees in the process of investigating the physiologic/biomedical effects of bioactive constituents of foods, dietary supplements, and natural products often develop analytical methods to identify and/or quantify constituents contained in their test agents or their metabolites in animal/human tissue. These methods may or may not be validated within the laboratory that developed them, and the availability of the methods or their validation may not be available to the research community. Validated methods are critical to advancing the quality of research.

A method intended to be performed in only one laboratory can be validated within that laboratory. This would be a single-laboratory validation (SLV). However, the results of a SLV method cannot necessarily be compared to results obtained using a different method or the same SLV method in a different laboratory. The SLV is the mechanism for demonstrating method performance prior to subjecting the method to a multi-laboratory collaborative study. Often a two-laboratory study is an intermediate step before proceeding to a collaborative study. This intermediate step may, in the long run, save time and resources.

The multiple-laboratory collaborative study is the gold standard. Multiple laboratories perform the same test on the same samples. If results from most of the laboratories are the same, the method performance is deemed adequate. AOAC International evaluates the validation study results and publishes the methods in the Journal of AOAC International. A successful collaborative study may lead to listing the method as an AOAC Official Methods of Analysis (http://www.aoac.org/vmeth/oma_program.htm).

PURPOSE AND REQUIREMENTS

The purpose of this Notice of Availability of Administrative Supplements is to seek applications for the planning, coordination, management, and conduct of single- and two-laboratory validation studies that lead to optimization and validation of analytical methods for quantitative determination of constituents in, or metabolites from, a variety of foods, dietary supplements, other orally administered natural products, and their raw source materials.

Application for multiple-laboratory collaborative studies will not be accepted at this time.

The SLV study must conform to the requirements of the AOAC International. AOAC has prepared a set of guidelines for conducting a SLV study: AOAC Guidelines for Single laboratory Validation of Chemical Methods for Dietary Supplements and Botanicals. Download the guidelines as a PDF file (http://www.aoac.org/Official_Methods/slv_guidelines.pdf). The grantee is expected to publish the SLV study method and results in a peer-reviewed journal.

ODS and NCCAM funding of $800,000 will be available for administrative supplements to existing research projects, cooperative agreements, program projects, and center grants. Administrative supplements are generally limited to less than 25 percent of the Council-approved direct costs for the current budget year of the project or under $100,000, whichever is less. Supplements may be requested for up to one year and expected performance period may extend no longer than the parent grant. Optimization and a SLV study are not expected to take longer than one year from initiation, including submission of the SLV publication. If a performance period of greater than one year is expected, contact Program Staff listed under Inquiries.

The requested budget may include the cost of AOAC validation methods training, consultants, and fees, if any, paid to AOAC International. Contact AOAC International or Program Staff for the availability of SLV training opportunities. If the requested direct costs exceed 25 percent of approved costs or $100,000, the grantee should contact Program Staff listed under Inquiries.

Grantees may not contract with external laboratories to perform the SLV study, but may contract with an external laboratory for a two-laboratory validation study.

Supplemental funding will be awarded no sooner than 6 weeks after receipt of the request.

This announcement is for supplements to active NCCAM-supported research grants (e.g., R21, R01, R42, R44), cooperative agreements (e.g., U01), and program project and center grants (e.g., P01, P50).

To be eligible, the parent grant must be active, and the research proposed in the supplement must be accomplished within the competitive segment. The proposed supplement must be within the general scope of the peer-reviewed activities and aims approved within the parent grant.

IMPORTANT: The research proposed by the NIH grantee in the supplement application must be within the original scope of the NIH-supported grant project. The funding mechanism being used to support this program, administrative supplements, can be used to cover cost increases that are associated with achieving certain new research objectives as long as they are within the original scope of the project. Any cost increases need to result from making modifications to the project in order to take advantage of opportunities that would increase the value of the project consistent with its originally approved objectives and purposes.

To be considered for an administrative supplement, the request must be signed by the Authorized Organizational Representative/Signing Official (AOR/SO), and must describe the need for additional funding and the categorical costs.

Submit one original, hard copy of the request packet (with original signatures of the authorized business official) to the address listed below:

George Tucker, M.B.A.
Chief, Grants Management Officer
Grants Management Branch
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-54-75 (express courier use: Rockville, MD 20852)

In addition, applicants are encouraged to send an electronic copy of the submitted supplement request as an e-mail attachment in PDF format to ATeRANotifications@mail.nih.gov and to both Program Contacts listed below under Inquiries.

Requests should be submitted on the PHS398 Application Guide forms (font size and other formatting rules apply as designated in the instructions), as indicated below. Include only the following elements:

Cover Letter which cites this Notice, and the following information:

• Project Director/Principal Investigator (PD/PI) name
• Parent grant number and title
• Amount of the requested supplement
• Name and title of the institutional official, and
• Phone, email, and address information for both the PD/PI and institutional official.
• The cover letter must be signed by the authorized organizational representative/institutional official.

PHS 398 Form Page 1 (Face page)

• The title of the project should be the title of the parent award.
• This Notice should be cited in Box 2, and the yes box should be checked.
• The Principal Investigator (PI) must be the same as the PI on the parent award. For Multiple PI parent awards, the Contact PI must be the PI listed on the supplement request, and the supplement cannot change the Multiple PI team.
• The remaining items on the face page should be filled out in accordance with the PHS 398 application instructions.

PHS 398 Form Page 2

• Note: The project summary is that of the administrative supplement, not the parent grant.

A brief proposal describing the project, including:

• Application introduction should not exceed one page.
• Scope of the overall project and the anticipated contribution of the requested supplement (not to exceed five pages).
  • Provide a brief description of the scope of the overall project on which the supplemental request is based.
  • This section should include a description of the supplement's specific aims, including research design and methods and data analysis. Describe the relationship of the supplement request to the parent grant.
• Budget for the supplement with a justification that details the items requested, including Facilities and Administrative costs.

Budget format should be presented in the same format as the parent grant.

• Biographical Sketch for all new key personnel (those who are additions on the supplemental project
• Human Subjects/ Vertebrate Animal documentation (if applicable).
  • Include a current Human Subjects/IRB or Vertebrate Animals/IACUC approval letter, if available. Otherwise, this will be required at the time of funding. All appropriate IRB and IACUC approvals must be in place prior to a supplement award being made.
  • Any differences in the involvement or use of human subjects or specimens, or use of vertebrate animals, between the administrative supplement activity and the parent grant should be noted.
  • When appropriate, details should be provided on the protection of human subjects and inclusion of women, children, and minorities. Additional guidance on Human Subjects Research and Vertebrate Animals is provided under Part II of the PHS 398 instructions.
• PHS 398 Checklist Form

Administrative supplement requests will be reviewed administratively by NIH Staff. Selection factors will include the following:

• Relevance of the proposed activities to the parent grant
• Adequate progress of the parent grant appropriate to the current stage of the project
• Appropriate and well-described plan to accomplish the goals within the timeframe proposed
• Expertise of the research team proposed to conduct and achieve the goals the supplemental study.

Inquiries and discussion of plans for responding to this Notice are strongly encouraged.

Program Contacts for general inquiries concerning the supplement program and detailed content of the request:

Barbara C. Sorkin, Ph.D.
Office of Dietary Supplements
National Institutes of Health
6100 Executive Blvd., Suite 3B01
North Bethesda, MD
Phone: 301 435 3605
Email: sorkinb@od.nih.gov

D. Craig Hopp, Ph.D.
Program Officer
Division of Extramural Research
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Phone: (301) 496-5825
Email: hoppdc@mail.nih.gov

Grants Management Contact for inquiries regarding administrative and fiscal matters:

George Tucker, M.B.A.
Chief Grants Management Officer
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475 (express courier use: Bethetsda, MD 20817)
Phone: (301) 594-9102
Email: tuckerg@mail.nih.gov