Summary of January 2014 Applicant Assistance Webinar

The Office of Dietary Supplements (ODS) and the National Center for Complementary and Alternative Medicine (NCCAM) at the US National Institutes of Health (NIH) issued two companion Funding Opportunity Announcements (FOAs) on December 5, 2013.

The ODS and NCCAM partnered to provide opportunities for applicants to learn about these FOAs from the relevant NIH Program, Review and Grants Management contacts, and to ask them questions about the research focus and requirements of the FOAs.

The first of these, a webinar held on January 21, 2014, focused on RFA OD 14-001, Botanical Dietary Supplements Research Centers (BDSRC), using the NIH P50 mechanism. A teleconference held on January 27, 2014, focused on the companion FOA, the RFA-AT-14-006, Centers for Advancing Natural Products Innovation and Technology (CANPIT). This summary covers the information, questions and answers covered during the January 21 BDSRC applicant assistance webinar.

The webinar covered the following:

1. Relationship between the BDSRC and CANPIT FOAs.
2. RFA OD-14-001 goals and objectives, and the 2013 NIH Botanical Research Expert Panel Summary.
3. RFA OD-14-001 purview.
   1. Research on "whole botanicals."
   2. Research relevant to health maintenance and/or resilience.
   3. Focus on mechanistic, preclinical research.
4. RFA OD-14-001 requirements.
1. Eligibility.
2. Budget.
5. Structure of the BDSRC.
6. Application Submission System & Interface for Submission Tracking (ASSIST).
7. Letters of intent.
8. Questions and answers.

Summary of material covered in the webinar

1. Relationship between RFA OD 14-001 (BDSRC) and RFA AT 14-006 (CANPIT)
   1. It is expected that BDSRC investigators will contribute to the research resources to be developed by the CANPIT.
   2. It is anticipated that the research focus of the awarded CANPIT and at least some of the newly awarded BDSRC will include areas of shared interest such that there will be opportunities for synergistic research interactions among the awards.
   3. Key personnel from the BDSRC and the CANPIT will be expected to participate in a joint annual meeting.
   4. An applicant institution may submit applications to both RFAs, and key personnel, including the Program Director/Principal Investigator (PD/PI) may participate in both applications, BUT
   5. Applicants should ensure that PD/PI and other key personnel time commitments are credible for the work proposed.
   6. For personnel on two applications there must be a plan to ensure total effort does not exceed 12CM/100% in the event both applications receive awards.
   7. Reviewers will be asked to consider the ability of the PD/PI(s) to effectively and productively manage the proposed projects.
2. RFA 14-001 Goals and objectives
   1. Long-term goals to be addressed by this FOA:
      1. Apply rigorous, cutting-edge, synergistic research approaches to elucidate the mechanisms of action of complex botanicals as they relate to human health, including use of relevant preclinical models, ranging from in silico through in vivo models, including invertebrate models.
      2. Develop the preclinical data required for the optimal design of rigorous, definitive clinical research on complex botanical products.
   2. Objectives of the FOA in reference to the Botanical Research Expert Panel deliberations:
      1. Interdisciplinary, transdisciplinary, multi-sector collaboration;
      2. Apply cutting-edge methodologies/approaches to complex mixtures, to assess safety, mechanism of action including component interactions;
      3. Optimize sharing of/access to materials, tools, techniques;
      4. Support training of the next generation of transdisciplinary botanical researchers;
      5. Consider current prevalence of use and traditional use in prioritizing research;
      6. Focus on models of resiliency and health maintenance.
   3. RFA OD 14-001 objectives from the FOA:
      1. Development or adaptation of cutting-edge approaches to improve botanical identification and characterization, and assessment of potential for toxicity, drug interactions, and efficacy;
      2. Elucidation of mechanisms of botanical constituent interactions;
      3. Development of models to improve understanding of complex botanical mechanisms of action;
      4. Development of optimized approaches to obtain clearly interpretable outcomes of strong potential clinical relevance from studies of complex botanical mixtures;
      5. Development of approaches to assess host modulation of botanical activities (e.g., metabolism, safety) by, e.g., genetics, environment, microbiome.
3. RFA OD 14-001 purview
   1. For the purposes of the BDSRC, botanical research is defined as follows:
      1. Research on terrestrial plants OR macroscopic fungi and products derived from them;
      2. Research on isolated constituents of the above other than essential nutrients where required for elucidation of mechanisms of action;
      3. All materials to be studied must comply with NCCAM’s Product Integrity Policy;
      4. Applications focused on methods to improve large scale production of individual natural products or their derivatives, or on tools to chemically modify natural products for the purpose of improving potency, will be considered unresponsive and will not be reviewed.
   2. Focus on outcomes relevant to health maintenance or resilience:
      1. At least one-third of the specific aims of each proposed BDSRC must focus on objective, quantitative outcome measures
         • for which relevance to resilience or improved health outcomes is well documented and
         • that are validated for the context in which they will be used, or for which there is strong evidence of validity for the proposed use.
      2. See the FOA text, Part 2, Section I for examples of potentially relevant measures.
      3. Applications proposing to use models of chronic diseases or conditions in which the focus is solely on treatment rather than on outcomes relevant to health maintenance or resilience will be considered unresponsive and returned without review.
   3. Focus on mechanistic, preclinical research:
      1. Applications will be considered NOT responsive (and not reviewed) if more than one Research Project includes NIH-defined human subjects or clinical research.
      2. Applications will be considered NOT responsive if ALL the specific aims of any Research Project focus on NIH-defined human subjects or clinical research.
4. RFA OD 14-001 requirements
   1. Eligible applicants:
      1. Non-US entities (foreign institutions) and non-US components of US organizations are NOT eligible as the applicant organization, but foreign components, as defined in the NIH Grants Policy Statement, can participate in a BDSRC application as collaborators.
      2. Only one BDSRC application per applicant institution will be accepted.
      3. All applicants must complete all required registrations, see Part 2, Section III.1 of the RFA.
   2. Budget and project period:
      1. See Part 2, Section II of the RFA;
      2. May not exceed $1.25 million per year direct costs;
      3. Must reflect the actual costs of the proposed research;
      4. Scope (requested project length) may not exceed five years;
      5. Scope should reflect the proposed research;
      6. Funds must be included in the Administrative Core for travel of key personnel to the annual BDSRC meeting (with U41 personnel), for pilot projects, and for BDSRC administration, including expenses for an External Advisory Committee to meet at least annually.
5. Structure of the BDSRC
   1. Each BDSRC must include three or four synergistic Research Projects.
   2. Synergy is reviewed (all applicants should familiarize themselves with the FOA-specific review criteria in Part 2, Section V of RFA OD 14-001 early in the process of preparing an application).
   3. Each BDSRC must include at least one Research Core that provides in-depth expertise and capacity for quantitative and qualitative analysis of the chemical components and overall chemistry of botanicals.
   4. Each proposed Research Core (including the botanical Research Core) is expected to contribute to advancing the power of relevant methods and approaches, as well as to the success of at least two Research Projects.
   5. Core resources should not duplicate resources already available to BDSRC investigators. Where fee-for-service arrangements (i.e., BDSRC use of existing facilities) satisfy analytical or other needs of the BDSRC, use of these should not be considered as constituting, in and of itself, a separate Research Core.
   6. Each BDSRC must include an Administrative Core that:
      1. Coordinates and supports all BDSRC components;
      2. Includes plans to obtain additional funding or utilize existing resources to support training and career development for the next generation of transdisciplinary botanical researchers;
      3. Includes a plan to aggressively solicit, review, and support pilot projects (please see the Administrative Core instructions in Part 2, Section IV.2 of the RFA);
      4. Includes plans for an External Advisory Committee (EAC) and an Internal Steering Committee (ISC). Applicants submitting NEW applications should NOT name potential EAC members in their applications, nor contact them prior to award.
      5. Include plans to maintain or contribute to maintenance of a regularly updated BDSRC website.
      6. Funds from the BDSRC cannot be allocated for website development or maintenance, newsletters, consumer information or outreach activities.
6. The Application Submission System & Interface for Submission Tracking (ASSIST)
   1. To submit BDSRC applications you must use ASSIST OR your own institution’s "system-to-system data solution."
   2. From the FOA online you’ll be linked directly to ASSIST instead of downloading an application package.
   3. ASSIST leverages eRA Commons profile data to pre-populate some fields.
   4. Data for different application components can be entered simultaneously by multiple staff at the applicant institution and authority to enter data may be delegated to collaborating institutions.
   5. ASSIST validates grants.gov and NIH business rule compliance prior to application submission through grants.gov.
   6. ASSIST enables complete application image preview PRIOR to submission.
   7. ASSIST automatically generates the application Table of Contents and overall budget from the individual application components.
   8. Applicants can track grants.gov and eRA Commons submission status in ASSIST.
   9. For additional information on ASSIST, please see this AND this.
7. Letters of intent to submit an application in response to RFA OD-14-001
   1. are due on Monday, April 7, 2014,
   2. are NOT required nor binding, and do not enter into the review of subsequent applications.
   3. Letters of intent must include the following information, but may contain additional information:
      1. Descriptive title of the proposed activity,
      2. Name(s), address(es), and telephone number(s) of the PD(s)/PI(s),
      3. Names of other key personnel,
      4. Participating institution(s),
      5. Number and title of this funding opportunity.
   4. Should be sent to:
      Barbara C. Sorkin, Ph.D.
      Director, Botanical Research Centers Program
      Office of Dietary Supplements, NIH
      6100 Executive Blvd., Room 3B01, MSC 7517
      Bethesda, MD 20892-7517
      Telephone: 301-435-3605
      Fax: 301-480-1845
      Email: sorkinb@mail.nih.gov
8. Questions and Answers

   Q: For current Botanical Research Center awards, can the title of the competitive renewal application be different from that of the prior award to reflect the shift in focus of the research towards health maintenance/resilience?

   A: Yes. The application should still be submitted as a competitive renewal, but the letter of intent should reflect this change so that the NIH system can be alerted, to ensure that the application is entered as a competitive renewal and not as a new award. The project number will stay the same, while the title changes.

   If Research Projects or Cores are discontinued, the Overall section of the competitive renewal application should explain the rationale and justification for such changes.

   Q: Since the budget for the P50 cannot directly support training per se, does this mean that graduate student stipends cannot be included in the P50 budget?

   A: Stipends cannot, by NIH policy, be supported on NIH research grants.

   The Administrative Core component of each BDSRC application must describe plans for obtaining funds (or utilizing existing resources) to provide training and career development opportunities. Supplemental funding for training and career development could be sought from NIH institutional training grants (T32), individual fellowships (F31, F32), mentored career development awards (K01, K08), and other sources including, but not limited to, the parent institution and private foundations.

   Q: Would research on Β-glucans or micro-algae be within the purview of the BDSRC RFA?

   A: Research on microorganisms other than plant endophytes, and on marine organisms would be considered unresponsive to this RFA, and applications with such a focus will NOT be reviewed.

   Research on macroscopic fungi is an area of interest for the BDSRC RFA, so research on the contribution of fungal &Beta-glucans to health-relevant effects of macroscopic fungi would be within scope.

   Q: Is it acceptable in a BDSRC application to propose to use commercially available products?

   A: Yes, as long as the applicant can convincingly demonstrate that they have a plan to ensure access to consistent product for the conduct of research throughout the project period, and for replication of the research, and to independently assure and verify product integrity, as required by NCCAM’s Product Integrity Policy.

   Q: What do you mean by essential nutrients?

   A: Essential nutrients would include protein as a nutrient (as opposed to a specific modifier of function, e.g., an enzyme or cofactor), carbohydrate (as calories, as opposed to, e.g., a specific modifier of function), vitamins, and minerals. These important compounds have substantial research support through other mechanisms, and are not eligible for support as a primary research focus for awards pursuant to RFA OD-14-001.

   Q: The RFA states that applications with human subjects or clinical research in more than one Research Project, or with all the specific aims of such a Research Project focused on human subjects or clinical research are not responsive to the BDSRC RFA. What is allowed in human subject research?

   A: Only one of the Research Projects may include NIH-defined human subjects or clinical research. Proposals in which more than one Research Project includes NIH-defined human subjects or clinical research will be considered unresponsive and NOT reviewed. Proposals in which ALL the specific aims of a Research Project that includes NIH-defined human subjects or clinical research are focused on such research will be considered unresponsive and NOT reviewed. Specific aims using samples from human subjects or clinical research that is already funded (as part of a separate award or other Research Project) to address research questions not inherently addressed elsewhere would not render an application unresponsive.

   Q: What are the limits on information provided in the letter of intent?

   A: There is no length limit for letters of intent, and they are only required to provide the information listed in 7, above; however applicants are welcome to provide additional information in their letters, although they are urged to be concise.

   Q: What information should applicants provide regarding External Advisory Committee (EAC) members?

   A: Those submitting new applications should describe the expertise that would be appropriate for EAC members, but should NOT name potential members in their applications, nor contact them. This leaves a larger pool of experts available for peer review.

   Those submitting competitive renewal applications should list people who have served on their EACs, as these individuals are in conflict for purposes of peer review. Potential NEW EAC members should NOT be named in competitive renewal applications.

   Q: The requirement for a focus on health maintenance or resilience is quite explicit, yet only one-third of the specific aims are required to have such a focus. Can you explain?

   A: This is a minimum requirement – applicants are welcome to include a greater focus on health maintenance/resilience. Staff was concerned that given the disease focus of much NIH-supported research, there might be a very limited number of teams with substantial preliminary data relevant to health maintenance or resilience that would support three or four synergistic Research Projects.

   Q: If the P50 are limited to one human subject or clinical Research Project, and not all the specific aims of that project can be focused on human subjects or clinical research, but at the same time at least one-third of the specific aims must be relevant to health maintenance or resilience, is that contradictory?

   A: We believe that you can do research relevant to human health maintenance or resilience in non-human models; certainly in preclinical animal models, and perhaps also in in silico and in vitro models. Some of the outcomes listed as possible resilience-relevant outcomes in Part 2, Section I of the RFA, under "Purview of the FOA," could be studied in preclinical models, and arguments made supporting their relevance to humans.

   Q: Could you say a little more about how NIH views pilot projects in the context of this BDSRC renewal FOA?

   A: Requirements for (and restrictions on) the BDSRC pilot project program are described in the Administrative Core section of Part 2, Section IV of the FOA.

   Goal of the pilot program:
   We see pilot projects in this program as a way to draw in researchers new to botanical research, and give them an opportunity to acquire preliminary data with the support of a research team and cores that have cutting-edge expertise in this research. The goal is to bring promising young investigators, or experienced investigators who have not previously participated in botanical research, into the research area.

   Budget requirements:
   Each Administrative Core must include funds for soliciting, reviewing, selecting, supporting and monitoring pilot projects.

   Not more than $100,000 per year (direct costs) from the P50 budget may be allocated to pilot projects, but additional support for pilot projects (or other aspects of the P50) from outside or institutional funds is welcome.

   Restrictions: Pilot projects:

   • Must be within the research scope of the P50.
   • Must be approved by NIH.
   • Cannot be awarded to the Center PD(s)/PI(s), Research Project Leaders, Core Leaders, or other scientists listed in the initial grant application.
   • Are limited to one or two years duration each.
   • Eligible applicants for pilot projects must be independent faculty at the awardee institution or another member of the P50 consortium.
   • Eligible applicants for pilot projects cannot have been otherwise supported by the P50 grant, or collaborated with Center key personnel on botanical research within the two years prior to receipt of pilot project support.
   
   

   Program staff contact information:

   Barbara C. Sorkin, Ph.D.
   Office of Dietary Supplements (ODP)
   Telephone: 301-435-3605
   Email: sorkinb@mail.nih.gov

   D. Craig Hopp, Ph.D.
   National Center for Complementary and Alternative Medicine (NCCAM)
   Telephone: 301-496-5825
   Email: hoppdc@mail.nih.gov

   Grants Management staff contact information:

   George Tucker, MBA
   National Center for Complementary and Alternative Medicine (NCCAM)
   Telephone: 301-594-9102
   Email: gt35v@nih.gov