Dietary Supplement Research Dietary Supplement Research Centers: BotanicalsCenters: BotanicalsRFA OD-04-002 RFA OD-04-002

Applicant Information MeetingApplicant Information MeetingFebruary 6, 2004February 6, 2004Bethesda MDBethesda MD

Christine A. Swanson, Ph.D.Christine A. Swanson, Ph.D.Office of Dietary Supplements, NIHOffice of Dietary Supplements, NIHswansonc@od.nih.govswansonc@od.nih.gov

OverviewOverview

Dietary Supplement Research CentersDietary Supplement Research Centers Botanical Research Center ProgramBotanical Research Center Program

Expert Panel ReviewExpert Panel ReviewNIH Presentation to PanelNIH Presentation to PanelPanel RecommendationsPanel Recommendations

RFA OD-04-002RFA OD-04-002 New FeaturesNew FeaturesGuidance DocumentsGuidance Documents

Congressional MandateCongressional Mandate (FY 1999) (FY 1999)

“ “ establish a botanical research establish a botanical research initiative with major research initiative with major research institutions in the United States”institutions in the United States”

Dietary Supplement Research Centers: Dietary Supplement Research Centers: BotanicalsBotanicals

Awards:Awards:•University of California Los Angeles University of California Los Angeles •University of Illinois at Chicago University of Illinois at Chicago •University of Arizona University of Arizona •Purdue University/University of Alabama Purdue University/University of Alabama •University of Missouri University of Missouri •Iowa State University/University of Iowa Iowa State University/University of Iowa

Budget:Budget: $1.0-1.5 Million/Year for 5 Years$1.0-1.5 Million/Year for 5 Years

Awarding Organizations:Awarding Organizations:•ODS, NCCAM, NIEHSODS, NCCAM, NIEHS•Additional support from NIGMS, ORWHAdditional support from NIGMS, ORWH

Presentation to Expert Panel Presentation to Expert Panel

February 21, 2003February 21, 2003

Botanical Research Centers ProgramBotanical Research Centers Program

PurposePurpose: To establish Specialized : To establish Specialized Research Centers to investigate the Research Centers to investigate the biological effects of botanicals, including biological effects of botanicals, including those available as ingredients in dietary those available as ingredients in dietary supplementssupplements

GoalsGoals To foster interdisciplinary research to To foster interdisciplinary research to

promote rigorous scientific study of promote rigorous scientific study of botanicalsbotanicals

To explore the potential of botanicals To explore the potential of botanicals (dietary supplements) to improve health (dietary supplements) to improve health carecare

To develop models to evaluate the efficacy To develop models to evaluate the efficacy and safety of botanicalsand safety of botanicals**

* * Modified in RFA OD-04-002Modified in RFA OD-04-002

Spectrum of Research Spectrum of Research ActivitiesActivities

(Major Areas of Emphasis)(Major Areas of Emphasis)

Identify and characterize botanicalsIdentify and characterize botanicals

Assess bioavailability and bioactivity Assess bioavailability and bioactivity

Identify active constituentIdentify active constituent(s)(s) and and explore mechanismexplore mechanism(s)(s) of action of action

Conduct clinical research Conduct clinical research

Required ElementsRequired Elements

Institutional CommitmentInstitutional Commitment Administrative CoreAdministrative Core Two Research CoresTwo Research Cores

Botanical Core RequiredBotanical Core Required * *Three to Four Research ProjectsThree to Four Research Projects

Pilot Research ProgramPilot Research ProgramTraining and Career DevelopmentTraining and Career Development * *Consumer Information Consumer Information **

* * Modified in RFA OD-04-002Modified in RFA OD-04-002

AdministrativeAdministrativeCoreCore

Research ProjectsResearch Projects

P1P1 P2P2 P3P3

RC 2RC 2 RC 3RC 3

Resource CoresResource CoresResource CoresResource Cores

RC 1RC 1

Lessons LearnedLessons Learned

RFARFA Required Elements Clearly IdentifiedRequired Elements Clearly Identified

The Grant ApplicationThe Grant Application Scientific Merit (R01 Projects)Scientific Merit (R01 Projects) Research Experience of InvestigatorsResearch Experience of Investigators Research Resources (Contemporary)Research Resources (Contemporary) Collaborative Effort (Synergy) Collaborative Effort (Synergy)

Administrative OversightAdministrative Oversight Administrative Core of Research CenterAdministrative Core of Research Center External Advisory CommitteeExternal Advisory Committee NIH Program StaffNIH Program Staff

Questions to Expert PanelQuestions to Expert Panel

Research ThemeResearch Theme FocusFocus

Center StructureCenter Structure Cores (Botany ?)Cores (Botany ?) Synergy/CollaborationSynergy/Collaboration

ProductivityProductivity CriteriaCriteria

Expert Panel RecommendationsExpert Panel Recommendations

High-impact themeHigh-impact theme

Studies of basic mechanisms and human Studies of basic mechanisms and human health, with a high level of translational health, with a high level of translational

interaction between the twointeraction between the two

Innovative TechnologyInnovative Technology

** Emphasis on quality assurance/quality Emphasis on quality assurance/quality controlcontrol

http://nccam.nih.gov/training/centers/bot-research-index.htmhttp://nccam.nih.gov/training/centers/bot-research-index.htm

GuidanceGuidance Document Document

NCCAM Policy on the Quality of Natural NCCAM Policy on the Quality of Natural Products Research (see RFA)Products Research (see RFA)

http://nccam.nih.gov/research/policies/natualproducts.htmhttp://nccam.nih.gov/research/policies/natualproducts.htm

RFA OD-04-002RFA OD-04-002Dietary Supplement Research Centers: Dietary Supplement Research Centers: BotanicalsBotanicals

RFA OD-04-002RFA OD-04-002

Developed in Collaboration with NIH Offices, Developed in Collaboration with NIH Offices, Centers and Institutes (ODS, NCCAM, NIEHS) *Centers and Institutes (ODS, NCCAM, NIEHS) *

Important DatesImportant Dates Letter of Intent Receipt Date: May 18, 2004Letter of Intent Receipt Date: May 18, 2004 Application Receipt Date: June 15, 2004Application Receipt Date: June 15, 2004 Peer Review Date: October/November 2004Peer Review Date: October/November 2004 Council Review: January 2005 Council Review: January 2005 Earliest Anticipated Start Date: April 2005Earliest Anticipated Start Date: April 2005

* Other ICs may participate* Other ICs may participate

Botanical (Definition)Botanical (Definition)For the purpose of this RFA, “botanical” For the purpose of this RFA, “botanical” is defined as plants, plant parts (e.g., is defined as plants, plant parts (e.g., bark, leaves, stems, roots, flowers, bark, leaves, stems, roots, flowers, fruits, seeds, berries), plant exudates, fruits, seeds, berries), plant exudates, algae, and macroscopic fungus. algae, and macroscopic fungus.

The definition of “botanical” is further The definition of “botanical” is further extended to include botanical extracts extended to include botanical extracts and isolated bioactive constituents and isolated bioactive constituents other than essential nutrients. other than essential nutrients.

Examples of Botanical Examples of Botanical Ingredients in Dietary Ingredients in Dietary

Supplements Supplements

PhytomedicinesPhytomedicines St. John’s Wort, Valerian, Ginkgo St. John’s Wort, Valerian, Ginkgo Foods Foods Soy, Garlic, Green Tea, BlueberrySoy, Garlic, Green Tea, Blueberry

Bacterial or yeast fermentation products are not Bacterial or yeast fermentation products are not included.included.

Synthetic compounds derived from botanical Synthetic compounds derived from botanical sources are not encouraged as test materials sources are not encouraged as test materials for research conducted under this initiative. If for research conducted under this initiative. If the applicant proposes to study synthetic the applicant proposes to study synthetic compounds, their use must be scientifically compounds, their use must be scientifically justified. justified. This RFA is not supportive of This RFA is not supportive of applications aimed at new drug discovery.applications aimed at new drug discovery.

Excluded test materialsExcluded test materials

Botanical Ingredients: Foods or DrugsBotanical Ingredients: Foods or Drugs((Intended Use)Intended Use)

1. FDA Regulation: Dietary supplements 1. FDA Regulation: Dietary supplements are not intended to diagnose, cure, are not intended to diagnose, cure, mitigate, treat or prevent disease. mitigate, treat or prevent disease.

2. NIH recognizes FDA regulations but 2. NIH recognizes FDA regulations but research on botanicals, for the research on botanicals, for the purpose of this RFA, is not purpose of this RFA, is not necessarily bounded by the above necessarily bounded by the above constraints. constraints.

Frequently Asked QuestionsFrequently Asked Questions

Rationale for Selection of

1. Test materials

2. Biological Process

3. Health Outcomes

4. Theme

RFA OD-04-002RFA OD-04-002PurposePurpose

Promote interdisciplinary collaborative study Promote interdisciplinary collaborative study of botanicals, particularly those that are found of botanicals, particularly those that are found as ingredients in dietary supplements as ingredients in dietary supplements

Conduct research of high potential for being Conduct research of high potential for being translated into practical benefits for human translated into practical benefits for human healthhealth

RFA OD-04-002RFA OD-04-002ObjectivesObjectives

1. Build collaborative research teams to 1. Build collaborative research teams to advance the basic scienceadvance the basic science to inform clinical to inform clinical studies:studies:

Characterize chemical composition of Characterize chemical composition of botanicals and study biological effects to botanicals and study biological effects to provide better predictions of safety and provide better predictions of safety and efficacy in humansefficacy in humans

Expand research base with development Expand research base with development and improvement of preclinical model and improvement of preclinical model systemssystems

RFA OD-04-002RFA OD-04-002ObjectivesObjectives

2. Cultivate the use of contemporary 2. Cultivate the use of contemporary technologies and innovative technologies and innovative approachesapproaches

3. Conduct Clinical Studies (optional)3. Conduct Clinical Studies (optional)

Clinical StudiesClinical Studies

OptionalOptional Phase I or early Phase IIPhase I or early Phase II

NCCAM Requirement: Review of NCCAM Requirement: Review of Funded Projects (OCRA)Funded Projects (OCRA) NCCAM Guidance Document (see RFA) NCCAM Guidance Document (see RFA)

IND ClearanceIND Clearance Is an IND Required?Is an IND Required? Questions addressed to FDAQuestions addressed to FDA See RFA for FDA contactSee RFA for FDA contact