BOTANICAL PRODUCTS DEVELOPMENT: SBIR AND STTR

Release Date:  June 22, 2000

RFA:  AT-00-003

National Center for Complementary and Alternative Medicine
 http://nccam.nih.gov/

National Institute of Diabetes and Digestive and Kidney Diseases
 http://www.niddk.nih.gov/

Letter of Intent Receipt Date:  September 7, 2000
Application Receipt Date:       November 14, 2000

PURPOSE

The purpose of this Request for Applications (RFA) is to support projects that 
could lead to development of appropriate standardized products and provision 
of a reliable constant supply of these products as reference reagents for 
clinical research, including human trials, as well as basic research. The 
NCCAM has identified at least four herbs (feverfew, valerian root, echinacea, 
and milk thistle) that warrant further testing in Phase II and/or Phase III 
trials. Before supporting such trials, several issues regarding the choice of 
the clinical trial material require special attention, for example:  (1) use 
of different parts of the plants (e.g., roots, aerial parts, whole plant); (2) 
use of different cultivars and species; (3) optimal growing and harvest 
conditions; (4) whether to use whole extract or a specific fraction; (5) the 
method of extraction (e.g., alcoholic, tea, pressed juice); (6) chemical 
standardization of the product; (7) presentation of the medication (e.g., 
extract, tablet, capsule); and (8) the dose and length of administration.  The 
goal of each project would be to develop a well-defined product the next step 
for which would be scaled up to satisfy research needs. 

This RFA provides a flexible system within the Small Business Innovation 
Research (SBIR) and Small Business Technology Transfer (STTR) programs to 
accommodate the extensive needs and complex development process. It invites 
grant applications for SBIR and STTR projects with award duration and amounts 
greater than those routinely allowed under the SBIR/STTR program. This RFA 
provides a flexible system within the SBIR/STTR program to cover the extensive 
needs and complex development processes needed to identify/characterize and 
develop a botanical product.

This RFA must be read in conjunction with the Omnibus Solicitation of the 
National Institutes of Health, Centers for Disease Control and Prevention, and 
Food and Drug Administration for Small Business Innovation Research (SBIR) and 
Small Business Technology Transfer (STTR) Grant Applications (PHS 2000-2) 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.htm).  The NIH has 
announced that applicants may request a larger budget and period of support if 
necessary for completion of the project (See NIH Guide for Grants and 
Contracts, January 12, 2000) at:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-012.html

All of the instructions within the Omnibus SBIR/STTR Solicitation apply with 
the following exceptions:

o  Special receipt dates
o  Initial review convened by the NCCAM Division of Extramural Research, Training 
and Review
o  Modification of review criteria and/or application instructions
o  Increased award amount and duration
o  Additional award consideration  
o  Opportunity for 1 year of Phase I support and 3 years of Phase II support 

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas. AHealthy People 2010" does not specify a 
complementary and alternative medicine (CAM) objective, although this RFA, 
Botanical Products Development: SBIR/STTR, may be applied to several different 
priority areas with "Healthy People 2010".  Potential applicants may obtain a 
copy of "Healthy People 2010" at http://health.gov/healthypeople/


ELIGIBILITY

Eligibility requirements for SBIR and STTR are described in the NIH Omnibus 
Solicitation for SBIR/STTR grant applications 
(http://grants.nih.gov/grants/funding/sbir.htm).  Any small business, 
independently owned and operated by United States citizens or permanent 
resident aliens may apply. It must be organized for-profit, cannot be dominant 
in its field of expertise, and must have its principal place of business in 
the United States. Including any affiliates, the company can be the employer 
of no more than 500 people.  Eligibility is determined at the time of award of 
Phase I and Phase II

The NCCAM will pursue SBIR/STTR funding mechanisms for the four projects 
described by this RFA. A small business may apply for development of all four 
botanical products or only one.  For each botanical product, the small 
business must submit a separate application. Only one award will be made for 
each botanical product project; however, a small business may be awarded 
projects for more than one botanical product.

Note: Applicants may submit investigator-initiated applications for 
development of botanical products in addition to the four mentioned in the 
RFA; however, only those applications for feverfew, valerian root, echinacea, 
and silymarin will be considered responsive to the RFA.  Investigator-
initiated SBIR/STTR applications will be subject to the standard receipt, 
review, and award processes described in the Omnibus Solicitation. They will 
compete for available funds with all other favorably recommended SBIR/STTR 
applications.  

MECHANISM OF SUPPORT B PHASE 1/PHASE 2 FAST TRACK

This RFA is a one-time solicitation and will use the National Institutes of 
Health (NIH) Small Business Innovation Research (SBIR) and Small Business 
Technology Transfer (STTR) Phase I/Phase II Fast Track (R44/R42) award 
mechanism. Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant. Applications for Phase 
I/Phase II Fast Track grants should be prepared following the directions for 
Fast Track applications as described in the Omnibus Solicitation, which is 
available electronically at: http://grants.nih.gov/grants/funding/sbir.htm

A limited number of paper copies of the Omnibus Solicitation are available 
from 

PHS SBIR/STTR Solicitation Office
13687 Baltimore Avenue
Laurel, MD 20707-5096
Telephone: 301-206-9385
FAX: 301-206-9722
E mail: a2y@cu.nih.gov

PROJECT PERIOD AND AMOUNT OF AWARD

SBIR Phase I awards normally may not exceed $100,000 total costs (direct 
costs, indirect costs and negotiated fixed fee) for a period normally not to 
exceed 6 months and SBIR Phase II awards normally may not exceed $750,000 
total costs for a period normally not to exceed two years.  STTR Phase I 
awards normally may not exceed $100,000 total costs for a period of 1 year and 
STTR Phase II awards normally may not exceed $500,000 total costs for a period 
normally not to exceed two years.  

Because the length of time and cost of research involving development and 
evaluation of botanical products often exceeds that routinely awarded for 
SBIR/STTR grants, modifications of award durations and amounts will be 
allowed. The NCCAM will entertain well-justified Phase I/Phase II Fast Track 
applications for an SBIR/STTR award with Phase I projects up to one year and 
Phase II projects up to three years and a budget not to exceed a total cost of 
$500,000 [direct costs, indirect costs, and negotiated fixed fee] per year.

PERFORMANCE OF WORK


In addition, because these projects may involve multiple disciplines (e.g., 
horticulture, taxonomy, botany, pharmacognosy, chemistry) and several project 
sites (e.g., agricultural fields, laboratories), the NCCAM will entertain very 
well-justified Phase I/Phase II Fast Track applications for an SBIR award with 
greater than 33% contractual costs in Phase I and greater than 50% in Phase II 
when those costs are necessary to support development and evaluation of herbal 
products. Normally the total amount of all consultant costs and contractual 
costs may not exceed 33% or 50% of the total costs requested for Phase I and 
Phase II SBIR applications, respectively. Even larger budgets than indicated 
in PROJECT PERIOD AND AMOUNT OF AWARD could be considered if required to 
develop a Drug Master File and if appropriately justified in the application. 

FUNDS AVAILABLE

It is expected that four awards (one each for feverfew, valerian root, 
echinacea, and silymarin) will be made in FY01.  The number of awards will be 
dependent upon receipt of a sufficient number and diversity of applications 
with high scientific merit. Total costs (direct costs, indirect costs, and 
negotiated fixed fee) for all four awards in the first year will be up to 
$2,000,000. Total costs for all four awards over all years will be up to 
$6,000,000.  Awards will be made for either SBIR or STTR grants from funds set 
aside for these programs.  

RESEARCH OBJECTIVES

Background

Definitive randomized, controlled, double-blinded trials investigating the 
efficacy of feverfew, valerian root, echinacea, and milk thistle for any 
medical condition have not been reported in the literature. Of the randomized 
controlled trials that have been done, it is difficult to adequately quantify 
the clinical effects of the herbs because study designs, outcome 
methodologies, subject characteristics, dosage, and phytochemical content of 
the various preparations differ. Given this background, it would be premature 
for the NCCAM to support large-scale Phase III trials or possibly even Phase 
II trials with these non-standardized botanical products. 

Feverfew as Treatment for Migraine

Several small, short-term, double-blind, placebo-controlled, randomized 
clinical trials suggested feverfew (Tanacetum parthenium) to be effective in 
reducing the frequency of migraine attacks (Johnson 1985; Murphy 1988), the 
accompanying nausea and vomiting (Johnson 1985; Murphy 1988; Palevitch 1997), 
and pain intensity (Palevitch 1997).  De Weerdt (1996), however, showed no 
differences in frequency of headache attacks. Each study used different 
formulations of feverfew, including capsules of freeze-dried, powdered leaves 
(harvested at one time only), capsules of air-dried powdered leaves (harvested 
throughout the year), and capsules containing an ethanol extract standardized 
using parthenolide.


The mechanism of action of feverfew in migraine is not known. The plant is 
rich in sesquiterpene lactones, the principal one being parthenolide. A 
definitive chemical link between the etiology of migraine and parthenolide or 
any other of the feverfew constituents has still not been established. The 
lack of effectiveness of de Weerdt's study, for example, could be due to the 
absence of essential therapeutic components of the granulated feverfew leaves 
which were either not sufficiently extracted or perhaps degraded during the 
preparation.

More research is needed, both on a larger scale and with various feverfew 
extracts, including parthenolide-rich and parthenolide-free preparations. 
First, a comprehensive profiling of feverfew leaf secondary compounds, 
examining both the whole leaf and extracts of a broad range of feverfew 
components, is warranted.

Valerian Root for Insomnia

There seems to be considerable evidence for the sleep-inducing effects of 
valerian (Lindahl 1989; Schmitz 1998; Klasser 1984; Gerhard 1996; Balderer 
1985; Schultz 1994; Leathwood 1982), and it would appear to be a relatively 
safe substitute for drugs, such as benzodiazepines, to aid onset of sleep 
(Houghton 1999; Wagner 1998; Barrett 1999). In addition to valerian alone, 
other studies with preparations consisting of mixtures of valerian and hops 
have also shown significant improvement in sleep quality. Because of study 
limitations, however, it is difficult to adequately quantify the sleep-
promoting effects of valerian. Nevertheless, valerian's sedative effect is 
relatively well established through animal experimentation (Barrett 1999), and 
the adverse effects profile appears favorable.

Valerian is the common name given to a crude drug consisting of the 
underground organs of species of Valeriana. In Europe the drug is derived from 
Valeriana officinalis L., but other species are used as crude drugs in other 
parts of the world (Houghton 1999).  

Valerian's mechanism of action has not been fully elucidated (Klepser 1999). 
Valerian is a classical example of an herbal where the overall effect may be 
due to several types of constituents and modes of activity. The activity of 
any particular valerian preparation could be due to both the profile of the 
types and amounts of the constituents present. This underlines the importance 
of standardizing the preparation both qualitatively and quantitatively, not 
only in terms of one constituent (Houghton 1999). Since the chemical basis of 
the observed activities is still not fully known, more work needs to be 
carried out before a satisfactory standard can be formulated that relates to 
activity.

Echinacea for Prevention/Treatment of Upper Respiratory Infections

Few rigorous clinical trials have been performed to demonstrate the efficacy 
of echinacea as an immune stimulator, although this is a reason for its common 
use in the United States. A recent systematic review (Melchart 1994) 
identified 26 controlled trials testing 34 treatments. After consideration of 
the methodological quality of the trials, the authors were only able to 
identify one trial (Braunig 1992) that demonstrated clear efficacy and nine 
trials that demonstrated "indications of efficacy." In a followup article, 
Melchart (1995) identified 16 randomized trials claiming positive results of 
treatment (e.g., Dorn 1989, Reitz 1990, Zimmer 1985) and prevention (e.g., 
Schmidt 1990) of upper respiratory infections. Three of these trials used 
monopreparations (a species of echinacea alone) and several trials tested 
preparations that contained plant extracts, homeopathic dilutions, or 
echinacea as part of a herbal mixture. The authors concluded that while 
echinacea may be an  efficacious immunomodulator, the evidence is still 
insufficient for clear therapeutic recommendations as to which preparation to 
use and which dose to employ.


There are nine different echinacea plants, but only three are used for 
medicinal purposes:  E. purpurea, E. pallidea, and E. angustifolia  These 
three echinacea plants have been chemically characterized and found to contain 
the following compounds in varying quantities:  polysaccharide, flavonoids, 
caffeic acid derivatives, essential oils, polyacetylenes, alkylamides, and 
miscellaneous chemicals (Bauer Wagner 1990). Extracts from the three echinacea 
species can not be clearly distinguished from each other in terms of their 
apparent beneficial activity (Dorn 1989). Without knowing a preparation's 
chemical composition, extrapolation of the results obtained with that 
preparation compared to others is impossible (Melchart 1995).

Multiple chemicals apparently contribute to echinacea's mechanisms of action. 
To date, there is no universally agreed-on standardization procedure to ensure 
comparability among products. Given the unequal distribution of active 
constituents in the flowers, leaves, and roots of the three species, and 
variation by season, soil type, and climate, it is difficult to determine 
exactly what kind of standardization would be optimal (Reichling 1998). Also, 
the dose of echinacea depends on the type of echinacea used, as well as the 
preparation procedure (Blumenthal 1998). There are different guidelines for 
extracts, tablets, or capsules.

Milk Thistle in the Treatment of Hepatic Diseases

Silybum marianum (milk thistle) is currently the most well researched plant in 
the treatment of liver disease. Silymarin, which is found in the entire plant 
but is concentrated in the fruit and seeds, is an extract of milk thistle 
which contains the flavonoids silybinin, silydianan, and silichristin. 
Silybinin constitutes 60-90% of silymarin and is the component with the 
greatest degree of biological activity.  Milk thistle extracts are usually 
standardized to contain 70-80% silybinin. Milk thistle is not water soluble 
and is typically administered as an encapsulated standardized extract.

The use of silymarin in chronic liver disease was recently reviewed in the 
NIDDK/NCCAM symposium, Complementary and Alternative Medicine in Chronic Liver 
Disease (Seeff 1999 draft). The hepatoprotective properties of silybinin 
against a variety of hepatotoxins are established by experimental data. The 
mechanisms that provide silymarin's hepatoprotective effects are many and 
varied, and include antioxidation, anti-lipid peroxidation, enhanced 
detoxification, and protection against glutathione depletion.  

In contrast, the clinical benefits of silymarin therapy are difficult to 
establish. Conflicting data has emerged from randomized controlled studies in 
the treatment of chronic liver disease with differing results. No randomized 
trials have yet been performed in patients with chronic hepatitis C, although 
small pilot studies have shown a lowering of serum enzymes without 
accompanying loss of HCV RNA levels.

It seems apparent that silymarin has a clearly positive effect on the liver 
with little to no accompanying side effects, and is therefore deserving of 
more rigorous clinical trials. The first challenge will be to identify a pure 
and standardized product and then to consider which form of liver disease is 
likely to benefit from rigorously developed and conducted treatment trials 
(NIH Symposium 1999).

Significance


Standardized formulations of botanical products have not occurred in either 
the US market or research arena. The development and use of standardized 
products in research will (1) allow for comparisons across studies using the 
same products, (2) allow for comparisons between known products, and (3) lead 
to subsequent, large randomized controlled clinical trials. A reliable and 
constant source for these products will assure the quality of study outcomes. 

Objectives

The goal of each project is to characterize for each of the four herbs 
(feverfew, valerian root, echinacea, and milk thistle or silymarin) the 
standardized product(s) suitable for testing in NIH-sponsored research, 
including Phase II and Phase III trials. The objectives to achieve this goal 
are listed below and may be divided between Phases I and II of the SBIR/STTR 
project as justified by the applicant. Some may be developed as measurable 
goals for Phase I. After completion of Phase 2, the next step (using other 
funding sources) would be the production of these products at least in 
sufficient supply for clinical research. Successful applicants would be 
expected to participate in an annual meeting in the Washington, DC, 
metropolitan area with other grantees developing botanical products.

It is anticipated that each grant application will include the following:

- Review in detail the state of the knowledge on the use of the herb, 
differentiating between human clinical, animal, and in vitro data, in order to 
determine the appropriate botanical product(s) to develop and standardize;

- Identify accurately the species for the selected herb (botanical 
description, including comparative descriptions of different species as 
needed); 

- Describe the macro- and microscopic physical characteristics;

- Provide a standard, high-quality source of the raw material, describing how 
the plant is grown; where the material is gathered; how and when it is 
collected, dried and stored to maintain optimal constituent profile; and 
adulterations and contaminations (presence of insecticide, herbicide, and 
toxic contaminants);

- Develop and document substantiated, qualitative and quantitative analytic 
methods for the analysis of crude materials;

- Identify the constituent (chemical) profile [the HPLC or other profile need 
not be based on the purported active ingredients, but could serve as a marker 
or fingerprint (DNA or other) for active constituents]; markers may be defined 
as those constituents known to be present in the plant that are not 
necessarily the active constituent;

- For each standardized botanical product, identify and describe the species 
and plant parts from which it is derived, how it is derived (or extracted), 
the form in which it is provided;

- Assess bioavailability, pharmacology, and pharmacokinetics of selected 
constituents of the profile;

- Conduct stability testing of the standardized formulation;

- If more than one product for the same herb is developed, compare 
bioavailability among the different products;

- Establish protocols for the production, under Good Manufacturing Practices 
(GMP), of standardized dosage forms;


- Develop the capability to provide the standardized botanical product to NIH-
sponsored pre-clinical and clinical trials;

- Develop and maintain a Drug Master File at the Food and Drug Administration 
that will be freely available for cross-reference by researchers participating 
in clinical trails of the herb.

NOTE: It is not the intent of this RFA for the applicant to isolate single 
active ingredients for drug development.  Isolation of single active 
ingredients is appropriate for identification and standardization of optimal 
whole products.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which was published in the Federal Register of March 28, 1994 (FR 
59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 
11, March 18, 1994, and is available on the web at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them. This 
policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES. Program staff may also provide additional relevant 
information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations. Unless otherwise specified in an NIH solicitation, 
internet addresses (URLs) should not be used to provide information necessary 
to the review because reviewers are under no obligation to view the Internet 
sites. Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site.

LETTER OF INTENT


Prospective applicants are asked to submit, by the receipt date listed at the 
beginning of this RFA, a letter of intent that includes a descriptive title of 
the proposed research, the name, address, and telephone number of the 
Principal Investigator, the identities of other key personnel and 
participating institutions, and the number and title of the RFA in response to 
which the application may be submitted. Although a letter of intent is not 
required, is not binding, and does not enter into the review of a subsequent 
application, the information that it contains allows NCCAM staff to estimate 
the potential review workload and plan the review.

The letter of intent is to be sent (fax, e:mail, or post) to Marguerite Evans, 
NCCAM, at the address listed under INQUIRIES.

APPLICANT INFORMATION

It is expected that applicants will have questions concerning the RFA.  In 
order to clarify the issues and improve the quality of applications submitted 
in response to this RFA, a Question/Answer web site will be constructed and 
may be accessed through the NCCAM website: http://nccam.nih.gov/

APPLICATION PROCEDURES

This RFA must be read in conjunction with the most current Omnibus 
Solicitation of the Public Health Service for Small Business Innovation 
Research (SBIR) and Small Business Technology Transfer (STTR) Grant 
Applications (http://grants.nih.gov/grants/funding/sbir.htm). An example of a 
sample SBIR Phase I application can be found on the internet at:  
http://www.nhlbi.nih.gov/funding/sbir/modelsbi.htm.  All of the instructions 
within the Omnibus Solicitation apply except as noted otherwise in this RFA.

Applications in response to this RFA are to be prepared as described in the 
Omnibus Solicitation for the SBIR/STTR Programs, which are available 
electronically at (http://grants.nih.gov/grants/funding/sbir.htm). 
Phase I/Phase II Fast Track applications must be prepared according to the 
Fast Track instructions in the Solicitation  
http://grants.nih.gov/grants/funding/sbirsttr1/6method.htm#6g.  Applications 
are to be submitted on the applicable grant application forms as follows:

PHASE I SBIR GRANT APPLICATION FORM (PHS 6246-1) and REMINDER SHEET
http://grants.nih.gov/grants/funding/sbirsttr1/11instructions.htm

PHASE II SBIR GRANT APPLICATION FORM (PHS 6246-2) 
http://grants.nih.gov/grants/funding/sbir2/index.htm

OR

PHASE I STTR GRANT APPLICATION FORM (PHS 6246-3) and REMINDER SHEET 
http://grants.nih.gov/grants/funding/sbirsttr1/11instructions.htm

PHASE II STTR GRANT APPLICATION FORM (PHS 6246-4) 
http://grants.nih.gov/grants/funding/sttr2/index.html

Phase I application forms are also located in the back pages of the Omnibus 
Solicitation.

Applicants submitting under the SBIR/STTR Fast Track process must prepare and 
submit both a Phase I and Phase II application together for concurrent initial 
peer review and evaluation.  Fast Track applications must specify clear, 
measurable goals for Phase I that should be achieved prior to Phase II 
funding. Failure to provide measurable goals in the Phase I application and/or 
sufficient detail in the Phase II application may be sufficient reason for the 
peer review committee to exclude the application from consideration. The Phase 
II application must be a logical extension of the Phase I research and must 
include a concise Product Development Plan as described in Section VI, item G 
of Omnibus Solicitation. 

Projects may be presented for SBIR/STTR support at all stages of the botanical 
product development process. Projects will be evaluated on overall innovation 
and success potential of the research path proposed to botanical product 
characterization/development.

PHASE I:  Larger budgets (SBIR and STTR) and longer project period (SBIR) will 
be considered for Phase I if required for conduct of the research and 
appropriately justified in the application.  Phase I milestones are determined 
by the applicant but must address some of the objectives outlined in the 
section RESEARCH OBJECTIVES of this RFA.  

PHASE II: As with Phase I, requests for larger budgets and longer project 
periods will be considered. Even larger budgets than indicated in PROJECT 
PERIOD AND AMOUNT OF AWARD could be considered if required to develop a Drug 
Master File and is appropriately justified in the application. The second 
phase of support will be contingent upon the NCCAM programmatic evaluation to 
ensure that investigators are accomplishing Phase I milestones and time lines 
presented in the original application. The project=s Phase II objectives 
should include the objectives outline in the RESEARCH OBJECTIVES section of 
this RFA that were not addressed in Phase I.

In addition, in the Phase II application, applicants should develop a detailed 
plan for the release of data and the sharing of research materials in order to 
ensure that data and research materials generated under the SBIR/STTR grant 
are accessible to the research community for future studies.  The adequacy of 
this plan will be reviewed as one of the criteria for award.

Finally, applicants are reminded that the grantee institution is required to 
disclose each subject invention to the Federal Agency providing research funds 
within two months after the inventor has disclosed it in writing to grantee 
institution personnel responsible for the patent matters.  NCCAM will monitor 
the patenting activity associated with these awards to determine to what 
extent the patenting of program-funded inventions has interfered with the 
timely dissemination of research data, results and materials.  If the approach 
above is insufficient to ensure the timely sharing of data and materials, the 
NIH will consider invoking a determination of exceptional circumstances to 
restrict or eliminate the right of grantee parties to retain title to 
intellectual property under future grants.

Applicants are encouraged to see the Federal Register Notice published on 
December 23, 1999, entitled, "PRINCIPLES FOR RECIPIENTS OF NIH RESEARCH GRANTS 
AND CONTRACTS ON OBTAINING AND DISEEMINATING BIOMEDICAL RESEARCH RESOURCES" 
(64 FR 72090) for an in-depth discussion of NIH principles and guidelines for 
sharing biomedical research resources.  This Notice is also available at an 
NIH Internet site: http://www.ott.nih.gov/policy/rt_guide_final.html.  
All of the instructions within the Omnibus Solicitation apply with the 
following exceptions:

- Receipt date;
- Increased award amount and duration;
- Additional award consideration.

Applications will be accepted on or before November 14, 2000. If an 
application is received after the application receipt date, it will be 
returned to the applicant without review. The Center for Scientific Review 
will not accept any application in response to this RFA that is essentially 
the same as one currently pending review, unless the applicant withdraws the 
pending application. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

For purposes of identification and processing, the title and number of this 
RFA must be shown in item 2 on the face page of the SBIR/STTR Phase I 
applications and in item 1A of the face page of Phase II grant applications 
(e.g., RFA-00-003, Botanical Products Development: SBIR/STTR).

The completed original application and one exact, signed copies must be sent 
or delivered to:

CENTER FOR SCIENTIFIC REVIEW

NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE
ROOM 1040-MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, mail one additional complete copy of the 
application to the following RFA program administrator:

Dr. Richard L. Nahin
Director, Division of Research, Training and Review
National Center for Complementary and Alternative Medicine
9000 Rockville Pike
Building 31, Room 5B58
Bethesda, MD  20892-2182
Telephone: (301) 496-4792
FAX: (301) 402-4741
Email: nahinr@od.noh.gov 

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the NIH Center 
for Scientific Review and responsiveness by NCCAM. Incomplete or non-
responsive applications will be returned to the applicant without further 
consideration.

Applications will be reviewed for scientific and technical merit by a special 
emphasis panel convened by the National Center for Complementary and 
Alternative Medicine, in accordance with the standard NIH peer review 
procedures. As part of the initial merit review, all applications will receive 
a written critique and undergo a process in which only those applications 
deemed to have the highest scientific merit will be discussed and assigned a 
priority score.  Scored applications will receive a secondary review by the 
NCCAM Advisory Council.

REVIEW CRITERIA

Review criteria are described in the Omnibus Solicitation. The Phase I 
application should specify clear, measurable goals (milestones) that should be 
achieved prior to initiating Phase II. Failure to provide clear, measurable 
goals may be sufficient reason for the study section to judge the application 
non-competitive.  In addition, the adequacy of a plan for the release of data 
and the sharing of research materials will be reviewed as one of the criteria 
for award.


AWARD CRITERIA

The following will be considered when making funding decisions: quality of the 
proposed project as determined by peer review, program balance among research 
areas of the announcement, the availability of funds, and the 
commercialization status where the small business concern has received more 
than 15 Phase II awards in the prior five (5) fiscal years, if applicable (see 
this application requirement under "Prior SBIR Phase II Awards" found in the 
"Grant Application Preparation Instructions and Requirements" portion of the 
Omnibus Solicitation).

ADVICE ON SUBMITTING APPLICATIONS

Potential applicants are strongly encouraged to contact program staff for pre-
application guidance and/or for more specific information on the research 
topics described in this RFA. They are also encouraged to read the advice and 
information on SBIR/STTR programs located on the Internet at:  
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf

INQUIRIES


Written and telephone inquiries are encouraged. The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Inquiries regarding programmatic issues may be directed to:

Marguerite Evans
Division of Extramural Research, Training, and Review
National Center for Complementary and Alternative Medicine
National Institutes of Health
Building 31, Room 5B58
Bethesda, MD 20892
Telephone: (301) 402-5860
FAX: (301) 402-4741
Email: evansm@od.nih.gov

Direct inquiries regarding fiscal matters to:

Suzanne White*
Grants Operations Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
Two Rockledge Center,Room 7150, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-7926
Telephone: 301-435-0170
FAX: 301-480-3310
Email: sw52h@nih.gov
 
* The NHLBI is the Grants Management Service Center for the NCCAM.

Inquiries regarding review issues should be directed to:

Dr. Richard L. Nahin
Director, Division of Extramural Research, Training and Review
National Center for Complementary and Alternative Medicine
9000 Rockville Pike
Building 31, Room 5B58
Bethesda, MD 20892-2182
Telephone: (301) 496-4792
FAX: (301) 402-4741
Email: nahinr@od.nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.213. Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92. This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products. In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care or early 
childhood development services are provided to children. This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


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