INNOVATIVE TOXICOLOGY MODELS FOR DRUG EVALUATION:  SBIR/STTR INITIATIVE

Release Date:  October 25, 2000
 
PA NUMBER:  PAR-01-004

National Cancer Institute
National Institute of Diabetes, Digestive and Kidney Diseases
National Institute of Drug Abuse

Letter of Intent Receipt Dates:  December 7, 2000 and October 10, 2001
Application Receipt Dates:       January 11, 2001 and November 14, 2001

PURPOSE

Recent advances in cancer biology, molecular biology, combinatorial chemistry, 
and screening technology provide unprecedented opportunities for discovery of 
new disease therapies.  Drug discovery can now be focused on specific 
molecular or regulatory sites within cells. The National Cancer Institute 
(NCI) considers exploitation of this knowledge and technology for discovery of 
new agents to treat or prevent cancer a high priority as stated in its “Bypass 
Budget” (http://2001.cancer.gov).  It is expected that research focused on 
discovery and validation of new targets for therapy and screening design 
efforts to identify agents that effect these targets will result in a 
multitude of new chemical and biological agents with potential for clinical 
benefit.  However, before such agents can be tested and used widely in 
patients, safety and acceptable toxicity to critical organs must be 
demonstrated.  Current practices and procedures for safety evaluations are 
costly and time consuming.  Developments in genomics and proteomics will 
provide new approaches to quickly and effectively evaluate the expected large 
numbers of new agents. 

This Program Announcement (PA) encourages the small business community to 
develop, standardize, and validate new and innovative assays which determine 
or predict specific organ toxicities (e.g., cardiotoxicity, gastrointestinal 
toxicity, hepatotoxicity, nephrotoxicity, ototoxicity, bladder toxicity, 
neurotoxicity, pulmonary toxicity, and endocrine toxicity, including 
pancreatic beta cell toxicity) of potential therapeutic agents for the 
treatment and prevention of diseases of interest to the NCI, National 
Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) and the National 
Institute of Drug Abuse (NIDA).  Agents that have been evaluated in both 
animals and man can be utilized retrospectively to validate the utility, 
sensitivity, and reproducibility of the assay and to determine if other 
factors such as agent stability, protein binding, or metabolic activation are 
important parameters for interpretation and validation of the assay.

This Program Announcement (PA) must be read in conjunction with the OMNIBUS 
SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, SMALL BUSINESS INNOVATION 
RESEARCH (SBIR) and SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT 
APPLICATIONS (PHS 2000-2).
 
All of the instructions within the Omnibus Solicitation apply with the 
following exceptions:
  
o  Special receipt dates    
o  Initial review convened by the NCI, Division of Extramural Activities    
o  Additional review considerations

For this PA, the Modular Grant format will not be used.  

This program will utilize the SBIR and STTR mechanisms, but will be run in 
parallel with a program of identical scientific scope that will utilize 
Exploratory/Developmental Grants mechanism, PAR-00-003 (see 
http://grants.nih.gov/grants/guide/pa-files/PAR-00-003.html).

This PA will expire on November 15, 2001. NIH Grants policies apply to these 
awards.

RESEARCH OBJECTIVES

Background

Recent advances in all branches of medical sciences provide new insight into 
the underlying mechanisms in malignancy and suggest new targets and approaches 
for therapy diseases of interest to the NCI, NIDDK, and NIDA.  For example 
drug discovery can now be focused on targeting key regulatory pathways or 
specific macromolecules relevant to cancer and AIDS.  Key growth regulatory 
pathways and mutated genes are being identified, array technology for 
expression of thousands of genes as well as computer-assisted evaluation of 
data are available.  New technologies in chemistry which allow facile 
synthesis of millions of new chemicals, and high resolution structures of 
important target proteins are becoming available. These advances taken 
together and coupled with high throughput screening, allow identification of 
hundreds and maybe thousands of agents which could be seriously considered for 
clinical evaluation. Translation of these new technological discoveries and 
innovations into clinical benefit for the patient through these newly 
discovered agents is essential; however, the later stages in this drug 
development process are lengthy and costly.  Obviously new procedures are 
necessary to decide which of the multitude of new agents should be tested in 
humans.  It is reasonable to consider that new technological advances which 
lead to discovery of new agents could likewise be exploited to expedite the 
development and decision process.

Investigations focusing on the hazards of potential drugs or biologicals to 
healthy organs in intact experimental animals are the final steps in the 
preclinical stages of new drug development.  Data generated from these studies 
on each new drug are evaluated in light of potential human toxicity and form a 
major portion of the information required by the Food and Drug Administration 
(FDA) for an Investigational New Drug (IND) application.  Preclinical 
toxicology studies are generally conducted in two animal species with the 
following objectives: to define the Maximum Tolerated Dose (MTD), Dose 
Limiting Toxicities (DLTs), schedule-dependency of toxicity, reversibility of 
adverse effects, and a safe clinical starting dose (SD).  Procedures to obtain 
such information for IND filing have significant limitations in aspects such 
as cost and time requirements as well as prediction of problems to be 
encountered when agents are administered to humans.  For example, since animal 
studies are very expensive and time-consuming, it is generally impractical to 
evaluate numerous analogs of a class of compounds in a species prior to 
selection of the best developmental candidate or to decide which of a 
multitude of “hits” identified from screening models should be brought to 
clinical evaluation.  Another concern is the lack of information gained from 
these toxicological studies in regard to molecular or mechanistic mechanisms 
for observed toxicities.  It cannot be determined if toxicities of new agents 
designed to attack a key molecular target are related to actions of inhibition 
of that target or to other unknown aspects of the drug’s action in various 
organs.

New technology to improve toxicology approaches and define toxicity at the 
molecular level are emerging, but as yet none have been validated and accepted 
for common use.  For example, bacterial strains and transgenic mice have been 
engineered to detect mutational activities of agents.  “Toxicogenomics”, e.g., 
analysis of the transcription profile in a cell or organ following toxic agent 
administration [Molecular Carcinogenesis 24:153-159 (1999)] is under 
development using a variety of approaches, including DNA array analysis.  Data 
analysis software programs are being written to predict toxicological 
endpoints. Individually, these activities may not be sufficient, but they may 
be highly valuable when combined with other approaches to develop a total 
toxicological profile of specific organ toxicity and molecular mechanisms 
responsible for this toxicity.

Objectives and Scope

The goal of this PA is the discovery, development and validation of new assays 
and procedures to quickly and cheaply determine toxicological profiles of 
potential drugs.  It is expected that a molecular definition of toxicity in 
the affected organ, tissue or cell would be a component of the procedure.  
Approaches for new toxicology assays in response to this initiative are broad 
and are determined by the creativity of the applicant.  Genetically modified 
animals or cell lines, various non-mammalian organisms, in vitro assays 
utilizing primary mammalian cells, tissue slices, isolated organs, sub-
cellular fractions or purified enzymes could be utilized for the model.  
Computer modeling utilizing existing biological and toxicological data bases 
would be appropriate. Genomic and proteomic technology could be exploited to 
profile total gene activity or protein expression and thereby establish 
molecular correlations with specific toxicities.  Molecular endpoints to 
evaluate toxicity and high throughput toxicity screening could be used to help 
decide which agent of a chemical series should be pursued, to allow 
exploration of toxicity at an earlier stage in drug development, or to define 
the toxicity profile of agents selected for clinical trial.

The NCI, through the Developmental Therapeutics Program: 
http://dtp.nci.nih.gov/, on occasion utilizes its internal resources to foster 
drug development by small businesses.  For this PA, toxicology data from 
previous drug development for cancer and AIDS sponsored by NCI may be made 
available to awardees.  For additional informational contact Dr. Adaline C. 
Smith at the address listed under INQUIRIES.

The overall objective of this PA is to provide a flexible funding mechanism 
with regard to budgets and time of funding for small businesses to support the 
research activities required to develop and validate innovative toxicology 
assays.

MECHANISM OF SUPPORT 

Support for this PA is through the SBIR and STTR mechanisms which are set-
aside programs.  This PA is a one-time announcement which may be reissued. 
Responsibility for the planning, direction and execution of the proposed 
project will be solely that of the applicant. Awards will be administered 
under NIH grants policy stated in the NIH Grants Policy Statement, NIH 
publication 99-8 October 1998.

Applications can be submitted for support as Phase I STTR (R41) or Phase I 
SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the 
SBIR/STTR  FAST-TRACK option as described in the OMNIBUS SOLICITATION (PHS 
2000-2).  Phase II applications in response to this PA will only be accepted 
as competing continuations of previously funded NIH Phase I SBIR/STTR awards.  
The Phase II application must be a logical extension of the Phase I research.

Information on the FAST-TRACK process and the OMNIBUS SOLICITATION are 
available at: http://grants.nih.gov/grants/funding/sbirsttr1/index.htm

ELIGIBILITY REQUIREMENTS

Eligibility requirements are described in the OMNIBUS SOLICITATION for 
SBIR/STTR grant applications.  Any small business, independently owned by 
United States citizens or permanent resident aliens, and located in the United 
States may apply.  The small business 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.  For both Phase I and Phase II, the R&D must be 
performed in its entirety in the United States.  Including any affiliates, the 
company can be the employer of no more than 500 people.  

Racial/ethnic minority individuals, women, and persons with disabilities are 
encouraged to apply as principal investigators.

INQUIRIES 

Inquiries concerning this PA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:
 
Adaline C. Smith, Ph.D., D.A.B.T.
National Cancer Institute
Division of Cancer Treatment and Diagnosis
Toxicology and Pharmacology Branch
6116 Executive Blvd  Room 5113, MSC 7458
Bethesda, MD  20892-7458
Telephone:  (301) 496-8777
FAX: (301) 480-4836
Email: smithad@mail.nih.gov

Robert Star, M.D.
Senior Scientific Advisor
National Institute of Diabetes, Digestive and Kidney Diseases
Building 31, Room 9A35
31 Center Drive MSC 2560
Bethesda, MD 20892-2560
Telephone: (301) 594-7715
FAX: (301) 496-2830
Email: robert_star@nih.gov

David J. McCann, Ph.D.
Chief, Medications Discovery & Toxicology Branch
National Institute on Drug Abuse
Division of Treatment Research & Development
6001 Executive Boulevard, Room 4123, MSC 9551
Bethesda, MD 20892-9551
Telephone: (301) 443-2999
FAX: (301) 443-2599
Email: dmccann@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
National Cancer Institute 
Executive Plaza South, Room 243
6120 Executive Blvd, MSC 8635
Bethesda, MD  20892-7150
Telephone:  (301) 496-8635
FAX: (301) 496-8601
Email: shinok@gab.nci.nih.gov 

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8109, MSC 8329
Bethesda, MD 20892-8329
Telephone: (301) 496-3428
FAX: (301) 402-0275 
Email: tf12w@nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit, by the dates listed on the first 
page of this PA, 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 PA 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 NCI staff to estimate the potential 
review workload and plan the review.

NCI policy requires that all applicants requesting greater than $500,000 
direct costs in any one year must obtain approval from NCI Program staff prior 
to submission of the application.  If greater that $500,000 per year is 
requested, this fact must be clearly indicated and approval requested in the 
letter of intent. 

The letter of intent is to be sent to Dr. Adaline C. Smith at the address 
listed under INQUIRIES.

APPLICATION PROCEDURES

This PA must be read in conjunction with the OMNIBUS SOLICITATION FOR SMALL 
BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER 
(STTR) GRANT APPLICATIONS (PHS 2000-2).  All instructions within the 
solicitation apply with the following exceptions:
- special receipt dates
- initial review convened by the NCI Division of Extramural Activities
- additional review considerations

Information on the SBIR and STTR programs, OMINBUS SOLICITATION, application 
forms, and helpful advice on preparation of applications are available at:  
http://grants.nih.gov/grants/funding/sbir.htm.  Hard copies of the 
SOLICITATIONS, subject to availability, may be obtained from the PHS SBIR/STTR 
Solicitation Office, telephone (301) 206-9385; FAX (301) 206-9722; email 
a2y@cu.nih.gov.

Applications received in response to this PA are to be prepared as described 
in the OMNIBUS SOLICITATION (PHS 2000-2).  Phase I applications are located in 
the back pages of the SOLICITATION.  All applications and proposals for NIH 
funding must be self-contained within specified page limitations. 

Applications will be accepted up to the dates indicated on the first page of 
this PA.  The PA title and number must be typed in line 2 on the face page of 
the application form.

If an application is received after the application receipt dates, it will be 
returned to the applicant without review.  The Center for Scientific Review 
(CSR) will not accept any application in response to this PA 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 previously reviewed.

Applications can be submitted for Phase I or Phase II support, or as a 
combined Phase I and II (FAST-TRACK).  A Phase II application will be accepted 
only as continuation of a previously funded Phase I grant.  The Phase II 
proposal must be a logical extension of the Phase I research but not 
necessarily a Phase I project supported in response to this initiative.  
   
PHASE I:  Demonstration of feasibility of the innovative approach. Research 
should be proposed to provide sufficient reason to continue the assay 
development in Phase II.  It would be expected that assay methodology would be 
established.  If two years of support are requested, the goals for the first 
year should be clearly stated and not simply a reiteration of specific aims.  
Support for the second year will be contingent upon NCI programmatic 
evaluation to ensure that investigators are accomplishing the goals presented.

PHASE II:  Development of approach to stage at which the assay can be used for 
toxicology purposes.  Extensive studies designed to validate the approach 
would be expected.  Validation should include analysis of compounds with known 
organ toxicities.  Innovative aspects of the research necessary to complete 
the projects such as development of new in vivo models which may require 
“surrogate endpoints” should be clearly described.  Goals and milestones for 
each year of support should be clearly presented.  Support for years two to 
four, if requested, is dependent upon NCI Programmatic review of progress and 
achievement of the proposed goals.  For example, if a goal cannot be achieved 
such as identification of a known toxicity, the continuation years may not be 
supported.

FAST TRACK: Applications may be submitted for combined Phase I and Phase II, 
FAST TRACK consideration as described in the OMNIBUS SOLICITATION.  However, 
due to the complex nature of toxicological assay development, it is 
recommended that only well defined and more advanced projects be proposed for 
support through this mechanism.  

Phase I, FAST TRACK applications must specify clear, measurable milestones 
that should be achieved prior to Phase II funding.  Failure to provide such 
information 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 Phase II from consideration.  If so, the applicant may apply later 
for Phase II support.  Such applications will be reviewed by an appropriate 
scientific review group convened by the NIH. 

Special provisions described in this PA pertaining to Phase I and Phase II 
also apply to FAST TRACK applications.

An additional requirement of the FAST TRACK mechanism is the Product 
Development Plan.  The small business must submit a Product Development Plan 
(limited to ten pages) as an Appendix to the Phase II application addressing 
the four areas described in the instructions for FAST TRACK applications in 
the OMNIBUS SOLICITATION.   

The OMNIBUS SOLICITATION indicates the normal levels of support and period of 
time for SBIR and STTR Phase I and Phase II awards.  However, for this PA, 
budgets up to $250,000 total costs per year (direct costs, indirect costs, and 
fixed fee) and time periods up to 2 years for Phase I and $650,000 total costs 
per year (direct costs, indirect costs, and fixed fee) and up to 4 years for 
Phase II can be requested.  For FAST-TRACK applications the total duration of 
Phase I plus Phase II cannot exceed 5 years. 

SBIR Phase I applications requesting in excess of $100,000 total costs (direct 
costs, indirect costs, and fixed fee) per year will use “Budget for Phase I 
Direct Costs” (form page 3 of PHS 6246-1), and justify this request using 
“Budget Justification” form page 4 of PHS 6246-1.

STTR Phase I applications requesting up to $100,000 total costs (direct costs, 
indirect costs, and fixed fee) will request budgets using “Budget 
Justification” (form page 5 of PHS 6246-3) ONLY.  Present the total amount 
requested for direct costs on line 2a of the Face Page of PHS 6246-3.  The 
applicant small business organization should not submit “Budget of Applicant 
Organization for Phase I - Direct Costs Only” (form page 3 of PHS 6246-3); it 
is to be used as a “worksheet” only.  However, the single, “partnering” 
research institution must complete “Budget of Research Institution  for Phase 
I” (form page 4) in an abbreviated manner by: (1) Entering the amount of its 
participation in the project under “Total Costs” and (2) Signing and dating 
the “Certificate of Research Institution Participation” portion of the form.

STTR Phase I applications requesting in excess of $100,000 total costs (direct 
costs, indirect costs, and fixed fee) will use “Budget of Applicant 
Organization for Phase I - Direct Costs Only” (form page 3 of PHS 6246-3) and 
justify this request using “Budget Justification” (form page 5). 

Phase I SBIR and STTR applications requesting a budget more than one year 
should follow the following procedures: Photocopy Form Page 3, “Budget for 
Phase I-Direct Costs Only”, and number it Form Page 3a; Use Form Page 3 for 
the first year budget and title Form Page 3a “Phase I-2nd year budget”.  (This 
page will not be counted against the 25 page limit.); Provide the 
appropriate/requested information in the narrative justification (Form Page 4) 
for years 1 and 2; Indicate on the Phase I Face page Field 6, Dates of Project 
Period, the dates for the ENTIRE project period; Indicate on the Phase I Face 
Page in Field 7, the requested Direct Costs and Total Costs for the entire 
project period; The summary statement will reflect the recommended budget for 
the -01 and -02 years.

Potential applicants are encouraged to contact program staff for guidance and 
to read the advice and information on the web sites.  However, responsibility 
for planning, direction, and execution of the proposed research will be solely 
that of the applicant.

The completed original application and one legible 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
(20817 for express/courier service)

To expedite the review process, at the time of submission, send one additional 
copies of the application to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD 20852 (for express/courier service)
Telephone:    (301) 496-3428
FAX:    (301) 402-0275

Applications must be received by the receipt dates listed at the top of the 
first page of this PA.

REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed by CSR staff for completeness and 
by NCI program staff for adherence to guidelines.  Incomplete applications and 
applications not adhering to instructions described above will be returned to 
the applicant without further consideration.

Applications that are complete and adhere to the guidelines of this PA will be 
evaluated for scientific and technical merit and the documented ability of the 
investigators to meet the RESEARCH OBJECTIVES of this PA by an appropriate 
peer review group convened by the NCI, Division of Extramural Activities, in 
accordance with the peer review criteria listed below.  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, generally the top half of the applications under review, will be 
discussed, assigned a priority score, and receive a second level review by the 
appropriate advisory Council of NCI, NIDDK, or NIDA.

Review Criteria:

Review criteria are described in the NIH Omnibus Solicitation and available on 
the web at the following URL address: 
http://grants.nih.gov/grants/funding/sbirsttr1/index.htm

The goals of NIH-sponsored research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
Within this framework, the specific goals of this PA are the discovery and 
validation of new and innovative assays which predict specific toxicities of 
potential drugs.  Assays developed under this PA would be expected to be 
effective for a quick and cost effective determination of  toxicity of 
specific compounds and, importantly, to decrease the number of animals 
required. The reviewers will comment of the following aspects of the 
application in their written critiques in order to judge the likelihood that 
the proposed research will have a substantial impact on the pursuit of these 
goals.  Each of the criteria will be addressed and considered in assigning the 
overall score weighting them as appropriate for each application. Note that 
the application does not need to be strong in all categories to be judged 
likely to have a major impact and thus deserve a high priority rating.  For 
example, an investigator may propose to carry out important research that by 
its nature is not overly innovative but may be essential for development of a 
valuable assay.

In considering the scientific and technical merit of each application, the 
following criteria will be used as described in the OMNIBUS SOLICITATION (PHS 
2000-2).

Significance.  Does the study address an important problem?  Does the proposed 
project have commercial potential to lead to a marketable product or process?  
What may be the anticipated commercial and societal benefits of the proposed 
activity?  If the aims of the application are achieved, how will scientific 
knowledge be advanced?  Does the proposal lead to enabling technologies 
(instrumentation, software, etc.) for further discoveries?   Will the 
technology have a competitive advantage over existing/alternative technologies 
that can meet the market needs?

Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Is the proposed plan a sound approach for establishing technical and 
commercial feasibility?  Does the applicant acknowledge potential problem 
areas and consider alternative strategies?  Are the milestones and evaluation 
procedures appropriate?

Innovation.  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies?  Are the aims original and 
innovative?

Investigator.  Is the principal investigator capable of coordinating and 
managing the proposed SBIR/STTR?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers including 
consultants and sub-contractors  (if any)?

Environment.  Is there sufficient access to resources (equipment, facilities, 
etc.)?  Does the scientific and technological environment in which the work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements?

For Phase II applications: In addition to the above criteria, to what degree 
was progress toward the Phase I objectives met and feasibility demonstrated in 
providing a solid foundation for the proposed Phase II activity?

For Phase I/Phase II Fast Track applications, the following additional 
criteria will be applied: Does the Phase I specify clear, measurable goals 
(milestones) that should be achieved prior to initiating Phase II?  Did the 
applicant submit a concise Product Development Plan that adequately addresses 
the four areas described in Section VI. G. of the SBIR/STTR solicitation?  To 
what extent was the applicant able to obtain letters of interest, additional 
funding commitment and/or resources from private sector or non-SBIR/STTR 
funding sources that would enhance the likelihood for commercialization?  

For all SBIR/STTR applications, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following: adequacy of 
plans to include both genders, minorities, and their subgroups as appropriate 
for the scientific goals of the research; plans for the recruitment and 
retention of subjects; adequacy of the proposed protection for humans, animals 
or the environment, to the extent they may be adversely affected by the 
project proposed in the application; appropriateness of the proposed budget 
and duration in relation to the proposed research.

AWARD CRITERIA

Applications will compete for available funds with all other recommended SBIR 
and STTR applications.  Funding decisions for Phase I or Phase II applications 
will be based on quality of the proposed project as determined by peer review,  
program priority, potential for commercial success, and availability of funds. 
A portion of the SBIR/STTR allotment will not be designated for this 
initiative.

FAST TRACK, Phase II applications may be funded following submission of the 
Phase I progress report and other documents necessary for continuation.  Phase 
II applications will be selected for funding based on the initial priority 
score, grant Program staff’s assessment of the Phase I progress and 
determination that Phase I goals were achieved, the project’s potential for 
commercial success, and the availability of funds.

SCHEDULE

Letter of Intent Receipt Dates:	December 7, 2000 and October 10, 2001
Application Receipt Dates:		January 11, 2001 and November 14, 2001
NCAB Review Dates:  		May 2001 and May  2002
Earliest Anticipated Award Date	July 1, 2001 and July 1, 2002

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 sub-populations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is 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 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

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 clear and compelling 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 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of the policy from the program staff 
listed under INQUIRIES, and under funding opportunities at the web site: 
http://dtp.nci.nih.gov

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.

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.  This PA, “Innovative Toxicology Models 
for Drug Evaluation”, is related to the priority area of cancer.  Potential 
applicants may obtain a copy of "Healthy People 2010" 
at:  http://www.health.gov/healthypeople/.

AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.395, 93.847, 93.848, and 93.849. 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.


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