FLEXIBLE SYSTEM TO ADVANCE INNOVATIVE RESEARCH FOR CANCER DRUG DISCOVERY BY 
SMALL BUSINESSES (FLAIR)

Release Date:  December 15, 1999

PA NUMBER:  PAR-00-030

National Cancer Institute

Letter of Intent Receipt Dates:  February 16, 2000, and October 18, 2000
Application Receipt Dates:       March 22, 2000, and November 22, 2000
 
This Program Announcement (PA) replaces RFA: CA-98-022, which was published 
in the NIH Guide, August 20, 1998.

PURPOSE

Discovery and development of new cancer therapeutics, including both drugs 
and biological response modifiers, normally involve lengthy and costly 
projects.  The multiple components of the overall process including 
discovery, efficacy testing, development of lead agents, toxicology and 
pharmacology, Investigational New Drug Application (IND) filing, and clinical 
evaluation, may require years and several million dollars. The small business 
community is an active participant in the cancer therapy discovery effort.  
The Small Business Innovation Research (SBIR) and Small Business Technology 
Transfer (STTR) programs have supported these efforts; however, the extent of 
such support has been limited by the stringent guidelines of the Phase I and 
Phase II components.  For example, feasibility of the approach or of the drug 
as a potential clinical agent has often been difficult to establish within 
the limited Phase I time and budget guidelines.  This PA provides a flexible 
system within the SBIR and STTR programs to accommodate the extensive needs 
of the complex discovery and development process, at least partially, from 
basic discovery through proof of principle demonstration in clinical trials.  
 
This PA must be read in conjunction with the OMNIBUS SOLICITATION OF THE 
PUBLIC HEALTH SERVICE FOR SMALL BUSINESS INNOVATION RESEARCH GRANT (SBIR) 
APPLICATIONS (PHS 2000-2) and the OMNIBUS SOLICITATION OF THE NATIONAL 
INSTITUTES OF HEALTH FOR SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT 
APPLICATIONS (PHS 2000-3).  All of the instructions within the omnibus 
solicitation apply with the following exceptions:
-Special receipt dates
-Initial review convened by the Division of Extramural Activities, National 
Cancer Institute (NCI)
-Additional review considerations
-More flexible time and budget specifications

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a 
PHS-led national activity for setting priority areas.  This PAR, “Flexible 
System to Advance Innovative Research for Cancer Drug Discovery by Small 
Businesses”, is related to the priority area of cancer.  Potential applicants 
may obtain a copy of "Healthy People 2000" (Full Report:  Stock No. 
017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No. 
017-001-00473-1) through the Superintendent of Documents, Government Printing 
Office, Washington, DC 20402-9325 (telephone 202- 512-1800), or at 
http://odphp.osophs.dhhs.gov/pubs/hp2000

ELIGIBILITY REQUIREMENTS
								
Eligibility requirements are described in the OMNIBUS SOLICITATIONS.  Any 
small business independently owned by United States citizens or permanent 
resident aliens and located in the United States may apply. 

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.

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 SOLICITATIONS.  
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 proposal must be a logical extension of the Phase I research.

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

All PHS and NIH grant policies will apply to applications received in 
response to this program announcement.

RESEARCH OBJECTIVES

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.  For example, key growth regulatory pathways and 
genes mutated in cancer cells 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. NCI has made approaches for 
drug discovery based on these directions a high priority: 
http://2001.cancer.gov/.  Translation of these new discoveries and 
innovations into clinical benefit for the cancer patient is essential; 
however, the process is lengthy and costly.  Following initial discovery and 
lead optimization, potential drugs must undergo a series of rigorous pre-
clinical evaluations which may culminate in a clinical trial.  The actual 
procedures for this process vary somewhat with each agent to be tested, and, 
with innovative approaches often required for new agents, an extensive 
research effort may be necessary for successful development and eventual 
commercialization. The objective of this PA is to provide a flexible funding 
mechanism with regard to budgets and time of support to support the research 
activities required to enable small businesses to bring their innovative 
efforts for drug discovery and development to clinical evaluation. 

Flexibility within the PA allows for projects to be presented at all stages 
of the drug discovery and development process.   Projects will be evaluated 
on overall innovation, strength of the drug discovery approach, and 
probability of clinical success, with less emphasis on the nature of the 
specific stage proposed in the application.  This latter aspect is especially 
important if applications are focused on later stages of the drug discovery 
and evaluation process that are generally more routine and often considered 
less innovative as stand-alone projects. 

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 
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register of March 20, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, 
Volume 23, Number 11, March 18, 1994, available at  
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

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

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

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 avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. George S. Johnson at the address 
listed under INQUIRIES.

APPLICATION PROCEDURES

Applications received in response to this PA are to be prepared as described 
in the OMNIBUS SOLICITATIONS for the SBIR and STTR programs.  OMNIBUS 
SOLICITATIONS are available electronically through the NIH, Office of 
Extramural Research “Small Business Funding Opportunities at  
http://grants.nih.gov/grants/funding/sbir.htm.  Hard copies, 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.  Helpful 
information for preparation of the application can be obtained at 
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf

Phase I applications are to be submitted on the grant application form PHS 
6246-1(SBIR) or PHS 6246-3 (STTR), which are located in the back pages of the 
OMNIBUS SOLICITATIONS.  Use PHS 6246-2  for SBIR Phase II, and PHS 6246-3 for 
STTR Phase II applications.  For FAST-TRACK, Phase I and Phase II 
applications must be submitted together for concurrent initial peer review.  
Applications will be accepted on March 22, 2000, and November 22, 2000.  THE 
TITLE AND NUMBER OF THIS PA MUST BE TYPED IN LINE 2 ON THE FACE PAGE OF THE 
APPLICATION.

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. Revised applications may be submitted, but 
such applications must include an introduction addressing the previous 
critique.

The OMNIBUS SOLICITATIONS indicate 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, Facilities and 
Administrative Costs, and fixed fee) and time periods up to 2 years for Phase 
I and $650,000 total costs per year (direct costs, Facilities and 
Administrative 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.  Applications requesting a budget up to 
$100,000 (direct costs) per year should use the Modular Grant format 
http://grants.nih.gov/grants/funding/sbir1/modular.htm . Other applications 
should provide a detailed budget.

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 for the next step in the drug 
discovery and development process.   It would be expected, but not required, 
that Phase I would support relatively early discovery and evaluation 
projects.  Phase I projects should focus on research required to advance to 
the next stage in the development process.  Applicants should emphasize 
innovative aspects of the agent or approach as well as the potential for 
clinical relevance. Applications should include a plan for development of the 
agents and clearly state how the proposed Phase I fits into this plan.

If two years of support are requested, the goals for the first year should be 
clearly stated.  Support for the second year will be contingent upon NCI 
programmatic evaluation to ensure that investigators are accomplishing the 
goals presented.

PHASE II: Continuing support for development of preclinical activities and 
for establishment of proof of principle in clinical trials.  Support can be 
requested for preclinical developmental activities including pharmacology, 
formulation and toxicology.  Innovative aspects of the research necessary to 
complete the projects such as development of new in vivo evaluation  models 
which may require “surrogate endpoints” should be clearly described.  Support 
for clinical trial evaluation up to the point of establishing proof of 
principle (or through Phase II development) can be requested to commence 
following completion of the pre-clinical activities and approval of the IND 
by the FDA.  A brief plan for the clinical trial should be presented in the 
RESEARCH PLAN section.  Also, IN THE HUMAN SUBJECTS SECTION, INCLUDE THE 
COMPLETE CLINICAL PROTOCOL.  Informed consent form(s) must be included.  NIH 
will treat as confidential any scientific, preclinical, clinical or 
formulation data and information that the sponsor deems to be proprietary and 
confidential.  For each trial, provide a Gender and Minority Inclusion Report 
in the format provided in the 398 form instructions.
 
The 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 more 
effective analog or acceptable toxicity cannot be demonstrated, additional 
years may not be supported.

The NCI, through the Developmental Therapeutics Program 
(http://dtp.nci.nih.gov) and the Cancer Therapy Evaluation Program 
(http://ctep.info.nih.gov), on occasion utilizes its internal resources to 
foster drug development and clinical trials of agents discovered by small 
businesses.   For additional informational contact Dr. George S. Johnson at 
the address listed under INQUIRIES.  

FAST TRACK: Applications may be submitted for combined Phase I and Phase II, 
FAST TRACK consideration as described in the OMNIBUS SOLICITATIONS.  However, 
due to the complex nature of the drug development process, 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 a standing 
Study Section of CSR or by a special review group convened in response to a 
re-issuance of this PA, if applicable.

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 SOLICITATIONS.   

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
BETHESDA, MD  20817 (for express/courier service)

One additional copy of the application must also be sent to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
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 beginning of 
this PA.

REVIEW CONSIDERATIONS 

Upon receipt, applications will be reviewed by CSR staff for completeness and 
by NCI program staff for responsiveness. Applications not adhering to 
application instructions described above and those applications that are 
incomplete or non-responsive will be returned to the applicant without 
review.

Applications that are complete and responsive to the PA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened 
by the NCI in accordance with the review criteria stated below.  As part of 
the initial merit review, all applicants will receive a written critique and 
may undergo a process in which only those applications deemed to have the 
highest scientific merit generally the top half of the applications will be 
discussed, assigned a priority score, and receive a second level review by 
the National Cancer Advisory Board (NCAB).

Review Criteria:

Review criteria are essentially as described in the OMNIBUS SOLICITATIONS 
with the additional considerations specified for this PA.  Reviewers will 
comment on 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 these 
criteria will be addressed and considered by the reviewers 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 
highly meritorious. 

1.  The soundness and technical merit of the proposed approach (Preliminary 
data are not required for Phase I applications).  Does this study address an 
important problem?  If the aims of the application are achieved, how will 
scientific knowledge be advanced?  What will be the effect of these studies 
on the concepts or methods that drive this field?   Are the conceptual 
framework, design, methods, and analyses adequately developed, well-
integrated, and appropriate to the aims of the project?  Does the applicant 
acknowledge potential problem areas and consider alternative tactics?  Is it 
likely that the drug or vaccine can be developed in a reasonable time frame?   
Is the approach feasible and cost effective? For systems intended for 
clinical research, the following, additional criteria will be considered: to 
what degree is the analysis appropriate for clinical research and likely to 
have utility for the analysis of clinical specimens or patients?

2.  The qualifications of the proposed principal investigator, supporting 
staff, and consultants.  Is the investigator appropriately trained and well 
suited to carry out this work?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers (if 
any)?

3.  The scientific, technical, or technological innovation of the proposed 
research.  Does the project employ novel concepts, approaches, or methods?  
Are the aims original and innovative?  Does the project challenge existing 
paradigms?   

4.  The potential of the proposed research for commercial application or 
societal impact.

5.  The appropriateness of the budget requested.

6.  The adequacy and suitability of the facilities and research environment.

7.  Where applicable, the adequacy of assurances detailing the proposed means 
for (a) safeguarding human or animal subjects and/or (b) protecting against 
or minimizing any adverse effect on the environment.

8.  Innovative aspects of the overall drug discovery and development plan.

9.  Potential clinical relevance of the research and agent proposed. 

For FAST TRACK, the initial review group will evaluate the Phase I 
application for measurable goals to be achieved prior to initiating Phase II.  
Failure to provide clear, measurable goals may be sufficient reason for the 
initial review group to judge the application non-competitive.

The initial review group will also examine the adequacy of plans to recruit 
and retain both genders, minorities and their sub-groups, and children as 
appropriate for the scientific goals of the research and plans for the 
recruitment and retention of subjects; the provisions for the protection of 
human and animal subjects; and the safety of the research environment.

AWARD CRITERIA

Applications will compete for available funds with all other recommended SBIR 
and STTR applications.  A portion of the SBIR/STTR allotment will not be 
designated for this initiative. 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 clinical success, and 
availability of funds.

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, NCI’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.
  
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:
 
George S. Johnson, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute 
Executive Plaza North, Room 841
6130 Executive Blvd
Bethesda, MD  20892-7456
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: johnsong@exchange.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
National Cancer Institute 
Executive Plaza South, Room 243
6120 Executive Blvd
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
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062
Bethesda, MD 20892-8329
Telephone: (301) 496 -3428
FAX: (301) 402-0275 
Email: tf12w@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance No. 
93.395.  Awards are made under authorization of the 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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