SMALL BUSINESS GRANTS FOR IDENTIFYING MOLECULAR SIGNATURES OF CANCER

RELEASE DATE:  October 22, 2002

PA NUMBER: PA-03-013

EXPIRATION DATE: August 31, 2004, unless reissued.

National Cancer Institute (NCI) 
 (http://www.nci.nih.gov/)

THIS PROGRAM ANNOUNCEMENT (PA) CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanisms of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

The Cancer Diagnosis Program of the National Cancer Institute (NCI) invites 
Small Business Innovation Research (SBIR) or Small Business Technology 
Transfer (STTR) grant applications proposing the identification of molecular 
signatures in human cancer.  Applicants should propose the application of 
existing comprehensive molecular technologies to the discovery of DNA, RNA, 
or protein signatures in human specimens.  These molecular signatures should 
correlate with important clinical parameters in cancer or address questions 
or needs in clinical cancer research.  Identifying signatures of molecular 
alterations that occur during the initiation, progression, treatment, and 
recurrence of cancer may provide information that allows physicians to make 
improved clinical decisions for individual cancer patients.
 
A major goal of this PA is to foster multi-disciplinary collaborations 
between the small business community and cancer researchers with insights 
into the important clinical questions and appropriate clinical resources.  
Application of genomics or proteomics technologies to clinical specimens 
requires both technical expertise and an understanding of the underlying 
biology or clinical questions relevant to the specimens being analyzed.  
Thus, this PA encourages interdisciplinary teams of investigators to refine 
and/or translate molecular analysis technologies to uncover molecular 
profiles of cancer.

This PA must be read in conjunction with the current 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-2002-2) (see 
http://grants.nih.gov/grants/funding/sbir.htm).  All of the instructions 
within the OMNIBUS SOLICITATION apply for this PA.

RESEARCH OBJECTIVES
  
Background

The ultimate goal of identifying molecular signatures of tumors is to develop 
more effective strategies for management of individual cancer patients.  
Molecular signatures provide a snapshot of the complex alterations that take 
place during the initiation, progression, treatment, or recurrence of cancer.  
These signatures will help identify changes in cellular processes and 
pathways that are causative of or result from malignant transformation.  Data 
are accumulating to demonstrate that alterations in panels of molecules 
correlate with clinical outcome.  Molecular signatures of an individual 
cancer patient's specimen may lead to earlier detection or more accurate 
diagnosis of cancer.  These signatures may also provide more accurate 
prognosis for patients and allow clinicians to select effective therapies.  
Molecular profiles should also aid physicians in identifying the primary 
tumor sites for cancers of unknown origin at the time of diagnosis.

Profiling molecular alterations during the initiation, progression, 
treatment, and recurrence of diseases for the ultimate goals of developing 
improved diagnostics and therapeutics has received international attention.  
This PA invites the small business community to participate in this global 
effort.  In addition, this PA facilitates collaborations between the small 
business and academic research communities to achieve the goals of projects.

Research Goals and Scope

This PA is intended to encourage application of rapidly emerging analysis 
technologies to the discovery of molecular signatures during the initiation, 
progression, treatment, or recurrence of cancer.  Applicants should propose 
to employ high-throughput, automated genomics technologies or proteomics 
technologies to detect, quantitate, and identify alterations of DNA, mRNA, or 
proteins in tissue specimens or body fluids of cancer patients.  This PA does 
not encourage continued technology refinement and development.  However, 
applicants may propose minor adaptations necessary for the integration of two 
or more technologies in order to apply them to clinical specimens.

This PA is also intended to promote collaborations between small business 
investigators with technical expertise and academic investigators who have 
important cancer-related questions and high-quality clinical resources.  
These multi-disciplinary teams should propose projects to identify molecular 
signatures that correlate with clinical parameters or specific stages of the 
cancer development, or that address questions or needs in clinical cancer 
research.  Successful completion of these projects will require the active 
participation of both sets of investigators.

Applicants are not restricted in the molecular signatures they propose to 
identify.  They may propose: to profile gene expression at the level of mRNA 
or proteins; to establish correlations between mRNA and protein expression 
profiles; to analyze DNA aberrations; to map single-nucleotide polymorphisms; 
to profile epigenetic changes such as DNA methylation patterns; to identify 
protein signatures for individual subcellular compartments of a tumor; to 
profile post-translationally modified proteins; to profile immune responses 
to cancer; or to generate cancer signatures on the basis of differential 
binding of affinity reagents from molecular diversity libraries such as 
antibodies, chemical ligands, nucleotide aptamers, peptide ligands, antibody 
mimics, or others.

Applicants would need to clearly document a strategy for obtaining access to 
high-quality cancer specimens for the proposed project.  The collection and 
storage of cancer specimens should be described in detail to show the 
preservation of analytes of interest.  The strategy of assessing the high-
quality of analytes should be in place.  Applicants would also need to 
demonstrate that the specimens to be analyzed have the appropriate 
demographic and clinical data to evaluate the clinical correlations.  
Applicants must describe proposed plans for the protection of patient 
confidentiality.

During the performance of the projects, grantees may identify needs for 
additional cancer specimens.  NCI program staff will assist grantees in 
obtaining access to additional specimen resources by facilitating 
interactions and collaborations between the grantees and other NCI-supported 
research efforts, e.g., the clinical trials groups, SPOREs, NCI-supported 
collaborative research networks, NCI Cancer Centers, and other NCI-supported 
specimen resources.

Applicants are strongly encouraged to describe adequate bioinformatics and 
statistical tools for the effective management and analysis of large 
quantities of data to be generated.  The study design needs to ensure that 
reproducible differences among molecular profiles can be identified.

As a result of these projects, it is anticipated that molecular signatures or 
targets will be identified which can be the basis for the development of 
cancer diagnostics.  In Phase II and FAST-TRACK applications, the small 
business investigators are required to provide their business strategies for 
the development of potential commercial products, e.g., robust multiplex 
tools and reagents for clinical uses in the detection, diagnosis, prognosis, 
prediction of responses to cancer therapies, and management of patients 
during the recurrence of cancer, in their Product Development Plan.

MECHANISMS OF SUPPORT 

Support for this PA is through the SBIR and STTR mechanisms, which are set-
aside programs.  As an applicant, you will be solely responsible for 
planning, directing, and executing the proposed project.

Except as otherwise stated in this PA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, March 2001, 
available at: http://grants.nih.gov/grants/policy/nihgps_2001/.

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.  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.pdf.    

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the OMNIBUS SOLICITATION.  Small 
business concerns are eligible to submit applications.  A small business 
concern is one that, on the date of award for both Phase I and Phase II 
agreements, meets ALL of the following criteria:

o is organized for profit, with a place of business located in the United 
States, which operates primarily within the United States or which makes a 
significant contribution to the United States economy through payment of 
taxes or use of American products, materials or labor;

o is in the legal form of an individual proprietorship, partnership, limited 
liability company, corporation, joint venture, association, trust or 
cooperative, except that where the form is a joint venture (as defined in 
this section) there can be no more than 49 percent participation by foreign 
business entities in the joint venture;

o is at least 51 percent owned and controlled by one or more individuals who 
are citizens of, or permanent resident aliens in, the United States; has, 
including its affiliates, not more than 500 employees, and meets the other 
regulatory requirements found in 13 CFR Part 121.  Business concerns, other 
than investment companies licensed, or state development companies qualifying 
under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are 
affiliates of one another when either directly or indirectly, (a) one concern 
controls or has the power to control the other; or (b) a third-party/parties 
controls or has the power to control both. Control can be exercised through 
common ownership, common management, and contractual relationships.  The term 
"affiliates" is defined in greater detail in 13 CFR 121.3-2(a).  The term 
"number of employees" is defined in 13 CFR 121.3-2(t).

Business concerns include, but are not limited to, any individual (sole 
proprietorship), partnership, corporation, joint venture, association, or 
cooperative.  Further information may be obtained by contacting the Small 
Business Administration Size District Office at http://www.sba.gov/size/.     

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.  On an SBIR, the principal investigator 
must have his/her primary employment with the small business at the time of 
award and for the duration of the project.  

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research, financial or grants management issues:

o Direct your questions about scientific/research issues to:

Min H. Song, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Executive Plaza North, Room 6035
Bethesda, MD 20892
Telephone:  (301) 402-4185
FAX:  (301) 402-7819
E-mail:  ms425z@nih.gov

o Direct your questions about financial or grants management matters to:

Shane Woodward
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD 20892
Telephone:  (301) 496-8649
FAX:  (301) 496-8601
E-mail:  Shane_Woodward@nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application (rev. 5/2001) must be used.  
Instructions and forms are available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  PHS 398 forms 
specific to SBIR applications are available at 
http://grants.nih.gov/grants/funding/phs398/398_SBIRSTTRforms.doc.   Refer 
to Chapter VI of the PHS 398 for specific instructions for SBIR and STTR 
applications. This version of PHS 398 is available in an interactive, 
searchable PDF and HTML format.  The NIH will return applications that are 
not submitted on the 5/2001 version.  For further assistance contact 
GrantsInfo, Telephone: (301) 710-0267, Email: mailto:GrantsInfo@nih.gov. 

The SBIR/STTR OMNIBUS SOLICITATION is available electronically through the 
NIH, Office of Extramural Research Small Business Funding Opportunities web 
site: http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.  The 
solicitation contains information about the SBIR and STTR programs, 
regulations governing the programs, and instructional information for 
submission.  Applicants are required to use the PHS398 forms for all SBIR and 
STTR submissions.  Helpful information for advice and preparation of the 
application can be obtained at: 
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.  All instructions 
within the solicitation apply for this PA.

The title and number of this PA must be typed on line 2 of the face page of 
the application.

In order to ensure maximum progress in the projects funded by this PA and to 
realize the maximum benefit for the cancer research community, all funded 
investigators will be invited to an annual meeting of investigators funded by 
SBIR/STTR Award and Phased Innovation Award mechanisms under the NCI's 
Innovative Molecular Analysis Technology program.  The annual meeting will 
facilitate sharing of progress and research insights with other 
investigators.  Applicants should request travel funds in their budgets for 
the principal investigator and one additional senior investigator to attend 
this annual meeting.

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 PA.  
   
In order to apply for the FAST-TRACK option, applications for both Phase I 
and Phase II must be submitted together according to the instructions for 
FAST-TRACK applications as described in the OMNIBUS SOLICITATION.  The Phase 
I application must specify clear, well-defined quantifiable milestones that 
should be achieved prior to Phase II funding.  Failure to provide measurable 
milestones and sufficient detail may be sufficient reason for the peer review 
committee to exclude the Phase II application from FAST-TRACK review.

Phase II and FAST-TRACK applications must include a concise Product 
Development Plan addressing the four areas described in the instructions for 
PHS 398, Chapter VI, Section C. 9. j.

APPLICATION RECEIPT DATES: Applications submitted in response to this PA will 
be accepted at the standard application deadlines (April 1, August 1, and 
December 1). 

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package 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)

APPLICATION PROCESSING: Applications must be received by or mailed on or 
before the receipt dates described above.  The CSR will not accept any 
application in response to this PA that is essentially the same as one 
currently pending initial review unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is essentially the 
same as one already reviewed.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group(s) convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o 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 and assigned a priority score

Those that receive a priority score will undergo a second-level review by the 
appropriate national advisory council or board. 

REVIEW CRITERIA

Review criteria are found at: 
http://grants.nih.gov/grants/funding/sbirsttr_ReviewCriteria.htm.

ADDITIONAL CONSIDERATIONS: In addition to the above criteria, the following 
will also be considered:

o PROTECTIONS:  The 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.

o INCLUSION:  The adequacy of plans to include subjects from both genders, 
all racial and ethnic groups (and subgroups), and children as appropriate for 
the scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below).
 
o BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended SBIR and STTR applications.  The following will be 
considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

For FAST-TRACK applications, the Phase II portion may not be funded until a 
Phase I final report and other documents necessary for continuation have been 
received and assessed by program staff that the Phase I milestones have been 
successfully achieved.

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

Clinical trials supported or performed by NCI require special considerations.  
The method and degree of monitoring should be commensurate with the degree of 
risk involved in participation and the size and complexity of the clinical 
trial.  Monitoring exists on a continuum from monitoring by the principal 
investigator/project manager or NCI program staff or a Data and Safety 
Monitoring Board (DSMB).  These monitoring activities are distinct from the 
requirement for study review and approval by an Institutional review Board 
(IRB).  For details about the Policy for the NCI for Data and Safety 
Monitoring of Clinical trials see: 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  For Phase I and II 
clinical trials, investigators must submit a general description of the data 
and safety monitoring plan as part of the research application.  See NIH 
Guide Notice on "Further Guidance on a Data and Safety Monitoring for Phase I 
and II Trials" for additional information: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data safety monitoring plans for 
clinical trials funded by the NCI is available: 
http://www.cancer.gov/clinical_trials/.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  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 clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete 
copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of 
clinical research; updated racial and ethnic categories in compliance with 
the new OMB standards; clarification of language governing NIH-defined Phase 
III clinical trials consistent with the new PHS Form 398; and updated roles 
and responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy 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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  A 
continuing education program in the protection of human participants in 
research in now available online at http://cme.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.   Furthermore, 
we caution reviewers 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 "Health y 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. 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 No. 93.394, Cancer Detection and Diagnosis 
Research, and is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.  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 
described at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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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