CANCER PROGNOSIS AND PREDICTION:  SBIR/STTR INITIATIVE

Release Date:  March 1, 2001 (see replacement PAR-03-099)

PA NUMBER:  PAR-01-062

National Cancer Institute

Letter of Intent Date:     May 9, 2001, November 6, 2001, May 2, 2002, 
                           and November 7, 2002
Application Receipt Date:  June 13, 2001, December 11, 2001, June 11, 2002, 
                           and December 11, 2002

PURPOSE

The Cancer Diagnosis Program of the National Cancer Institute invites 
applications for research projects to evaluate the utility and pilot the 
application of new strategies for determining prognosis or predicting response 
to therapy. This will provide tools to improve clinical decision-making in the 
care of cancer patients.  This program is intended to accelerate the 
translation of new discoveries into clinical practice by enabling 
investigators to apply new diagnostic strategies to clinical problems.  The 
primary objective is to move research quickly and directly from the promising 
exploratory stage through further assay development into initial confirmatory 
testing in a clinical setting.  

This program will utilize the Small Business Innovation Research (SBIR) and 
Small Business Technology Transfer (STTR) mechanisms, but will be run in 
parallel with a program of identical scientific scope, 
http://grants.nih.gov/grants/guide/pa-files/PAR-01-061.html, that will utilize 
the newly-created Phased Application Award mechanism. The SBIR and STTR 
applications received in response to this program announcement will undergo 
initial scientific review convened by the NCI Division of Extramural 
Activities and will be subject to cost and duration limitations comparable to 
the parallel Phased Application Award applications.

This Program Announcement (PAR) 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, available online at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf
 
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

RESEARCH OBJECTIVES

Background

The number of clinical laboratory assays currently in routine use in oncology 
is very small.  For example, estrogen and progesterone receptor status of 
breast cancers is used to predict response to hormonal therapy.  Blood levels 
of prostate specific antigen and human chorionic gonadotropin in prostate 
cancer and germ cell cancer, respectively, are used to assess the 
effectiveness of treatment and to detect recurrence.  Patients whose tumor 
cells exhibit over-expression or amplification of the Her2/neu gene may be 
offered Herceptin®, forerunner of a new class of therapeutic agents directed 
against specific molecular targets.  These markers are the exception, not the 
rule. During the past five years the College of American Pathologists, ASCO 
Expert Panels and the American Joint Committee on Cancer have carefully 
considered many new markers proposed for use in managing breast, colon and 
prostate cancer, but have found none with proven clinical utility sufficient 
to justify their adoption for routine practice.

Recently the NCI has sought to encourage the rapid appraisal of new candidate 
prognostic and predictive markers through a series of program announcements 
soliciting exploratory (R21) studies.  An increasing number of publications 
have described new molecules, new patterns of gene expression and new aspects 
of tumor cell growth that appear to be correlated with known prognostic 
factors.  However, very few markers progress beyond the stage of an initial 
promising result.  Studies to move the development of a new diagnostic test 
beyond the exploratory stage require large numbers of patient samples with 
associated clinical data, a robust, efficient assay format and substantial 
statistical input. 

The transition from an exploratory marker study to initial confirmatory 
testing in a clinical setting may involve additional developmental work.  For 
example, the study design may change from a retrospective to a prospective 
analysis or from a single institution to a multi-institutional setting.  
Frequently an assay format must be modified, which may require the generation 
and characterization of additional reagents. Procedures for standardization 
between collaborating laboratories may be needed.

Research Goals and Scope

This program is intended to support projects that test the value of new 
strategies for predicting the course of the disease or the response to therapy 
as tools in clinical decision-making.  The desired outcome will be studies 
with sufficient statistical power using efficient assay techniques that are 
conclusive enough to support the initiation of larger clinical trials designed 
to influence practice recommendations or to pursue FDA approval of a new 
device or analytic reagent.

Partnerships of appropriate medical institutions with biotechnology companies 
and medical device manufacturers are encouraged.

Phase I applications will be considered exploratory, so that extensive 
preliminary data from the applicant's own laboratory are not required.  
However, the project must be based on a strong rationale, and the applicant 
should provide evidence that the initial clinical evaluation of the proposed 
diagnostic strategy is promising.  Applicants should justify their proposals 
on the strength of the clinical study proposed for a future Phase II project; 
the Phase I award provides time for necessary preliminary work such as, for 
example, the substantial modification of an assay format. 

Applicants for Fast-Track (combined Phase I/II) projects need to provide 
information in the application or to propose milestones that will demonstrate 
the feasibility of the Phase II project.  Milestones must be designed to 
permit a straightforward decision as to whether or not the applicant is ready 
to initiate Phase II.  Milestones should also be provided to show that the 
assay format to be used in Phase II meets necessary performance standards for 
sensitivity, specificity and reproducibility.  Phase II projects must be 
described in sufficient detail to permit reviewers to assess the significance 
and innovation of the proposed work and the strength of the experimental 
design.  

Applicants are expected to provide promising evidence of clinical utility for 
their proposed diagnostic strategy and to show how their new test or procedure 
will aid the process of clinical decision-making for a specific group of 
patients.  The application should clearly state the clinical question that the 
new test or procedure is intended to address: for example, diagnosis, 
prognosis, prediction of response to therapy, disease monitoring, etc.  
Investigators should plan to report correlations between the new diagnostic 
test and other measures used in the same clinical setting, and they should 
describe what additional information beyond standard clinical parameters that 
the new test is expected to provide. Investigators who propose prospective 
studies must clearly describe the arrangements for collection and analysis of 
patient outcome data, especially if follow-up will be required beyond the end 
of the award period.  Proposals will be evaluated on the strength of the 
scientific rationale, the significance of the problem to be addressed, the 
adequacy of the proposed statistical design, the feasibility of accrual of 
study participants or human tissue specimens and the choice of assay format 
and analytic performance criteria.

MECHANISM OF SUPPORT

Responsibility for the planning, direction and execution of the proposed 
project will be solely that of the applicant.  Except as otherwise stated in 
this program announcement, awards will be administered under NIH grants policy 
as stated in the NIH Grants Policy Statement, rev. March 2001.

Support for this PAR is through the SBIR and STTR mechanisms, which are set-
aside programs.  

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 under 
the SBIR/STTR  FAST-TRACK option as described in the OMNIBUS SOLICITATION 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).
  Phase II applications in response to this PAR 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.

Because the length and time of clinical research projects often exceeds that 
normally awarded for SBIR/STTR grants, NCI will entertain well-justified Phase 
I applications with a project period up to two years and a budget not to 
exceed $100,000 per year direct costs, excluding subcontractor indirect costs.

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

Unless otherwise noted, all NIH grants policies apply.

ELIGIBILITY REQUIREMENTS

Eligibility requirements are described in the OMNIBUS SOLICITATION. 

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Tracy G. Lugo, Ph.D.
Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room 6042
Rockville, MD  20892
Telephone:  (301) 496-1591
FAX:  (301) 402-7819
Email: TL82S@nih.gov
 
Direct inquiries regarding fiscal matters to:

Ms. Kathleen J. Shino
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd., EPS Room 243
Bethesda, MD  20892-7150
Telephone:  (301) 846-1016
FAX:  301-846-5720
Email:  shinok@gab.nci.nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
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 
Email: tf12w@nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit, by the dates listed on the first 
page of this PAR, 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 PAR 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 IC staff to estimate the potential 
review workload and plan the review.
 
The letter of intent is to be sent to Dr. Tracy Lugo at the address listed 
under INQUIRIES  by the letter of intent receipt date. 

APPLICATION PROCEDURES

OMNIBUS SOLICITATION for both the SBIR and STTR programs are available 
electronically through the NIH, Office of Extramural Research small Business 
Funding Opportunities web site at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.  Helpful information 
for preparation of the application can be obtained at 
http://grants.nih.gov/grants/funding/sbir_policy.htm  

Applications are to be submitted on the grant application form PHS 398, 
http://grants.nih.gov/grants/funding/phs398/phs398.html, and will be accepted 
at the application deadlines as indicated on the first page of this document. 
THE TITLE AND NUMBER OF THIS PAR MUST BE TYPED IN LINE 2 ON THE FACE PAGE OF 
THE APPLICATION. 

The OMNIBUS SOLICITATION gives the normal levels of support and period of time 
for SBIR and STTR Phase I and II awards.  However, these award levels are 
guidelines and not ceilings.  Therefore, larger budgets with longer periods of 
time may be requested if required to complete the proposed research.  As 
stated under MECHANISM OF SUPPORT section, Phase I applications submitted in 
response to this PAR can have a project period of up to two years and a budget 
not to exceed $100,000 per year direct cost excluding subcontractor Facility 
and Administrative costs. 

An annual meeting of all investigators funded through this program will be 
held to share progress and research insights that may further progress in the 
program.  Applicants should request travel funds in their budgets for the 
principal investigator and one additional senior investigator to attend this 
annual meeting

Applicants requesting a budget period of more than 1 year for Phase I should 
follow these procedures:

o  Photocopy Form Page 3 “Budget for Phase I-Direct Costs Only”, number it 
Form Page “3a”.
o  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” total.
o  Provide the appropriate/requested information in the narrative 
justification (Form Page 4) for years 1 and 2
o  Indicate on the Phase I Face Page in Field 6, Dates of Project Period, the 
dates for the ENTIRE project period (e.g., Nov. 15, 2000-Nov. 15, 2002).
o  Indicate on the Phase I Face Page in Field 7 the requested Direct Costs for 
the entire project period and the Total Costs for the entire project period 
(e.g., 2 years).  

Phase II applications submitted in response to this PAR have no budget 
limitations.  The total duration (Phase I and Phase II application) cannot 
exceed five years.  The SBIR Phase II application and instructions can be 
obtained at  http://grants.nih.gov/grants/funding/sbir2/index.htm 

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. Milestones should be located in 
a separate section at the end of the Research Plan of the Phase I and should 
be indicated in the Table of Contents.  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. If so, 
at a later date, the applicant may apply for Phase II support through normal 
application procedures.  Such applications will be reviewed by a standard 
Study Section of the Center for Scientific Review or by a special review group 
convened in response to a re- issuance of this PAR, if applicable.  

An additional requirement of the FAST-TRACK mechanism is the Product 
Development Plan.  The small business must submit a concise 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.  In the event that an 
applicant feels that technology is too proprietary to disclose, applicants at 
a minimum should  provide a demonstration (e.g., results) of the capabilities 
of the proposed technology.  

All clinical trials supported or performed by NCI require some form of 
monitoring. 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 to 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 of the NCI for Data 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.

Submit a signed, typewritten original of the application, including the 
Checklist, and one signed, photocopy, 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)

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

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8239
Bethesda, MD  20892-8239
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 PAR.

REVIEW CONSIDERATIONS

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

Applications that are complete and adhere to the guidelines of this PAR 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

The 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.pdf, 

The reviewers will comment on the six 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 the goals of this 
PAR.  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 likely to have a major scientific impact and thus 
deserve a high priority score.  For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is essential 
to move a technology forward. 

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).

1.  Significance.  Does this study address an important problem? Does the 
proposed project have commercial potential to lead to a marketable product or 
process?  If the aims of the application are achieved, how will scientific 
knowledge be advanced?  What may be the anticipated commercial or societal 
benefits?  How is the proposed diagnostic strategy superior to existing 
alternatives?  What will be the impact on the design of future clinical trials 
or on clinical practice?  Does the proposal lead to enabling technologies 
(e.g., instrumentation, software) for further discoveries? Will the technology 
have a competitive advantage over existing/alternate technologies that can 
meet the market needs?

2.  Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  This includes the statistical rationale for the study design and the 
choice of sample size. Is the proposed plan a sound approach for establishing 
technical and commercial feasibility?  Does the applicant acknowledge 
potential problem areas and consider alternative tactics?  Has the applicant 
considered how the Phase II study, if promising, could proceed into eventual 
definitive testing of the diagnostic strategy?  What additional uses can be 
projected for the proposed assay(s), or what additional groups of patients 
might benefit from the new diagnostic strategy?

3.  Milestones (FAST-TRACK applications only).  How appropriate are the 
proposed milestones against which to evaluate the demonstration of feasibility 
for transition to Phase II?
  
4.  Innovation.  Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project challenge 
existing paradigms or develop new methods or technologies? What is the 
throughput and cost effectiveness of the proposed assay(s)?  

5.  Investigator.  Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR project?  Is the work proposed appropriate to 
the experience level of the principal investigator and other researchers (if 
any)?

6.  Environment.  Is there sufficient access to resources (e.g., equipment, 
facilities)? Does the scientific 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? Are the planned statistical and data management 
resources adequate?

For FAST-TRACK, the Phase I application should specify clear, well defined 
quantifiable milestones that should be achieved prior to initiating Phase II. 
Failure to provide clear, measurable milestones may be sufficient reason for 
the study section to judge the application non-competitive.  

Additional Considerations

For all applications, the initial review group will also examine: the 
appropriateness of the proposed project budget and duration; the adequacy of 
plans to include both genders and minorities and their subgroups, 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.  
Reviewers will comment on the appropriateness of the proposed budget and its 
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, 
availability of funds, and program priority.

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.

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 are 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 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 is 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 the following URL 
address:  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.  Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
policy that was published in the NIH Guide for Grants and Contracts, June 5, 
2000 (Revised August 25, 2000), available at the following URL address 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html

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 PAR, Cancer Prognosis And 
Prediction: SBIR/STTR Initiative, 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 No. 
93.394, (use appropriate program number). 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 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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