CANCER PROGNOSIS AND PREDICTION: SBIR/STTR INITIATIVE

RELEASE DATE:  April 8, 2003

PA NUMBER:  PAR-03-099    

EXPIRATION DATE:  December 12, 2003, unless reissued

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

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.394

LETTER OF INTENT RECEIPT DATES:  May 14, 2003 and November 13, 2003

APPLICATION RECEIPT DATES:  June 11, 2003 and December 11, 2003

This Program Announcement (PAR) replaces PAR-01-062, which was published in 
the NIH Guide on March 1, 2001.

NOTICE: This program announcement (PAR) 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. The solicitation (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf) contains information 
about the SBIR and STTR programs, regulations governing the programs, and 
instructional information for submission. All instructions within the Omnibus 
Solicitation apply with the following exceptions:
o  special receipt dates and mailing instructions
o  initial review convened by the NCI Division of Extramural Activities
o  additional review considerations
o  more flexible time and budget specifications
o  special provision for competitive renewal of certain R44 or R42 awards
o  special provision for competitive supplements to support extended 
development studies, including clinical trials

THIS PAR CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PAR 
o Research Objectives
o Mechanisms of Support 
o Project Period and Amount of Award
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Receipt and Review Schedule
o Required Federal Citations

PURPOSE OF THIS PAR 

The Cancer Diagnosis Program of the National Cancer Institute invites small 
business 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 PAR 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-03-098.html), that will 
utilize the Phased Innovation Award (R21/R33) mechanism.  Applicants are 
strongly encouraged to read both announcements.  

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 Her-2/neu gene may be 
offered trastuzumab, forerunner of a new class of therapeutic agents directed 
against specific molecular targets.  These markers are the exception, not the 
rule.  During the part 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 
clinical 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.

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.

All 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.

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.  

For example, milestones could be used to demonstrate the feasibility of the 
Phase II project in the following ways:

o Establish assay conditions: types of specimens, fixation processes, antigen 
retrieval methods, reagents and other components of the assay system, 
detection system, positive and negative controls, etc.

o Define procedures for scoring and for reporting data.

o Demonstrate that the assay or test system proposed for use in the R33 phase 
has the required sensitivity, specificity and reproducibility.

o Establish procedures for standardization and demonstrate that comparable 
results can be obtained from assays performed at multiple sites.

o Estimate the prevalence of the marker on a pilot set of  specimens of the 
same type (fixed, frozen, etc.) and the same patient characteristics as the 
set proposed for the R33 study.

o Provide evidence that the number of participants or specimens required by 
the study design in the R33 phase can be accrued. 

This list is intended for illustration, and is not meant to prescribe or to 
limit the milestones an application may include.  See below (SUBMITTING AN 
APPLICATION) for examples.

MECHANISMS OF SUPPORT 

This PAR uses the SBIR and STTR mechanisms, which are set aside programs. This 
PAR is a one-time announcement that may be reissued. As an applicant, you will 
be solely responsible for planning, directing, and executing the proposed 
project.  Future unsolicited, competing-continuation applications based on 
this project will compete with all SBIR/STTR applications and will be reviewed 
according to the customary peer review procedures.

This PAR uses just-in-time concepts.  For this PAR, the modular budgeting 
format will not be used. Except as otherwise stated in this PAR, 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/, or as revised.

The SBIR/STTR mechanism requires that the intent of the research be the 
commercialization of a product or service.

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 PAR 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 but not 
necessarily a Phase I project supported in response to this PAR.

PROJECT PERIOD AND AMOUNT OF AWARD

The Omnibus Solicitation indicates the statutory guidelines of funding support 
and project duration periods for SBIR and STTR Phase I and Phase II awards.  
However, some projects are likely to require longer time periods and/or larger 
budgets to accomplish the proposed aims.  Therefore, if adequately justified, 
for this PAR budgets up to $100,000 direct costs per year and time periods up 
to 2 years for Phase I can be requested.  Phase II applications submitted in 
response to this PAR have no budget limitations and may request up to four 
years of support. For FAST-TRACK applications the total duration of Phase I 
plus Phase II cannot exceed 5 years.

This PAR encourages projects with aims focusing on clinical evaluation of new 
diagnostic strategies. Accomplishing these aims may require expertise not 
present in the applicant small business, and a sub-contract site within the 
award may be required.  Costs for this research may exceed the normal 
expectations for percent of the total grant budget allocated to subcontracts 
described in the Omnibus Solicitation.  If adequately justified, for this PAR 
applications may exceed this guideline. Resources provided for such research 
activity will be limited for that activity and cannot be rebudgeted.

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only 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 criteria as described in the SBIR/STTR Omnibus 
Solicitation.

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 application, the principal investigator 
must have his/her primary employment (more than 50%) with the small business 
at the time of award and for the duration of the project. The PI on an STTR 
application may be employed with the small business concern or the 
participating non-profit research institution as long as s/he has a formal 
appointment with or commitment to the applicant small business concern, which 
is characterized by an official relationship between the small business 
concern and that individual.

SPECIAL REQUIREMENTS 

An annual meeting of all investigators funded through this program will be 
held to share results 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.

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Tracy G. Lugo, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room EPN 6035A
Bethesda, MD  20892
Telephone:  (301) 496-1591
FAX: 301-402-7819
Email: lugot@mail.nih.gov
(for general inquiries and for projects specifically related to breast cancer, 
gynecologic cancers, gastric cancer, pancreatic cancer or brain tumors)

Magdalena Thurin, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room EPN 6035A
Bethesda, MD  20892
Telephone:  (301) 496-1591
FAX: 301-402-7819
Email: thurinm@mail.nih.gov
(for projects related to colon cancer, skin cancers including melanoma, 
sarcomas, or acute leukemias)

James V. Tricoli, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room EPN 6035A
Bethesda, MD  20892
Telephone:  (301) 496-1591
FAX: 301-402-7819
Email: tricolij@mail.nih.gov
(for projects related to prostate cancer, renal or bladder cancer, liver 
cancer, lymphomas or chronic leukemias)

Barbara Conley, M.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room EPN 6035A
Bethesda, MD  20892
Telephone:  (301) 496-1591
FAX: 301-402-7819
Email: conleyb@mail.nih.gov
(for projects related to lung cancer, head and neck cancer or esophageal 
cancer)

o Direct your questions about peer review issues to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Telephone: (301) 496-3428
FAX: (301) 402-0275 
Email:  ncirefof@dea.nci.nih.gov

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

Mr. Shane Woodward
Grants Administration Branch
Office of Management
National Cancer Institute
6120 Executive Blvd.
Room EPS 243
Bethesda, MD 20892
Phone: 301-496-8649
Fax: 301-496-8601
e-mail: woodwars@mail.nih.gov

LETTER OF INTENT 

Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this PAR 

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.
 
The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to:

Tracy G. Lugo, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd., Room EPN 6035A
Bethesda, MD  20892
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-1591
FAX: 301-402-7819
Email: lugot@mail.nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application must be used for all SBIR/STTR Phase I, 
Phase II and FAST-TRACK applications (new and revised.)  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare 
your application in accordance with the SBIR/STTR Omnibus Solicitation and the 
PHS 398. Helpful information on the preparation of the application can be 
obtained at: http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.  The 
NIH will return applications that are not submitted using the PHS 398 grant 
application.  For further assistance contact GrantsInfo, Telephone: (301) 435-
0714, Email: GrantsInfo@mail.nih.gov

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

NIH will treat as confidential any scientific, pre-clinical, or clinical data 
that the applicant deems to be proprietary and confidential. Applicants are 
encouraged to include all information required for adequate evaluation by 
reviewers.  However, in the event that assays and technology are not yet 
patent protected and the applicant does not wish to include complete details, 
the application should at a minimum provide a demonstration (results) of the 
capabilities of the proposed approach.

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.  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.  The second year of the Phase I budget should be included and 
clearly identified on the Budget Justification page, using categorical totals 
if costs deviate significantly from the first year of the budget, with 
narrative justifications for the increase(s).  If the second year simply 
escalates due to cost of living factors, a statement to that effect with the 
escalation factor should be included rather than categorical totals.  The cost 
for the first year must be entered on box 7 and the cost for the entire 
project period must be entered in box 8 on the Face Page of the application.

Support for the second year will be contingent upon Institute programmatic 
evaluation to ensure that investigators are accomplishing the goals presented.

PHASE II:  Development of approach to a stage at which the assay or procedure 
can be tested in a clinical setting. Goals for each year of support should be 
clearly presented.  Support for years two to four, if requested, is dependent 
upon Institute programmatic review of progress and achievement of the proposed 
goals.  For example, if a goal such as timely accrual of study participants is 
not achieved, the continuation years may not be supported.

Item d of the Research Plan should include a statistical section that 
discusses the choice of the study design and laboratory methods. Sample sizes 
must be clearly stated and justified with power calculations. The statistician 
involved with the project should be identified and a letter of support 
included if no effort is requested in the budget. Plans for data management 
and verification of clinical research data should also be described. 
Collaborative arrangements should be clearly documented, and where 
collaborations involve NCI-sponsored clinical trials the protocol numbers 
should be provided.  Letters of support should be included in the application 
to substantiate plans for collection of follow-up information beyond the 
period of award. Where appropriate, applicants are strongly encouraged to 
include a copy of the complete clinical protocol in the Appendix.

See "REQUIRED FEDERAL CITATIONS" below for further requirements for data and 
safety monitoring requirements for NCI-supported clinical trials.

FAST-TRACK: Applications may be submitted for combined Phase I and Phase II, 
FAST- TRACK consideration as described in the Omnibus Solicitation.  

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 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. 

The following examples are provided to illustrate the recommended level of 
detail for milestones, but should not be considered an exhaustive list of 
potentially appropriate milestones.  Nor is this list intended to recommend 
the use of specific statistical tests.  You should apply those methods that 
are most appropriate for your data.

o  Assay conditions will be optimized to achieve conditions where the analytic 
sensitivity is at least X and the specificity is at least Y when Z samples, 
half of which are truly positive for the analyte, are studied.
 
o  The assay to be used in the R33 phase will perform reproducibly as defined 
by a coefficient of variation less than Y in a series of X test specimens.

o  Show that the marker, as defined by a cut-off value of X,  is correlated 
with the outcome of interest in the patient population for the R33 phase by 
demonstrating that there is a difference of at least Y% in the prevalence of 
the marker when comparing N1 patients with outcome type 1 to N2 patients with 
outcome type 2.

o  The prognostic significance of molecular profiles defined in the training 
set will be demonstrated in an independent set of X specimens. This milestone 
will be met if values of Y% or higher are achieved for both sensitivity and 
specificity in predicting the clinical outcome of interest for the R33 phase.

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

COMPETING CONTINUATION PHASE II APPLICATIONS:  A competitive renewal of Phase 
II for up to an additional three years be requested for current Phase II 
awards which have successfully developed cancer diagnostic tests that should 
be considered for testing in a clinical trial.  Research activities supported 
by the competing continuation award would be expected to include steps 
required to seek FDA approval.  All Phase II provisions stated in this PAR 
apply to the Phase II competitive renewal application.

COMPETING SUPPLEMENTS:  A competing supplemental application may be submitted 
at the receipt dates presented on page 1 of this PAR to request support for a 
significant expansion of an existing project's scope, research protocol or to 
add new specific aims.  The time requested for support may not extend beyond  
the term of the existing award, but new aims supported by a supplement may be 
included in an application for a competitive renewal of an eligible Phase II 
award (see above). Phase II awardees who wish to add research aims to obtain 
data required for PMA or IDE filing or to conduct clinical trials are 
encouraged to apply for supplemental funding.  Instructions for application 
can be found in the PHS 398 instructions, Chapter VI, Section 9, Research 
Plan.  Awardees should consult with the Program Director prior to submission 
of the supplement request. 

ADMINISTRATIVE SUPPLEMENTS: Supplements to extend a peer-reviewed and funded 
specific aim for reasons that were unpredicted at the time of application can 
be requested at any time.  New aims to the award cannot be added with this 
process.  Examples appropriate for this PAR would be, but are not limited to, 
requirements for additional studies requested by the FDA as part of the 
regulatory approval process that were not included in the original research 
plan.  Administrative supplement requests should be discussed with and 
submitted to the Program Director.

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.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and three 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)

At the time of submission, two additional copies of the application must be 
sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD  20892-8329
Rockville, MD  20852 (for express/courier service)

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE 
WILL NO LONGER BE ACCEPTED.  This policy does not apply to courier deliveries 
(i.e. FEDEX, UPS, DHL, etc.) (http://grants.nih.gov/grants/guide/notice-files
/NOT-CA-02-002.html)  This change in practice is effective immediately.  
This policy is similar to and consistent with the policy for applications 
addressed to Centers for Scientific Review as published in the NIH Guide 
Notice http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

RECEIPT OF APPLICATIONS:  Applications must be received by or mailed before 
the receipt dates described on the first page of this program announcement.  
The CSR will not accept any application in response to this PAR 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.  This does 
not preclude the submission of a substantial revision of an application 
already reviewed, but such application must include an Introduction addressing 
the previous critique.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.

PEER REVIEW PROCESS

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 review.

Applications that are complete and adhere to the guidelines of this PAR will 
be evaluated for scientific and technical merit and the documented ability of 
the investigators to meet the RESEARCH OBJECTIVES of this PAR 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:

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
o  Those that receive a priority score will undergo a second level review by 
the National Cancer Advisory Board.

REVIEW CRITERIA 

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 PAR include the development and 
testing of new strategies for cancer diagnosis in clinical settings by 
SBIR/STTR awardees. In the written comments, the reviewers will be asked to 
discuss the following aspects of the application in order to judge the 
likelihood that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

ALL SBIR/STTR APPLICATIONS:

1.  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 do they 
advance scientific knowledge?  Does the proposal lead to enabling technologies 
(instrumentation, software, etc.) for further discoveries? What is the 
throughput and cost effectiveness of the proposed assay(s)? Will the 
technology have a competitive advantage over existing/alternative technologies 
that can meet the market needs? What will be the impact on future clinical 
trials or on clinical practice?

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 strategies?  Has the 
applicant considered how the Phase II study, if promising, could proceed into 
eventual definitive testing of the diagnostic strategy? 

3.  Innovation:  Does the project challenge existing paradigms or employ novel 
technologies, approaches, or methods?  Are the aims original and innovative?  
How is the proposed diagnostic strategy superior to existing alternatives?  
What additional uses can be projected for the proposed assay(s), or what 
additional groups of patients might benefit from the new diagnostics strategy? 

4.  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)?

5.  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?  Are the planned 
statistical and data management resources adequate?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be applied to ALL applications in the determination of scientific 
merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participations 
in the proposed research will be assessed. (See additional information and 
criteria included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: 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 additional information and Inclusion Criteria in the sections 
on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the required five items described under Vertebrate 
Animals (section f of the Research Plan instructions) will be assessed.  

Human Subjects: 

1.  Protection of Human Subjects from Research Risks - for all studies 
involving human subjects. See instructions and "Guidance for Preparing the 
Human Subjects Research Section." 

If an exemption is claimed, is it appropriate for the work proposed? If no 
exemption is claimed, are the applicant's responses to the six required points 
appropriate? 

Are human subjects placed at risk by the proposed study? If so, are the risks 
reasonable in relation to the anticipated benefits to the subjects and others? 
Are the risks reasonable in relation to the importance of the knowledge that 
reasonably may be expected to be gained? 

Are the plans proposed for the protection of human subjects adequate? 

2.  Inclusion of Women Plan - for clinical research only.  Does the applicant 
propose a plan for the inclusion of both genders that will provide their 
appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

3.  Inclusion of Minorities Plan - for clinical research only.  Does the 
applicant propose a plan for the inclusion of minorities that will provide 
their appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

4.  Inclusion of Children Plan- for all studies involving human subjects.  
Does the applicant describe an acceptable plan in which the representation of 
children of all ages (under the age of 21) is scientifically appropriate and 
recruitment/retention is addressed realistically? If not, does the applicant 
provide an appropriate justification for their exclusion? 

5.  Data and Safety Monitoring Plan – for clinical trials only.  Does the 
applicant describe a Data and Safety Monitoring Plan that defines the general 
structure of the monitoring entity and mechanisms for reporting Adverse Events 
to the NIH and the IRB? 

Animal Welfare:  If vertebrate animals are involved, are adequate plans 
proposed for their care and use? Are the applicant's responses to the five 
required points appropriate? Will the procedures be limited to those that are 
unavoidable in the conduct of scientifically sound research? 

Biohazards:  Is the use of materials or procedures that are potentially 
hazardous to research personnel and/or the environment proposed? Is the 
proposed protection adequate? 

ADDITIONAL CONSIDERATIONS: The following items may be also be considered by 
reviewers but will not be included in the determination of scientific merit.

BUDGET:  The reasonableness of the proposed budget may be considered.  Is the 
percent effort listed for the PI appropriate for the work proposed?  Is each 
budget category realistic and justified in terms of the aims and methods?

PERIOD OF SUPPORT:  The appropriateness of the requested period of support in 
relation to the proposed research.

PHASE II APPLICATION REVIEW CRITERIA:  In addition to the above criteria:

1.  How well did the applicant demonstrate progress toward meeting the Phase I 
objectives, demonstrating feasibility, and providing a solid foundation for 
the proposed Phase II activity? 

2.  Did the applicant submit a concise Commercialization Plan [formerly 
Product Development Plan] that adequately addresses the seven areas described 
in the Research Plan item J? 

3.  Does the project carry a high degree of commercial potential, as described 
in the Commercialization Plan? 

AMENDED APPLICATIONS:  In addition to the above criteria, the following 
criteria will be applied to revised applications.

1.  Are the responses to comments from the previous SRG review adequate? 

2.  Are the improvements in the revised application appropriate?

PHASE I/PHASE II FAST-TRACK APPLICATION REVIEW CRITERIA:  For Phase I/Phase II 
FAST-TRACK applications, the following criteria also will be applied.

1.  Does the Phase I application specify clear, appropriate, measurable goals 
(milestones) that should be achieved prior to initiating Phase II? 

2.  Did the applicant submit a concise Commercialization Plan [formerly 
Product Development Plan] that adequately addresses the seven areas described 
in the Research Plan, item J? 

3.  To what extent was the applicant able to obtain letters of interest, 
additional funding commitments, and/or resources from the private sector or 
non-SBIR/ STTR funding sources that would enhance the likelihood for 
commercialization? 

4.  Does the project carry a high degree of commercial potential, as described 
in the Commercialization Plan? 

Phase I and Phase II FAST-TRACK applications that satisfy all of the review 
criteria will receive a single rating. Failure to provide clear, measurable 
goals may be sufficient reason for the scientific review group to exclude the 
Phase II application from FAST-TRACK review.

COMPETING CONTINUATION APPLICATIONS: In addition to the above criteria, the 
following criteria will be applied to competing continuation applications.

1.  Does the activity as proposed address issues related to Federal 
regulatory approval processes?

2.  What will be the effect of these studies on the concepts or methods that 
drive this field?

AWARD CRITERIA

Applications submitted in response to a PAR will compete for available funds 
with all other recommended SBIR and STTR applications.  Portions of the SBIR 
and STTR allotments will not be designated for this initiative.  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.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Dates:  May 14, 2003 and November 13, 2003
Application Receipt Dates:  June 11, 2003 and December 11, 2003
Council Review Dates:  February 18, 2004 and June 8, 2004
Earliest Anticipated Award Date:  April 1, 2004 and July 1, 2004

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving clinical trials, including Phase I and Phase II 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/

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PAR in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application. 
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH processes 
involving the review, funding, and progress monitoring of grants, cooperative 
agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.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.  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 "Healthy People 
2010," a PHS-led national activity for setting priority areas. This PAR 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 see http://www.cfda.gov/, 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.  

Return to Volume Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.