TRANSLATION OF TECHNOLOGIES TO DETECT ALTERATIONS IN HUMAN TUMORS

Release Date:  December 1, 1999

PA NUMBER:  PAR-00-013

National Cancer Institute

This Program Announcement (PA) replaces PAR-97-021, which was published in 
NIH Guide, Vol. 25, No. 44, December 20, 1996.
 		
PURPOSE

The Technology Development Branch of the Cancer Diagnosis Program, Division 
of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), 
invites Program Project grant applications (P01s) proposing the application 
of comprehensive molecular analysis technologies to tumor specimens to 
address questions of importance in clinical cancer research.  This PA 
provides a mechanism for supporting continued refinement and application of 
the technologies produced under other NCI technology development initiatives.  
This program announcement is primarily targeted to technologies that are 
ready for translation to the analysis of clinical tissue specimens.  NCI is 
aware that molecular analysis technologies are at varying stages of 
development and that it is unclear which technologies will best serve 
clinical research.  

This PA is targeted to those translational research projects that will 
benefit from a P01 structure.  Investigators considering projects that do not 
require the P01 structure should consult with the Program Staff listed under 
Inquiries about other NCI initiatives supporting technology development and 
application.  The PA encourages translational studies in which molecular 
analysis technologies, including nucleic acid- or protein-based technologies, 
will be adapted to the analysis of human clinical specimens.  Application of 
these new or improved comprehensive technologies will allow investigators to 
effectively address questions in cancer diagnosis and prognosis, in selection 
of therapies for individual patients, and in monitoring response to therapy.  
The NCI’s intention is to promote an integrated team approach, where 
technology developers and cancer researchers will work closely together to 
refine and adapt technologies to develop clinically useful systems.  The 
technical challenges of these projects are expected to require input from a 
diverse group of investigators, such as engineers, pathologists, molecular 
biologists, chemists, biologists, and informatics specialists.  The process 
of moving the technologies forward toward clinical application will require 
input from clinical cancer researchers with access to clinical specimens.  
The goal of the program projects should be the development of integrated 
systems that can analyze molecular alterations in large numbers of human 
clinical specimens.

This PA will be active for two years, up to and including the October 1, 2001 
P01 receipt date.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of  Healthy People 2000,  a PHS-
led national activity for setting priority areas.  This Program Announcement 
(PA), Translation of Technologies to Detect Alterations in Human Tumors, is 
related to the priority area of cancer.  Potential applicants may obtain a 
copy of  Healthy People 2000  (Full Report:  Stock No. 017-001-00474-0 or 
Summary Report:  Stock No. 017-001-00473-1) through the Superintendent of 
Documents, Government Printing Office, Washington, D.C. 20402-9325 (telephone 
202-512-1800), or at http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic, for-profit, and nonprofit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal Government.  Applications may not be submitted by foreign 
institutions, however, an application from a domestic institution may include 
foreign components as research projects or core activities, as defined below 
under mechanism of support.  Each application must be from a single 
institution but may include collaborating institutions.  Collaborative 
projects between companies developing technologies and institutions with 
clinical resources and expertise are encouraged.  Racial/ethnic minority 
individuals, women and persons with disabilities are encouraged to apply as 
Principal Investigators (PIs).   

MECHANISM OF SUPPORT

This program announcement will use the National Institutes of Health (NIH) 
program project grant (P01) mechanism.  Responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  The period of support for applications submitted in response to 
this PA may be for up to five years.  This PA will be in effect for two 
years, up to and including the October 1, 2001 P01 receipt date.

An application should be constructed using the P01 application guidelines of 
the NCI, which are available at http://deainfo.nci.nih.gov/awards/P01.pdf or 
from the NCI Referral Officer as described below under Application 
Procedures.  The P01 mechanism is designed to support multiple, interacting 
projects focused on a central theme.  P01s must have a minimum of three 
research projects and may include cores.  A core is a separately budgeted 
component of a P01 that provides essential facilities or services to two or 
more of the proposed research projects.  A core may not count as one of the 
three research projects.  Collaborative funding arrangements with industry 
are encouraged, but detailed project descriptions must be provided even if no 
funds are requested for a project or core activity.  P01s may support 
projects that are performed at multiple sites but coordinated by a single 
Principal Investigator at the grantee institution.  An award will be made 
only to the PI’s institution.

RESEARCH OBJECTIVES

Background

Recent advances in our understanding of cancer at the molecular level coupled 
with the on-going development of comprehensive molecular analysis 
technologies have great potential to change the way we diagnose and treat 
cancer patients.  The process of developing and adapting comprehensive 
molecular analysis technologies for the analysis of clinical specimens is 
technically challenging, particularly in early-stage translational studies as 
attempts are made to employ the technologies to address clinical questions.

Molecular analysis technologies have continued to develop rapidly since the 
initial release of this program announcement in December 1996.  The past 
three years have seen an explosion in the development of microarray 
technologies and many other technologies for the simultaneous detection of 
multiple molecular alterations in tissues.  These systems range from high-
throughput approaches to mutation scanning to comprehensive, quantitative 
proteomics.  The technologies have largely been developed using model 
systems, and most have been developed solely for the research market or for 
marketing to large pharmaceutical companies.  Concurrently, cancer 
researchers have been increasingly interested in using comprehensive 
molecular analysis technologies to address clinical needs.  This program 
announcement is designed to promote collaborations between clinical 
investigators and technology developers in the context of P01 grant 
applications.

Research Goals and Scope

This initiative invites program project (P01) grant applications proposing 
the continued development and adaptation of technologies for analysis of the 
spectrum of molecular alterations in human tumor tissues.  Applications in 
response to this program announcement may propose to study any of a variety 
of technologies including comprehensive approaches to the detection of 
alterations in DNA, changes in patterns of gene expression at the level of 
both mRNA and proteins, or changes in post-translational modifications of 
proteins.  Projects exploring relationships between alterations in genomic 
DNA sequence, mRNA expression level, protein expression level, or protein 
modification are also encouraged.  This information will facilitate reaching 
the ultimate goal of discovering reliable molecular markers or targets for 
the detection, diagnosis, prognosis, and treatment of cancer.

The long-term goal of this initiative is the development of integrated 
molecular analysis systems.  Components of these systems are anticipated to 
include integrated technologies for specimen handling and preparation, 
analytical technologies, and integrated technologies for data management and 
analysis.  However, when appropriate, projects may focus on development and 
adaptation of individual components of the molecular analysis system.   

Interdisciplinary research projects to be supported by this initiative will 
require collaborations between technology/instrument developers, clinicians, 
pathologists, basic scientists, and informatics specialists.  This initiative 
encourages collaborations among commercial or academic organizations with 
appropriate genomics or proteomics programs in technology development and 
academic institutions with expertise and ongoing programs in cancer biology 
with the access to appropriate tumor tissue resources.  Ideally, the program 
projects, through these collaborations, will result in the development of 
analytical systems with integrated sample handling and preparation, refined 
molecular analysis technologies, and informatics tools.  These systems will 
be ready for analysis of molecular alterations in large numbers of human 
clinical specimens.

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 subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register of March 20, 
1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and 
Contracts, Volume 23, Number 11, March 18, 1994 , available on the web at the 
following URL address:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

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

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are clear and compelling scientific and ethical reasons 
not to include them.  This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
 NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects  that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent at least 60 
days prior to the anticipated submission date.  The letter should include a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the PA in 
response to which the application may be submitted.  Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows NCI staff 
to estimate the potential review workload and avoid conflict of interest in 
the review.  The letter of intent is to be sent to the program staff listed 
under INQUIRIES.
 
APPLICATION PROCEDURES

Applications are to be submitted on the research grant application form PHS 
398 (rev. 4/98) and will be accepted on the standard P01 receipt dates of 
February 1, June 1, and October 1. Applications in response to this PA must 
be in conformance with the P01 APPLICATION GUIDELINES of the NCI (rev. 4/99), 
which are available via the World Wide Web at 
http://deainfo.nci.nih.gov/awards/P01.pdf
and from the NCI Referral Officer identified under Inquiries. PHS 398 
application kits are available at most institutional offices of sponsored 
research and may be obtained from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, e-mail: 
grantsinfo@nih.gov.  For those applicants with internet access, the 398 kit 
may be found at: http://grants.nih.gov/grants/forms.htm

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:

Ms. Toby Friedberg
Referral Officer 
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239 
Rockville, MD 20852 (express service) 
Bethesda, MD 20892-8239

The Center for Scientific Review (CSR) will not accept any application in 
response to the 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.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by the NCI.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

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

Review Criteria

Review criteria used to evaluate P01 applications will be used in the review 
of these applications.  Peer review of the overall scientific and technical 
merit emphasizes a synthesis of two major aspects: 1) review of the P01 as an 
integrated effort focused on a central theme and 2) review of the merit of 
individual research projects and core components in the context of the 
proposed P01.  Applicants are strongly encouraged to study the evaluation 
criteria cited in the P01 GUIDELINES (referred to in  APPLICATION PROCEDURES, 
http://deainfo.nci.nih.gov/awards/P01.pdf) before preparing their 
applications. 

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications assigned to the NCI.  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 Responsiveness to the goals and objectives of the PA 

INQUIRIES 

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

Direct inquiries regarding programmatic issues to:

Min H. Song, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Executive Plaza North, Room 700
6130 Executive Boulevard
Bethesda, MD 20892
Telephone:  (301) 402-4185 
FAX:  (301) 402-7819
E-mail: ms425z@nih.gov

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Referral Officer 
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
Rockville, MD 20852 (express service) 
Bethesda, MD 20892 - 8239
Telephone: (301) 496-3428
FAX: (301) 402-0275
E-mail: tf12w@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Jill Rogers
Grants Administration Branch 
National Cancer Institute
Executive Plaza South, Room 243
Rockville, MD 20852 (express mail) 
Bethesda, MD 20892
Telephone: (301) 496-8699
FAX: (301) 496-8601
E-mail: Rogersj@gab.nci.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.394, Cancer Detection and Diagnostic Research.  Awards are made under 
authorization of the Sections 301 and 405 of the Public Health Service Act  
as amended (42 USC 241 and 284) and administered under NIH grants policies 
and Federal Regulations 42 CFR Parts 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 Public Health Service (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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