RELEASE DATE:  January 30, 2003

PA NUMBER:  PA-03-064 (This PA has been replaced by, PA-05-062)

EXPIRATION DATE: March 1, 2005 

National Cancer Institute (NCI)

APPLICATION RECEIPT DATE:  Standard receipt dates. 

This Program Announcement (PA) replaces PA-01-015, which was published in the 
NIH Guide on November 13, 2000.


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


This Program Announcement (PA) is intended to support correlative studies by 
using tumor specimens collected during multi-institutional trials funded by 
the National Cancer Institute (NCI). The Cancer Therapy Evaluation Program 
(CTEP), the Cancer Diagnosis Program (CDP) and the Cancer Biomarkers Research 
Group (CBRG) from the NCI will cooperatively sponsor this PA with the 
following objectives:

1. To provide investigators with support for correlative studies using trial 
related tumor specimens to compare genetic variations and molecular changes 
from cell nucleus, cytosol, cell surface and extracellular matrix to 
tumorigenesis and progression, drug resistance, therapeutic effectiveness of 
interventions, and various patients' clinical outcomes.

2. To decipher valuable information from these tumor specimens and to 
discover new cancer interventions by utilizing these tumor tissue resources 
and accumulated clinical trial results/outcomes for better cancer risk 
assessment, early detection and prediction for response to various cancer 
therapies and prevention. 

3. To promote translational research and foster collaborations and 
interactions between basic researchers and clinical investigators from 
academia, private industry and non-profit organizations to perform 
correlative studies to ensure that new findings will be rapidly translated 
into clinical practice. 



The Cancer Therapy Evaluation Program (CTEP) and the Cancer Diagnosis Program 
(CDP), Division of Cancer Treatment and Diagnosis (DCTD) support a program of 
integrated national networks of clinical investigators and institutions (NCI 
Clinical Trials Cooperative Groups) for the conduct of large scale, 
multi-institutional clinical trials. The Community Oncology and Prevention 
Trials Research Group, Division of Cancer Prevention (DCP), supports programs 
to improve clinical oncology in community settings and conducts prevention 
and control trials. The Early Detection Research Network (EDRN) of the 
Division of Cancer Prevention has created a research platform for 
collaborating with the clinical trials community and appointed liaisons for 
the various NCI Cooperative Groups.  The EDRN is available for assistance in 
validation studies and researchers may form collaborations through its 
Associate Member Program (

For the past five years, there have been more than 1409 NCI sponsored 
clinical trials including cancer treatment and prevention trials. More than 
200,000 cancer patients have participated in these trials. Among these 
trials, there have been 660 clinical trials conducted by Cooperative Groups 
and 410 trials that were conducted in cancer/clinical centers. Many of these 
trials have accumulated a large number of tumor specimens enriched with well-
annotated information about patients' demographics, pretrial/baseline 
history, diagnoses, treatment, follow-up data from cancer interventions and 
prognoses. These tumor specimens contain many valuable diagnostic and 
prognostic biomarkers, molecules and proteins relating to cell cycle or 
intracellular signal transduction pathways, and informative molecular 
profiles relevant to specific cancer intervention and cancer progression. 
Thus, utilizing these extremely valuable resources is a tremendous 
opportunity to identify new mechanisms and develop more effective cancer 
interventions at a molecular level. Furthermore, using these specimens linked 
to annotated clinical data in correlative studies will extend NCI's previous 
scientific efforts and also complement NCI's current and future endeavors in 
identifying new targets for cancer intervention in a cost-effective manner.

With advances in the understanding of molecular cancer genetics and basic 
cancer biology as well as the development of powerful new technologies 
including microarrays, proteomics and bioinformatics, both basic and clinical 
investigators are now in a better position to conduct correlative studies 
with the well-annotated tumor specimens. This PA further encourages 
researchers to take advantage of newly developed technologies and existing 
tumor specimens, and promotes collaborations and interactions between basic 
researchers and clinical investigators. Now, it is feasible to compare a 
spectrum of molecular and genetic changes from cell nucleus, cytosol, cell 
surface, and extracellular matrix to tumorigenesis, tumor progression, drug 
resistance, and therapeutic effectiveness of various cancer interventions. In 
addition, investigators can link 1) newly identified biomarkers to specific 
cancers for early detection and diagnosis; 2) activation/deactivation of 
signal transduction pathways to specific cancer prevention, treatment, drug 
resistance and clinical outcome; 3) tumor cellular and molecular changes to 
various clinical trials= success and failure. Furthermore, the tumor 
specimens will enable researchers to conduct correlative studies not only 
vertically within an individual trial but also horizontally among multiple 
trials. All of these advances will help investigators to improve future 
clinical trials and to develop better cancer interventions.

NCI encourages correlative laboratory studies linked to large scale 
multi-institutional clinical trials to improve therapeutic and preventive 
approaches. Currently, many laboratory investigators may not have access to 
patient specimens or outcome data for large scale analysis. The Clinical 
Trials Cooperative Groups have established tumor and specimen banks for 
specific diseases, and reference laboratories necessary for the diagnosis and 
monitoring of patients. These clinical trials organizations maintain 
statistical databases and are capable of comparing and correlating laboratory 
data to clinical outcome. This initiative proposes to create new 
collaborations and provides a funding mechanism. For an only relatively small 
additional investment, researchers will be able to obtain definitive data on 
the relationship of molecular biological features and the clinical behavior 
of the human tumors. Objectives and approaches will be investigator-initiated 
with NCI assisting investigators with accessing specimens to ensure that 
promising new approaches will be moved rapidly into clinical practice.

Research Goals and Scope

The objectives of this PA are to foster collaborations and interactions 
between basic researchers, private industry, and clinical investigators to 
perform clinical translational research on promising predictive and 
prognostic markers. These studies should focus on clinical correlative or 
mechanistic studies that will be useful for cancer risk assessment, early 
detection, prognosis, and predicting response to therapy and to prevention 
interventions. These studies should focus on correlations between biologic 
features of tissue specimens collected from the NCI Cooperative Groups or 
other large multi-institutional clinical trials and patient outcomes.

This PA will utilize the R01 investigator initiated research grant mechanism 
to support clinical correlative studies on large multi-institutional clinical 
trials for validation of promising predictive or prognostic markers, and the 
exploratory/pilot grant mechanisms (R21) to support pilot exploratory 
studies.  For the R01 grant submissions, preliminary data, including relevant 
animal models or analysis of patient specimens, that supports the hypotheses 
must be provided.  Because the R21 grant mechanism is designed to support 
pilot or feasibility studies, preliminary data as evidence of feasibility are 
not required. The correlative studies should be based on strong and testable 
hypotheses. A clear rationale should be given for the experimental design and 
technical methodologies selected. The hypotheses tested must relate to 
potential clinical applications such as patient monitoring for preventive or 
therapeutic interventions, development of new therapeutic strategies or 
testing new biomarkers for the identification of patient subsets for specific 
prevention or treatment approaches. The laboratory assays must use specimens
from patients receiving defined treatments in large clinical trials such as 
phase III clinical trials.  Applications must include a statistical section 
describing the study design and plans for analysis of data designed to test 
the hypotheses. All investigators are encouraged to work with multi-
institutional organizations or form a consortium in order to access 
sufficient numbers of patient specimens and clinical information to test the 
proposed hypotheses.

Some examples of therapeutic laboratory correlates may include but are not 
limited to: (1) phenotypic or genotypic alterations which appear to correlate 
with the development of therapy resistance; (2) loss or inactivation of tumor 
suppressor genes related to prognosis; (3) analysis of basal membrane factors 
or genes related to tumor invasion and metastases; (4) studies of chromosomal 
rearrangements or deletions that may be used for risk assessment, early 
detection, or prognosis; (5) correlation of tumor growth factors or oncogenes 
with response to therapies during cancer progression; (6) alterations in cell 
cycle control; (6) characterization of immune response with association to 
new immunotherapies for prevention or treatment; (7) evaluation of  serum or 
tumor biomarkers for risk assessment, early detection, or prognosis; (8) 
analyses of expression of cellular receptors for growth factors or 
differentiating agents; (9) defining and targeting specific signal 
transduction pathways and populations of cells for therapy; (10) analysis of 
in vitro response of tumor cells to growth factors/differentiating agents; 
and (11) evaluating accessible sites for precancerous changes occurring in 
less accessible sites, for instance the oral cavity as a surrogate site for 
the lung in smokers. Surrogate sites may be anatomically-associated, such as 
oral cavity to lung cancer, or may be functionally related, such as scalp 
hair follicles to prostate cancer, both of which have androgen receptors.

Researchers who have previously not collaborated with the NCI Cooperative 
Groups or Division of Cancer Prevention Programs are encouraged to contact 
them and discuss potential collaborations to obtain access to NCI-supported 
specimen banks and outcome data for laboratory analysis under this PA.  NCI 
staff (please see WHERE TO SEND INQUIRES) will be able to provide assistance 
in identifying NCI Cooperative Groups that would be interested in 
collaborating with basic science investigators on laboratory and clinical 
studies of new markers. The NCI Tissue Expediter is available to assist 
investigators in determining the appropriate tissue resource for their 
research project 
Information on how to access NCI-supported specimen banks including contacts 
for the NCI Cooperative Group banks is available at the following web 
address: The NCI Cooperative Groups 
have mechanisms in place to review proposals for access to NCI Cooperative 
Group tissue banks from prevention and treatment trials.  A letter from the 
appropriate NCI Group Chair confirming approval to provide specimens in the 
event of NCI funding of the PA grant application should be included in the 
grant application.  For Intergroup tissue banks, a letter from the Intergroup 
tissue bank chair should also be included.


Support of this program will be through the National Institutes of Health 
(NIH) research project grant (R01) mechanism and the 
exploratory/developmental grant (R21) mechanism.  Applicants will be 
responsible for the planning, direction, and execution of the proposed 
project.  All PHS and NIH grants policies will apply to applications received 
and awards made in response to this PA.  Applicants for the R21 grant 
mechanism may request up to $100,000 direct costs (four budget modules) per 
year unless the application includes consortium costs, in which case the 
limit is $125,000 direct costs (five budget modules) per year and support may 
not exceed two years.  The R21 grants are non-renewable and competitive 
continuation of projects developed under this program will be through the R01 
research grant mechanism.  Applications for the R01 grant mechanism may not 
exceed five years. NIH grants policies apply to these awards.

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise follow the instructions for non-
modular research grant applications.


You may submit (an) application(s) if your institution has any of the 
following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based or community-based organizations


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.


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

Direct your questions about scientific/research issues to:

Drs. Roy Wu, Heng Xie, Steven Krosnick
Clinical Grants & Contracts Branch 
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Executive Plaza North, Rm. 7009
6130 Executive Boulevard
Bethesda, MD 20892-7432
Rockville, MD 20852 (express mail)
Phone: 301-496-8866
Fax: 301-480-4663

Magdalena Thurin, Program Director
Cancer Diagnosis Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute/NIH
Executive Plaza North, Rm. 6130/6034
6130 Executive Boulevard
Bethesda, MD 20892
Rockville, MD 20852 (express mail)
Phone: 301-496-8639
Fax: 301-402-7819

Sudhir Srivastava, Program Director
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute/NIH
6130 Executive Plaza North, Suite 3142
Bethesda, MD 20892
Rockville, MD 20852 (express mail)
Phone: 301-435-1594
Fax: 301-402-8990

Direct your questions about financial or grants management matters to:

Jill Rogers
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Rockville, MD 20852 (express mail)
Phone: (301) 496-8699 or (301) 496-7800
FAX: (301) 496-8601

Crystal Wolfrey
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Rockville, MD 20852 (express mail)
Phone: (301) 496-8634
FAX: (301) 496-4801


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001, Updated: 6/28/2002).  The PHS 398 is 
available at in an 
interactive format. For further assistance contact GrantsInfo, telephone 
(301) 710-0267, email:

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at  Application 
deadlines are also indicated in the PHS 398 application kit.

requesting up to $250,000 per year in direct costs must be submitted in a 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at

Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

1)  Contact the NCI program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2)  Obtain agreement from the NCI program staff that the institute will 
accept your application for consideration for award; and,

3)  Identify, in a cover letter sent with the application, the NCI program 
staff who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at 

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

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

WILL NO LONGER BE ACCEPTED.  This policy does not apply to courier deliveries 
(i.e. FEDEX, UPS, DHL, etc.)
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 

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


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
( will evaluate applications for scientific 
and technical merit.  

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

o  Receive a written critique
o  Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o  Those that receive a priority score will undergo a second level review by 
the National Cancer Advisory Council.


The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR:  Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your 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?  Is there evidence of institutional 

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.

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

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.


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

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


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 
(; a 
complete copy of the updated Guidelines are available at
_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 

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

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  A 
continuing education program in the protection of human participants in 
research in now available online at:

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

Applicants may wish to place data collected under this PA 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.

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 PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.393, 93.394, and 93.395, 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 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) - Government Made Easy

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.