RELEASE DATE:  November 4, 2003

PA NUMBER:  PA-04-017

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. 
Replacement R21 (PA-06-304) funding opportunity announcement has been issued 
for the submission date of June 1, 2006 and submission dates 
for AIDS and non-AIDS applications thereafter.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for All R01 Applications: November 2, 2006. (Expiration date 
extended, see NOT-CA-05-026) 

Department of Health and Human Services (DHHS)

National Institutes of Health (NIH) 
Agency for Healthcare Research and Quality (AHRQ) 

National Cancer Institute (NCI/NIH) 


This Program Announcement (PA) replaces PA-02-005, which was published in the 
NIH Guide on October 5, 2001.


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


It is estimated that the economic burden of cancer in the United States in 
2002 was equivalent to $172 billion, including $61 billion in direct medical 
expenditures.  As cancer survival improves and as the U.S. population ages, 
it is likely that the economic aspects of cancer will loom larger in policy 
discussions.  Over the coming decades the U.S. health care system, including 
public sector programs such as Medicare and Medicaid, will face the challenge 
of covering an increasing array of health care procedures and services with 
fiscal resources that are limited by global budget constraints.  Under these 
circumstances, there will be increased need for understanding how economic 
resources are used across the cancer continuum, from prevention through end-
of-life care, and in the context of different organizational settings, for 
careful economic evaluation of conventional and innovative cancer control 
interventions and for a better understanding of how economic factors 
influence the welfare of cancer patients, and decision process about the use 
of cancer prevention, screening and treatment interventions.  These are the 
types of issues addressed by this Program Announcement.

The Division of Cancer Control and Population Sciences (DCCPS), National 
Cancer Institute (NCI), and the Agency for Health Care Research and Quality 
(AHRQ), invite investigator-initiated grant applications for research 
directed at increasing the knowledge base in the area of the economic aspects 
of cancer prevention, screening and care. The goal of this program 
announcement is to generate new economic knowledge that will promote the 
optimal design of cancer prevention and control trial studies and 
interventions and will facilitate the formulation of effective health care 
policy related to cancer prevention and control.  NCI has an interest in 
economic and health services studies with particular emphasis on meeting the 
goals of the NCI Quality of Cancer Care Initiative (see This Program Announcement (PA) 
also relates to the general health services and outcomes and effectiveness 
research supported by the AHRQ for a wide range of clinical conditions, 
including cancer. The overall goal of this Initiative is to enhance the 
state-of-the-science on the quality of cancer care and inform federal 
decision making on care delivery, coverage, and regulation.  This initiative 
requests research applications on new methods development, the synthesis and 
extension of existing methods, and innovative data gathering strategies.  
Applications that propose to implement actual data collection on a pilot or 
full-scale basis as well as analytical studies that use existing data and 
methodology may also be submitted.


There is increasing interest in the collection and analysis of valid, 
accurate, and reliable economic data related to specific disease entities and 
preventive, screening, and treatment interventions related to specific 
disease entities.  For example, the 2003 report of the Organization for 
Economic Co-operation and Development (OECD), A Disease-base Comparison of 
Health Systems, (Paris 2003) assesses economic resources, treatment 
processes, and health outcomes for the specific disease entities of breast 
cancer, heart disease, and stroke across twenty-one OECD countries.  

Scope of Activity

This initiative supports research directed at increasing our understanding of 
studies of the economics of cancer prevention, screening, and care.  Cancer 
is a heterogeneous chronic disease characterized by innovation in treatment 
and care approaches.  Studies that cover the national population of all ages 
on an episodic basis fail to capture an adequate sample of cancer patients or 
the full scope and duration of cancer costs.  Studies that focus on a 
convenience sample of cancer patients in a single health care delivery 
setting or community can be criticized as lacking external validity.  Studies 
proposed in response to this PA will be expected to address these issues and 
propose innovative methods of overcoming these limitations.  

Examples of research topics that would be considered relevant to meeting the 
goals of this PA include but are not limited to:

1.  The economic burden to the individual cancer patient, family, and society 
resulting from cancer and cancer treatment, including time costs, reduced 
employment opportunities, and reduced access to health and life insurance.

2.   Economic factors at the individual, community and health system levels 
that effect access to and outcomes following the use of cancer-related 
prevention, screening, diagnostic, and treatment services.

3.  The costs and organizational structures of delivering cancer prevention, 
screening, and treatment services in relation to various health care delivery 
settings and health care market structure conditions.

4.  Cost-utility, cost-effectiveness, or cost-benefit of specific cancer 
prevention and screening trials and cancer prevention and control 

5.  The interactions of cost, cost-effectiveness, and other factors in 
decision-making processes related to the provision and delivery of cancer 
prevention, screening, and treatment at the physician-patient, health system, 
and health policy levels.

6.  The roles of economic factors and financial incentives in determining the 
levels of participation of patients, physicians, and health care delivery 
systems in cancer prevention, screening, and treatment clinical trials. 

7.  The identification, development, and validation of data resources needed 
to support relevant and generalizable economic evaluation studies related to 
cancer prevention, screening, and treatment 

8.  Methodological studies on the measurement, evaluation, and presentation 
of data on cost and cost-utility/effectiveness/benefit in relation to cancer-
specific issues.

Examples of Research Funded by this PA

Over forty research articles have been published since 1998, when the first 
version of this PA was issued, from grants funded by earlier issuances of 
this PA.  Research topics include:

-  Descriptive studies of the economic burden of cancer
-  Cost-effectiveness analyses of cancer screening and treatment
-  The relationship between health care organization and the receipt of care
-  The influence of regulatory and taxation policies on health behaviors 

Selected examples of recently published research from PA-02-005 grants are:

Bradley CJ, Bednarek HL, Neumark D. Breast cancer survival, work, and 
earnings. Journal of Health Economics 2002;21:757-79.

Earle CC, Neumann PJ, Gelber RD, Weinstein MC, Weeks JC. Impact of referral 
patterns on the use of chemotherapy for lung cancer.  Journal of Clinical 
Oncology 2002;20:1786-92.

Gazelle GS, Hunink MG, Kuntz KM, et al. Cost-effectiveness of hepatic 
metastasectomy in patients with metastatic colorectal carcinoma: a state-
transition Monte Carlo decision analysis.  Annals of Surgery 2003;237:544-55.

Haas JS, Phillips KA, Sonneborn D, et al. Effect of managed care insurance on 
the use of preventive care for specific ethnic groups in the United States.  
Medical Care 2002;40:743-51.

Lee-Feldstein A, Feldstein PJ, Buchmueller T. Health care factors related to 
stage at diagnosis and survival among Medicare patients with colorectal 
cancer.  Medical Care 2002;40:362-74.

Mandelblatt JS, Lawrence WF, Gaffikin L, et al. Costs and benefits of 
different strategies to screen for cervical cancer in less-developed 
countries.  Journal of the National Cancer Institute 2002;94:1469-83.

O’Malley AS, Lawrence W, Liang W, et al. Feasibility of mobile cancer 
screening and prevention.  Journal of Health Care for Poor and Underserved. 

Plevritis SK. A mathemamtical algorithm that computes breast cancer sizes and 
doubling times detected by screening. Mathematical Bioscience 2001;171:155-

Taylor DH, Hasselblad V, Henley SJ, et al. Benefits of smoking cessation for 
longevity. American Journal of Public Health 2002;92:990-6.


This PA will use the NIH investigator-initiated research grants (R01) and 
exploratory/developmental (R21) award mechanisms.  As an applicant, you will 
be solely responsible for planning, directing, and executing the proposed 
project.  The total project period for an application submitted in response 
to this PA may not exceed 5 years for an R01 application and 2 years for an 
R21 application.

For R21 submissions, applicants may request up to $100,000 direct costs (four 
budget modules) per year unless the application includes consortium cost, in 
which case the limit is $125,00 direct costs (five budget modules)per year.
This PA uses just-in-time concepts.  It also uses the modular budgeting 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 budget format.  Otherwise, follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at  
Since AHRQ study sections require complete budget information in their 
review, all applications assigned, after initial submission, to AHRQ for 
review and funding considerations will be requested to submit detailed budget 
pages prior to the study section review.


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 institutions/organizations
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 to 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research, and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Martin L. Brown, Ph.D.
Health Services and Economics Branch
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, EPN Room 4005
Bethesda, MD  20892-7344
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-5716
FAX:  (301) 435-3710

Yen-pin Chiang, Ph.D.
Center for Outcomes and Effectiveness Research
Agency for Health Care Policy and Research
540 Gaither Road 
Rockville, MD 20850 
Telephone:  301-427-1493 

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

Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
–6120 Executive Boulevard, EPS Room 243
Bethesda, MD  20892
Telephone:  (301) 496-8634
FAX:  (301) 496-4801


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 document is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email:

The title and number of the PA must be typed on line 2 of the face page of 
the application form and the YES box must be checked.

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.

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 staff that the NCI will accept your 
application for consideration for award; and,
3. Identify, in a cover letter sent with the application, the National Cancer 
Institute and the staff member who agreed to accept assignment of the 

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)

APPLICATION PROCESSING:  Applications must be 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 unfunded version 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.


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 Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council 
or board  


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 evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review 
group will address and consider each of these criteria in assigning the 
application’s overall score, weighting them as appropriate for each 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
The 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, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 

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

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

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

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

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

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

subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. See
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 will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below.)

be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  


Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. 

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


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. See

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy, 
effectiveness and comparative trials (phase III). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or 
more in direct costs in any single year are expected to include a plan for 
data sharing or state why this is not possible. 
Investigators should seek guidance from their institutions, on issues related 
to institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule. Reviewers will 
consider the data sharing plan but will not factor the plan into the 
determination of the scientific merit or the priority score.

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 "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
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 is 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.

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 
( 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

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 at and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at

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)
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Bethesda, Maryland 20892
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