This Program Announcement expires on October 2, 2003, unless reissued

CLINICAL CANCER THERAPY RESEARCH
 
Release Date:  October 2, 2001
 
PA NUMBER:  PA-02-002 (see replacement PA-04-046)
 
National Cancer Institute

THIS PA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER 
YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION C OF THE PHS 398 
(REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

This Program Announcement (PA) replaces PA-99-046, which was published in the 
NIH Guide on January 22, 1999.
 
PURPOSE

The National Cancer Institute (NCI) seeks grant applications to conduct 
clinical therapeutic studies/trials of neoplastic diseases in humans. Clinical 
research, by definition, is research conducted with human subjects (or on 
material of human origin such as tissues, specimens and cognitive phenomena) 
for which an investigator (or colleague) directly interacts with human 
subjects. Excluded from this definition are in vitro studies that utilize 
human tissues that cannot be linked to a living individual. This Program 
Announcement (PA) encompasses a full range of therapeutic studies and clinical 
trials employing drugs, biologics, radiation, and surgery. The intent of the 
PA is to encourage clinical researchers to translate insights in cancer 
biology and the development of new agents into innovative cancer therapeutic 
studies.

RESEARCH OBJECTIVES  

Background

Highly productive research efforts into understanding the basic biology of the 
cancer cell have resulted in discoveries concerning the role of growth 
factors, genes that promote and suppress neoplasia, mechanisms of treatment 
sensitivity and resistance, and the biology of the immune systems.  These 
discoveries have provided the basis for the development of novel and improved 
cancer treatments especially related to inhibitors of specific molecular 
targets/pathways.  The rate of progress in the treatment of cancer depends 
upon the translation of these basic and preclinical discoveries into clinical 
cancer therapies. The NCI supports an extensive network of clinical and 
laboratory research studies related to cancer therapy through contracts, 
grants and cooperative agreements. At present, the traditional research grant 
mechanism (R01) is underutilized by clinical investigators for the support of 
clinical research. NCI is committed to supporting clinical trials research and 
encourages clinical investigators to submit clinical therapeutic studies to 
move advances in basic biology and drug development into the clinical setting.
 
OBJECTIVES AND SCOPE
 
The overall aims of this initiative are two-fold: (1) to stimulate development 
of innovative therapeutic clinical trials with or without laboratory 
correlations (2) to support innovative correlative laboratory studies linked 
to therapeutic clinical trials to foster the development of interactions 
between basic science laboratories and clinicians performing the clinical 
trials. Investigators may address either aim in their applications. 

Clinical studies/trials must involve human subjects and be therapeutic in 
design. The clinical studies must be based on a strong rationale and 
preclinical or clinical data which supports the underlying hypotheses. The 
applications may include single or multi-institutional research studies with 
appropriate biological correlates linked to these studies.  New clinical 
therapeutic trials may employ drugs, biologics, radiation, or surgery used as 
single agents/modalities or in combination. Biological correlative studies 
that have clinical relevance to therapeutic studies and are aimed at improving 
cancer treatment are also appropriate.

Support for the conduct of the clinical trial and/or patient monitoring and 
correlative laboratory studies that have clinical relevance to the therapeutic 
clinical trial may be requested. A rigorous description of the rationale and 
methodology for the laboratory components of the study, as well as a 
description of how the results will be analyzed in conjunction with the 
results of the clinical trial, should be provided. Laboratory studies using 
patient specimens from the clinical trial may include patient monitoring 
studies (i.e., pharmacokinetics, immune response, etc.) or clinical 
correlative studies that may guide clinical development of the new agent or 
approach or identify patient subsets for specific therapies. Laboratory 
studies of the underlying mechanisms of intervention, the mechanisms of 
disease pathogenesis, or surrogate markers of disease activity and therapeutic 
effect are encouraged.  Statistical design issues should be addressed in the 
research plan for both the clinical protocol and the laboratory analyses. The 
proposed research plan should convince reviewers that the planned studies are 
well conceived, that the methodology is solidly grounded and practical for use 
in a clinical trails setting, and that the analysis plan is sensible and 
likely to be informative.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) research project 
grant (R01).  Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total project 
period for an application submitted in response to this PA may not exceed five 
years. Investigators interested in submitting R21 grant applications in this 
research area are referred to PA-00-047,  Quick-Trials for Novel Cancer 
Therapies  (http://grants.nih.gov/grants/guide/pa-files/PA-00-047.html) and 
PA-01-010,  Exploratory Studies in Cancer Detection, Prognosis and Prediction  
(http://grants.nih.gov/grants/guide/pa-files/PA-01-010.html) and PA-01-015, 
 Correlative Studies using Specimens from Multi-Institutional Prevention and 
Treatment Trials  
(http://grants.nih.gov/grants/guide/pa-files/PA-01-015.html). PA-01-015 also 
solicits for R01 grants in addition to R21 grants.
 
Because the nature and scope of the research proposed in response to this PA 
may vary, it is anticipated that the size of an award will vary also.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by the 
NIH. Complete and detailed instructions and information on Modular Grant 
applications have been incorporated into the PHS 398 (rev. 5/2001).  
Additional information on Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State or local governments, and eligible 
agencies of the Federal government. Racial/ethnic minority individuals, women, 
and persons with disabilities are encouraged to apply as Principal 
Investigators.

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:
 
Dr. Roy Wu or Dr. Heng Xie
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Executive Plaza North, Room 7009
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
Email:  rw51j@nih.gov
Email:  xieh@ctep.nci.nih.gov

Direct inquiries regarding fiscal matters to:
 
Ms. Kelli Oster
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-8627
FAX:  (301) 496-8601
Email:  osterk@mail.nih.gov

APPLICATION PROCEDURES  

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the 
application kit.  This version of the PHS 398 is available in an interactive, 
searchable PDF format. Although applicants are encouraged to begin using the 
5/2001 revision of the PHS 398 as soon as possible, the NIH will continue to 
accept applications prepared using the 4/1998 revision until January 9, 2002. 
Beginning January 10, 2002, however, the NIH will return applications that are 
not submitted on the 5/2001 version.  For further assistance contact 
GrantsInfo, Telephone 301/710-0267, Email: GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
National Cancer Institute (NCI) program staff before submitting the 
application, i.e, as plans for the study are being developed.  Furthermore, 
the application must obtain agreement from the NCI staff that NCI will accept 
the application for consideration for award.  Finally, the applicant must 
identify, in a cover letter sent with the application, the staff member and 
Institute or Center who agreed to accept assignment of the application.  

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT 

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only when 
there is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and NIH staff.  
The research grant application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions.  Applicants are permitted, however, 
to use the 4/1998 revision of the PHS 398 for scheduled application receipt 
dates until January 9, 2002.  If you are preparing an application using the 
4/1998 version, please refer to the step-by-step instructions for Modular 
Grants available at http://grants.nih.gov/grants/funding/modular/modular.htm.  
Additional information about Modular Grants is also available on this site.

Submit a signed, typewritten original of the application, including the 
checklist, and five signed, exact, single-sided 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)

REVIEW CONSIDERATIONS
 
Applications will be assigned based on established PHS referral guidelines.  
Applications will be evaluated for scientific and technical merit by an 
appropriate scientific review group convened in accordance with the standard 
NIH peer review procedures.  As part of the initial merit review, all 
applications will 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 applications under review, will be discussed, assigned a 
priority score, and receive a second level review by the appropriate national 
advisory council or board. 

Review Criteria

The five criteria to be used in the evaluation of grant applications are 
listed below.
 
The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  The 
reviewers will comment on the following aspects of the application in their 
written critiques in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered by the reviewers in assigning the 
overall score weighting them as appropriate for each application.  Note that 
the application does not need to be strong in all categories to be judged 
likely to have a major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field forward.
  
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 analyzes 
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 method?  
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?  

The initial review group will also examine: 

o  the appropriateness of proposed project budget and duration, 
o  the adequacy of plans to include both genders, minorities (and their 
subgroups), and children as appropriate for the scientific goals of the 
research and plans for the recruitment and retention of subjects, 
o  the provisions for the protection of human subjects, 
o  the safety of the research environment,
o  the adequacy of the proposed plan to share data.  
 
AWARD CRITERIA
 
Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS  

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification 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 research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), 
a complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups, if applicable, and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.
  
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS.  

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

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

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

DATA AND SAFETY MONITORING PLAN

All clinical trials supported or performed by NCI require some form of 
monitoring.  The method and degree of monitoring should be commensurate with 
the degree of risk involved in participation and the size and complexity of 
the clinical trial.  Monitoring exists on a continuum from monitoring by the 
principal investigator/project manager or NCI program staff to a Data and 
Safety Monitoring Board (DSMB).  These monitoring activities are distinct from 
the requirement for study review and approval by an Institutional Review Board 
(IRB).  For details about the Policy of the NCI for Data Safety Monitoring of 
Clinical Trials see http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  
For Phase I and II clinical trials, investigators must submit a general 
description of the data and safety monitoring plan as part of the research 
application.  See NIH Guide Notice on  Further Guidance on a Data and Safety 
Monitoring for Phase I and II Trials  for additional information:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data safety monitoring plans for 
clinical trials funded by the NCI is available to 
http://www.nci.nih.gov/clinicaltrials/conducting/dsm-guidelines.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
NIH policy on education in the protection of human research participants now 
required for all investigators, which is published in the NIH Guide for Grants 
and Contracts, June 5, 2000 (Revised August 25, 2000), available at the 
following URL address:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  
A continuing education program in the protection of human 
participants in research is 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 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.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site. 

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS led national 
activity for setting priority areas.  This PA, Clinical Cancer Therapy 
Research, is related to priority area of cancer.  Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/.

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.395, Cancer Treatment Research.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 
and 284) and administered under NIH grants policies and Federal Regulations 42 
CFR 52 and 45 CFR Parts 74 and 92.  This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.

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