STRATEGIES FOR SUCCESS: 

HOW TO WRITE A GRANT IN CANCER CAM 

The National Cancer Institute’s 

Office of Cancer Complementary and Alternative Medicine 

Research Development and Support Program 

March 2003 

i 

PREFACE 

As cancer patients continue to explore alternative treatments and practices, the need for reliable 

scientific data increases. The National Cancer Institute (NCI) remains devoted to the rigorous 

investigation of potential treatments and modalities in the prevention and treatment of cancer and 

its symptoms, whether the source is unconventional or unexpected. Rigorous scientific 

investigations in Complementary and Alternative Medicine (CAM) can and should be conducted. 

Unfortunately, the development of competitive research proposals in cancer CAM and securing 

federal funding is often challenging. Cancer CAM applications to the National Institutes of 

Health (NIH) must meet all the general criteria required of any application. In addition, 

competitive applications are successful at addressing some of the challenges specific to cancer 

CAM topics. 

This document not only compiles information from existing NIH grant writing resources, it 

highlights some of the issues unique to CAM and CAM related research areas. We have included 

many of the issues raised by review committees and presents some of the potential solutions for 

applicants. We hope this is helpful in the preparation of grant proposals to the NCI and to other 

peer-review funders interested in providing funding support for scientific research in cancer 

CAM. 

Jeffrey D. White, MD 

Director 

Office of Cancer Complementary and Alternative Medicine 

National Cancer Institute 

Wendy B. Smith, Ph.D. 

Program Director 

Research Development and Support Program 

Office of Cancer Complementary and Alternative Medicine 

National Cancer Institute 
ii 

Major Source Documents and Helpful Websites: 

Everything You Wanted to Know About the NCI Grants Process....but Were Afraid to Ask. 

Prepared by the NCI Grants Administration Branch, NIH Publication No.02-1222, Revised April 

2002. http://www3.cancer.gov/admin/gab/index.htm

Qualitative Methods in Health Research: Opportunities and Considerations in Application and 

Review. Office of Behavioral and Social Sciences Research, National Institutes of Health; 

Bethesda, MD, NIH Publication No. 02-5046, December 2001. http://obssr.od.nih/Publications/ 

Qualitative.PDF

Expert Panels in Cancer CAM Research: Developing the State of the Science in Research 

Methodologies. Expert Opinions on Methodology: Development of Cancer CAM Symptom 

Research, NCI’s Office of Cancer Complementary and Alternative Medicine, National Cancer 

Institute, Bethesda, MD. 
iii 

TABLE OF CONTENTS 

Preface.............................................................................................................................................. i 

Introduction......................................................................................................................................1 

Types of Funding Instruments .........................................................................................................2 

Grant Mechanisms and Grant Announcements ...............................................................................3 

Grant Application Process: Preparation, Development, Receipt, 

Assignment and Review ............................................................................................................5 

 Preparation .................................................................................................................................5 

 Development..............................................................................................................................6 

 Grant Application Development..........................................................................................6 

 Specific Aims.................................................................................................................7 

 Background and Significance ........................................................................................7 

 Research Design and Methods.......................................................................................9 

 Budget..........................................................................................................................15 

 Additional Application Requirements .........................................................................15 

 Human Subjects .....................................................................................................15 

 Data Safety Monitoring..........................................................................................16 

 Investigational New Drug (IND) Applications......................................................17 

 Common Issues in Cancer CAM Applications: Suggestions for Applicants ....................17 

 Submission.........................................................................................................................19 

 Receipt, Assignment and Review ......................................................................................20 

Summary........................................................................................................................................25 

Appendix I: Budget Mechanisms...................................................................................................26 

Appendix II: Receipt, Review and Award Cycles.........................................................................35 

Appendix III: Glossary of Terms for Human Subject Requirements ............................................36 

Appendix IV: NIH Policy for Data and Safety Monitoring ..........................................................42 

Appendix V: Answers to Frequently Asked Questions about NIH Grants ...................................46 

1

INTRODUCTION 

NCI Organization 

The current NCI organizational structure can be seen in Figure 1. Four extramural research 

divisions, one intramural research division and one intramural research center monitor and 

administer NCI’s cancer-research activities through extramural and intramural research 

programs. The Office of the Deputy Director for Extramural Science (ODDES), which is part of 

the Office of the Director, coordinates initiatives across NCI’s four extramural research 

divisions: the Division of Cancer Biology (DCB); the Division of Cancer Control and Population 

Science (DCCPS); the Division of Cancer Prevention (DCP); and the Division of Cancer 

Treatment and Diagnosis (DCTD). The Office of Cancer Complementary and Alternative 

Medicine (OCCAM) is located within the ODDES (see Figure 2). The ODDES also monitors 

and administers the Centers, Training, and Resources Program, as well as the Center for Health 

Disparities Research and the grant program supporting minority initiatives. 

Office of the Director 

NCI

Office of the Deputy Director for 

Extramural Science

Division 

of Cancer 

Treatment 

& 

Diagnosis

Center for 

Cancer 

Research

Office of 

Centers 

Training 

& 

Resources 

Division of 

Cancer 

Epidemiology 

& Genetics

Division 

of 

Cancer

Biology

Division of 

Cancer 

Prevention

Office of the Director 

NCI

Office of the Deputy Director for 

Extramural Science

Division 

of Cancer 

Treatment 

& 

Diagnosis

Center for 

Cancer 

Research

Office of 

Centers 

Training 

& 

Resources 

Division of 

Cancer 

Epidemiology 

& Genetics

Division 

of 

Cancer

Biology

Division of 

Cancer 

Prevention

Figure 1. NCI Organizational Structure 

Office of the Director 

NCI

Office of the Deputy Director

for Extramural Science

OESI OCCAM Office of Centers, 

Training & Resources

Figure 2. NCI Office of the Director Organizational Structure 
2

NCI Mission 

The mission of the NCI is to eliminate cancer and prevent the devastation that cancer imposes on 

individuals, families, and society as a whole. NCI’s goal is to stimulate and support scientific 

discovery and its application to achieve a future where all cancers are uncommon and easily 

treated. NCI works toward this goal in two major ways: 1) NCI provides vision to the nation and 

leadership for NCI-funded researchers across the United States and around the world; and 2) NCI 

works to ensure that the results of research are used in clinical practice and public-health 

programs to reduce the burden of cancer for all people. The National Cancer Institute coordinates 

the National Cancer Program, which conducts and supports research, training, health information 

dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment 

of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families 

of cancer patients. 

NCI’s Office of Cancer Complementary and Alternative Medicine 

The National Cancer Institute has a long history of interest and support of cancer CAM research. 

In 1998, the National Cancer Institute established the Office of Cancer Complementary and 

Alternative Medicine t(OCCAM) o support the scientifically rigorous study of CAM modalities 

as they relate to the diagnosis, prevention, and treatment of cancer and its symptoms. The NCI’s 

OCCAM is committed to developing the foundation for scientifically rigorous research in cancer 

CAM and symptom management. 

A major goal of the OCCAM is to foster the integration of quality cancer CAM research within 

all appropriate divisions of the NCI. To further this aim, the OCCAM Research Development 

and Support Program creates initiatives, activities, and funding opportunities to attract, 

encourage and support the development of scientifically rigorous cancer CAM research. 

TYPES OF FUNDING INSTRUMENTS 

Using a variety of funding instruments, including contracts, grants, and cooperative agreements, 

the NCI accomplishes much of its mission through services provided by non-federal entities. 

Each instrument has a specific purpose and application, thus creating different relationships 

between the parties. 

Contracts 

The NCI uses the contract instrument to procure cancer-research services and other resources 

needed by the federal government. Contracts are used when the principal purpose of the 

transaction is to acquire a specific service or end product for the direct benefit of, or use by, the 

NCI. 

Grants and Cooperative Agreements 

In contrast to contracts, grants and cooperative agreements are federal financial assistance 

mechanisms used to support and stimulate research. Assistance relationships are established 

when the principal purpose of the transaction is to transfer money, property, services, or anything 

of value to a recipient to accomplish a public purpose or to stimulate a particular area of research 

authorized by law. The two types of assistance mechanisms used by the NCI are the grant and 

the cooperative agreement. 
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Grants are used when: 1) no substantial programmatic involvement is anticipated between the 

NCI and the recipient during the performance of the activities, thus allowing the recipient 

significant freedom of action in carrying out the research project; and 2) there is no specified 

service or end product expected for use by the NCI. 

Cooperative agreements are used when: 1) the applicant is responding to a specific NCI 

announcement for cooperative agreements and must tailor the proposal to the announcement’s 

requirements; and 2) substantial programmatic involvement is anticipated between the NCI and 

the recipient during the performance of the activities. 

This document focuses on these assistance mechanisms: grants and cooperative agreements (for 

more detail, see Everything You Wanted to Know About the NCI Grants Process...but Were 

Afraid to Ask http://www3.nci/nih.gov/admin/gab/98GPB/98GPBtoc.htm). 

GRANT MECHANISMS AND GRANT ANNOUNCEMENTS 

Investigators should be familiar with these terms and how they are used at the NIH. Grant 

mechanisms refer to the type of research grant while a grant announcement refers to a call for 

applications for specific types of grant mechanisms. 

Grant Mechanisms 

Research Project Grants 

Research Project Grants are awards for investigator-initiated research proposals. Several types of 

awards are made in this category, which vary in type of mechanism, type of eligible applicant, 

total amount of support, and length of time. Fiscal year 2001 research project grant expenditures 

totaled $1,696,603,000, accounting for 45.2 percent of the NCI budget. In Fiscal Year 2002, the 

NCI supported approximately 315 CAM and CAM-related research projects. As of March 2003, 

the NCI has supported an additional 62 projects. 

P01 Research Program Project Grant 

Research Program Project Grants (P0ls) support an integrated, multi-project research approach 

involving a number of independent investigators who share knowledge and common resources. 

A P01 has a defined central research focus involving several disciplines or several aspects of one 

discipline. Each individual project should contribute to or directly relate to the common theme of 

the total research effort, thus forming a system of research activities and projects directed toward 

a well-defined research program goal. 

R01 Research Project Grant 

Research Project Grants (R01s) support a discrete, specified research project to be performed by 

the named investigator(s) in an area representing his/her specific interest and competencies. This 

is generally referred to as a traditional research project grant. R01 proposals in cancer CAM 

topics may face a challenging review process because these proposals require strong supportive 

preliminary data. Many cancer CAM research areas lack the kind of preliminary data necessary 
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to support a competitive R01 proposal. Other mechanisms, such as the R03 and R21, are 

available to provide funds for pilot and preliminary studies. 

R03 Small Research Grant 

Small Research Grants (R03s) provide research support specifically limited in time and amount 

for studies in categorical program areas. Small research grants provide flexibility for initiating 

studies that are generally for preliminary short-term projects. These grants are non-renewable. 

R21 Exploratory/Developmental Grant 

Exploratory/Development Grants (R21s) support the development of new research activities in 

categorical program areas. Support is generally restricted in level of support and time. In cancer 

CAM research, the R21 is one of the most important available mechanisms because it can be 

used to support preliminary research proposals. When preparing an R21 proposal, it is important 

to include some description of how this project fits into an overall research plan and how this 

project may be developed into a R01 proposal. From the beginning of fiscal year 2002 to March 

2003, the NCI has funded or plans to fund 35 R21 proposals. The NCI only accepts applications 

for R21 grants that are in response to a specific grant announcement. 

For a list and detailed information about all NCI grant mechanisms, see Appendix I. 

Grant Announcements 

The principal investigator (PI) usually initiates an application for a grant. Investigators may send 

unsolicited proposals (investigator initiated) in response to a specific grant announcement. Under 

some circumstances, applications will be accepted only when a specific grant announcement is 

identified. 

For new, expanded and/or high-priority programs, the NCI may encourage the submission of 

grant applications by using the following types of solicitations: Program Announcements (PAs), 

Program Announcements Reviewed in an Institute (PAR) and Requests for Applications (RFA). 

Each of these announcements has certain characteristics related to funding and/or review 

procedures. 

Program Announcements (PAs) 

PAs describe continuing, new, or expanded program interests for which grant or cooperative 

agreement applications are invited. Applications in response to PAs are reviewed the same 

manner as unsolicited grant applications (i.e. by chartered peer review committees of the Center 

for Scientific Review (CSR) or by NCI Initial Review Groups (IRGs)). 

Funds for Program Announcements may or may not be set-aside. Program Announcements with 

set aside funds are called PASs. 

Program Announcements Reviewed in an Institute (PARs) share the same characteristics as PAs 

with the addition of special referral guidelines and are reviewed by a specific Institute’s IRG. 

A PA, PAR or PAS will generally have three receipt dates per year and will be open for two 

years before being considered for renewal. 
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Requests for Applications (RFAs) 

RFAs are issued to invite grant applications in a well-defined scientific area to stimulate activity 

in NCI programmatic priority areas. A single application receipt date is specified, and the 

announcement identifies the amount of funds earmarked for the initiative and the number of 

awards likely to be funded. Applications are evaluated for responsiveness to the RFA before 

review. Applications received in response to a particular RFA are reviewed by an appropriate 

NCI IRG or by a special review group. 

All PAs and RFAs are published in the NIH Guide for Grants and Contracts 

(http://www.nih.gov/grants/guide/index.html). A list of funding opportunities in cancer CAM 

can be found on the NCI’s Office of Cancer Complementary and Alternative Medicine’s website 

at http://cancer.gov/cam. 

It is important to note that applications in cancer CAM topics may be appropriate and considered 

responsive to many NCI announcements that may not necessarily have CAM related language in 

the title or text. Therefore, announcements list program staff contacts. Applicants are strongly 

encouraged to contact staff to discuss the appropriateness of a cancer CAM proposal to a specific 

announcement. 

Letters of Intent (LOIs) 

Notices of PAs and RFAs will generally indicate dates for Letters of Intent. These letters, though 

optional, provide useful information for the determination of the potential workload of the 

review group and for the identification of potential reviewers with relevant expertise. Therefore 

for CAM applications, the submission of such letters may significantly increase the quality of an 

application’s review. 

THE GRANT APPLICATION PROCESS: PREPARATION, DEVELOPMENT, 

RECEIPT, ASSIGNMENT AND REVIEW 

Because it takes approximately nine months from the time an application is received until NCI 

funding determinations are completed and awards are issued, it is essential for applicants to 

submit strong and competitive proposals (see Appendix II for details). 

Grant Preparation 

This is the initial stage of the process. At this point, investigators may have identified the type of 

research project, how long it would take to accomplish, what level of funding it would require, 

and the potential team of investigators or expertise needed for its successful completion. 

Applicants should contact relevant program staff as early in the process as possible. See NCI’s 

website for a listing of program staff http://www.nci.nih.gov/researchfunding/

scientificprograms/. Program Director contact information is also listed in announcements 

(RFAs, PAs, etc.), and staff are usually identified by Institute or interest area. 
6

Foreign applications: 

Applications from foreign institutions are accepted. However, funding of such applications 

depends upon whether the topic is relevant to the American public and whether or not there is 

unique expertise at the foreign institution. Applicants from foreign institutions are strongly 

encouraged to contact program staff prior to preparation and submission of a grant proposal. 

Program staff can help identify the funding potential of applications and may be able to suggest 

potential US partners when appropriate. 

All applicants are strongly encouraged to contact program staff because it may be 

particularly challenging to prepare competitive grant proposals in cancer CAM research. 

Program staff may assist investigators in several ways including: 

• assisting applicants in locating funding opportunities; 

• directing applicants to grant mechanisms that match the goal or intent of the project and 

experience of the investigator and find the “best fit”); 

• discussing the science and research relevant to the program director’s program; 

• providing technical assistance to the applicant; 

• describing the program’s priorities and areas of increased interest; 

• helping applicants network and identify areas of needed expertise; 

• assisting in identifying appropriate review committees and potential ad hoc reviewers; and 

• accepting proposals with budgets greater than $500,000 (applicants must contact and have 

Program Director approval to submit such projects). 

Program Directors serve as a source of information, support and guidance throughout the grant 

development, review, award and administrative process. 

Grant Development: Challenges in Developing Proposals in Cancer CAM 

Grant Application Development: 

Grant applications should contain these sections: Abstract, Introduction, Specific Aims, 

Significance (literature review and background), Research Plans (methodology), Budget, and 

Biographical Sketch. 

Applicants should be familiar with the required sections of the grant application. Challenges in 

developing research proposals are not always unique to cancer CAM. The Cultural and 

Qualitative Research Special Interest Group at the NIH developed a document which describes 

the required Research Sections. Relevant sections have been adapted here for cancer CAM 

research (for the complete document, see Qualitative Methods in Health Research: 

Opportunities and Considerations in Application and Review, 

http://obssr.od.nih/Publications/Qualitative.PDF). 

Detailed descriptions of these sections as well as specific issues related to cancer CAM research 

are described in the following. 
7

Specific Aims 

The specific aims are the questions, hypotheses, or overall theories that the research is seeking to 

address or test. The applicant should describe the long-term goal or ultimate purpose as well as 

the specific aims to be accomplished during the proposed research. 

Cancer CAM research may address broad and complex questions that are not always fully 

articulated. The applicant expects that key insights may emerge during the course of the research 

that will steer the project in future directions. It is necessary to strike a balance between 

reasonably achievable aims and openness to unanticipated findings. As the term “specific aims” 

implies, reviewers expect clearly delineated, precise research goals. Failure to move beyond 

broadly phrased, general statements in this section to specific goals weakens the argument that 

the study will produce important findings. 

It is generally best to state a limited number of clearly focused aims. The applicant should 

carefully consider whether to frame the aims as hypotheses or as questions. A succinct 

description stressing the innovative nature of the study will help to engage the reader and 

underscore the project’s significance. The researcher should take care not to overstate the 

anticipated outcomes or appear overly confident of the intended effects. This is especially 

problematic in CAM intervention proposals. While investigators may show confidence in a 

particular intervention, the application should maintain a neutral tone and reflect the 

investigator’s objectivity to avoid concerns of “true believer” biases. The aims should be feasible 

for the given time, methods, and stated goal. A clearly and precisely worded statement about the 

examination of under-studied issues or uncertain relationships that appears to be achievable 

within the timeframe and resources available is recommended. 

Once the specific aims are formulated the applicant should articulate exactly how these aims 

relate to each of the remaining application sections. For example, specific aims should be 

strongly linked to the research methods and the analytical processes. Be sure to edit to insure that 

the statements and restatements of the goal and aims are consistent throughout the various 

sections. 

Background and Significance 

This section briefly sketches the background leading to the present application, critically 

evaluates existing knowledge, and specifically identifies the knowledge gaps which the project is 

intended to fill. It also concisely states the importance and health relevance of the research 

described in the application by relating the specific aims to the broad, long-term objectives. 

Here, the applicant has the opportunity to display knowledge of the field, ability to critically 

analyze the extant research, and to show how the proposed work will extend a research area, fill 

a gap, and, most importantly address public health. The background and significance section 

provides a well-reasoned and compelling argument for the importance of the research aims 

described in the “Specific Aims” section and for the appropriateness of the methodological 

approach proposed in the “Research Design and Methods” section. 

The literature review should focus on research that is highly relevant to the planned study in such 

as way as to communicate gaps in existing understanding, to suggest the importance of the 
8

planned study to address these gaps, and to expand the frontiers of scientific knowledge. 

Reviewers expect a thoughtful, balanced, and critical evaluation of the research literature not just 

a summary of what has been reported in other studies. The literature review should also provide 

the basis for the choice of concepts being investigated, the conceptual framework underlying the 

research, and the methodological approach proposed. In cancer CAM research, it may be 

challenging to find substantial supportive preliminary data. When possible, applicants should 

provide evidence that the CAM approaches have worked well for studies that have similar 

characteristics to the planned study. An applicant may wish to provide specific examples of how 

results of their previous similar research have made a significant contribution. 

A commonly identified weakness in applications is that applicants spend too much effort citing 

too broad a range of material that has been written on the general topic and not enough effort on 

organizing the review in light of the specific area they want to investigate. On the other hand, 

reviewers will be looking to see that the review is complete and that all important studies or 

areas are included. Applicants should be careful to include the appropriate and relevant range of 

research studies Care should be taken to write with a balanced tone while identifying and 

conveying the strengths and the weaknesses of existing studies. Finally, although the 

“Background and Significance” section should be substantive and demonstrate insight, breadth, 

and mastery, the applicant is advised to stay within the recommended page-limit guidelines. 

The applicant should state the background to the issue or topic of study (that is, its general and 

broadest implications and relevance to various public constituencies) and the significance of the 

study aims to particular public health issues, concepts, data, and/or current practices, as 

appropriate. Applicants should keep in mind that “Significance” is one of the five review criteria 

by which the application will be evaluated (see Research Project Evaluation Criteria, page 22) 

and should consider the following questions in conceptualizing and describing the project: 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? Supportive evidence for the significance is provided through the 

literature review. 

Preliminary Studies 

This section should provide an account of the principal investigator’s preliminary studies 

pertinent to the application and/or any other information that will help to establish the experience 

and competence of the investigator to pursue the proposed project. 

The preliminary studies should provide the basis for the argument to conduct the study in the 

manner proposed. In this section, the applicant has the opportunity to demonstrate competence 

with the methods and issues of concern to the proposed study, and to describe related work and 

data that led to the proposal. This section can document the applicant’s competencies at concept 

development, data collection and modes of analyses, and successful project completion and 

publication. Provide brief but detailed statements about prior studies, including aims, size of 

study group, design, kinds of data, analytic techniques, and key findings. Be sure to identify 

strengths and weaknesses. Describe how prior work contributed to the proposed design and 

methods. Reasoning through the limitations of previous work is useful, especially if the applicant 

can propose substantial improvement and expansion. 
9

This section provides a forum to show precisely how the applicant’s past cancer research (both 

conventional and related to CAM) has led to useful findings and supports the ability to undertake 

the proposed research. Establishing the applicant’s record of publications pertaining to the 

specific population or methodology is essential. If necessary, amplify features about the 

investigators not stated in the biographical sketch. 

In many areas of cancer CAM, writing about preliminary studies can present a challenge. If this 

is the situation, the applicant should showcase the staff’s specific experience and expertise that 

makes them uniquely suited to conduct the proposed research. If they have used similar methods 

and techniques in a different substantive area, a short description of such studies, focusing on the 

methodological similarities, would be appropriate. Some pilot work could strengthen the 

application. A preliminary analysis of even a small amount of data allows the applicant to 

demonstrate the feasibility of the proposed data collection and analysis process. 

Research Design and Methods 

The Research Design and Methods section of the PHS 398 application for grant support (page 

16) instructs applicants to: 

Describe the research design and procedures to be used to accomplish the specific 

aims of the project. Include how the data will be collected, analyzed, and 

interpreted. Describe any new methodology and its advantage over existing 

methodologies. Discuss the potential difficulties and limitations of the proposed 

procedures and alternative approaches to the achieve the aims. As a part of this 

section, provide a tentative sequence or timetable for the project. Point out any 

procedures, situations, or materials that may be hazardous to personnel and the 

precautions to be exercised. 

Each of the components comprising this section of the research plan are discussed below. There 

are certain features of a good application that apply equally across all components. Two critical 

characteristics of a good design section are consistency in language and concepts throughout and 

integration of aims and questions through all parts of the plan. In addition, discussion of the 

strengths and limitations of the methods that will be used as compared to alternatives not 

selected is a useful aspect of the justification for the overall research plan. Another characteristic 

is a well-balanced, critical analysis of the information the study can and cannot provide. 

The research questions or overall theory that will be addressed were described in the specific 

aims, and the background and significance sections of the research plan. The research design and 

methods section describes how the specific aims will be accomplished. The key consideration in 

laying out this section of the application is whether the proposed research design, sampling 

strategy, data-collection methods and procedures, and data analysis and interpretation approaches 

are the most appropriate, all things considered, for accomplishing the specific aims of the study. 

A plan that is well-thought-out, scientifically logical, and flows smoothly is one part of the 

proposal. In addition to sound scientific rationale, a good proposal also provides sufficient 

descriptive detail for each step and a timeline for the overall process. 
10

Each element of the research plan, for example, the conceptual/theoretical framework guiding 

the study, sampling methods and sample characteristics, the data-collection approaches and 

procedures, and the analysis and interpretation of the data, is equally important in the overall 

plan for how the study will be conducted. The discussion of each research design element can be 

organized and presented in a way that conveys the linkage between the specific aims of the study 

and all other elements of the research plan and emphasizes the logical flow and integration of the 

research plan. 

Design 

The first part of this section describes the type of research design used. A brief introductory 

statement of the overall research strategy and the defining features of the design provides an 

overview of how the research will actually be conducted and may offer a restatement of the links 

between the theoretical and methodological perspectives reflected in the study. A brief overview 

could convey for example, whether the aims of the study are descriptive, hypothesis testing, or 

some combination; whether one approach, or an integrated approach will be used; whether data 

will be collected at one or multiple points in time; and how the population is defined. The chosen 

design is reflected in the specific aims and its influence over ensuing plan components is noted in 

each section. 

There are several challenging issues in the research design of cancer CAM trials. In recognition 

of these issues, the NCI’s Office of Cancer Complementary and Alternative Medicine 

established a series of expert panels to assess and critique the state of the science in research 

methodologies in cancer CAM research. Panelists from both conventional and CAM research 

apply their knowledge and expertise to specific topic areas within cancer CAM. Panelists 

identify the major methodological challenges in cancer CAM research and propose potential 

solutions. This process serves to assist grant applicants by illustrating the types of issues that 

should be addressed in cancer CAM research proposals. See Figure 3 for a summary table of 

strategies proposed by the first expert panel (Expert Panels in Cancer CAM Research: 

Developing the State of the Science in Research Methodologies. Expert Opinions on 

Methodology: Development of Cancer CAM Symptom Research, Bethesda, Maryland, 2001. 

Copies of this document are available through the NCI’s Office of Cancer Complementary and 

Alternative Medicine at ncioccam-r@mail.nih.gov). In addition to the issues raised by this panel 

on symptom research there are other methodological concerns relevant to a variety of types of 

cancer CAM research. 

Placebo/Controls 

One of the most challenging issues applicants face in developing cancer CAM research designs 

involves the development of appropriate controls, shams, and placebo interventions. The creation 

of truly inert controls that will not cause independent beneficial or harmful effects in a research 

trial is of fundamental importance in the design of rigorous CAM research. 

In developing placebo controls in botanical or dietary supplements, it is preferable to use placebo 

substances with same taste, smell, and size. In developing controls for CAM intervention trials, it 

may strengthen a proposal to include control groups that are designed to control for specific 

confounding variables. It is helpful to identify potential confounding variables and explain how a 

particular control group was selected and which confounds it is designed to address. Make sure 
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the control/group fits the stage of the project. If a feasibility study is proposed, control groups are 

not needed. The rationale for inclusion of control groups, details about the kinds of groups and 

what variables they are designed to address, should be clearly discussed in the proposal. If a 

feasibility study is proposed, the design should include endpoints that make sense for a 

feasibility study. If a pilot study is proposed, appropriate control groups and endpoints should be 

included that make sense for pilot studies. 

Standardized vs. Individualized approaches 

There has been an ongoing debate among clinicians and researchers alike regarding the most 

appropriate approach to study certain CAM interventions. Some investigators propose that to 

study an intervention, it is most appropriate to study it in the manner in which it is practiced, 

which often means providing interventions that are tailored to the individual. Researchers may 

balk at this approach, concerned that individualizing an intervention precludes its scientific 

study—an intervention needs to be standardized across subjects in order to draw meaningful 

conclusions. Proponents of individualized approaches counter with the concern that once an 

intervention is standardized, its efficacy may be compromised, and the research no longer 

utilizes the most potent and clinically useful form of the intervention. This is a complex 

methodological issue which crosses all areas of CAM research, but is more problematic for 

therapeutic interventions drawn from alternative systems of medicine (i.e. Traditional Oriental 

Medicine, Auyervetic) as well as for behavioral or mind-body approaches to symptom 

management. 

There are two major study design issues to consider in CAM intervention research: an 

individualized approach or a standardized intervention. The controversy concerns achieving a 

balance between conducting a trial of a single intervention that does not accurately reflect true 

clinical practice or designing a multifaceted intervention trial that is complicated to design and

implement and may not reflect the actual practice of the CAM intervention. 

In proposing clinical research with a CAM intervention, the Research Design section should 

include a rationale for choosing the type of approach. Both approaches have advantages and 

disadvantages. The critical issue for applicants is to include a compelling rationale for the design 

approach selected. The proposal should demonstrate that the applicant is aware of these issues 

and is thinking carefully about them in developing the research design. 

Study Design: Phase ? 

Clearly define if a clinical research proposal is for a Phase I, II or III trial. Whatever phase trial is 

proposed, applicants should include a compelling rationale for its use for this intervention in this 

study population. Researchers often propose moving directly to a Phase III clinical trial with 

CAM products and interventions based upon the history of their use in alternative medical 

systems. While its history may help support its use in research, it is not necessarily sufficient to 

justify moving directly to Phase III trials. Prior experience may not have been with the same 

population (e.g. cancer patients) or may not have been used in combination with current cancer 

treatment regimens. 
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Strategies for Applicants in Cancer CAM Symptom Research

Placebo/Shams/Control Groups: 

Use placebo to demonstrate whether a therapeutic intervention has effect. 

Use active comparison to demonstrate how strong an effect an intervention may have. 

Create placebos and shams as similar as possible to intervention. 

Defend strategy of including or not including comparison groups. 

Individualized or Standardized Approach to CAM Interventions: 

Discuss advantages and disadvantages of each approach. 

Provide compelling rationale for choice. 

Consider integrating individualized approach within standardized format. 

Measurement Issues: 

Include hypotheses/rationale about why intervention would affect these symptoms. 

Use standardized tools that have demonstrated validity and reliability. 

Use tools that measures most common and most distressing symptoms. 

Consider tools that measure multiple symptoms. 

Consider and address patient burden. 

Selecting Phase: 

Defend proposing Phase III without Phase I or Phase II data—does “thousands of years use” suffice? 

Address dosing issues—if don’t know dosage information, get preliminary data 

Give enough detail for replication 

Investigational New Drug (IND) Issues: 

May require IND even if available over the counter—depends upon use. 

For NIH proposals, INDs may not be required—contact FDA and NIH program staff to inquire. 

Phase I/II studies may not require preclinical data: Phase III may require more toxicity data. 

INDs encouraged as the process can improve study design and increase likelihood of usable data. 

Ethics: 

Demonstrate value of CAM research as a legitimate adjunct to conventional medical research. 

Disclosure of conflict of interest to patients is essential. 

Describe how vulnerable patients are recruited and enrolled to clarify and ensure informed consent. 

Statistical Issues: 

Define primary and secondary endpoints. 

Choose measurement tools that focus on those endpoints. 

Include appropriate power analysis. 

Use stratification to account for confounds. 

Detail how to address patient attrition and/or missing data. 

Discuss both statistical significance and clinical significance. 

Figure 3. Strategies for Applicants in Cancer CAM Symptom Research 
13

Additional Methodological Issues in Cancer CAM Research 

Multidisciplinary Approaches in Cancer Treatment 

Often investigators are interested in investigating multidisciplinary approaches in cancer care. 

The advantages of studying the entire approach versus a step-by-step method of isolating and 

adding approaches should be discussed, and a compelling rationale defending the chosen 

approach should be included in the proposal. 

Accrual and Selection Biases 

Another important aspect of the research design is the specification of the criteria for 

determining who will, and will not, be included in the sample. For example, will only a certain 

age range, gender, or diagnostic group be included? Related to the selection criteria is the issue 

of the representativeness of the sample. 

In addition, applicants need to be realistic in their estimates of accrual rates in clinical CAM 

research. Accrual in clinical investigations using CAM products and interventions may be 

particularly challenging in accrual especially if randomization of subjects is planned. Subjects 

may object to randomization to a non-intervention arm as these interventions are often available 

outside the experimental setting. Applicants should also address issues related to potential 

selection bias. Subjects who are willing to enroll in CAM research may or may not be 

representative of the proposed study population. Potential impact of this type of bias should be 

discussed in the application. 

Extra-experimental Use of CAM 

The applicants should address the issue of concomitant use of CAM experimental products or 

interventions. In traditional cancer research, investigators do not have to be concerned that 

subjects in the control group will take the active experimental drug or treatment because they 

simply cannot get access to it outside of the trial. In CAM research, subjects often can easily buy 

the same or a similar product as that under study or visit a practitioner who can administer an 

intervention (e.g. acupuncture). Investigators need to include discussion of this issue and 

appropriate steps taken to address this concern. 

Study Population 

The issues of acculturation and language may raise methodological (for example, access, 

consent, recruitment and retention) as well as scientific (for example, instrument validity and 

translation) problems to be addressed in research on ethnic populations. There are also special 

issues involved in sampling for hidden populations (for example, access) that may require 

specific strategies. Applications should include a discussion of these potential challenges. 

Description of CAM Product or Intervention 

Applicants interested in investigations that involve complex natural products (e.g., botanical 

extracts) need to provide enough detailed information in their proposals for NCI staff and review 

committees to evaluate whether these products are of sufficient quality for research. Applicants 

need to describe how the quality of the products will be insured. Information about supplier, lot, 

and potential containments should be included. If applicants plan to study a complex mixture, 

rationale for the use of that mixture should also be included. A discussion of the advantages and 

disadvantages of using mixtures (isolation versus potential synergy) is often helpful. The levels 
14

of characterization, standardization, stability, purity, and optimization of the presumed active 

ingredient or ingredients may vary. Natural products should be chemically characterized as 

thoroughly as possible, using the most appropriate state-of-the-science method for this process. 

Some investigators using proprietary mixtures struggle with how much detail about the mixture 

to include in a proposal. Applicants should provide enough detail for appropriate scientific 

review. 

For CAM interventions with practitioners, specific issues are often raised in review. Often there 

are no standards of practice for many of these interventions. It is important to demonstrate 

reliability and consistency of the practitioners of these interventions. Applicants should discuss 

in detail rationale for using one practitioner or for using several. When using several, detailed 

information about how practitioners will be chosen, trained to participate in the research, 

monitored and evaluated for reliability is important to include in the proposal. 

Data Collection, Analyses, and Interpretation: 

This section of the application addresses data collection instruments, methods, and procedures. It 

should include complete explanations of each of these areas and how the methods used will 

address the research questions. 

Data collection strategies should be specific, in as much detail as possible, and include 

procedures for monitoring the quality of the data, including, for example, how data collectors 

will be trained and supervised and how information will be cross checked and triangulated with 

information from other data sources. Elements of quality monitoring of the data collection 

process might also include periodic checking of the intervention for reliability and consistency. 

Some researchers videotape practitioners to assess quality control. 

Measurement Issues 

Among the most important issues in the development of a clinical research design in cancer CAM is 

the appropriate selection of measurement tools. If available, applicants should use standardized tools 

that have demonstrated validity and reliability in the current study population. Care should be taken to 

define primary and secondary endpoints and choose the measurement tools that focus on those 

endpoints. In addition, applicants should strive to use the fewest number of instruments possible to 

assess the most compelling information. 

In addition, consideration of patient burden, that is people's tolerance and stamina for completing 

measurement tools (both an issue of data quality and of human subjects protections) is an 

important issue. Applications that include non-English speakers will want to address the 

language of the interviews, translation procedures, and the use of translators. 

Once again, a clear explanation of how each instrument or data collection method relates to and 

answers a specific aim is useful in demonstrating continuing integration and consistency in the 

plan. 

 

Data Analysis 

The data analysis strategy lays out the specific procedures for addressing each of the research 

questions and/or hypotheses, and the nature and form of the expected results. 
15

Pilot data can be helpful in constructing a preliminary or hypothetical coding scheme. Similarly, 

tables can be used to demonstrate the hypothetical kinds of data that will be obtained and how 

they will be analyzed. 

Data Interpretation 

While there is no heading for data interpretation in the application kit, it is useful to describe the 

process for how the investigator will arrive at data integration and conclusions. The potential 

significance of the findings for both the immediate questions and broader issues can be addressed 

here. The process and procedures for integration and interpretation of data from various sources 

is particularly important when using more than one data source. 

Budget 

All general principles of developing and describing a research budget apply to cancer CAM 

research as they would to any research methodology. Significant budgeting problems faced in 

cancer CAM research include the added cost of collaborating with expert CAM practitioners for 

clinical intervention protocols, the costs associated with obtaining a quality controlled product 

and developing appropriate placebos for botanical products and dietary supplement studies. 

Applicants encounter problems in review when the budget does not adequately reflect these 

needs. Applicants frequently make the mistake of underestimating their budgets. The budget and 

timeline must reflect the effort needed to conduct a good data analysis. When reviewers are faced 

with an unrealistically low budget or short timeline for a project, they may interpret this as lack 

of experience or judgment on the part of the researcher and view the application negatively. 

In December of 1998, NIH announced the use of modular budgets for certain grant applications. 

Applications whose total direct costs do not exceed $250,000 per year are eligible to be 

submitted as modular grant applications. For the purpose of streamlining applications and budget 

development, modular budgets are submitted in modules of $25,000.00 rather than being broken 

down into greater detail. If the applicant thinks there may be anything at all unusual or 

inordinately expensive about a proposed budget, he or she would be wise to include such a 

detailed justification as an appendix. Full information on NIH modular grants is available at 

http://grants.nih.gov/grants/funding/modular/modular.htm. Any questions about this are 

appropriately directed to the applicant’s program official. 

Additional Application Requirements: 

All applications must contain sections that address the following: Human Subjects, Inclusion of 

Certain Populations, and Data Safety Monitoring. Failure to include any of these sections results 

in the application being returned to the investigator without review. It is important to read all 

requirements carefully. In addition, applicants who are proposing clinical research projects with 

botanical and dietary supplement products should investigate the need for an Investigational New 

Drug application. 

Human Subjects: 

Since this is an area subject to constant change, one area in which applicant error can have dire 

consequences, it is best to begin with the official sources. All participants in the NIH application 

process are encouraged to be thoroughly familiar with the latest federal research regulations. The 

Office for Protection from Research Risks (OPRR) has moved from the NIH into the Office of 
16

the DHHS Secretary and has been renamed the Office for Human Research Protections (OHRP) 

with a web site at http://ohrp.osophs.dhhs.gov. The guidelines span the different levels of 

research involvement and discuss numerous special topics. Readers of this document may find 

the Belmont Report, which annotated the principles that apply across all types of research, of 

particular interest. There is also a web site for the NIH Human Subjects Committee 

(http://odoerdb2.od.nih.gov/oer/committees/hsp/hsp.htm) which is composed of subcommittees 

that address specific items within the other guideline document. For additional information 

regarding Human Subject Terms, see Appendix III. 

There are also revised guidelines for the inclusion of various populations in research designs. 

The modified policy can be found at http://ohrp.osophs.dhhs.gov/index.htm and reflects revision 

to the relevant standard language for RFAs, PAs, and RFPs and awards. These modifications 

require that applications, or protocols provide a description of plans to conduct analyses to 

address differences by sex/gender and/or racial/ethnic groups and that all investigators are to 

report accrual, and conduct and report analyses by sex/gender and/or racial/ethnic group 

differences. The results of the analyses must also be reported to NIH in Progress Reports, 

Competitive Renewal Applications (or Contract Renewals/Extensions) and in the Final Progress 

Report. 

In addition, for the purposes of generalizing research results and increasing the range of 

individuals who benefit from research, NIH is mandating the inclusion of women, children, and 

diverse ethnic groups in its funded applications. Applicants can check for the latest regulations at 

a new web site for Inclusion of Women and Minorities which can be found at 

http://grants.nih.gov/grants/funding/women_min/women_min.htm and contains the relevant 

documents. 

Overall, competitive applications involving human subjects must demonstrate an awareness of 

the most current ethical guidelines and address all of the possible ethical concerns of the planned 

study. Applicants should show that they have thought of the worse-case scenario, have taken 

proactive measures to prevent it, and have remedies in place to deal with it. Applications 

involving special populations, such as children or cognitively compromised individuals, must 

demonstrate the researcher’s ability to ethically and effectively work with the target population. 

Regardless of the particular human subject issues involved in the proposal, applicants can do 

much of the work on this section long before proposal submission. 

It is important to note that while investigators must include a discussion of these topics in their 

proposals, investigators do not necessarily have to include all groups in their research. There are 

occasionally scientifically acceptable reasons for study populations to be limited (e.g., women 

are not required to be included in clinical investigations of prostate cancer). It is not sufficient, 

however, to have limited representation in a study population due to difficulty or expense in 

accrual of these populations. 

Data Safety Monitoring 

If a clinical research trial is proposed, the applicant must specify plans for monitoring to insure 

the safety of participants. The type of monitoring depends on the size and complexity of the trial 

and on the degree of risk to participants. 
17

Phase I and Phase II studies require a Data and Safety Monitoring Plan (DSMP), which may be 

administered by the investigator, by a project manager, by a member of the NCI program staff, 

or by an individual designated by the investigator or NCI staff. Or, some combination of these 

individuals may work together to administer the plan. 

A Data and Safety Monitoring Board (DSMB) is required for all Phase III clinical trials. 

Phase III trials are tests of interventions which, if found to be successful, would likely influence 

clinical- or public-health practice. 

For more information about the topics to be included in the discussion of data and safety 

monitoring, see the NCI Data and Safety Monitoring Guidelines: Summary in Appendix IV. 

Investigational New Drug (IND) Applications: 

Current federal law requires that a drug be the subject of an approved marketing application 

before it is transported or distributed across state lines. Because a sponsor will probably want to 

ship the investigational drug to clinical investigators in many states, he/she must seek an 

exemption from that legal requirement. The IND is the means through which the sponsor 

technically obtains this exemption from the FDA. 

During a new drug's early preclinical development, the sponsor's primary goal is to 

determine if the product is reasonably safe for initial use in humans, and if the compound 

exhibits pharmacological activity that justifies commercial development. When a product is 

identified as a viable candidate for further development, the sponsor then focuses on collecting 

the data and information necessary to establish that the product will not expose humans to 

unreasonable risks when used in limited, early-stage clinical studies. 

Please review the FDA website for further information: 

http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm

Common Issues in Cancer CAM Applications: Suggestions for Applicants 

NCI’s Office of Cancer Complementary and Alternative Medicine program staff has identified 

some of the most common problems and weaknesses in cancer CAM grant proposals to the NCI. 

Specific suggestions to applicants are provided below. 

Tips for preparation: 

Contact program directors. Program directors are available for technical assistance as their 

schedules allow. Applicants are encouraged to submit concepts/abstracts of their projects to the 

program director so he or she may guide the applicant to the most appropriate grant mechanism 

and provide technical assistance when appropriate. 

Confirm appropriate mechanism. Applications need to be prepared with the review criteria in 

mind. Confirm budget limitations, page limitations and other requirements. Read and re-read 

announcements very carefully. Confirm receipt dates. 
18

Include essential sections and information. Include Human Subjects, Inclusion of Gender, 

Minorities and Children in research, and address Data Safety Monitoring. In the near future, 

applicants will also be instructed to address Data Sharing (for more information, see 

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html). 

Use state-of-the-science methodological designs appropriate for the cancer topic (e.g., 

appropriate immunology assays) as well as for the CAM component. NCI expects the highest 

quality science regardless of the CAM nature of these projects. 

Create the appropriate research team. Get the highest level of expertise and include letters 

confirming participation in the application. Make sure these consultants and co-investigators 

participate in the development of the proposal. 

Include experienced co-investigators and consultants on the research team to strengthen the 

proposal. By enlisting a consultant, you show the reviewers that you are aware of your scientific 

limitations and know where to find the appropriate expertise. Have the consultants participate in 

preparing the application. 

Demonstrate in writing the proposal that you know what you are doing. Convince the reviewers 

and NCI that you are also aware of limitations and that you have the appropriate expertise to 

guide you. Identify the review committee, if possible. IRGs are listed on the Center for Scientific 

Review (CSR) website at http://www.csr.nih.gov/studysec.htm. Special Emphasis Panels (SEPs) 

are created as needed, but whenever possible, applicants should familiarize themselves with the 

range of expertise on review committees and write the grant proposal with this audience in mind. 

Tie the proposal to the research priorities of the NCI. Review the most recent NCI Budget 

Document for identified areas of interest (The National Cancer Institute, The Nation’s 

Investment in Cancer Research, A Budget Proposal for Fiscal Year 2003. Copies can be ordered 

by fax at 301-330-7968, by email at cisocc@nih.gov or by telephone at 1-800-4-CANCER. 

These documents may also be viewed online at http://www.nci.nih.gov). 

Investigate the necessity for filing an IND application with the Federal Drug Administration 

(FDA). Contact FDA or NCI program staff for information or appropriate referral for 

information. Just because a natural product or dietary supplement is available “over the counter” 

does not necessarily mean that a product is exempt from IND regulations in a research proposal. 

Inclusion criteria for the presence of the dependent variable in the study population should be 

included. This is especially an issue for research in cancer symptom management. It is essential 

to document that the study population experiences whatever is the focus of the study. 

Write the proposal for the appropriate funding mechanism and remind the reviewers of this 

mechanism. If the proposal describes a developmental project, remind the reviewers, who are 

more frequently reviewing R01 studies, by using that language in the text. Include information 

on where this project will go next. Suggesting a “larger trial” will follow is typically not 

sufficient. Describe how this project fits into a research program, how it moves the science 
19

forward, and how the developmental project answers specific issues that need to be addressed 

prior to a larger R01 investigation. Give the reviewers some sense of what the R01 will look like. 

When preparing the application, it is important to clearly define the timeline. Past studies that 

have been performed and their timelines can be used to strengthen your proposal. Applicants 

should clearly state specific project activities at key points in the project timeline. These 

activities should coincide with your budget development. 

Justify the requested funding and provide a comprehensive picture of the current state-of-thescience and what more is needed to support further research on your proposed topic. 

Applications that reflect the input of expert statisticians are clearly evident to reviewers.

Including a statistician in the development of a proposal strengthens its competitiveness. 

Have a colleague that is unfamiliar with your topic read your application. This objective review 

will prevent you from making assumptions in your proposal that are not clearly stated. You know 

what you are planning to do, but this helps ensure that someone reading your application will 

also know what you are planning to do. 

Don’t leave anything open for interpretation. Be very clear and concise. 

When developing a research proposal, carefully consider your choice of intervention and 

provide a compelling rationale for your choice. Include a discussion of the data and potential 

theories supporting your hypotheses. Also address the issues that may not support the research so 

you can effectively present the case for the value of the proposed research. 

Carefully consider your study population. Your application should include a compelling 

rationale for the use of this intervention in this specific study population. 

Applicants should address potential safety issues when CAM products and interventions are 

proposed for clinical research. Specific information should be included that addresses potential 

toxicities as well as concerns when using CAM in combination with conventional cancer 

therapies. The addition of CAM modalities in treatment should not compromise the safety and 

efficacy of conventional cancer therapy. 

Submission 

Cover Letters: 

Approval from program staff is needed for applications requesting over $500,000 in direct costs. 

NIH policy requires that any competing application (new, continuation, revised, supplement) 

requesting over $500,000 in direct costs in any year must be accepted by an Institute or Center 

prior to assignment for review. For more information, visit 

(http://grants/nih.gov/grants/guide/notice-files/not98-030.html). 

Upon receipt, each application is assigned to one Program Director. The Center for Scientific 

Review assigns the application to an Institute or Center and to a Initial Review Group (IRG) or 

Special Emphasis Panel (SEP). The Institute or Center’s referral personnel will then assign the 
20

application to the appropriate program. Applicants may request in a cover letter the assignment 

of the application to a particular Institute and/or IRG. These requests are taken into consideration 

by CSR. Applicants may also request secondary assignment of their application. This enables the 

applicant to be considered for funding by more than one Institute. The Program Director may 

help identify appropriate Institutes for secondary assignment. In the case of cancer CAM 

applications, several Institutes may be listed as secondary assignments as well. Program 

Directors may also assist in identifying appropriate review committees for cancer CAM 

applications. 

Applicants who have received assistance in their grant preparation or who have contacted 

program staff for approvals prior to submissions (i.e. budget limitations) should also mention in 

their cover letter the program staff member by name and provide that person’s contact 

information. When appropriate, applicants may include in their cover letter requests for specific 

review expertise. Especially in cancer CAM topics, it may be helpful for applicants to identify 

certain areas of expertise and request ad hoc reviewers if necessary. 

Instructions for Submission: 

Unless stated otherwise, applications must be sent to the Center for Scientific Review (CSR) and 

on the appropriate application form (usually the PHS398). (For additional information on this 

process and submission details, please refer to http://grants.nih.gov/grants/funding/phs398/ 

phs398.html). It is important to refer to the CSR website for notification of changes in 

procedures or policies in grant submissions. 

Applicants need to submit the materials in one package by the due date specified in the 

announcement or the regular receipt dates. If an applicant is responding to a specific 

announcement (RFA, PA, etc.), it is important to indicate the announcement on the face page of 

the application. 

There may be additional instructions for submission of responses to Requests for Applications. 

Applicants submitting Investigator-Initiated Interactive Research Project Grant (IRPG) 

applications should include all of the applications and appendix material in one package with a 

cover letter identifying the applications as such. 

Receipt, Assignment and Review 

The Public Health Service receipt, review, and award schedule is provided in Appendix II. 

Applicants are strongly encouraged to confirm receipt dates with program staff. 

Submit a complete application. Incomplete applications will be grounds for the application to be 

without peer review. An application will be returned if it is illegible, if the instructions were not 

followed, or if the material presented is insufficient to permit an adequate review. 

Unless specifically required by these instructions (e.g., vertebrate animals certification), do not 

send supplementary or corrective material after the receipt date unless the Scientific Review 

Administrator (SRA) of the Scientific Review Group solicits or agrees to accept this information. 

The application must be complete and accurate at the time of submission because there is no 

guarantee that the peer reviewers will consider late material. 
21

Submission of identical applications to different agencies within the PHS or to different 

Institutes within an agency is not allowed. Essentially identical applications will not be reviewed 

except for: 1) individuals submitting an application for an Independent Scientist Award (K02) 

proposing essentially identical research in an application for an individual research project; and 

2) individuals submitting an individual research project identical to a subproject that is part of a 

program project or center grant application. 

Application Assignment Information 

As soon as possible after the receipt date, usually within six weeks, the CSR will send the 

principal investigator/program director and the applicant organization the application's 

assignment number; the name, address, and telephone number of the Scientific Review 

Administrator of the SRG to which the application has been assigned; and the assigned Institute 

contact and phone number. 

All inquiries regarding the assignment, review, or recommendation on funding of applications 

are to be made only to NIH officials. It is inappropriate to contact consultants serving on 

advisory or review committees regarding these issues. 

The Peer Review Process 

Competing grant applications submitted to the NIH must be submitted through the Division of 

Receipt and Referral, CSR, NIH unless otherwise stated. Administrative information about the 

application is entered into a computer system. The application is then assigned to the appropriate 

SRG and Institute(s). Assignment is based on the scientific content of the application using 

established referral guidelines. 

Most applications submitted to the CSR will be reviewed through a two-tier system. The first 

level of review will be performed by an SRG, often called a study section or review committee. 

The purpose of the SRG is to evaluate the scientific and technical merit of applications. The SRG 

does not make funding decisions. 

SRG members will be instructed to evaluate research applications by addressing five review 

criteria (see below) and assigning a single, global score for each scored application. The score 

will reflect the overall impact that the proposed research could have on the field based on 

consideration of the following NIH research evaluation criteria. RFAs and other types of grants 

may have different and/or additional review criteria. It is important to carefully read the RFA or 

other announcement for any specific review criteria for that announcement. 

Note: Applicants must never contact reviewers regarding their applications since discussion of 

the scientific content of an application or an attempt to influence review outcome will constitute 

a conflict of interest in the review. Reviewers are required to notify the SRA if they are contacted 

by an applicant. Communication by the applicant to a reviewer will result in the return of the 

application without peer review. 
22

Research Project Evaluation Criteria 

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? It is important when describing a CAM or CAM-related 

intervention to address its potential significance in terms of scientific knowledge or potential 

improvements in clinical practice beyond what may be available in conventional Western 

medical approaches. For example, reviewers may questions whether studying acupuncture would 

be compelling if it is used for an outcome for which there is an inexpensive, safe and effective 

conventional treatment already in use. 

Approach 

Are the conceptual framework, design, methods, and analyses adequately developed, wellintegrated, 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? In cancer CAM topics, novel concepts are not difficult to identify. However, 

presenting a compelling rationale for the use of the novel CAM approach to a specific research 

problem is important to include in grant proposals. 

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)? In cancer CAM, it is often necessary to seek out consultants and, in clinical research, 

practitioners. Program staff can assist in identifying expertise and providing opportunities for 

networking. Applicants that have identified the strengths of investigators and sought out 

appropriate expertise by including appropriate consultants and practitioners are often more 

competitive in the review process. 

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? 

While these review criteria are intended for use primarily with unsolicited research project 

applications (e.g., R01, P01), to the extent reasonable, they will also form the basis for the 

review of solicited applications and non-research activities. Additional review criteria may be 

listed in specific announcements. 

Human Subjects/Vertebrate Animals 

In conducting peer review for scientific and technical merit, SRGs will also evaluate the 

involvement of human/animal subjects and proposed protections from research risk relating to 
23

their participation in the proposed research plan according to the following four review criteria: 

(1) risk to subjects; (2) adequacy of protection against risks; (3) potential benefits of the 

proposed research to the subjects and others; and (4) importance of the knowledge to be gained. 

When human subjects are involved in the proposed clinical research, the SRG will also evaluate 

the proposed plans for inclusion of minorities and members of both sexes/genders, as part of the 

scientific assessment of Approach criterion. The evaluation will be factored into the overall score 

for scientific and technical merit of the application. 

Dual-Level Peer Review 

As part of the initial merit review, all applicants will receive a written critique based on the 

comments and recommendations of the SRG. The review of most research applications will also 

include 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. 

The second level of review will usually be performed by the Advisory Council or Board of the 

potential awarding component (Institute, Center, or other unit). Council or Board 

recommendations are based not only on considerations of scientific merit, as judged by the 

SRGs, but also on the relevance of the proposed study to an Institute's programs and priorities. 

The review criteria can be found on the NIH Web site, http://grants.nih.gov/grants/peer/peer.htm

or obtained from GrantsInfo, (301) 435-0714, Email: GrantsInfo@nih.gov. 

Most common critiques for R21 applications in cancer CAM: 

NCI’s OCCAM program staff have attended as many review committee meetings of cancer 

CAM proposals as possible. Based upon this experience, the most common critiques from review 

committees of R21 cancer CAM grant proposals are presented below. 

Too ambitious: The applicant is proposing too many Specific Aims to accomplish within the 

constraints of the funding mechanism.

Inadequate budget: The applicant has not included an appropriate budget for the proposed 

study. This critique is common when an applicant’s Specific Aims are too numerous or complex 

for the constraints of the funding mechanism. 

Needs additional expertise: The applicant failed to identify areas of weakness and develop an 

appropriate research team. 

Weak statistics section: The application does not reflect the input of an experienced 

statistician. Often these applications lack an appropriate power analysis for the proposed design. 

Unclear or poorly written: The proposal has spelling errors, or inconsistent details throughout 

application. This often results from applicants copying sections of their proposals from other 

documents and inserting them into the proposals. 
24

Lack of detail: The application does not include enough information for reviewers to understand 

what is proposed and how it will be accomplished. 

Lack of natural products characterization: The applicant has failed to include enough 

information about the chemical characterization of a natural product or adequate information 

about the source and quality of a product to be used in the research. 

CAM intervention design issue: The applicant did not include a compelling rationale for the 

use of an individualized or standardized approach to CAM intervention or other methodological 

issues. 

Conventional design issue: The proposal includes too many measures or too many variables 

to complete the study as proposed and/or to result in meaningful data. 

Missing or inappropriate control group: Applicant did not include a compelling rationale for 

the placebo or control condition. This is an issue in preclinical as well as clinical research in 

cancer CAM. 

After Review 

Applications that are judged to be competitive (usually those in the top half of the scoring range), 

are assigned a priority score that ranges from 100 to 500 and, if reviewed by a CSR committee, 

given a percentile. The score represents a “raw” number; the percentile puts the score in the 

context of the overall voting pattern of that committee. Applications that are reviewed by Special 

Emphasis Panels are only given a priority score. All applicants are notified of their score (and 

percentile if appropriate) and are sent a summary statement of the critique and discussion of the 

review committee (sometimes called the “pink sheet”). 

Feedback to applicants is very important. Once the principal investigator receives the summary 

statement, s/he may contact the appropriate Program Director (noted on the summary statement) 

for an interpretation of the reviews and the disposition of the application. In addition, program 

directors typically make every effort to attend review meetings in person and can assist 

investigators through the revision process as well. 

It is important to note that there is a two-year and two-amendment limitation: the number of 

revisions of an application is limited to two, which must be submitted within two years of the 

original version of the application (see http://grants.nih.gov/grants/guide/notice-files/not97-

011.html) Revised applications must include an Introduction that discusses the previous review 

and should mark the text to show where changes have been make. For more details on 

requirements related to application revisions see: 

http://grants.nih.gov/grants/funding/phs398/section_1.html#intro_revised
25

SUMMARY 

In summary, applications to NIH featuring cancer CAM must meet all general criteria required of 

any application. NIH instructions should be followed carefully. Program staff should be contacted 

for questions and assistance during application development. Do not wait until the time of 

submission. The applicant should consult program announcements and descriptions for guidance on 

content. The research plan described in the application must lay out a systematic plan of research 

and clearly specified data collection and analytic procedures. All sections of the plan should be 

clearly related to each other. The plan should flow directly from the specific aims, with direct 

discussion of how each aim will be achieved through particular data collection and specific 

analyses. It is highly recommended that this section be distributed to experienced reviewers 

(successful NIH grant writers) for comment and revision prior to grant submission. The section 

should be revised and re-written multiple times to remove all identifiable ambiguities and to be 

certain that all procedures are clearly and precisely laid out. Finally the entire product should 

present a coherent, clear and well-documented argument for the importance of conducting this 

particular research in the particular method specified. 
26

APPENDIX I 

Budget Mechanisms 

http://www3.cancer.gov/admin/gab/index.htm

The NCI's budget is organized according to the following nine major funding areas: 

• Research Project Grants. 

• Cancer Centers and Specialized Programs of Research Excellence. 

• Other Research Grants. 

• Training. 

• R&D Contracts. 

• Intramural Research. 

• Research Management and Support. 

• Cancer Prevention and Control. 

• Construction. 

The following section, organized in the order outlined above, details each of the funding 

mechanisms used by the NCI. 

Research Project Grants 

Research Project Grants are awards for investigator-initiated research proposals. Several types of 

awards are made in this category, which vary in of the type of mechanism, type of applicant, 

total amount of support, and of length of time. Fiscal year 2001 research project grant 

expenditures totaled $1,696,603,000 accounting for 45.2 percent of the NCI budget. 

P01 Research Program Project Grant 

Research Program Project Grants (P0ls) support an integrated, multiproject research approach 

involving a number of independent investigators who share knowledge and common resources. 

A P0I has a defined central research focus involving several disciplines or several aspects of one 

discipline. Each individual project should contribute or be directly related to the common theme 

of the total research effort, thus forming a system of research activities and projects directed 

toward a well-defined research program goal. 

R01 Research Project Grant 

Research Project Grants (R01s) support a discrete, specified research project to be performed by 

the named investigator(s) in an area representing his/her specific interest and competencies. This 

is generally referred to as a traditional research project grant. 

R03 Small Research Grant 

Small Research Grants (R03s) provide research support specifically limited in time and amount 

for studies in categorical program areas. Small research grants provide flexibility for initiating 

studies that are generally for preliminary short-term projects. These grants are non-renewable. 

R21 Exploratory/Developmental Grant 

Exploratory/Development Grants (R21s) support the development of new research activities in 

categorical program areas. Support generally is restricted in level of support and in time. 
27

R29 First Independent Research Support and Transition (FIRST) Award 

FIRST Awards (R29s) provide a sufficient initial period of research support for newly 

independent biomedical investigators to develop their research capabilities and demonstrate the 

merit of their research ideas. This award mechanism is in the process of being phased out. 

R33 Exploratory/Developmental Grant-Phase II 

Phase II of the Exploratory/Development Grants (R33s) provide a second phase for the support 

for innovative, exploratory, and developmental research activities initiated under the R21 

mechanism. 

R35 Outstanding Investigator Grant (OIG) 

OIGs (R35s) provide long-term support to encourage experienced investigators with an 

outstanding record of research productivity to embark on long term projects of unusual potential 

in a categorical program area. This award mechanism is in the process of being phased out. 

R37 Method to Extend Research in Time (MERIT) Award 

MERIT Awards (R37s) provide long-term grant support to investigators whose research 

competence and productivity are distinctly superior and who are highly likely to continue to 

perform in an outstanding manner. Investigators may not apply for a MERIT Award. After initial 

review, NCI staff and the National Cancer Advisory Board review competing R01 applications 

to select MERIT awardees. An initial five-year MERIT Award is followed by an opportunity for 

an extension of one to five more years, based on an expedited review of the accomplishments 

during the initial period. 

R41 Small Business Technology Transfer (STTR) Grant—Phase I 

Phase I STTR Grants (R41s) support cooperative research and development projects between 

small domestic for-profit organizations and research institutions. R41s are limited in time and 

amount and are used to establish the technical merit and feasibility of ideas that have a potential 

for commercialization. Generally, support for Phase I STTR awards may not exceed $100,000

for direct and indirect costs and a fixed fee for a period normally not to exceed one year. Note: 

Phase I award levels and project periods are statutory guidelines. Therefore, applicants are 

encouraged to propose a budget and project that is appropriate for completion of the research 

project. Deviations from the guidelines must be well justified. 

R42 Small Business Technology Transfer (STTR) Grant—Phase II 

Phase II STTR Grants (R42s) support in-depth development of cooperative research and 

development projects between small domestic for-profit organizations and research institutions, 

limited in time and amount, for which feasibility has been established in Phase I (R41) and 

which have potential for commercialization. Generally, support for Phase II awards may not 

exceed $500,000 for direct and indirect costs and a fixed fee for a period normally not to exceed 

two years. Note: Phase II award levels and project periods are statutory guidelines. Therefore, 

applicants are encouraged to propose a budget and project that is appropriate for completion of

the research project. Deviations from the guidelines must be well justified. 
28

R43 Small Business Innovation Research (SBIR) Grant—Phase I 

Phase I SBIR Grants (R43s) support research efforts by for-profit domestic small businesses. The 

objective of this phase is to establish the technical merit and feasibility of proposed research or 

research and development (R&D) efforts and determine the quality of performance of the small 

business awardee organization prior to providing further Federal support in Phase II (R44). 

Generally, support for Phase I awards may not exceed $100,000 for direct and indirect costs and 

a fixed fee for a period normally not to exceed six months. Note: Phase I award levels and 

project periods are statutory guidelines. Therefore, applicants are encouraged to propose a budget 

and project that is appropriate for completion of the research project. Deviations from the 

guidelines must be well justified. 

R44 Small Business Innovation Research (SBIR) Grant—Phase II 

Phase II SBIR Grants (R44s) continue those R&D efforts started in Phase I (R43). Awards will 

be based on the results of Phase I and the scientific and technical merit and commercial potential 

of the Phase II application. Only Phase I awardees are eligible for Phase II. Generally, support 

for Phase II may not exceed $750,000 for direct and indirect costs and a fixed fee for a period 

normally not to exceed two years. Note: Phase II award levels and project periods are statutory 

guidelines. Therefore, applicants are encouraged to propose a budget and project that is 

appropriate for completion of the research project. Deviations from the guidelines must be well 

justified. 

R55 James A. Shannon Director's Award 

Shannon Awards (RS5s) provide a limited award to investigators to further develop, test, and 

refine research techniques; perform secondary analysis of available data sets; test the feasibility 

of innovative and creative approaches; and conduct other discrete projects that can demonstrate 

their research capabilities and lend additional weight to their already meritorious applications. 

U01 Research Project Cooperative Agreement 

Cooperative Agreements (U01s) support discrete, specified, circumscribed projects to be 

performed by the named investigator(s) in an area representing their specific interest and 

competencies. This mechanism is utilized when substantial programmatic involvement is 

anticipated between the NCI and the recipient during performance of the contemplated activity. 

U19 Research Program Cooperative Agreement 

Research Program Cooperative Agreements (U19s) support research programs that have multiple 

projects directed toward a specific major objective, basic theme, or program goal, requiring a 

broadly based multidisciplinary and often long-term approach. Substantial Federal programmatic 

staff involvement is intended to assist investigators during performance of research activities, as 

defined in the terms and conditions of award. This mechanism can provide support for certain 

basic shared resources, including clinical components, which facilitate the total research effort. 

U43 Small Business Innovation Research (SBIR) Cooperative Agreement—Phase I 

(see R43) 

Phase I SBIR Cooperative Agreements (U43s) support projects, limited in time and amount, to 

establish the technical merit and feasibility of research and development (R&D) ideas that may 
29

ultimately lead to commercial products or services. This mechanism is utilized when an 

assistance relationship will exist between the NCI and a recipient and in which substantial 

programmatic involvement is anticipated between the NCI and the recipient during performance 

of the contemplated activity. Cooperative agreement applications will be considered only for the 

topics specifically listed in the current SBIR Omnibus Solicitation. Note: Phase I award levels 

and project periods are statutory guidelines. Therefore, applicants are encouraged to propose a 

budget and project that is appropriate for completion of the research project. Deviations from the 

guidelines must be well justified. 

U44 Small Business Innovation Research (SBIR) Cooperative Agreement—Phase II 

(see U43 and R44) 

Phase II SBIR Cooperative Agreements (044s) support in-depth development of R&D ideas for 

which feasibility has been established in Phase I (U43) and that are likely to result in commercial 

products or services. Note: Phase II award levels and project periods are statutory guidelines. 

Therefore, applicants are encouraged to propose a budget that is appropriate for completion of 

the research project. Deviations from the guidelines must be well justified. 

Cancer Centers and Specialized Programs of Research Excellence 

The Cancer Research Centers Program as a whole contains a great diversity of research 

approaches to the problem of cancer, incorporating all applicable disciplines. Fiscal year 2001 

Cancer Research Centers Program expenditures totaled $279,731,000, accounting for 7.5 percent 

of the NCI budget. 

P20 Planning Grant 

Planning Grants (P20s) support planning for new programs, expansion or modification of 

existing resources, and feasibility studies for new approaches. Such awards have been 

particularly useful in the development of cancer centers and SPORES. 

P30 Cancer Center Support Grant 

Cancer Center Support Grants (P30s) provide support primarily for the research infrastructure of 

an active and unified cancer center for the purpose of consolidating and focusing cancer-related 

activities, increasing research productivity, promoting shared use of research resources and 

improved quality control, stimulating and promoting interdisciplinary and collaborative research, 

and increasing the rate at which research discoveries are translated into medical benefits. 

P50 Specialized Center Grant 

Specialized Center Grants (P50s) support any part of the full range of research and development 

from very basic to clinical activities and may involve ancillary supportive activities such as 

protracted patient care necessary to the primary research or R&D effort. The spectrum of 

activities comprises a multi-disciplinary attack on cancer. These grants differ from Program 

Project Grants in that they are usually developed in response to an announcement of the 

programmatic needs of the NCI and later receive continuous attention from its staff. Centers may 

also serve as regional or national resources for special research purposes. 
30

U54 Specialized Center—Cooperative Agreement 

Specialized Center Cooperative Agreements (U54s) support any part of the full range of research 

and development from very basic to clinical; may involve ancillary supportive activities such as 

protracted patient care necessary to the primary research or R&D effort. The spectrum of 

activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem 

area. These differ from program project in that they are usually developed in response to an 

announcement of the programmatic needs of an Institute or Division and subsequently receive 

continuous attention from its staff. Centers may also serve as regional or national resources for 

special research purposes, with funding component staff helping to identify appropriate priority 

needs. At the NCI, U54s support comprehensive partnerships between Minority Serving 

Institutions (MSIs) and the NCI-designated Cancer Centers for the benefit of both. These 

partnerships focus on cancer research and one or more target areas in cancer research training or 

cancer research career development at the MSI. These partnerships may also focus on cancer 

research and target areas in cancer education for or cancer outreach to minority communities. 

Other Research Grants 

Other grants include the Research Career Program and all other research grants not included in 

Research Project Grants, Research Centers, and/or Cancer Prevention and Control except for 

National Research Service Awards. The NCI Research Career Program includes all "K" awards. 

Fiscal year 2001 other research expenditures totaled $269,201,000, accounting for 7.2 percent of 

the NCI budget. 

K01 Mentored Research Scientist Development Award 

Mentored Research Scientist Development Awards (K01s) provide research scientists with an 

additional period of sponsored researd1 experience as a way to gain expertise in a research area 

new to the applicant or in an area that would demonstrably enhance the applicant's scientific 

career. NCI supports two K01 awards: the Howard Temin Award and the Mentored Career 

Development Award. 

K05 Senior Scientist Award 

Senior Scientist Awards (K05s) support outstanding established scientists who have 

demonstrated a sustained, high level of productivity, research accomplishments and contributions 

to cancer prevention, control and population sciences research. These awards provide protected 

time to devote to research and to act as mentors for young investigators. 

K07 Academic Career Award 

Academic Career Awards (K07s) support more junior candidates who are interested in 

developing academic and research expertise in a specific area or to support more senior 

individuals with acknowledged scientific expertise and leadership skills who are interested in 

improving the curricula and enhancing the research capability within an academic institution. 

K08 Mentored Clinical Scientist Development Award 

Mentored Clinical Scientist Development Awards (K08s) support the development of 

outstanding clinical research scientists. These awards provide specialized study for clinically 

trained professionals who are committed to a career in research and have the potential to develop 
31

into independent investigators. NCI provides support for the K08 through the Clinical 

Investigator Award and the Minorities in Clinical Oncology Award. 

K12 Mentored Clinical Scientist Development Program Award 

Mentored Clinical Scientist Development Program Awards (K12s) support newly trained 

clinicians appointed by an institution for development of independent research skills and 

experience in a fundamental science within the framework of an interdisciplinary research and 

development program. 

K22 Career Transition Award 

Transition Awards (K22s) support newly trained basic or clinical investigators to develop their 

independent research skills through a two-phase program – an initial period involving an 

intramural appointment at NIH and a final period of support at an extramural institution. The 

award is intended to facilitate the establishment of a record of independent research by the 

investigator in order to sustain or promote a successful research career. The NCI supports two 

K22 awards: the Scholars Program and the Transition Development Award. The NCI Scholars 

Program provides an opportunity for new investigators to begin independent research careers 

first intramurally within the special environment of the NCI and then to continue their careers 

extramurally at an institution of their choice. The NCI Transition Career Development Award is 

a fully portable mechanism that facilitates the transition of talented clinician cancer scientists, 

clinicians in patient-oriented cancer research and researchers in cancer prevention, control and 

the population sciences from the mentored stage of their careers to junior faculty or equivalent. 

K23 Mentored Patient-Oriented Research Career Development Award 

Mentored Patient-Oriented Research Career Development Awards (K23s) provide support for 

the career development of investigators who focus their research endeavors on patient-oriented 

research. The mechanism provides support for a period of supervised study and research for 

clinically trained professionals who have the potential to develop into productive clinical 

investigators 

K24 Mid-Career Investigator in Patient-Oriented Research Award 

Mid-Career Investigator in Patient-Oriented Research Awards (K24s) provide clinicians the 

opportunity to dedicate time for patient-oriented research and to mentor other clinical 

investigators. 

K25 Mentored Quantitative Research Career Development Award 

Mentored Quantitative Research Career Development Awards (K25s) support the career 

development of investigators with quantitative scientific and engineering backgrounds outside of 

biology or medicine who have made a commitment to focus their research endeavors on 

behavioral and biomedical research (basic or clinical). 

K30 Institutional Curriculum Award 

Institutional Curriculum Awards (K30s) support the development, conduct, and evaluation of the 

curriculum designed to improve the quality of the training available to aspiring clinical 

investigators. 
32

R13 Conference Grant 

Conference Grants (RI3s) support national or international meetings, conferences, and 

workshops that are of value in promoting the goals of the National Cancer Program. 

R15 Academic Research Enhancement Award (AREA) 

AREA Grants (RI5s) support small scale research projects conducted by faculty in primarily 

baccalaureate degree-granting domestic institutions. Awards are for up to $75,000 in direct costs 

(plus applicable indirect costs) for periods not to exceed 36 months. 

R24 Resource-Related Research Project 

Resource-Related Research Projects (R24s) support research projects that will enhance the 

capability of resources to serve biomedical research. 

R25 Cancer Education Grant 

Cancer Educations Grants (R25s) support the development and implementation of programs 

related to education, information provision, training, technical assistance, coordination, or 

evaluation. The NCI supports two distinct Cancer Education programs: the Cancer Education 

and Career Development Program and the Cancer Education Grant Program (CEGP). The NCI 

Cancer Education and Career Development Program (R25T) is an institutional grant program 

that supports the development and implementation of curriculum- dependent programs to train 

predoctoral and postdoctoral candidates in cancer research settings that are highly interdisciplinary and collaborative. The NCI Cancer Education Grant Program (CEGP) is a flexible, 

curriculum-driven program aimed at developing and sustaining innovative educational 

approaches that ultimately will reduce cancer incidence, mortality and morbidity, as well as on 

improving the quality of life of cancer patients. The CEGP awards (R25Es) address a need that is 

not fulfilled adequately by any other grant mechanism available at NIH. These awards are 

dedicated to areas of particular concern by the NCI. 

S06 Minority Biomedical Research Support (MBRS) 

Minority Biomedical Research Support (MBRS) grants provide funds to strengthen the 

biomedical research and research training capability of ethnic minority institutions, thus creating 

a more favorable milieu for increasing the involvement of minority faculty and students in 

biomedical research. 

T09 Scientific Evaluation 

Scientific Evaluation awards (T09s) provide the chairman of a training committee funds for 

operation of a review group. 

U09 Scientific Review and Evaluation (Cooperative Agreement) 

Scientific Review and Evaluation Cooperative Agreements (U09s) provide the chairman of an 

Initial Review Group (IRG) funds for operation of the IRG. 

U10 Clinical Research Cooperative Agreement 

Clinical Research Cooperative Agreements (U10s) support clinical evaluations of various 

methods of therapy and/or prevention in specific disease areas. These represent cooperative 
33

programs between sponsoring institutions and participating principal investigators, and are 

usually conducted under established protocols. 

U13 Conference Cooperative Agreement 

Conference Cooperative Agreements (U13s) support international, national, or regional 

meetings, conferences, and workshops where substantial programmatic NCI staff involvement is 

planned to assist the recipients. 

U24 Resource-Related Research Project Cooperative Agreement 

Resource-Related Research Project Cooperative Agreements (U24s) support projects 

contributing to the improvement of the capability of resources to serve biomedical research. 

U56 Exploratory Grant -Cooperative Agreement 

Exploratory Grant Cooperative Agreements (U56s) support planning for new programs, 

expansion or modification of existing resources, and feasibility studies to explore various 

approaches to the development of interdisciplinary programs that offer potential solutions to 

problems of special significance to the mission of the NIH. These exploratory studies may lead 

to specialized or comprehensive centers. Substantial Federal programmatic staff involvement is 

intended to assist investigators during performance of the research activities, as defined in the 

terms and conditions of award. 

Training 

The National Research Service Award (NRSA) is the major mechanism for providing long-term, 

stable support for a wide range of promising scientists and research clinicians. Fiscal year 2001 

NRSA expenditures totaled $57,927,000, accounting for 1.5 percent of the NCI budget. 

F31 Predoctoral Individual National Research Service Award 

Predoctoral Individual National Research Service Awards (F31s) provide predoctoral individuals 

with supervised research training in specified health and health-related areas leading toward the 

research degree (e.g., Ph.D.). 

F32 Postdoctoral Individual National Research Service Award 

Postdoctoral Individual National Research Service Awards (F32s) provide postdoctoral research 

training to individuals to broaden their scientific background and extend their potential for 

research in specified health-related areas. 

F33 National Research Service Award for Senior Fellows 

National Research Service Awards for Senior Fellows (F33s) provide opportunities for 

experienced scientists to make major changes in the direction of research careers, broaden 

scientific background, acquire new research capabilities, enlarge command of an allied research 

field, or take time from regular professional responsibilities for increasing capabilities to engage 

in health- related research. 

T32 Institutional National Research Service Award 

Institutional National Research Service Awards (T32s) support training opportunities at the 

predoctoral or postdoctoral level at qualified institutions. Applicants must have the staff and 
34

facilities for the proposed program. After the award is made, the institution's training program 

director is responsible for selecting the trainees and for administering the program. This program 

does not support residencies. 

T36 MARC Ancillary Training Activities (Grant) 

Minority Access to Research Careers (MARC) Ancillary Training Activities Grants (T36s) 

increase the number of well-trained minority scientists in biomedical disciplines and to 

strengthen the research and teaching capabilities of minority institutions. The NCI cofunds these 

grants with the National Institute of General Medical Sciences. 
35

APPENDIX II 

Receipt, Review, and Award Cycles 

(http://grants.nih.gov/grants/funding/phs398/section_2.html#number) 

Receipt, Review, and Award Cycles 

Types of Applications Cycle I Cycle II Cycle III 

Application Receipt Dates 

Institutional National Research Service 

(NRSA) Awards 

All new, competing continuations, 

supplements and revised applications 

January 10 May 10 September 10 

Academic Research Enhancement Award 

(AREA) 

(All new, competing continuations, and 

revised applications) 

January 25 May 25 September 25 

New Research Grants, Conference 

Grants and Research Career Awards 

February 1 June 1 October 1 

Program Project Grants and Center 

Grants 

All new, competing continuations, 

supplements and revised applications)

February 1 June 1 October 1 

Interactive Research Project Grants 

(IRPGs) 

February 15 June 15 October 15 

Competing Continuation and 

Supplemental Grants 

Revised Research and Conference 

Grants, Research Career Awards 

March 1 July 1 November 1 

Small Business Innovation Research 

(SBIR), Small Business Technology 

Transfer (STTR) Grants 

(All new, supplements, and revised 

applications) 

April 1 August 1 December 1 

AIDS-Related Grants 

(All new, competing continuations, 

supplements and revised applications) 

May 1 September 1 January 2 

Review and Award Schedule 

Scientific Merit Review June–July October–

November 

February–

March 

Advisory Council Review September–

October 

January–

February 

May–June 

Earliest Project Start Date December April July 

Note: Several Institutes/Centers use only one or two of the receipt dates for institutional NRSA awards. Please check 

the program announcement, which is available at http://grants.nih.gov/training/nrsa.htm. 

For specialized grant applications, consult with the appropriate PHS awarding component prior to the preparation of 

an application. 
36

APPENDIX III 

Glossary of Terms for Human Subject Requirements 

(http://www.vrc.nih.gov/ncn/clinical/decisiontrees/hsgloss.htm) 

Decision Tree How to Write a Human Subjects Application 

Terms Defined: 

American Indian or Alaska Native Institutional Assurance of Protection for 

Analysis 

Assurance, Institutional Assurance of 

Protection for Human Subjects 

Human Subjects 

Majority Group 

Minimal Risk 

Black or African American Minority Group 

Certification, IRB Native Hawaiian or Other Pacific Islander 

Child NIH-Defined Phase III Clinical Trial 

Clinical Research Outreach Strategies 

Clinical Trial Racial and Ethnic Categories 

Clinical Trial NIH-Defined Phase III Scientifically Acceptable or Unacceptable 

Exemption Categories Significant Difference 

Gender Subpopulations 

Hispanic or Latino Valid Analysis 

Human Subject White 

Human Subjects Concern Women, see Gender 

IRB Certification 

American Indian or Alaska Native 

A person having origins in the original peoples of North, Central, or South America who 

maintains tribal affiliation or community. 

Analysis 

NIH requirements for analysis plans depend on the type of research proposed. They may include 

monitoring to detect and address adverse effects of the research as well as the ability to detect 

intervention differences among different types of human subjects, for example women and 

minorities, ethnic or racial subgroups, and children. Requirements also differ depending on the 

risk and complexity of the study and the probability of finding differences in the intervention 

effect for participant subgroups. For grantees, renewal applications (as well as contract 

proposals) must include the results of such subgroup analyses. See also valid analysis. 

Asian 

A person having origins in the original peoples of the Far East, Southeast Asia, or the Indian 

subcontinent including, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the 

Philippine Islands, Thailand, and Vietnam. 

Assurance, Institutional Assurance of Protection for Human Subjects 

See Institutional Assurance of Protection for Human Subjects. 
37

Black or African American 

A person having origins in the black racial groups of Africa. “Haitian” or “Negro” can be used in 

addition to “Black” or “African American.” 

Certification, IRB 

See IRB Certification. 

Child 

A person under age 21. 

Clinical Research 

Research conducted on human subjects or on material of human origin identifiable with the 

source person. Policy covers large and small-scale, exploratory, and observational studies. There 

are three types: 

1. Patient-oriented research -mechanisms of disease, therapeutic interventions, clinical trials, 

development of new technologies 

2. Epidemiologic and behavioral studies 

3. Outcomes research and health services research 

Training grants (T32) are exempt, but all projects to which trainees are assigned must comply 

with policies on inclusion of women and minorities. 

Clinical Trial 

For applications submitted to NIH, a prospective study of human subjects designed to answer 

questions about biomedical or behavioral interventions, e.g., drugs, treatments, devices, or new 

ways of using known treatments, to determine whether they are safe and efficacious. 

Phase I tests a new biomedical or behavioral intervention in a small group of people (20-80) for

the first time to evaluate its safety, e.g. determine a safe dosage range and identify side effects. 

Phase II studies the intervention in a larger group of people, usually several hundred, to 

determine efficacy and further evaluate safety. 

Phase III studies the efficacy of the intervention in large groups of several hundred to several 

thousand subjects by comparing it to other standard or experimental interventions monitoring 

adverse effects, and collecting information that will allow the intervention to be used safely. 

NIH-Defined Phase III Clinical Trial is a broadly based, prospective investigation, including 

community and other population-based trials, usually involving several hundred or more people, 

to evaluate an experimental intervention in comparison with a standard or control or to compare 

two or more existing treatments. Often the aim is to provide evidence for changing policy or 

standard of care. It includes pharmacologic, non-pharmacologic, and behavioral interventions for 

disease prevention, prophylaxis, diagnosis, or therapy. 
38

Phase IV done after the intervention has been marketed, monitors effectiveness of the approved 

intervention in the general population and collects information about adverse effects associated 

with widespread use. 

Exemption Categories 

The six categories of research that qualify for exemption from coverage by the regulations are: 

1. Research conducted in established or commonly accepted educational settings, involving 

normal educational practices, such as research on instructional strategies, or on instructional 

techniques, curricula, or classroom management methods. 

2. Research using cognitive, diagnostic, aptitude, and achievement educational tests, surveys, 

interviews, or observations of public behavior, unless human subjects are identifiable and 

disclosure of the responses outside the research could reasonably place the subjects at risk of 

liability or be damaging to their financial standing, employability, or reputation. 

3. Research using cognitive, diagnostic, aptitude, and achievement educational tests, surveys, 

interviews, or observations of public behavior cognitive, diagnostic, aptitude, and achievement 

educational tests, surveys, interviews, or observations of public behavior that is not exempt if the 

subjects are public officials or candidates for public office or federal statutes require that the 

confidentiality of identifiable information will be maintained. 

4. Research involving the collection or study of existing data, documents, records, pathological 

specimens, or diagnostic specimens, if the sources are publicly available or the information is 

recorded so that subjects cannot be identified. 

5. Research and demonstration projects conducted or approved by agency heads to study public 

benefit or service programs; procedures for obtaining benefits or services or other changes to 

those programs. 

6. Taste and food quality evaluation and consumer acceptance studies a) in wholesome foods 

without additives or b) in food containing a food ingredient at or below the level and use found 

to be safe, or agricultural chemical or environmental contaminant at or below the level deemed 

safe by FDA or approved by the Environmental Protection Agency or the Food Safety and 

Inspection Service of the U.S. Department of Agriculture. 

Gender 

The classification of research subjects into women and men. In some cases, gender cannot be 

accurately determined (e.g., pooled blood samples). 

Hispanic or Latino 

A person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture 

or origin, regardless of race. The term, “Spanish origin,” can also be used. 

Human Subject 

A living person with whom an investigator directly interacts or intervenes or obtains identifiable, 

private information. Regulations apply to human organs, tissues, body fluids, and recorded 

information from identifiable people. 

Human Subjects Concern 

Any actual or potential unacceptable risk or inadequate protection against risk to human subjects. 
39

IRB Certification 

Documentation from your Institutional Review Board that it has approved your research 

protocol, consent form (if applicable), monitoring and reporting procedures, and plans for 

analyzing intervention differences among different types of human subjects, for example women 

and minorities, ethnic or racial subgroups, and children. The IRB also approves your research 

annually with the noncompeting grant application and any time there are 

major changes in the research protocol or other procedures. The IRB must also certify its 

approval of the results of subset analyses in renewal applications and contract proposals. 

Registration with the Office of Human Research Protections, DHHS, is required for IRBs and 

(international research) Independent Ethics Committees (IECs) designated under an OHRP 

Federalwide Assurance of Protection for Human Subjects. See also Institutional Assurance of 

Protection for Human Subjects. 

Institutional Assurance of Protection for Human Subjects 

A document filed with the HHS Office for Human Research Protections (OHRP) formalizing the 

research institution's commitment to protect human subjects in its federally supported research. 

The OHRP has developed a new, simplified process for obtaining a Federalwide Assurance 

(FWA) of Protection for Human Subjects, applicable to all federal agencies. In the future, only 

the FWA will be accepted, although the deadline when it will replace other more limited 

assurances (e.g. the special project assurance for a specific research project) has been indefinitely 

extended. See also IRB certification. 

Majority Group 

White, not of Hispanic origin; a person having origins in the original peoples of Europe, North 

Africa, or the Middle East. 

Minimal Risk 

The probability and magnitude of harm or discomfort anticipated in the research are not greater 

in and of themselves than those ordinarily encountered in daily life or during the performance of 

routine physical or psychological examinations or tests. See the official regulations for more 

information at Section 46.102(i). 

Minority Groups 

A subset of the U.S, population distinguished by either racial, ethnic, or cultural heritage. 

Categories are: American Indian or Alaskan Native; Asian; Black or African American, Hispanic 

or Latino; Native Hawaiian, or other Pacific Islander. Applications and proposals should describe 

subgroups to be included. Inclusion should be determined by the scientific questions under 

examination and their relevance to racial or ethnic groups; not every study will include all 

minority groups or subgroups. 

NIH-Defined Phase III Clinical Trial 

See Clinical Trial. NIH-Defined Phase III. 
40

Native Hawaiian or Other Pacific Islander 

A person having origins in the original peoples of Hawaii, Guam, Samoa, or other Pacific 

Islands. 

Outreach Strategies 

Efforts by investigators and their staff to recruit and retain populations of interest into research 

studies. Such efforts should represent a thoughtful and culturally sensitive plan of outreach and 

generally involve other people and organizations relevant to the populations and communities of 

interest, e.g., family, religious organizations, community leaders, and public and private and 

organizations. The objective is to establish communication and cooperation to build mutual trust. 

Racial and Ethnic Categories 

Defined by the Office of Management and Budget Directive No. 15 and used by NIH to allow 

comparisons to national databases. 

Scientifically Acceptable or Unacceptable 

A determination based on whether proposed gender or minority representation conforms with 

NIH guidelines pertinent to the scientific purpose and type of study. A determination of 

unacceptable by the review panel bars the funding of an application or proposal until NIH staff 

resolve the issue. In addition, the definition changes if the research is a clinical trial as opposed 

to merely being clinical research. 

Six Human Subjects Points 

The six human subjects points were formerly part of the PHS 398 grant application instructions, 

but the instructions have been changed. Please see the updated How To Write a Human Subjects 

Application. 

Significant Difference 

A difference of clinical or public health importance based on substantial scientific data. This 

definition differs from the commonly used one, which refers to statistical significance. 

Subpopulations 

For each minority group, subpopulations are further defined by geographic origins, national 

origins, or cultural differences. There are different ways of defining and reporting subpopulation 

data. People assign themselves to a subpopulation through self-reporting. Mixed racial or ethnic 

descent also applies to subpopulations, and such combinations may have biomedical or cultural 

implications for the scientific question under study. 

Valid Analysis 

An unbiased assessment that generally yields the correct estimate of the difference in outcomes 

between two groups of subjects and that should be conducted for both small and large studies. A 

valid analysis does not need to have a high statistical power for detecting an effect. Principal 

requirements for ensuring a valid analysis are: allocation of study participants of both genders 

and from different racial and ethnic groups to intervention and control groups by an unbiased 

process such as randomization, unbiased evaluation of the outcome, and use of unbiased 
41

statistical analyses and methods of inference to estimate and compare the intervention effects 

among different groups. See also analysis. 

White 

A person having origins in any of the original peoples of Europe, the Middle East, or North 

Africa. 

Women 

See Gender. 
42

APPENDIX IV 

NIH Policy for Data and Safety Monitoring 

(http://grants2.nih.gov/grants/guide/notice-files/not98-084.html) 

Release Date: June 10, 1998 

P.T. 

National Institutes of Health 

Policy 

It is the policy of the NIH that each Institute and Center (IC) should have a system for the 

appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of 

participants and the validity and integrity of the data for all NIH-supported clinical trials. The 

establishment of the data safety monitoring boards (DSMBs) is required for multi-site clinical 

trials involving interventions that entail potential risk to the participants. The data and safety 

monitoring functions and oversight of such activities are distinct from the requirement for study 

review and approval by an Institutional Review Board (IRB). 

Background 

A clinical trial entails a relationship between participants and investigators, both of whom must 

fulfill certain obligations for the effort to succeed. Participants must be fully informed of the 

study requirements throughout the conduct of the trial and should comply with the rigors of the 

research protocol or be allowed the opportunity to withdraw from participation. The investigators 

must protect the health and safety of participants, inform participants of information relevant to 

their continued participation, and pursue the research objectives with scientific diligence. 

Although there are potential benefits to be derived from participation in clinical research, the 

IRBs and the NIH must ensure, to the extent possible, the safety of study participants, that they 

do not incur undue risk and that the risks versus benefits are continually reassessed throughout 

the study period. 

With this issuance, the NIH reaffirms the 1979 policy (NIH GUIDE, Volume 8, No, 8, June 5, 

1979) developed by the NIH Clinical Trials Committee. Among its recommendations was the 

concept that "every clinical trial should have provision for data and safety monitoring." The 

Committee further acknowledged that "a variety of types of monitoring may be anticipated 

depending on the nature, size, and complexity of the clinical trial. In many cases, the principal 

investigator would be expected to perform the monitoring function." 

In 1994, the Office of Extramural Research established the Committee on Clinical Trial 

Monitoring to review the oversight and management practices of the ICs for phase III clinical 

trials. One of the outcomes of this Committee's review was a strong recommendation that "all 

trials, even those that pose little likelihood of harm, should consider an external monitoring 

body." This policy affirms the Committee's recommendations concerning DSMBs. 

Principles of monitoring data and safety 

All clinical trials require monitoring—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); etc. 
43

Monitoring should be commensurate with risks—The method and degree of monitoring needed 

is related to the degree of risk involved. A monitoring committee is usually required to determine 

safe and effective conduct and to recommend conclusion of the trial when significant benefits or 

risks have developed or the trial is unlikely to be concluded successfully. Risk associated with 

participation in research must be minimized to the extent practical. 

Monitoring should be commensurate with size and complexity. Monitoring may be conducted in 

various ways or by various individuals or groups, depending on the size and scope of the 

research effort. These exist on a continuum from monitoring by the principal investigator or NIH 

program staff in a small phase I study to the establishment of an independent data and safety 

monitoring board for a large phase III clinical trial. 

Practical and Implementation Issues 

Oversight of Monitoring 

This policy provides each IC with the flexibility to implement the requirement for data and 

safety monitoring as appropriate for its clinical research activities. Thus, IC staff may either 

conduct or sponsor the monitoring of data and safety of ongoing studies or delegate such 

responsibilities to a grantee or contractor. Oversight of monitoring activities is distinct from the 

monitoring itself and should be the responsibility of the IC regardless of whether the monitoring 

is performed by NIH staff or is delegated. Oversight of monitoring must be done to ensure that 

data and safety monitoring plans are in place for all interventional trials, that the quality of these 

monitoring activities is appropriate to the trial(s}, and that the IC has been informed of 

recommendations that emanate from monitoring activities. 

Institutes’ and Centers’ Responsibilities 

Though ICs may perform a variety of roles in data and safety monitoring and its oversight, the 

following are the minimum responsibilities of sponsoring ICs. 

• Prepare or ensure the establishment of a plan for data and safety monitoring for all 

interventional trials. 

• Conduct or delegate ongoing monitoring of interventional trials. 

• Ensure that monitoring is timely and effective and that those responsible for monitoring 

have the appropriate expertise to accomplish its mission. 

• Oversee monitoring activities. 

• Respond to recommendations that emanate from monitoring activities. 

Performance of Data and Safety Monitoring 

The ICs will ensure the integrity of systems for monitoring trial data and participant safety, 

although they may delegate the actual performance to the grantee or contractor. Monitoring must 

be performed on a regular basis, and conclusions of the monitoring reported to the IC. 

Recommendations that emanate from monitoring activities should be reviewed by the 

responsible official in the IC and addressed. The ICs also have the responsibility of informing 

trial investigators concerning the data and safety monitoring policy and procedures. 

Considerations such as who shall perform the monitoring activities, the composition of the 

monitoring group (if a group is to be used), the frequency and character of monitoring meetings 

(e.g., open or closed, public or private), and the frequency and content of meeting reports should 
44

be a part of the monitoring plans. IRBs should be provided feedback on a regular basis, including 

findings from adverse-event reports, and recommendations derived from data and safety 

monitoring. 

Monitoring activities should be conducted by experts in all scientific disciplines needed to 

interpret the data and ensure patient safety. Clinical trial experts, biostatisticians, bioethicists, 

and clinicians knowledgeable about the disease and treatment under study should be part of the 

monitoring group or be available if warranted. 

Ideally, participants in monitoring outcomes of a trial are in no way associated with the trial. For 

trials that are conducted as part of a cooperative group, a majority of the individuals monitoring 

outcome data should be external to the group. ICs should require policies that evaluate whether 

the participants have conflicts of interests with or financial stakes in the research outcome; and 

when these conflicts exist, policies must exist to manage these in a reasonable manner. 

Generally, data and safety monitoring boards meet first in open session, attended by selected trial 

investigators as well as NIH program staff or project officers and perhaps industry 

representatives, and then in closed session where they review emerging trial data. When 

“masked” data are presented or discussed, no one with a proprietary interest in the outcome 

should be allowed. Participants in the review of “masked” or confidential data and discussions 

regarding continuance or stoppage of the study should have no conflict of interest with or 

financial stake in the research outcome. However, if there is an open session, they could be 

present. 

Confidentiality must be maintained during all phases of the trial including monitoring, 

preparation of interim results, review, and response to monitoring recommendations. Besides 

selected NIH program staff, other key NIH staff, and trial biostatisticians, usually only voting 

members of the DSMB should see interim analyses of outcome data. Exceptions may be made 

under circumstances where there are serious adverse events, or whenever the DSMB deems it 

appropriate. 

Individuals or groups monitoring data and safety of interventional trials will perform the 

following activities: 

• Review the research protocol and plans for data and safety monitoring. 

• Evaluate the progress of interventional trial(s), including periodic assessments of data 

quality and timeliness, participant recruitment, accrual and retention, participant risk 

versus benefit, performance of trial sites, and other factors that can affect study outcome. 

Monitoring should also consider factors external to the study when interpreting the data, 

such as scientific or therapeutic developments that may have an impact on the safety of 

the participants or the ethics of the study. 

• Make recommendations to the IC, IRB, and investigators concerning continuation or 

conclusion of the trial(s). 

• Protect the confidentiality of the trial data and the results of monitoring. 
45

Examples of Monitoring Operations 

The following provides examples of appropriate types of monitoring and oversight for different 

types of studies. These are illustrative only. The ICs must develop and implement monitoring 

activities and oversight of those activities appropriate to the study, population, research 

environment, and the degree of risk involved. 

Phase I: A typical phase I trial of a new drug or agent frequently involves relatively high risk to 

a small number of participants. The investigator and occasionally others may have the only 

relevant knowledge regarding the treatment because these are the first human uses. An IC may 

require the study investigator to perform continuous monitoring of participant safety with 

frequent reporting to IC staff with oversight responsibility. 

Phase II: A typical phase II trial follows phase I studies, and there is more information 

regarding risks, benefits and monitoring procedures. However, more participants are involved, 

and the toxicity and outcomes are confounded by disease process. An IC may require monitoring 

similar to that of a phase I trial or supplement that level of monitoring with individuals with 

expertise relevant to the study who might assist in interpreting the data to ensure patient safety. 

Phase III: A phase III trial frequently compares a new treatment to a standard treatment or to no 

treatment, and treatment allocation may be randomly assigned and the data masked. These 

studies usually involve a large number of participants followed for longer periods of treatment 

exposure. While short-term risk is usually slight, one must consider the long-term effects of a 

study agent or achievement of significant safety or efficacy differences between the control and 

study groups for a masked study. An IC may require a DSMB to perform monitoring functions. 

This DSMB would be composed of experts relevant to the study and would regularly assess the 

trial and offer recommendations to the IC concerning its continuation. 
46

APPENDIX V 

Answers to Frequently Asked Questions about NIH Grants 

(http://grants1.nih.gov/grants/funding/giofaq.htm) 

Abstracts? 

Abstracts are allowed in the appendix of an application. Up to 10 publications, manuscripts 

(accepted for publication), abstracts, patents, and other printed materials directly relevant to the 

project may be included. 

Appendix? 

Each page in the appendix may be double-sided. 

The appendix will be distributed to the primary and the secondary reviewers of the application 

assigned within the study section. One copy of the appendix is forwarded to the assigned NIH 

institute's program administrator, and one copy remains with the Scientific Review 

Administrator (SRA) until the review is complete. 

Assurance Forms—Civil Rights, Human Subjects & Animal Welfare? 

Civil Rights: Before a grant award can be made, a domestic applicant organization must certify 

that it has filed the DHHS Office for Civil Rights and Assurance of Compliance (Form HHS 

690) pertaining to four non-discrimination requirements. This form is required to be submitted 

only once by an institution; it may be obtained from grantsinfo@nih.gov or by telephone at 

301-435-0714. 

As a condition of receiving NIH Support, an applicant organization must certify compliance with 

a number of assurances. Most assurances and certifications are incorporated by reference in the 

PHS 398 application kit (see pp.27-36). For those assurances, the signature on the application 

face page of the duly authorized representative of the applicant institution certifies that the 

applicant organization will comply. The inclusion of human subjects or animals in research 

requires special certifications as described below. 

Human Subjects: The Federal Policy (Common Rule) for the protection of human subjects at 

Section 103(a) requires that each institution “engaged” in federally supported human subject 

research file an “Assurance” of protection for human subjects. The Assurance formalizes the 

institution's commitment to protect human subjects. The requirement to file an Assurance 

includes both “awardee” and collaborating “performance site” institutions. For additional 

information and guidance, please visit the Office for Human Research Protections (OHRP) web 

site at: http://ohro.osophs.dhhs.gov/. 

Animal Welfare: Research involving human and/or animal subjects must comply with the HHS 

regulations for the Protection of Human Subjects (45 CFR 46) and/or the PHS Policy on Humane 

Care and Use of Laboratory Animals. Institutions without an applicable Assurance of 

Compliance on file with the Office of Laboratory Animal Welfare (OLAW) must provide an 

appropriate Assurance prior to funding. For additional information and guidance, please visit the 

OLAW web site at: http://www.grants.nih.gov/grants/olaw/olaw.htm. 
47

Award Data? 

NIH award data is accessible on the NIH web site at: http://www.grants.nih.gov/grants/award/

award.htm. This site provides reports, charts and graphs, extramural trends, listings of awards 

arranged geographically by state, city, and grantee organization within the city and other awardrelated information. 

Center for Scientific Review (CSR) 

The Center for Scientific Review (CSR) is the new organizational name of the former Division 

of Research Grants (DRG). CSR is the central NIH organization that receives grant applications; 

creates a new computer record for each; assigns applications to initial review groups as well as to 

potential funding units of NIH and other cooperating health research agencies; and conducts peer 

review of grant applications. For more detailed information, please see the web site 

htm://www.csr.nih.gov/ and the section on peer review. At that site there is also an excellent 

overview of the NIH peer review and award process. 

Citations? 

Citations may not be scattered throughout the Research Plan of an application. They should be 

put in Section G, Literature Cited. 

Collaborators/Consultants? 

A collaborator is an individual involved with the principal investigator in the scientific 

development or execution of the project. These individuals would typically devote a specific 

percent of effort to the project and would be identified as key personnel. The collaborator may be 

employed by, or affiliated with, either the grantee organization or an organization participating in 

the project under a consortium or contractual agreement. 

A consultant is an individual who provides professional advice or services on the basis of a 

written agreement for a fee. These individuals are not normally employees of the organization 

receiving the services. 

NOTE: A biographical sketch (Form FF) is required for all key personnel. Collaborators and 

consultants should be included only when their level of involvement on the grant meets the key 

personnel definition and each biographical sketch must be no more than four pages. 

Concurrent Applications? 

Submission of more than one application within the same review cycle is permissible for some, 

but not all, award mechanisms: 

For a NRSA Fellowship (F series), only one application may be submitted in the same review 

cycle. 

For an investigator-initiated grant (R01), small grant (R03), career development award (K-Series, 

excepting K08), small business innovation research grant (SBIR), small business technology 

transfer grant (STTR), or a conference grant (RI3), more than one application in the same review 

cycle may be submitted, if each application describes a different research topic. 
48

An application for an investigator-initiated grant (R01) for support of the same research 

proposed as a subproject within an application for a program project grant (P01), or as a 

subproject within an application for other P-series grants, such as P30 or P50, may be submitted 

in the same cycle. 

Copies? 

Photocopies of blank application forms may be used as original forms for grant preparation. 

Instructions for the number of copies of research grant applications and appended materials to be 

submitted at the regular application receipt dates are detailed on page 21 of the PHS 398 

instructions. There may be additional instructions for submission of responses to Requests for 

Applications (RFAs) in the NIH Guide announcements of RFAs. 

Delivery of Applications? 

All applications and other deliveries to the Center for Scientific Review must either come via 

courier delivery or the USPS. Applications delivered by individuals to the Center for Scientific 

Review will no longer be accepted. 

For additional information, see the NIH Guide Notice (Nov. 13, 2001) 

http://www.grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html. 

Eligibility? 

In general, any organization is eligible to apply for regular NIH research grants, such as R01 

grants and other grant mechanisms. The applicant is the research organization, although a 

principal investigator (PI) writes the research proposal; and if a grant is awarded, the grantee is 

the organization that submitted the application. For some specific programs there may be special 

eligibility requirements, and those requirements are detailed in the Program Announcement (PA) 

or Request for Applications (RFA) published in the NIH Guide. (See next item for access to the 

NIH Guide.) 

Guide for Grants and Contracts? 

Current and past issues of the NIH Guide may be accessed from the NIH web site under the 

category of Funding Opportunities at http://www.grants.nih.gov/grants/oer.htm or a Table of 

Contents Email version of the NIH Guide may be obtained by subscription to the NIH Listserv. 

To subscribe to the Table of Contents, send an Email message to 

mailto:%20Iistserv@list.nih.gov in which the text of the mail should read ONLY: SUBSCRIBE 

NIHTOC- L Firstname Lastname (e.g. SUBSCRIBE NIH TOC-L Bill Jones) 

The message must originate from the same address where you would like the weekly Table of 

Contents to be received and read, circulated or filed. 

Indirect Costs? 

Reimbursement for indirect costs (also called facilities and administration costs, or F&A) is 

allowed on most types of NIH awards. Typically, indirect cost reimbursement is calculated using 

the institution's indirect cost rate as negotiated with HHS. The applicant institution's office of 

sponsored research or business office can provide this information. If an organization does not 

already have an HHS-negotiated indirect cost rate, refer to the PHS Grants Policy Statement, 
49

appendix 8, for the appropriate HHS Division of Cost Allocation office (for educational and 

other non-profit organizations) or PHS agency (for-profit organizations). 

Introduction? 

Required only on REVISED and SUPPLEMENTAL applications, the “Introduction” section of 

the application is not counted towards the Research Plan 25-page limit. It is separate from the 

Research Plan. 

Investigator-Initiated Applications? 

The term, Investigator-Initiated Application, means that the applicant has proposed research for 

funding by NIH that is not responding to any solicitation by NIH in announcements such as a 

Program Announcement (PA) or a Request for Applications (RF A). The research proposed by 

the applicant mostly likely would be related to the stated program interests of one or more of the 

Institutes of NIH in descriptions of their programs, but the scientist has proposed a research 

project that is independent of any particular solicitation by an Institute. The most frequently used 

mechanisms of support for such applications are the “R” series of grants, notably the R01 

research project grant. 

IRB & IACUC Approvals? 

According the Revised Policy for IRB Review of Human Subjects Protocols in Grant 

Applications, IRB approval is not required prior to NIH peer review of an application. However, 

no grant award can be made without IRB approval. Following NIH peer review and notification 

of priority score/percentile, institutions should proceed with IRB review for those applications 

that have not yet received IRB approval and that appear to be in a fundable range. The term 

“fundable range” does not signify a certainty of funding. For more information, please visit the 

following web site: http://www.grants.nih.gov/grants/irb_review_pol.htm. 

Institutional Animal Care and Use Committee (IACUC) approval is required when animal 

studies are involved. Beginning with applications submitted for the October 1, 2002, receipt date 

(and any other receipt dates that result in applications being reviewed for May/June 2003 

Councils), IACUC “just-in-time” will be in effect. That is, institutions will be permitted 

flexibility in the timing of IACUC review relative to submission of an application. The full NIH 

Guide Notice is available at: http://www.grants.nih.gov/grants/guide/notice-files/NOT-OD-02-

064.html. 

Key Personnel? 

The definition of key personnel in the PHS 398 kit is “individuals who contribute in a substantive way to 

the scientific development or execution of the project, whether or not salaries are requested.” 

Modular Grants? 

The modular grant application concept establishes a size (in dollars) of module 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. In addition, an applicant will need to 

submit certain information only when it is highly likely that NIH will make an award. It is 

anticipated that these changes will reduce the administrative burden for the applicants, reviewers, 

and Institute staff. The research grant application form PHS 398 (rev. 05/01) is to be used with 

the instructions for the modular grant application. 
50

Modular Grant applications request direct costs in $25,000 modules, and may request up to 

$250,000 (10 modules) for direct costs per year. Applications that request more than $250,000 

direct costs in any year must follow the traditional PHS 398 application instructions. 

The NIH Modular Research Grant Application web page 

http://www.grants.nih.gov/grants/funding/modular/modular.htm can guide you to detailed 

information about the application process, including samples of relevant pages from an 

application. 

Notification of Receipt? 

The snap-out mailer is the only official notification from the NIH that an application has been 

received by the Center for Scientific Review (CSR) Referral Office. It acknowledges receipt of 

the application, indicates the Initial Review Group (IRG), NIH Institute assignment, and 

provides the Scientific Review Administrator's (SRA) name and telephone number. The snap-out 

mailer is sent six to eight weeks after the receipt date to the addresses provided on the 

application face page. 

If additional proof that an application has been received is desired, the application may be hand 

delivered to the Rockledge Center before 5:00 p.m., Monday thru Friday, and the messenger can 

obtain a signature of receipt. 

Omitted Information? 

If information has been inadvertently omitted from a submitted application package that is 

critical to the receipt and assignment of the application, e.g., the face page or reference letters, 

the applicant should call the Center for Scientific Review (CSR) Referral Office at (301) 435-

0715. Otherwise, the applicant should wait for receipt of the snap-out mailer (about six to eight 

weeks after the receipt date), and then contact the Scientific Review Administrator (SRA) 

identified on the mailer. 

Other Support? 

According to the PHS 398 Instructions, “Other support information is required for all 

applications that are to receive grant awards; however, NIH will request complete and up to date 

“other support” information from applicants at an appropriate time after peer review. The 

institute's scientific program and grants management staff will review this information prior to 

award.” 

Page Numbering? 

The pages must be numbered with consecutive integers. If a continuation page is necessary for 

one of the pre-numbered forms pages, the requirement for consecutive integer numbering of the 

whole application takes precedence. 

Do not include “subpages” to the form pages in the kit (i.e., do not number the pages as 4, 4a, 4b, 

5). 

Photographs? 

Glossy photographs or color images that are represented in the Research Plan may be included in 

the appendix with the original application. DO NOT paste photographs in application. 
51

Graphs, diagrams, tables, and charts not needed in a glossy format to show detail must be 

included with the Research Plan and may NOT be included in the appendix. 

Do NOT use the appendix to circumvent the page limitations of the Research Plan. 

PHS 398 Application Kits? 

Beginning January 10, 2002, applicants are required to use the revised (05101 forms). The 

revised PHS 398 and PHS 2590 instructions are only available online at 

http:/www.grants.nih.gov/grants/forms.htm. Applicants are encouraged to access the instructions 

and forms via the Internet because they provide valuable links to current policy documents and 

allow easy navigation of the instructions. 

PHS 398 application kits cannot be faxed to applicants. 

PHS 416 Application Kits? 

The revised Ruth L. Kirschstein Individual National Research Service Award Application (PHS 

416-1) and Progress Report for Continuation Support (PHS 416-9) are available online in a 

fillable format at: http://www.grants.nih.gov/grants/fonns.htm. NOTE: For the April 2003 

application receipt date and beyond, use of the new version Rev. 6/02 is required. 

Programs? 

For general information about NIH research and research training programs, interested parties 

may contact grantsinfo@nih.gov. 

Information about the programs of a specific NIH institute can be found on the NIH website: 

http://www.nih.gov/. Click on Institutes and Offices. Also the NIH Extramural Programs 

describes the programs of the NIH and includes contacts for additional information at the 

website: http://www.grants.nih.gov/grants/funding/funding.htm. 

Each Program Announcement (PA) and Request for Applications (RFA) in the NIH Guide for 

Grants and Contracts includes contact information for the grants management officer and 

program administrator for additional information about that PA or RFA. 

Program Announcement (PA)? 

To obtain a specific program announcement, consult the NIH Guide for Grants and Contracts on 

the OER website, http://www.grants.nih.gov/grants/oer.htm or contact the Institute that issued 

the program announcement. The NIH Guide has a numerical list of the program announcements. 

Program Project Grants (P01)? 

Each of the NIH institutes that use P01s publishes its own guidelines for program project (P01) 

applications. For answers to questions regarding program project grants, applicants are 

encouraged to contact the NIH institute most likely to fund their project. Occasionally, an 

Institute's solicitation published in the NIH Guide will specify that a program project is the 

funding mechanism appropriate for a grant application in response to the announcement. 
52

Receipt Dates? 

The PHS application documents (i.e., PHS 398, PHS 416-1) contain the receipt dates that apply 

to grant applications unless special receipt dates have been specified in either a program 

announcement (PA), request for application (RF A), or program guidelines published in the NIH 

Guide for Grants and Contracts. A list of receipt dates is available from Grants info (301-435-

0714) by choosing Option 3 on the menu. Receipt date schedules are also posted on the NIH 

website: http://www.grants.nih.gov/grants/funding.htm under the category of Receipt Dates. 

WHENEVER A RECEIPT DATE FALLS ON A WEEKEND OR HOLIDAY, THE 

APPLICATION IS DUE ON THE FOLLOWING BUSINESS DAY. This applies to postmark 

dates as well. 

Unsolicited Applications. An unsolicited application is considered on time if it is: 

a. received by the published receipt date or, 

b. mailed on or before the published receipt date and a proof of mailing is provided. 

Proof of mailing may be either a dated receipt from a commercial carrier or the US Postal 

Service, or a legible US Postal Service postmark. (Private meter postmarks are not acceptable.) 

This policy also applies to unsolicited AIDS-related applications and to Academic Research 

Enhancement Award (AREA) applications. Unsolicited applications, with the exceptions of 

SBIR and STTR, are those submitted on the standard receipt dates stated in the grant application 

forms instruction books and in the table of receipt dates posted on the NIH website above. 

Solicited Applications. A solicited application or proposal must be received by the date specified 

in the request for applications (RF A) or program announcements with special receipt dates 

(PAR). However, an application received after the deadline may be acceptable if it carries a 

legible proof-of-mailing date assigned by the carrier that is AT LEAST ONE WEEK prior to the 

deadline date. Solicited applications include those submitted in response to RFAs; program 

announcements with special receipt dates (PARs); or solicitations for Small Business Innovation 

Research (SBIR) and Small Business Technology Transfer (STTR) applications. 

Reference Letters? 

In an application for a Fellowship Award (F32), or for selected Research Career Development 

Awards (see instructions for the K series of awards), three sealed, reference letters must be 

submitted with the application. If fewer than three letters are submitted with the application, the 

application will be returned to the applicant. 

The sealed envelopes should clearly indicate the application to which they belong, in case they 

are inadvertently separated from the application. It is not necessary to designate a person to 

receive them. 

The sealed letters must be attached to the front of the original application and included in the 

package with the original application and the copies. 

Resubmitted Applications?

See Revised/Amended Applications. 
53

Review Schedules?

For peer review and award schedules of grants, refer to the application instruction books, {PHS 

398, PHS 416-1), program announcements (PAs), requests for applications (RFAs), and program 

guidelines. Schedules depend upon the type of application submitted. Review and award cycle 

schedules are also posted on the NIB website: 

http://www.grants.nih.20v/grants/funding/funding.htm and click on Receipt Dates. 

Revised/Amended versus Renewal Application? 

A revised/amended application is one that has been modified in response to the critique in the 

summary statement of an application that was previously reviewed, but not funded. (“revised” 

and “amended” applications are synonymous.) 

A competing “renewal” is a grant for additional funds and period of award. 

A revised/amended application or an application for a competing “renewal” is made on the same 

PHS application form used for the initial grant or fellowship. 

An application for an R01grant submitted in response to a request for application (RFA) and not 

funded may be resubmitted as an unsolicited application. However, it must be submitted as a 

revised/amended application and include the changes made in response to the critique of the 

original submission. 

Salary Cap? 

Effective January I, 2002, the Executive Level I salary level increased to $166.700. 

The full announcement on Salary Limitation is available at: 

http://www.grants.nih.gov/grants/guide/notice-files/NOT-OD-02-030.html. For additional 

guidance, please contact the Grants management Office of the NIB institute most likely to fund 

your application. 

Sample Applications? 

Sample applications that have been funded are not available from central NIH sources. However, 

occasionally the NIH Guide announces regional seminars for assistance in grant preparation. 

Applicants may also find it helpful to ask advice from an experienced investigator and to contact 

the NIH administrator of the program most likely to fund their application. 

Scientific Areas Funded by NIB? 

Several resources exist to determine the areas of research types, and levels of funding: 

NIH Guide for Grants and Contracts issues Program Announcements (PAs) for ongoing 

programs as well as Requests for Applications (RFAs) in various scientific areas. The NIH 

Guide is published weekly on the OER web site, http://www.grants.nih.gov/grants/oer.htm. 
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Computer Retrieval of Information on Scientific Projects (CRISP) provides a brief description 

and the administrative data of each funded NIH research project. CRISP is updated quarterly on 

the OER Website. CRISP does not include amounts awarded on the grants. 

NIH Extramural Programs, a publication available electronically, outlines all ongoing NIH 

extramural research and research training programs. This resource also describes various 

information clearinghouses that provide information to the public on health and disease. It is 

available at the NIH website, http://www.grants.nih.gov/grants/funding/funding.htm. 

Scientific Review Administrator (SRA)? 

The scientific review administrator (SRA) is the designated federal official responsible for the 

administration of a study section which conducts the initial peer review of applications. This 

individual compiles a summary statement for each application upon the completion of the initial 

review. 

Signatures? 

Original signatures are required on the original face page of the application, but not on the 

copies. 

SRG and IRG? 

A scientific peer review group (SRG) is the generic functional term for any group engaged in 

scientific and technical peer review. SRGs may be individually chartered or they may be part of 

a larger chartered group (i.e., IRG). SRGs are commonly called study sections in CSR (formerly 

DRG) and are called review committees in the institutes and centers of NIH that have their own 

specialized peer review groups. An IRG (initial review group) is a cluster of SRGs with related 

scientific focus chartered as a single entity. 

Study Section Assignment? 

Applications are assigned to the most appropriate initial review group (IRG)—please see 

definitions of “IRG” and “SRG” under the SRG heading above—on the basis of the scientific 

emphasis of the application and the NIH Referral Guidelines. The assignments are made by NIH 

Referral Officers, senior science administrators who have had research and scientific review 

administrator experience. An applicant may suggest, in a cover letter, up to three study sections 

considered appropriate to review the application. 

Study Section Members? 

Members of study sections are selected by the scientific review administrators with the 

concurrence of their supervisors in the Center for Scientific Review (CSR). For specific 

information about the membership of study sections, see the website: 

http://www.csr.nih.gov/committees/rosterindex.as with member listings. Study section members 

are chosen for their expertise in the areas of science relevant to a particular review group, and for 

their ability and willingness to evaluate research grant applications. After studying the 

applications at home, they meet together, generally three times a year, for the purpose of 

reviewing the group of applications received at the latest deadline. The members serve for a 

period of three or four years. Recommendations of the study sections are forwarded to the 

funding Institutes of NIH where funding decisions are made for each of the grant applications. 
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A federal employee may serve as a study section member. However, most of the members of the 

study sections are researchers from universities and other research organizations throughout the 

United States. Applicants should not contact study section members directly. Contact the 

Scientific Review Administrator instead. 

Study Section Rosters? 

Rosters of the Center for Scientific Review (CSR) (formerly known as the Division of Research 

Grants- DRG) study sections are available electronically. They can be accessed from the CSR 

web site, http://www.csr.nih.gov/ that also has descriptions of the scientific areas covered by 

each study section. 

Supplements? 

There are two types of supplements: Administrative and Competitive. 

Administrative supplement: NIH awards additional funding to an existing grant to cover 

additional expenses within the scope of the existing award. 

For example: The supplements to train a minority research student or a student with disabilities 

are administrative supplements. It is awarded “administratively:” the application does not require 

review by a study section or national advisory council, nor does an applicant compete for this 

funding with other applicants. 

Competitive supplement: The applicant competes for additional funding to expand the scope of 

the existing grant, requiring additional personnel, equipment, and/or other expenses. A 

competitive supplement application must be peer reviewed.