CLINICAL TRIAL PLANNING GRANTS TO GUIDE TIMING, INTENSITY, AND DURATION OF 
REHABILITATION FOR STROKE AND HIP FRACTURE

Release Date:  September 20, 2001

RFA:  RFA-HD-01-022
 
National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov)

Letter of Intent Receipt Date:  January 18, 2002
Application Receipt Date:       February 14, 2002

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

PURPOSE

The purpose of the Clinical Trial Planning Grant is to provide support for the 
initial development and organization of an effective research team and the 
elements essential for conducting successful clinical trials.  The National 
Center for Medical Rehabilitation Research (NCMRR) of the National Institute of 
Child Health and Human Development (NICHD) wishes to support clinical trials 
focused on evaluating the timing, intensity, and duration of rehabilitation 
interventions for stroke and hip fracture.

Applications may address developing plans for patient recruitment, experimental 
design and protocols, testing of procedures, determining effect size in 
preparation for future clinical trials, data management, analysis techniques, 
facilities, administrative procedures, and collaborative arrangements.  Detailed 
information regarding the rationale for the clinical trial based on preclinical 
and preliminary clinical research must be included in the application for the 
Clinical Trial Planning Grant.  The purpose of the planning grant is, however, 
neither to obtain preliminary data nor to conduct studies to support the 
rationale for the clinical trial. 

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS-led 
national activity for setting priority areas.  This Request for Applications 
(RFA) is related to one or more of the priority areas.  Potential applicants may 
obtain "Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

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

Clinical trials planning support is for new projects and may not be used 
to supplement research projects already being supported or to provide 
interim support of projects under review.  Simultaneous submissions of 
applications for both a planning grant under this RFA and standard clinical 
trial research grant (R01) on the same topic will not be accepted.  

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Exploratory/ 
Developmental Research Grant (R21) award mechanism.  Responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the applicant.  This RFA is a one-time solicitation.  Applicants may 
apply for continuation of projects developed under this program using 
traditional, unsolicited grant mechanisms (e.g., R01, P01).  Future 
unsolicited competing continuation applications will compete with all 
investigator-initiated applications and be reviewed according to the 
customary peer review procedures.  

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

FUNDS AVAILABLE

The NICHD intends to commit approximately $1 million in total costs [direct plus 
Facilities and Administrative (F&A) costs] in FY 2002 to fund up to six new 
grants in response to this RFA.  An applicant may request a project period of 
two years and a budget for direct costs of up to $100,000 per year.  Although 
this program is provided for in the financial plans of the NICHD, awards 
pursuant to this RFA are contingent upon the availability of funds and the 
receipt of a sufficient number of meritorious applications.  

RESEARCH OBJECTIVES

Background 

Stroke and hip fracture are the leading health-care problems requiring 
rehabilitation services in older Americans.  Both are common, enduring and 
expensive in terms of medical costs, rehabilitation costs, caregiving costs and 
lost productivity.  Together, these two diagnoses account for the majority of 
days spent in rehabilitation, and are responsible for the largest expenditure of 
Medicare dollars spent in the area of rehabilitation.  

In the United States, the incidence of stroke is just over 500,000 individuals 
each year.  Among those who survive stroke, 50 percent are alive more than five 
years after the event.  The rehabilitation needs and goals of individuals with 
stroke vary considerably.  For some, the goal may be to return to full 
independence and resumption of all previous life activities.  For others, the 
goal may be to return home with family assistance.  The challenge for the health 
care system is to determine the type and setting of rehabilitation that most 
effectively meet the needs of the individual.  Rehabilitation is beneficial in 
promoting improvements in function areas such as mobility, performance of self-
care and community integration.  Important questions, however, remain regarding 
the effectiveness of individual treatment strategies, as well as the 
organization and intensity of rehabilitation services.  The effectiveness of 
stroke rehabilitation must also consider the natural recovery that occurs 
following stroke, as well as the individual patient characteristics associated 
with functional outcome.  In addition, stroke is a well-documented risk factor 
for hip fracture.  Population studies suggest that the risk of fracture is 
increased approximately two- to four-fold.

Hip fracture incidence increases exponentially with age for both men and women.  
Osteoporosis plays a central role in the pathogenesis underlying hip fracture.  
Although recent attention has focused on the growing array of pharmacologic 
agents that slow bone loss and reduce fracture risk, it is clear that large 
numbers of individuals will continue to experience hip fracture and that 
efficient and effective rehabilitation measures will become more important in 
the future.  The annual number of hip fractures is expected to rise dramatically 
in the future with continued aging of the population.  In the United States, for 
example, the number of individuals aged 65 years and over is expected to grow 
from 32 to 69 million between 1990 to 2050, while the number aged 85 years and 
over will grow from three to 15 million.  Hip fracture in seniors is a serious 
and costly health problem, accounting for 350,000 hospital admissions each year.  
Americans spend more than $10 billion in direct cost of care for the 250,000 hip 
fractures that occur each year.  Costs are expected to triple over the next 50 
years.  

The majority of patients who sustain hip fracture are frail elderly with 
multiple comorbitities.  The hip fracture itself imposes additional impairments 
and medical problems.  Of note are the significant numbers of deaths directly 
attributed to hip fracture.  In the initial stages of hip fracture recovery, 
emphasis traditionally has been placed on active range of motion exercises and 
functional training.  Recent studies suggest that pre-fracture status may not be 
achievable in many patients.  Rates of bone healing and reductions in average 
length of stay may preclude more aggressive rehabilitation during the sub-acute 
stay.    

Treatment to improve the ability to communicate and ambulate can dramatically 
increase the quality of life and functional independence for individuals 
following stroke or hip fracture.  These factors underscore the need to 
determine efficacious rehabilitation strategies for these disorders.  Patients 
beginning rehabilitation for either hip fracture or stroke, are faced with an 
imposing range of activities designed to help them regain lost skills or 
compensate for losses by acquiring new ones.  Central to rehabilitation, is the 
primary goal of functional independence and return to pre-injury or pre-surgical 
status.  The timing, intensity, and duration of therapeutic intervention 
influence how rapidly these rehabilitation goals are attained, affecting the 
duration and costs of care.  Although these issues underlie medical 
rehabilitation practice, few studies have demonstrated the most appropriate 
treatment course to help guide clinical practice. 

Across the medical disciplines involved in the care of individuals with hip 
fracture or stroke, there is a lack of empirical evidence to demonstrate which 
components in the rehabilitation continuum are most critical.  How best to 
maximize a patient’s ability to function in a given time frame has yet to be 
demonstrated empirically.  Most obviously missing is information regarding the 
timing, intensity, and duration of treatment interventions.  There is a paucity 
of empirical evidence regarding post-stroke rehabilitation.  Because of the 
diversity of the needs and goals of the stroke population, there is little 
agreement among professionals as to treatment strategies, the efficacy of stroke 
rehabilitation, or desired outcomes.  Neither is there clear evidence concerning 
the timing of interventions, nor the intensity of physical rehabilitation for 
patients following hip fracture. Different aspects of function appear to recover 
at different rates following hip fracture.  What is the sequence by which 
different areas of function recover following hip fracture and how can this 
information be used to design/guide intervention?  Can aggressive physical 
therapy directed to reduce the underlying impairment (strength and endurance) 
and regaining prior levels of activity be initiated earlier in the 
rehabilitation process.  Is there an optimum time for aggressive intervention?  
Is twice-a-day physical therapy more effective than once-a-day?  Is there a 
point in time when one or the other is more effective? 

The relationship among the timing, intensity, and duration of treatment is an 
issue that pervades all rehabilitation interventions.  The importance and 
timeliness of this topic was highlighted at the NICHD Patient Learning During 
Medical Rehabilitation Conference (1998), the NICHD Hip Fracture and Stroke 
Conference (August 2000), as well as the National Consensus Conference on 
Improving the Continuum of Care for Patients with Hip Fracture (May 2001).  The 
purpose of this initiative is to encourage studies that evaluate models of 
providing rehabilitation that consider timing, intensity, and duration of 
treatment.  Patients with a diagnosis of hip fracture and/or stroke comprise the 
majority of patients admitted to rehabilitation units and, therefore, provide a 
good model for study.  In addition, current practice has evolved in response to 
reimbursement guidelines, rather than clinical evidence.  This RFA will build on 
the recommendations of these workshops and promote and support clinical research 
studies that will establish optimal delivery schedules and amount of 
rehabilitation services for patients in different diagnosis groups or 
categories.

Research Scope

Current constraints on clinical researchers make the complex and time-consuming 
process of planning Phase III clinical trials problematic, especially in the 
field of medical rehabilitation, where there is not a well-established clinical 
research infrastructure.  These planning grants will provide a mechanism for 
early peer review of the rationale and design of the potential clinical trial, 
and provide successful applicants resources to assist development of detailed 
clinical trial study plans and collaborations.  It is hoped that these Planning 
Grants will help to facilitate clinical trial projects in areas of research need 
relevant to the National Center for Medical Rehabilitation Research (NCMRR), 
NICHD.

The range of activities that may be supported by this Clinical Trial 
Planning Grant includes:

1.  Development of a detailed experimental design, including:  translation of 
the clinical question into a statistical hypothesis; determination of the sample 
size and duration of the trial; selection of endpoint(s) and data to be 
collected; creation of inclusion/exclusion criteria.

2.  Development of specific protocols, including:  patient selection 
and informed consent procedures; randomization and masking procedures; 
data collection techniques; treatment administration and 
dose/quantity measurements; follow-up and quality control procedures.          

3.  Development of detailed plans for patient recruitment and 
retention, including women and minority individuals, and plans for recruitment 
outreach.

4.  Identification of other personnel necessary to perform the 
proposed research, including statisticians, data managers, and study 
coordinators.

5.  Identification of the physical resources necessary to perform the proposed 
research, including clinical space and equipment that are accessible to subjects 
and researchers with disabilities.

6.  Selection of specific methods of data analysis.

7.   Evaluation of models of the rehabilitation treatment process, 
including:  involvement of various professional disciplines, team approaches, 
and treatment settings, coordination of health care systems and resources.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines available at                
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.  The 
revisions relate to NIH-defined Phase III clinical trials and require:  a) all 
applications or proposals and/or protocols to provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender and/or 
racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

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

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

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

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  This policy announcement is found in the NIH Guide for Grants and 
Contracts Announcement dated June 5, 2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the Internet sites.  
Reviewers are cautioned that their anonymity may be compromised when they 
directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances. Data that are (1) first produced in a project 
that is supported in whole or in part with Federal funds and (2) cited publicly 
and officially by a Federal agency in support of an action that has the force 
and effect of law (i.e., a regulation) may be accessed through FOIA.  It is 
important for applicants to understand the basic scope of this amendment. NIH 
has provided guidance at:  
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description 
of the archiving plan in the study design and include information about this in 
the budget justification section of the application. In addition, applicants 
should think about how to structure informed consent statements and other human 
subjects procedures given the potential for wider use of data collected under 
this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of this RFA.  
Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NICHD staff to estimate the potential review workload and 
plan the review.

The letter of intent is to be sent to Dr. Beth Ansel at the address listed under 
INQUIRIES, below, by January 18, 2002.

APPLICATION PROCEDURES 

The PHS 398 research grant application instructions and forms (rev. 5/2001) 
at http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants. This version of the PHS 398 is available in an 
interactive, searchable PDF format.  Beginning January 10, 2002, the NIH will 
return applications that are not submitted on the 5/2001 version.  For further 
assistance contact GrantsInfo, Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only 
when there is a possibility for an award. It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers 
and NIH staff.  The research grant application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions.

Submission Instructions  

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
stapled to the bottom of the face page of the application and must display 
the RFA number HD-01-022.  A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note this 
is in the pdf format.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.

Submit a signed, typewritten original of the application, including 
the Checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application should 
be sent to:

Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03, MSC 7510
Bethesda, MD  20892-7510
Bethesda, MD  20852 (for express/courier service)

Applications must be received by February 14, 2002.  If an application is 
received after that date, it will be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The CSR 
will not accept any application that is essentially the same as one already 
reviewed. This does not preclude the submission of substantial revisions of 
applications already reviewed, but such applications must include an 
Introduction addressing the previous critique.

REVIEW CONSIDERATIONS

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

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

Review Criteria 

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

(1) 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?

(2) Approach:  Are the conceptual frameworks, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the aims 
of the project?  Does the applicant acknowledge potential problem areas and 
consider alternative tactics?

(3) 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? 

(4) 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)?

(5) 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?

In addition to the above criteria, in accordance with NIH 
policy, applications also will be reviewed with respect to the following:

o The adequacy of plans to include both genders, minorities and 
their subgroups, and children as appropriate for the scientific goals of 
the research.  Plans for the recruitment and retention of subjects also will 
be evaluated.

o The reasonableness of the proposed budget and duration in relation to 
the proposed research.

o The adequacy of the proposed protection for humans and the environment, to 
the extent they may be adversely affected by the project proposed in the 
application.

SCHEDULE

Letter of Intent Receipt Date:    January 18, 2002
Application Receipt Date:         February 14, 2002
Peer Review Date:                 June 2002
Council Review:                   September 2002
Earliest Anticipated Start Date:  September 2002

AWARD CRITERIA 

Criteria that will be used to make award decisions include:

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

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify 
any issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic issues to:

Beth M. Ansel, Ph.D., CCC-SLP
Director, Clinical Practices Research Program 
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 2A03, MSC 7510
Bethesda, MD  20892-7510
Telephone:  301-402-2242
FAX:  301-402-0832
E-mail:  Beth_Ansel@nih.gov   

Direct inquiries regarding fiscal matters to:

Christopher Myers
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17H, MSC 7510
Bethesda, MD  20892-7510
Telephone:  301-435-6996
FAX:  301-402-0915
E-mail:  cm143g@nih.gov  

AUTHORITY AND REGULATIONS

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

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


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