Release Date:  November 29, 2000

RFA:  MH-01-010

National Institute of Child Health and Human Development
National Institute on Deafness and Other Communication Disorders
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke

Letter of Intent Receipt Date:  February 15, 2001 
Application Receipt Date:       March 22, 2001



This Request for Applications (RFA) solicits applications to study the 
development or refinement of behavioral, pharmacological or other innovative 
treatment interventions for individuals with autism or other autism-spectrum 

In November 1999, the NIH Autism Coordinating Committee held a workshop to 
review the state of the field for treatment of autism and to develop 
recommendations for future National Institutes of Health (NIH) activities and 
initiatives.  A report of this workshop and the resulting recommendations can 
be viewed at  The 
workshop participants recommended further investigations into areas of basic 
knowledge that could provide a foundation for treatment development research 
and called for support of innovative applications linking brain and/or 
behavioral processes that are at least partially understood with possible 
interventions.  There was also a perceived need for pilot trials for 
treatments, and treatment efficacy or cost-effectiveness measures in several 
modalities.  These recommendations provided the impetus for this RFA.  One 
intention of the RFA is to encourage the formation of partnerships between 
investigators familiar with the phenomenology and treatment of autism on the 
one hand and basic behavioral or neuropharmacology investigators with 
innovative concepts on the other. 

This RFA seeks Exploratory/Development R21 applications in order to assist 
researchers in developing new treatments for autism and obtaining initial 
pilot data on the efficacy of new treatments.  It is designed to support 
phases of intervention development that are prerequisite to (but do not 
include) conducting a full-scale intervention study or trial. 

The NIH supports many types of research on autism diagnosis, psychopathology, 
neural substrates, and interventions.  PA-98-108 describes these interests and 
designates program contacts at the various institutes  (“Research in Autism 
and Autism Spectrum Disorders,” PA-98-108, located at


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 RFA, “DEVELOPMENT OF INNOVATIVE 
TREATMENT APPROACHES TO AUTISM,” is related to the priority area of mental 
health and mental disorders.  Potential applicants may obtain a copy of 
"Healthy People 2010" at


Applications may be submitted by 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.  Foreign institutions are not eligible for grants for 
this specific program.  Racial/ethnic minority individuals, women, and persons 
with disabilities are encouraged to apply as Principal Investigators.


This RFA will use the National Institutes of Health (NIH) Exploratory/ 
Development Grant (R21) award mechanism.  Responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  This type of award is limited in time and amount, encourages 
innovative approaches, and is less dependent upon pilot/feasibility data than 
are typical for an R01 application.  The total project period for an 
application submitted in response to this RFA may not exceed 3 years and 
funding is limited to a maximum of $100,000 per year in direct costs.  This 
RFA is a one-time solicitation. The anticipated earliest award date is 
September 15, 2001.

Specific application instructions have been modified to reflect “MODULAR 
GRANT” and “JUST-IN-TIME” streamlining efforts being examined by the NIH.  
Complete and detailed information about Modular Grant applications can be 
found at  Further 
modification and clarification of modular grant procedures can be found at 


The participating institutes intend to commit a total of approximately 
$1,000,000 in FY 2001 to fund about 6 new grants in response to this RFA.  An 
applicant may request a project period of up to 3 years and a budget of up to 
$100,000 in direct costs per year.  Because the nature and scope of the 
research proposed may vary, it is anticipated that the size of each award will 
also vary.  Direct costs will be awarded in modules of $25,000, less any 
overlap and other administrative adjustments.  Although the financial plans of 
the Institutes provide support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a sufficient 
number of applications of outstanding scientific and technical merit.


Currently, treatments for autism are limited in their effectiveness, providing 
only partial alleviation for the symptoms that characterize this disorder.  
Available pharmacological treatments are especially limited in the scope, 
duration, and degree of their efficacy in alleviating the core features of 
this disorder.  In addition, there is a lack of research data on the efficacy 
of existing pharmacological, psychotherapeutic, or other interventions.  Thus, 
both further characterization of existing treatments and the development of 
novel approaches are needed, as well as better measures of treatment efficacy 
and effectiveness.

This RFA is designed to support the early phases of treatment development and 
pilot testing, leading up to full-scale (e.g., randomized controlled, 
interrupted time series) studies or trials aimed at establishing efficacy and 
safety.  Treatment development can be considered to have three stages: 1) 
conceptualizing an intervention approach based on theory and empirical 
research; 2) developing and standardizing the intervention and/or intervention 
outcome measures; and 3) pilot testing.  This RFA solicits research 
applications for any of the above stages.  Investigators are not expected to 
necessarily complete all phases of intervention development during the three-
year duration of the award.  They should propose feasible and systematic goals 
that can be accomplished within the time and funding periods of this award 
while considering the final aim of completing the prerequisites for conducting 
a controlled study or trial. 

Conceptualizing an intervention approach (Stage 1) could include research on 
developing new psychosocial, pharmacological or biological interventions for 
subjects with autism, adapting existing interventions to specific needs of a 
subgroup of patients, or attempts to translate basic neuroscience research 
findings into clinical treatment applications.  These would be necessary 
preliminary steps to progressing to Stage 2, developing and standardizing an 

Intervention standardization (Stage 2) includes components such as the 
following: development of a treatment protocol; operationally defining 
intervention components for use in creating a manual (e.g., psychosocial 
intervention manual, initial medication dosing level); development or 
adaptation of relevant measures, including diagnostic, cost and outcome 
measurement; formulation of measures of provider competency; acceptance and 
adherence to the protocol; participant behavior change; and acceptance and 
adherence to treatment.

Pilot and feasibility studies (Stage 3) may include: testing and further 
refining of initial intervention manual and measures developed during Stage 2; 
gathering data to estimate intervention parameters (e.g., effect size, 
attrition rates, response rates) and performing preliminary power analyses; 
evaluating feasibility of procedures for implementing and evaluating the 
intervention in a controlled outcome study (e.g., participant and provider 
recruitment, sample definition, intervention assignment, and outcome 
measures).  Sample sizes for Stage 3 should be appropriately estimated to 
answer the relevant questions about the adequacy of the intervention 
development, or to establish reliable estimates of intervention effect 
parameters prior to trials, as applicable.

The goals of the study should be clearly outlined and related to specific aims 
and procedures pertinent to whichever phase(s) (i.e., Stages 1, 2, or 3) of 
intervention development will be pursued.  It is acknowledged that boundaries 
between the stages outlined above are non-discrete and therefore, 
investigators may propose ideas or methods including subsets of one or more 
categories.  However, the application should include a clearly operationalized 
description of each component step, with decision points indicating when each 
has been successfully completed and when to move on to subsequent components.  
The development of both empirically indicated and theory-driven interventions 
is encouraged.  Adaptation of existing treatments to new populations, 
settings, etc., is considered innovative within a public health model.

Research Goals and Topics

Types of Exploratory/Development Grants for Intervention Research

The following are illustrative, but not restrictive, topics for consideration: 

o  Identify clinical applications of basic neuroscience findings and develop 
applications relevant to the treatment of subjects with autism and autism-
spectrum disorders.

o  Test treatments that are often used but have not been examined for their 

o  Conduct pilot-testing, dose-finding, and exploratory studies of promising 
pharmacological, immunological, or dietary interventions for the treatment of 
subjects with autism and autism-spectrum disorders.

o  Validate and refine current approaches to the treatment of autism and 
autism spectrum disorders.

o  Analyze and define the critical features of effective interventions.   

o  Develop interventions for subjects with autism and common comorbid symptoms 
or disorders.

o  Develop procedures that measure both proximal and distal effects of 
interventions, including developmental, ecological and multisystemic outcomes. 

o  Develop family-based interventions to include maintenance and 
rehabilitative strategies.

o  Develop innovative behavioral, psychoeducational, psychopharmacological, or 
other biologically based treatments for children with autism and autism-
spectrum disorders.

o  Examination of the biological basis of early behavioral interventions and 
how biologic factors might predict treatment response.

o  Pilot-test early interventions for toddlers and young children diagnosed 
with autism or autism-spectrum disorders. 

o  Develop models to better understand variables (child-related, 
neurobiological, family-related, and/or cultural/environmental) that predict 
the range of responses to interventions.

o  Develop models to define the active components of interventions and 
possible relationship between dose and intensity of treatment on one side, and 
treatment outcomes on the other.

o  Develop procedures to identify developmentally sensitive outcomes, 
including behavioral and neurobiological outcome measures that are 
hypothesized to be associated with behavioral change.

o  Develop innovative approaches, including the use of newly emerging 
technologies for treating children who are not responding to current treatment 

o  Develop approaches to examine the effects of combined behavioral and 
psychopharmacological treatments, as compared to unimodal treatment. 

o  Examine the effects of polypharmacy, including interactions of drugs with 
each other and with nutrients.

o  Development of metabolic treatment strategies targeted at specific 
subgroups of subjects with autism or autism-spectrum disorders.

Examples of areas not supported by this RFA that are relevant to the more 
general autism Program Announcement:

o  Research that addresses the genetics and neurobiology of the disorder 
without directly focusing on treatment interventions.
o  Research that focuses on diagnostic assessments, subtyping, and clinical 
recognition, without a specific focus on treatment interventions.

o  Research on the epidemiology of the disorder.

o  Research on the identification of potential risk factors of the disorder.

All these areas of research are not included in the present RFA, but are all 
relevant to the PA “Research in Autism and Autism Spectrum Disorders” (PA-98-
108), which is located at


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 
a complete copy of the updated Guidelines are available at  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.


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" that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 

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


All applications 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.


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 the RFA in 
response to which the application may be submitted.  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 Institute 
staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent to Dr. Vitiello, at the address listed 
under INQUIRIES, by the letter of intent receipt date listed in the heading of 
this RFA.


The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone: (301) 710-0267, E-mail:  The application is also available at  The usual 25-page 
limit applies to the narrative portion of R21 applications under this RFA.


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 
Institute staff.  The research grant application form PHS 398 (rev. 4/98) is 
to be used in applying for these grants, with the modifications noted below.


Modular Grant applications will request direct costs in $25,000 modules, up to 
the total direct cost request of $100,000 per year allowed under this RFA.  
The total direct costs must be requested in accordance with the program 
guidelines and the modifications made to the standard PHS 398 application 
instructions described below:

PHS 398

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to the $100,000 maximum allowed under this RFA) and 
Total Costs [Modular Total Direct plus Facilities and Administrative (F&A) 
costs] for the initial budget period.  Items 8a and 8b should be completed 
indicating the Direct and Total Costs for the entire proposed period of 

of the PHS 398 (rev 4/98).  It is not required and will not be accepted at the 
time of application.

categorical budget tables on page 5 of the PHS 398 (rev. 4/98) Form.  It is 
not required and will not be accepted at the time of application.

o  NARRATIVE BUDGET JUSTIFICATION: Prepare a Modular Grant Budget Narrative 
page. (See for sample 
pages.) At the top of the page, enter the total direct costs requested for 
each year.  This is not a Form page.

o  Under Personnel, list all project personnel, including their names, percent 
of effort, and roles on the project.  No individual salary information should 
be provided.  However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the nearest 
$1,000.  List the individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort of all personnel, 
and the role on the project.  Indicate whether the collaborating institution 
is foreign or domestic.  The total cost for a consortium/contractual 
arrangement is included in the overall requested modular direct cost amount.  
Include the Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by  
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than 3 pages may 
be used for each person.  A sample biographical sketch may be viewed at 

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last 3 years;
- List selected peer-reviewed publications, with full citations.

o  CHECKLIST - This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate the 
type of agreement and the date.  All appropriate exclusions must be applied in 
the calculation of the F&A costs for the initial budget period and all future 
budget years.

o  The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review.

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application. Type the RFA Number 
(MH-01-010) on the label.  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, DEVELOPMENT OF 
line 2 of the face page of the application form and the YES box must be 

The sample modified mailing label available at has been modified to 
allow for this change.  Please note this is in pdf format.   

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

BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, one additional copy of the application must be sent 

Benedetto Vitiello, M.D.
Division of Services and Intervention Research
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 7149, MSC 9633
Bethesda, MD 20892-9633
Rockville, MD 20852 (for express/courier service)

Applications must be received by March 22, 2001.  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.


Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIH staff.  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 
NIH in accordance with the review criteria stated below.  As part of the 
initial merit review, a process will be used by the initial review group in 
which applications receive a written critique and undergo a process in which 
only those applications deemed to have the highest scientific merit, generally 
the top half of the applications under review, will be discussed, assigned a 
priority score, and receive a second level review by the National Advisory 

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

(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 

In addition to the above criteria, in accordance with NIH policy, all 
applications will also 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 will also be 

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

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


Letter of Intent Receipt Date:    February 15, 2001 
Application Receipt Date:         March 22, 2001
Peer Review Date:                 June/July 2001
Council Review:                   September 2001
Earliest Anticipated Start Date:  September 15, 2001


Award criteria that will be used to make award decisions are:

o  Scientific merit (as determined by peer review)
o  Availability of funds
o  Programmatic priorities


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

Direct inquiries regarding programmatic issues, including eligibility and 
responsiveness, to one of the program staff members listed below:

Benedetto Vitiello, M.D.
Division of Services and Intervention Research
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 7149, MSC 9633
Bethesda, MD 20892-9633
Telephone:  (301) 443-4283
Fax: (301) 443-4045

Deborah Hirtz M.D.
Neurodevelopment, Division of Extramural Research
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2143, MSC 9523
Bethesda, MD 20892
Telephone: (301)496-5821
Fax: (301)480-1080

Marie Bristol-Power, Ph.D.
National Institute of Child Health and Human Development
6100 Executive Blvd, Room 4B09, MSC 7510
Bethesda, MD 20892-7510
Telephone:  (301) 402-1822
Fax:  (301) 496-3791

Judith A. Cooper, Ph.D.
Scientific Programs Branch
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400C, MSC-7180 
Bethesda, MD 20892-7180 
Telephone: (301) 496-5061
Fax: (301) 402-6251 

Direct inquiries regarding fiscal matters to one of the following:

Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2805
Fax:  (301) 443-6885

Gladys Melendez-Bohler, M.S.
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3290, MSC 9537
Bethesda, Maryland 20892-9537
Telephone: (301)496-3929 
Fax: (301)402-0219

Laura Reidy
Grants Management Specialist
National Institute of Child Health and Human Development
6100 Executive Blvd., Room 8A07, MSC 7510
Bethesda, MD 20892-7510
Telephone:  (301) 435-7002
Fax:  (301 402-0915

Sherry Dabney 
Grants Management Branch
National Institute on Deafness and Other Communication Disorders 
6120 Executive Boulevard, Room 400B, MSC-7180 
Bethesda, MD 20892-7180 
Telephone: (301) 402-0909 
Fax: (301) 402-1758 


This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.242 and 93.858.  Awards are made under authorization of the Public Health 
Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-
158, 42 USC 241 and 285) and administered under NIH grants policies and 
Federal Regulations 42 CFR 52 and 45 CFR Part 74.  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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