LEARNING DISABILITIES:  MULTIDISCIPLINARY RESEARCH CENTERS

Release Date:  January 18, 2000

RFA:  HD-00-003

National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)

Letter of Intent Receipt Date:  February  28, 2000
Application Receipt Date:       April 21, 2000

PURPOSE

The Child Development and Behavior Branch (CDB) of the Center for 
Research for Mothers and Children (CRMC), National Institute of Child 
Health and Human Development NICHD), invites research grant 
applications to develop new knowledge in the areas of definition, 
classification, epidemiology, prevention (and preventative strategies), 
early intervention, etiology, diagnosis, and treatment of children who 
display learning disabilities (LD) in component oral language abilities 
(phonology, morphology, semantics, syntax, pragmatics), reading (word 
attack skills, word recognition skills, reading fluency and 
automaticity, reading comprehension), written expression abilities 
(spelling, composition), and mathematics (basic calculation skills, 
mathematical reasoning), and combinations and relationships among them.  
The specific focus of this RFA is on the discovery of cognitive, 
linguistic, perceptual, behavioral, genetic, hormonal, and 
neurobiological mechanisms that are influential in the expression of 
learning disabilities and the development of preventive and treatment 
approaches to ameliorate these disorders.

This RFA will result in grants supporting a combination of site-
specific research and collaborative efforts with other research sites 
currently within the NICHD Learning Disability and Reading Research 
Networks.

Within the context of these Learning Disabilities multidisciplinary 
research centers, the National Institute of Mental Health  (NIMH) 
encourages research on the diagnosis, assessment, and intervention for 
problems of inattention, hyperactivity, and impulsivity, including the 
psychiatric diagnosis of attention deficit hyperactivity disorder 
(ADHD).  Such studies should attempt to advance the scientific 
understanding of underlying mechanisms and risk processes related to 
ADHD, and may include basic research on dimensions of attention 
regulation and related systems that have implications for the etiology, 
identification, prevention and/or treatment of ADHD; and basic or 
applied research on etiology, risk factors, diagnosis and/or prevention 
of ADHD. 

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a 
PHS-led national activity for setting priority areas.  This Request for 
Applications (RFA), Learning Disabilities: Multidisciplinary Research 
Centers, is related to several priority areas.  Potential applicants 
may obtain a copy of “Healthy People 2000" at 
http://odphp.osophs.dhhs.gov/pubs/hp2000.
  
ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations such as universities, colleges, hospitals, schools, 
laboratories, units of state and local governments, and eligible 
agencies of the Federal Government.  Foreign institutions are not 
eligible to apply for these grants.  Racial/ethnic minority 
individuals, women, and persons with disabilities are encouraged to 
apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Specialized 
Research Center Grant (P50) award mechanism.  Responsibility for the 
planning, direction, and execution of the proposed project will be 
solely that of the applicant.  The total project period for an 
application submitted in response to this RFA may not exceed five 
years.  Potential applicants may obtain the NICHD P50 Specialized 
Research Center Grant Guidelines at 
http://www.nichd.nih.gov/funding/dsr_p50_guide.htm

FUNDS AVAILABLE

The NICHD intends to commit up to approximately $6 million Total Costs 
(Direct plus Facilities and Administrative) in FY 2001 to fund four new 
and/or competing continuation grants in response to this RFA.  An 
applicant may request a project period of up to five years and a budget 
for direct costs of up to $1 million, excluding Facilities and 
Administrative costs on consortium arrangements.  Because the nature 
and scope of the research proposed may vary, it is anticipated that the 
size of awards also will vary.  Although the financial plans of NICHD 
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 high scientific and technical 
merit.

The NIMH intends to commit up to approximately $1 million in FY 2001 in 
support of Centers that include a focus on basic or applied research on 
the etiology, risk factors, identification/diagnosis and/or 
interventions for ADHD and its symptoms.  Although the financial plans 
of the NIMH provide support for this program, awards persuant to this 
RFA are contingent upon the availability of funds and receipt of a 
sufficient number of applications of outstanding scientific and 
technical merit.
 
RESEARCH OBJECTIVES

Background

The National Institute of Child Health and Human Development (NICHD), 
NIH, has had a longstanding interest in the study of normal language 
and reading development, learning disabilities, and disorders that 
adversely affect the development of listening, speaking, reading, 
writing, and mathematics abilities in approximately 15 to 20 percent of 
children in the United States.  Since its inception in l963, the NICHD 
has funded research to delineate the basic biological and behavioral 
mechanisms that underlie normal language and normal reading development 
and specific deficits in attention, perception, language, cognition, 
and academic skills, particularly reading.  In January l987, a National 
Conference on Learning Disabilities, co-sponsored by the Interagency 
Committee on Learning Disabilities (of which the NICHD was designated 
as the lead agency) and the Foundation for Children with Learning 
Disabilities (FCLD, now NCLD), was held on the NIH campus.  The 
proceedings of this conference were combined with other sources to 
provide a comprehensive document titled "Learning Disabilities:  A 
Report to the U.S. Congress" (l987).  A major recommendation included 
in this report called for a systematic effort to conduct research to 
develop a valid and reliable definition and classification system that 
could provide a theoretical, conceptual, and empirical framework for 
the identification of different types of learning disabilities, as well 
as the identification of distinctions and interrelationships 
(comorbidities) between types of LD and other childhood disorders, 
including general academic underachievement, disorders of attention, 
mental retardation, genetic disorders, and emotional disturbance.  In 
addition, the "Report to Congress" called for a systematic effort to 
develop rigorous research strategies and intervention trials to examine 
the responses of children with LD to different forms of treatment.

Based on the l987 "Report to Congress" recommendations, NICHD funded 
three Multidisciplinary Learning Disability Research Centers (LDRCs) in 
l988 to initiate studies on the definition, classification, and 
etiology of LD and related disorders.  These three centers joined 
several program projects that, beginning in 1964, had been focused on 
the specific study of normal reading development, language processes 
related to reading, and dyslexia.  In l993, two additional research 
programs were funded to study the effects of treatment interventions on 
children with language-based reading deficits, with a third 
intervention project added in 1995.  

Research Scope

Studies conducted at the LDRCs, program projects, and reading 
intervention sites over the past three decades have yielded discoveries 
in several domains, summarized below according to research targets.  
Likewise, remaining gaps in the extant knowledge base which require 
additional systematic research also are identified for each domain.  
The research needs identified in the following sections are examples of 
research topics that applicants should consider when developing their 
responses to this initiative.  The examples provided are not 
exhaustive.

o  Classification/Definition:  Lessons Learned

1.  The definition and classification of different types of LD, 
dyslexia, and  attentional problems should be accomplished within a 
longitudinal developmental framework that does not require adherence to 
a priori assumptions reflected in current definitions.  The development 
of valid definitions requires that studies be conducted with 
representative groups of children over time and that document, with 
robust measurements and measurement models, how individual differences 
among children emerge, change, respond to treatment, and influence 
further development.  In developing definitions, a critical emphasis 
should be placed on the identification of valid inclusionary criteria.  

To date, the preponderance of the NICHD definitional studies have 
focused on the definition and classification of  disorders in basic 
reading skills with comorbid attentional problems.  Similar efforts now 
must be deployed to develop reliable and valid inclusionary definitions 
of learning disabilities in mathematics, written language, and reading 
comprehension.  Such efforts should also be designed to identify and 
describe comorbidities of these specific learning disabilities with 
attentional problems and specific genetic disorders affecting social, 
emotional, linguistic, and behavioral development. 

2.  With respect to LD in basic reading skills (dyslexia), current 
exclusionary definitions appear to be invalid if discrepancy criteria 
are used.  Reading disabled (RD) children with and without a 
discrepancy between IQ and reading achievement do not differ in 
information processing subskills (e.g., phonological and orthographic 
processing) that are critical to the reading of single words.  
Likewise, genetic and neurophysiological studies have not indicated 
differential etiologies for RD children with and without IQ-Achievement 
discrepancies.  In addition, recent intervention studies undertaken 
with RD children with and without discrepancies indicate that presence 
and magnitude of the discrepancy between IQ and reading achievement 
does NOT predict response to treatment.  It remains to be seen whether 
discrepancies between IQ and achievement constitute valid markers in 
the areas of oral language, reading comprehension, written expression, 
mathematics, or whether discrepancies are worthwhile predictors of 
response to treatment/interventions in these domains.

o  Reading and Language-Related Processes:  Lessons Learned

1.  LDRC longitudinal, epidemiological studies show that RD (dyslexia) 
affects at least 10 million children, or approximately one child in 
five.  These epidemiological data need to be further refined to 
identify specific linkages between reading failure and sociocultural, 
economic, and demographic factors.  Of particular import is the 
identification of specific effects of home literacy practices, parents’ 
reading levels and practices, the specific effects of poverty on 
reading failure, and the identification of risk and protective factors 
within these contexts.

2.  While public schools identify approximately four times as many boys 
as girls as RD, LDRC and program project longitudinal and 
epidemiological studies show that as many girls manifest RD as boys.  
What is not as well understood are the factors that predispose boys to 
a higher rate of identification.  Questions related to severity, 
classroom behavior, teacher expectations and perceptions, and the 
influence of comorbidities need to be addressed explicitly during this 
next five-year research cycle

3.  RD appears to reflect a persistent deficit rather than a 
developmental lag in linguistic (phonological) skills and basic reading 
skills.  LDRC and program project longitudinal studies show that of the 
children who are diagnosed RD in the third grade, 74 percent remain 
disabled in the ninth grade.  Given these findings, several questions 
remain and should be considered for study during the next five-year 
research cycle.  For example, what are the characteristics of those 
children who are no longer diagnosed RD?  Was their disability less 
severe in contrast to children with persistent RD?  Were particular 
treatments/interventions more effective with the compensated RD 
children than with those children who remained RD?  Do compensated RD 
children show differences in neurophysiological, linguistic, cognitive, 
and/or behavioral features?  What are the best predictors of outcome?  
Do predictors change as a function of type of intervention/treatment?  
Importantly, what are the conditions under which older children and 
adults can improve reading skills and what are the characteristics of 
the instructional programs in this regard with respect to intensity, 
duration, degree of explicitness, degree of integration among 
components of reading, and the instructional unit of analysis 
(letter/sound, onset-rime, syllable, word) employed in developing word 
reading skills? 

4.  Children with RD differ from one another and from other non-
disabled readers along a continuous distribution, and do not aggregate 
together to form a bi-modal distribution or a distinctive "hump" at the 
tail of the normal distribution.  Given that RD occurs along a 
continuum, it will be important to understand in future studies which 
"cut-points" are most valid and useful for establishing levels of 
severity for diagnostic and treatment planning purposes.  Intervention 
studies would be helpful in this regard.

5.  The ability to read and comprehend depends substantially upon rapid 
and automatic recognition and decoding of single words.  Slow, 
laborious, and inaccurate decoding are powerful predictors of 
difficulties in reading comprehension.  While this finding has been 
replicated across the LDRCs, program projects, and reading intervention 
sites, an identification of the multiple cognitive , linguistic, 
genetic and neurobiological sources that are required for comprehension 
and their relative importance to comprehension is not fully understood.  
More detailed and comprehensive studies are needed in this area, 
particularly with respect to the impact of individual differences in 
vocabulary development, extent of background knowledge, development and 
use of semantic, grammatical, and syntactical skills in deriving 
meaning from print, knowledge of writing conventions, verbal reasoning 
ability, and memory for verbal material, and the genetic and 
neurobiological factors that influence development in these domains.  
Applicants should consider research efforts to clarify these issues. 

6.  The ability to decode single words accurately and fluently appears 
dependent upon the ability to segment words and syllables into abstract 
constituent sound units (phonemes).  Converging evidence from the 
LDRCs, program projects, and reading intervention sites indicates that 
combined deficits in phonological awareness, letter and number naming, 
and print awareness serve as substantial predictors of reading failure.  
In future studies, it will be critical to determine whether the 
phonological deficit reflects a specific linguistic deficiency that 
interferes with the development of reading in and of itself, or whether 
deficits in phonology actually reflect deficiencies at lower levels of 
processing (e.g., rapid temporal processing of information irrespective 
of modality).  Within this context it is also critical to identify the 
relative influences of, and relationships between, deficits in 
phonological processing and timing and rate factors, particularly with 
respect to predicting individual differences in reading fluency and 
automaticity.  Studies that identify the genetic, hormonal,  and 
neurobiological underpinnings of phonological and rate deficits also 
need to be expanded to address these issues.

7.  Related to the rate and timing issues noted above, LDRC, program 
project, and reading intervention site data indicate that orthographic 
processing influences how reading develops in children.  Given this 
consistent finding, research is needed to fully define and identify the 
role of orthographic processing in both single word reading and 
comprehension, as well to identify and delineate other visual 
processing factors that may contribute to the developmental reading 
process.  Neurobiological, hormonal, genetic, cognitive, and treatment 
studies will be instrumental in this regard.

o  Attentional Problems and Comorbid RD and ADHD:  Lessons Learned

1.  The reviews of the literature conducted by the LDRCs and program 
projects indicate that a precise classification system and definition 
of problems in attention are not yet available.  A classification 
methodology that assesses BOTH internal and external validity of 
dimensional AND categorical models must be applied to the task.  
Further, any classification effort must be informed by a well developed 
model incorporating behavioral, environmental, neurobiological, 
genetic, and hormonal influences and their interrelationships. These 
efforts should be expanded during the five-year research cycle relevant 
to this RFA.  Until these definitional issues are clarified, any 
findings discussed with respect to attentional problems must be 
interpreted with caution.

2.  RD and ADHD, as one type of attentional problem, often co-exist, 
but the two disorders appear distinct and separable with respect to the 
effects of ADHD on cognitive tasks.  For example, it has been found 
that ADHD children perform poorly on rote verbal learning and memory 
tasks, but relatively well on naming and phonological awareness tasks.  
The converse appears to be the case for children with RD.  Clearly, 
research is needed to understand whether differential neurobiological 
and genetic mechanisms underlie disorders of attention versus other 
types of learning disabilities.  It will also be critical to understand 
whether comorbidity between RD and disorders of attention predispose a 
child to particular treatment response patterns.  Likewise, research is 
critically needed to identify the specific relationships that exist 
between individual differences in attention and the development of 
mathematics and written language capabilities.

3.  The severity and cognitive morbidity of RD are exacerbated by 
comorbid ADHD, with the co-occurance of the two disorders more frequent 
among males.  Thus, level of severity may be one reason that more males 
than females are identified as RD.  Neurobiological, hormonal, and 
genetic research will be critical to understanding the gender 
difference for comorbid RD, ADD and ADHD, and treatment studies will be 
critical in determining the types of interventions necessary to 
remediate severe RD with ADD/ADHD.  During this next five-year research 
cycle, it will be critical to expand this same type of effort to the 
study of  mathematics and written language disabilities with and 
without comorbid ADHD.

o  Genetics:  Lessons Learned

1.  A multiple regression analytic procedure has been developed  via 
NICHD support that allows for the analysis of the genetic etiology of 
deviant scores as well as individual differences in language/reading 
functions.  This is a highly unique and flexible methodology that can 
be extended to assess a wide range of possible main effects and 
interactions and to test for differential genetic and environmental 
influences.  Expansion of these types of models and procedures to the 
identification of heritability factors in reading comprehension, 
mathematics, and written language disorders, as well as disorders of 
attention, will be critical during the five-year grant cycle relevant 
to this RFA.

2.  Similarly, twin studies have found strong evidence for genetic 
etiology of reading disability, with deficits in phonological awareness 
reflecting the greatest degree of heritability.  There is also 
behavioral and molecular genetic evidence for degrees of heritability 
for orthographic processing, but this relationship is not well 
understood.  Efforts to uncover the genetic influence in the 
development of these components of reading must be continued, with 
efforts also being deployed to better understand the heritability of 
rate and fluency factors.  Linkage between genetic findings and 
neurobiological development in children is also of high importance.  
Integrated genetic and neuroimaging studies should be considered in 
this regard.

3.  Some data suggest that at least one type of reading disability can 
be linked to the HLA region of Chromosome 6, reflecting a possible 
association with autoimmune disorders.  Recent evidence obtained from 
twin and kindred siblings with severe deficits in reading performance 
show strong evidence for a Quantitative Trait Locus on  Chromosome 6.  
These studies need to be continued and replicated in combination with 
the search for additional chromosomal regions.  Moreover, studies 
improving on this type of methodology also should be applied to the 
identification of quantitative trait loci for deficits in cognitive 
components of mathematics development, written language, and attention.

o  Neurobiology (Neuroanatomy, Neurophysiology, Neuroimaging):  Lessons 
Learned

1.  Learning to read requires, among other skills, an awareness that 
spoken words can be decomposed into the phonological constituents that 
the alphabetic characters represent.  Phonological awareness is 
typically lacking in LD children with reading disorders (RD) making it 
difficult for them to link the alphabetic characters with the sounds of 
speech.  Recent advances in the application of functional neuroimaging 
modalities (e.g., fMRI) have indicated that neural activation patterns 
differ significantly between RD children and normal readers.  
Specifically, RD children show relative under-activation in posterior 
brain regions (Wernicke’s area, angular gyrus, striate cortex) and 
relative over-activation in anterior regions (inferior frontal gyrus).  
Post-mortem studies and investigations employing brain morphometry and 
electrophysiology converge on these findings, particularly with respect 
to differences identified between RD and normal readers in temporo-
parieto-occipital brain regions.

It will be critical during the next LDRC research cycle to replicate 
and extend these findings by employing a number of neuroimaging 
modalities (e.g., MRI, fMRI, MEG, MRS, Diffusion Tensor Imaging) and 
dependent measures to assess the organization of cognitive and 
linguistic skills critical to reading in the brain.  Moreover, in 
addition to identifying the neural organization for specific skills 
critical to basic reading development, studies designed to delineate 
the neural substrates and changes that are necessary for the 
development of automaticity and expertise in the application of these 
reading skills are critically needed.  Likewise, studies to delineate 
component cognitive and linguistic processes involved in reading 
comprehension and their neural activation signatures in disabled and 
non-disabled readers are needed.

2.  Preliminary data suggest that changes in reading behavior produced 
by well-defined early interventions are reflected in changes in neural 
activation in those brain regions implicated in the development of 
basic reading skills.  Integrated intervention-neuroimaging studies 
need to be replicated and expanded to better understand the specific 
impact of behavioral perturbation on brain development and function, 
and to determine whether the intensity and duration of the intervention 
required to produce both behavioral and neural changes vary as a 
function of chronological age.

3.  Advances in the application of structural and functional imaging 
modalities need to be expanded and applied to the study of brain-
behavior relationships relevant to disorders in the development of 
mathematics, written language, and attentional skills.  Likewise, 
neuroanatomical, neurophysiological, neuropsychological, and 
educational studies of development and disorders in executive function 
and social, nonverbal communication are critically needed.

o  Interventions and Instructional Studies:  Lessons Learned

1.  Since 1993, NICHD-initiated reading intervention studies have 
focused on the need to identify the instructional components that are 
most beneficial for well-defined children in well-defined settings at 
different points in reading development.  Converging data derived from 
several NICHD reading intervention sites indicate that for many (but 
not all) young children at-risk for reading failure, early explicit 
instruction designed to teach phoneme awareness, the alphabetic 
principle, and word recognition skills, within the context of a 
complete reading program, increases decoding skills, word recognition 
abilities, and, to some extent, reading comprehension skills.  
Moreover, studies with older disabled readers (grades 3 through 5) 
indicate that many (but not all) older children can significantly 
improve their basic reading skills with intensive intervention 
approaches that emphasize explicit remediation of phonological 
processing abilities and the systematic integration of these skills 
with instruction in phonics, textual reading, and reading 
comprehension.

Within this context, several critical research opportunities exist 
which may be addressed in response to this RFA.  First, several studies 
have found that interventions that are targeted primarily to the 
development of phonological, decoding, and word reading skills are not 
sufficient, in and of themselves, to ensure transfer of these skills to 
the fluent reading of textual reading formats.  Indeed, the development 
of fluency and automaticity in RD children remains poorly understood.  
This is unfortunate given that reading comprehension is critically 
dependent not only on word reading skills, but also on reading fluency 
and language comprehension abilities.  A major goal of this RFA is to 
stimulate intensive research efforts to delineate the instructional 
conditions that are necessary to produce improvements in ALL aspects of 
reading, with a significant focus on the development of reading 
fluency, automaticity, and reading comprehension strategies.

2.  While increased efforts must be deployed to better understand the 
development of reading fluency, automaticity and comprehension skills, 
intervention efforts also must be expanded to the development of well-
defined mathematics and written language skills in children at-risk for 
failure in these academic domains.  Applicants are encouraged to 
consider the design of intervention studies in these areas.   

Research Focus

As has been noted, current knowledge related to the etiologies, 
developmental courses, and diagnostic characteristics of children with 
LD who display primary deficits in written expression, reading 
comprehension, and mathematics is less well developed than that which 
is now known about aspects of oral language (e.g., phonology) and basic 
reading development.  As such, there exists a need to initiate studies 
of these types of LD, particularly with respect to establishing 
reliable and valid definitions and classification systems, reliable and 
valid measurement strategies and instruments, identifying critical 
etiological factors (cognitive, linguistic, genetic, neurobiological, 
experiential) associated with impairments in these domains, mapping the 
developmental course of skill and concept acquisition, and determining 
response to well-defined treatment interventions. For the purposes of 
this RFA, applicants are encouraged to incorporate studies of reading 
comprehension, written expression, and/or mathematics in their research 
plan even if the major emphasis of the proposal also targets basic 
reading skills and/or disorders of attention.  Applicants are 
encouraged to utilize state-of-the-art quantitative and qualitative 
research methodologies, and studies that combine methodologies are 
particularly encouraged.

In preparing applications in response to this RFA, applicants should 
ensure that the following methodological and organizational issues are 
addressed:

1.  Research Population

The selection of the research population should be based upon the need 
to conduct integrated prospective, developmental, longitudinal 
investigations incorporating neurobiological, cognitive/behavioral, and 
early (and later) treatment/intervention studies with children who 
manifest LD in one or more of several domains to include oral language, 
basic reading skills, reading comprehension, written expression, and 
mathematics development, as well as deficits in attention.  Within this 
context, longitudinal studies may be initiated with preschool and 
kindergarten children, with the children being followed as they enter 
and proceed through the early grades.  Cross-sectional studies of LD 
children of different ages ranging across the elementary and middle 
school age-span also should be considered, but such studies must be 
related meaningfully to the questions being asked within the 
longitudinal studies.

It is expected that not all children within the research population 
will manifest the entire range of oral language, written language, and 
mathematics deficits detailed above. Likewise, children selected for 
study likely will vary across cultural, familial, ethnic, racial, 
economic, and other demographic characteristics that could influence 
development.  As such, there likely will be subgroups and subtypes of 
children with significantly different patterns of demographic 
characteristics, academic deficits, different patterns of comorbidity, 
levels of severity, and different psychological/cognitive processing 
deficits.  Therefore, applicants should consider research protocols 
that are capable of identifying well-defined subgroups and subtypes 
that exist within the sample.  Investigators also should consider 
casting the sampling net wide enough to insure a representative number 
of subtypes and contrast groups within the study population.  For 
example, of interest are studies of subtypes of LD children of varying 
demographic characteristics, intellectual abilities, with primary 
deficits in one or more academic domains who display no comorbid 
deficits, a single comorbid deficit, or a combination of comorbid 
deficits in attention, behavior, and social competencies, etc..  

2.  Subject Selection Criteria

 The samples for study must be defined rigorously so that complete 
replication can be accomplished.  Within this context, applicants 
should provide clearly documented and operationalized definitions for 
their subject selection criteria.  These definitions and criteria must 
be specified in an a priori manner.  The selection of "school-
identified" or "clinic-identified” learning disabled children is 
clearly discouraged unless the demographic and diagnostic 
characteristics in these cases matches the applicant's 
a priori established selection criteria.  Likewise, criteria for 
selection of contrast group(s) must be specified in an a priori manner.

All children selected for study must be defined with reference to age, 
gender, grade level, length of time in special education placement (if 
applicable), type of current special education placement (if 
applicable), previous special education placement(s)(if applicable) to 
include intensity and duration, ethnicity, socio-economic status, 
primary learning disability, comorbid disabilities, severity of 
disability, familial and/or genetic findings, physical/neurological 
findings, intellectual status, cognitive-linguistic status, 
neurophysiological and neuropsychological status, levels of academic 
achievement in oral language, reading, mathematics, and written 
language, and presence or absence of attention deficit disorder.  

3.  Measurement Criteria

Standardized tests, laboratory tasks, observational measures, interview 
schedules, and other assessment procedures (e.g., dynamic assessment 
procedures, case studies, ethnographic studies) must be selected on the 
basis of known reliability, validity, trustworthiness, and 
appropriateness for the samples under study.  If reliability, validity 
and trustworthiness of the measurement/assessment/observational 
procedures are initially unknown, the application must include specific 
plans for establishing these measurement properties.  The valid 
measurement of change over time is critical to much of the research 
solicited via this RFA since the study of developmental course and 
treatment effectiveness is of primary concern.  If instructional 
treatment studies are proposed, applicants should be aware of and 
employ robust procedures for separating treatment effects from the 
effects of development, in general.  The use of growth curve models and 
longitudinal data is encouraged as is the collection if sufficient data 
prior to, during, and following the instructional/treatment study to 
allow for estimation of change over time. 

SPECIAL REQUIREMENTS

1.  Annual meetings for Investigators

Principal Investigators from Centers funded through this RFA will be 
expected to attend an annual NICHD meeting to share findings, research 
approaches, and core instrumentation.  The first meeting is expected to 
take place in January 2001 to discuss core instrumentation and 
replication strategies.  Provision for funds for travel to this annual 
meeting at the NIH should be included in the application budget request 
and budget justification.

2.  Advisory Boards

Because of their complexity and size, Research Center (P50) grants 
require guidance and interaction with senior members of the scientific 
community not directly involved in the conduct of the proposed research 
operations.  For the purposes of this RFA, applicants should propose 
and design an External Advisory Board to provide outside counsel and 
periodic review of the Research Center activities and progress.  
Applicants are not to select or contact proposed Advisory Board members 
at this time.  Details of the operation of the Board, including size, 
structure, function, and frequency of meetings should be specified, as 
well as the type of expertise and level of seniority of Board members 
to be recruited.  Members of the Advisory Board are to be selected and 
confirmed within three months of the award date and notification sent 
to program staff at NICHD.  Provision for costs of the Advisory Board 
are to be included in the application budget request and budget 
justification.

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 subpopulations 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 
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 “NIH Guidelines for Inclusion of Women and Minorities as 
Subjects in Clinical Research,” that was published in the Federal 
Register of March 28, 1994 (FR59 14508-14513) and in the NIH Guide for 
Grants and Contracts, Vol. 23, No. 11, March 18, 1994, available at 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.

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” that was published 
in the NIH Guide for Grants and Contracts, March 6, 1998, and is 
available at http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

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

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 avoid conflict of 
interest in the review.

The letter of intent is to be sent to G. Reid Lyon, Ph.D., at the 
address listed under INQUIRIES, by  February  28, 2000 .

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for these P50 grants.  These forms are available at most 
institutional offices of sponsored research, on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the 
Division of Extramural Outreach and Information Resources, National 
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 
20892-7910, telephone 301-435-0714, E-mail: Grantsinfo@nih.gov.

Applications for the P50 grant are to be prepared in a manner 
consistent with the information presented in the NICHD P50 Specialized 
Research Center Grant Guidelines, available from the contacts listed 
under INQUIRIES, below, and at 
http://www.nichd.nih.gov/funding/dsr_p50_guide.htm.

Submission Procedures

The RFA label available in the PHS 398 (rev. 4/98) application form 
must be stapled to the bottom of the face page of the application and 
must display the RFA number HD-00-003. 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 5E-03, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: 301/435-6911.

Applications must be received by April 21, 2000.  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 
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 the CSR 
and for responsiveness by NICHD staff.  Incomplete and/or non-
responsive applications will be returned to the applicant without 
further consideration.

Applications that are complete and responsive to this RFA will be 
evaluated for scientific and technical merit by an appropriate review 
group convened by the NICHD in accordance with the review criteria 
stated below.  As part of the initial merit review, a process may 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 will be discussed, assigned 
a priority score, and receive a second level review by the National 
Advisory Child Health and Human Development Advisory Council.

Review Criteria

Applications submitted in response to this RFA will be evaluated 
according to the review criteria described in the NICHD P50 Specialized 
Research Center Grant Guidelines, available from the contacts listed 
under INQUIRIES, below, and at 
http://www.nichd.nih.gov/funding/dsr_p50_guide.htm.

SCHEDULE

Letter of Intent Receipt Date:     February 28, 2000   
Application Receipt Date:          April 21, 2000
Peer Review Date:                  	   June 2000
Council Review:                  	   September 2000
Earliest Anticipated Start Date:  December 2000

AWARD CRITERIA

Criteria that will be used to make award decisions include scientific 
and technical merit as determined by peer review, availability of 
funds, and programmatic priorities.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.  
The opportunity to clarify any issues or questions from potential 
applicants is welcome.

Direct inquiries regarding programmatic and scientific issues to:

G. Reid Lyon, Ph.D.
Chief, Child Development and Behavior Branch
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Building, Room 4B05, MSC 7510
Bethesda, MD  20892-7510
Telephone:  301-496-9849
Fax:  301-480-7773
E-mail:  rl60a@nih.gov

Direct inquiries regarding research specific to ADHD to:

Farris Tuma, Sc.D.
Developmental Psychopathology and Prevention Research Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6200, MSC 9617
Bethesda, MD 20892
Telephone:  301-443-9232
Fax:  301-480-4415
E-mail:  ftuma@nih.gov

Direct inquiries regarding fiscal and administrative matters to:

E. Douglas Shawver
Grants Management Branch
National Institute of Child Health and Human Development
6100 Building, Room 8A17, MSC 7510
Bethesda, Maryland  20892-7510
Telephone:  301-496-1303
Fax:  301-402-0915
E-mail:  ds117g@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.365, Research for Mothers and Children.  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 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 and contract 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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