RELEASE DATE:  January 30, 2004
RFA Number:  RFA-GM-04-002 

Update: The following update relating to this announcement has been issued:

March 5, 2009 - This RFA has been reissued as (RFA-GM-10-002) for (R24).

January 30, 2009 - This RFA has been reissued as (RFA-GM-10-001) for (U01/U19).
(see corrections and updates NOT-GM-04-108)

Department of Health and Human Services (DHHS)
National Institutes of Health (NIH)

National Institute of General Medical Sciences (NIGMS)
National Cancer Institute (NCI)
National Heart, Lung and Blood Institute (NHLBI) 
National Human Genome Research Institute (NHGRI) 
National Institute on Drug Abuse (NIDA) 
National Institute of Environmental Health Sciences (NIEHS) 
National Library of Medicine (NLM)
Office of Research on Women’s Health (ORWH)

93.859, 93.395, 93.837, 93.838, 93.172, 93.279, 93.113, 93.879 


o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The purpose of this RFA is to solicit applications for an open re-
competition of the Pharmacogenetics Research Network and Knowledge Base 
(  This is a network of 
multidisciplinary, collaborative groups of investigators that 
contribute their data to the publicly available knowledge base 
PharmGKB, which is an open research tool accessible to all scientists.  

The research groups in the network have interests across a range of 
biological processes:  drug metabolism, small molecule transport, 
target receptors, and biological pathways involved in the drug 
treatment of cardiovascular diseases, asthma, cancer, and depression; 
other areas are welcome consistent with the interests of the funding 
institutes.  The groups are collecting comprehensive, integrative 
information about specific proteins and gene families important to the 
field of pharmacogenetics.  Some groups are using a genotype-to-
phenotype approach starting with the detection of all possible 
variants, while other groups are employing a phenotype-to-genotype 
approach beginning with well-characterized clinical samples.  All 
investigations are converging on the association of single nucleotide 
polymorphisms (SNPs) and haplotypes with drug responses.  The results 
are confirmed by studies of the mechanistic and clinical consequences 
of the molecular changes.  

The database groups in the network are working towards the goal of 
creating a centralized public knowledge base.  PharmGKB 
( is designed to categorize four types of 
phenotype information -- functional assays, pharmacokinetics, 
pharmacodynamics, and clinical outcomes -- correlated with genotype 
information.  The knowledge base uses standardized drug, disease, and 
genetic vocabularies and is linked to existing databases.  

The plans are to continue funding this network as a series of 
cooperative groups conducting studies to address a wide variety of 
common research problems in pharmacogenetics.  This initiative will 
further emphasize development of the PharmGKB knowledge base; it is 
envisioned as an information resource that will be useful to the entire 
pharmacogenetics research community to enable future hypothesis-driven 
research.  This competition is open to both new and renewal research 
and database groups.  

Pharmacogenetics can be defined as the influence of human genetic 
variation on drug responses.  It has long been known from family 
studies that variations found in enzymes of drug clearance have 
profound effects on the efficacy and duration of drug action, sometimes 
with significant adverse consequences.  Genetic variations in drug 
metabolizing enzymes can lead to the excessive build-up of a drug with 
a narrow therapeutic index (e.g., thiopurine methyl-transferase and 6-
mercaptopurine), or the lack of a therapeutic effect where metabolic 
activation is required (e.g., cytochrome P450 2D6 and codeine).  
Likewise, studies have shown that variations in target receptors can 
lead to a lack of beneficial effects of a drug, for example by 
increased desensitization (e.g., beta-2 adrenoreceptor and albuterol).  
Another mechanism impacting drug efficacy is altered binding kinetics 
(e.g., serotonin 1B receptors and fluoxetine).  Recent studies have 
shown that genetic variants can be linked to the susceptibility and 
progression of disease as well as to a response to a drug treatment 
(e.g., cholesterol ester transfer protein, atherosclerosis, and 
statins; or apolipoprotein E, Alzheimer’s disease, and tacrine).  There 
are multiple genetic mechanisms, including alterations in transcript 
stability, splice sites, or promotor binding regions, all of which can 
alter expression levels.  The impact of these changes on functional 
protein levels such as reduced amounts or stability, or compromised 
enzymatic function, requires further study.  Furthermore, how this fits 
into protein-protein interactions (e.g., coupling to second messengers) 
and biological pathways (e.g., redundant, competing, or complementary 
routes of clearance or signaling) needs to be understood in order to 
predict clinical consequences.  

With advances in genomic technology, large-scale accumulation of 
information on drug pathways (sometimes called pharmacogenomics) is 
possible.  These profiling studies can be DNA-based, transcript-based, 
or protein-based.  Both pharmacogenetics and pharmacogenomics studies 
are of interest under this solicitation.  It is essential to completely 
understand the significance of genetic variation at the molecular 
level, and the implications of the diverse genetic contexts present in 
different human populations.  The incidence of SNPs (singly and in 
combinations of haplotypes) and gene duplication or deletion events 
must be interpreted correctly to associate genetic variation with the 
prediction of drug effects, and this may require development of new 
analytical tools.  Population-based studies that examine the 
interactions between genetic predisposition for disease and the genetic 
factors determining medication responses are also of interest for this 

Ultimately, both a mechanistic understanding and robust statistical 
validation of putative pharmacogenetics effects are sought, and the 
translation to clinical impact is highly desirable.  The goal of the 
field is to be able to predict the effects of a medication in an 
individual based upon his/her genome, but much research must be 
performed before that is possible in a comprehensive manner.  Accurate 
descriptions of drug response phenotypes are challenging and difficult, 
and further research is required to define these phenotypes.  The 
Pharmacogenetics Research Network is intended to address this need to 
acquire basic research results and store the information in a knowledge 
base, which will lead to a more complete understanding of drug actions, 
clinical translation of the information, and future drug development. 

Objectives and Organization

The Pharmacogenetics Research Network will continue to be comprised of 
a series of multidisciplinary research and database groups, each of 
which is performing state-of-the-art studies in pharmacogenetics, 
either independently or in conjunction with other network groups.  
While pursuing the highest quality research studies, each network group 
must agree to meet the following expectations:  1) to further develop 
the knowledge base, PharmGKB, which is a database with accurate and 
detailed definitions of pharmacogenetic phenotypes linked to genotypes;  
2) to advance the research field, by defining common goals and needs, 
and contributing to solving problems of the field through discussions 
and workshops; 3) to produce and share resources, such as biological 
reagents, and experimental and computational tools, to be disseminated 
rapidly and with minimal restrictions; and 4) to communicate with 
scientists both within and outside the network, and to foster 
translation and application of this knowledge.  These requirements are 
further detailed below, and are included in the specific review 
A research group should be organized around a unifying theme, for 
example, a family of proteins with which drugs interact, a set of drug 
pathways leading to the site of action, or drug treatments for a 
particular disease.  The group should be comprised of a 
multidisciplinary team of investigators, minimally including personnel 
with backgrounds in cellular/molecular pharmacology, genetics/genomics, 
and clinical expertise.  Individuals from the fields of pharmacology, 
pharmaceutics, physiology, genetics, genomics, clinical medicine, 
medicinal chemistry, epidemiology, statistics, bioinformatics, and 
computational biology may be incorporated and must demonstrate that 
they can work together.  This research team should propose current, 
cutting-edge pharmacogenetics studies.  They should be  driven by the 
science  to produce the highest quality research results for deposition 
into PharmGKB and for publication.  The research groups will be 
responsible for serving as interactive resources for the developers of 
PharmGKB in their self-described areas.  

Applications should not simply be proposed as a series of projects from 
all investigators working in pharmacogenetics at an institution.  
Careful thought should be given to the definition of a research group’s 
goals, and the steps to be taken to accomplish those goals.  The best 
core or project teams to accomplish the research goals should be 
assembled; applications that cross multiple institutions are 
acceptable.  An application should discuss how existing databases were 
used to design and approach the solution of a pharmacogenetic problem, 
and how PharmGKB can better serve its users in the future.  The 
assembled group must justify their choice of a research area as the 
most appropriate, demonstrate their study design and power, and employ 
state-of-the-art technical approaches, including statistics and 
analyses.  The selected research problem in pharmacogenetics could be 
conceived starting with the identification of all possible variants (a 
genotype-to-phenotype approach) or beginning with well-characterized 
patient materials (a phenotype-to-genotype approach).  The applicant 
group should state the advantages and disadvantages of the approach 
chosen, and where convergence is expected with other studies ongoing in 
the field.

Correct and complete descriptions of phenotypes and association with 
genotypes form the core organizing principle underlying the 
Pharmacogenetics Research Network.  The research groups being funded 
are required to produce meaningful data sets suitable to populate 
PharmGKB.  Scientifically valid research questions should be 
constructed to yield data that contribute to advancing the 
understanding in the field, and that are appropriate for deposition 
into the knowledge base.  The types of data deposits that are expected 
should be described in detail, along with the time frame for their 
submission.  Both human and animal data, as well as non-mammalian 
systems, will be accepted.  Where animals or cell lines or model 
organisms are being examined, they should be justified as the 
appropriate reference models, consistent with the goal of identifying 
and interpreting human genetic drug response variants.  
Research groups should address how the pharmacogenetic researchers 
outside of the network can be positively impacted.  Useful sample sets 
should be offered to established repositories (e.g., the NIGMS Human 
Genetic Cell Repository at the Coriell Institute, for immortalization and distribution.  
Useful reagents (e.g., antibodies, primers) should be made easily 
available.  Software tools should be shared freely whenever possible.  
Current papers representative of the research field being studied 
should be deposited by the research groups into the community 
submissions project in PharmGKB.  Evidence of these steps taken will 
attest to the desire of the research group to serve in a scientific 
network and to share their findings with the scientific community, and 
should be presented in the application.

A database group applying to continue PharmGKB should present a plan to 
further develop the knowledge base as a research resource that will 
store, organize, present, and integrate pharmacogenetic knowledge.  
PharmGKB must display a variety of data types:  genetic variants, 
haplotypes, population frequencies, summary statistics, oligonucleotide 
and cDNA microarray data, molecular and functional screening assays, 
pharmacokinetic data, pharmacodynamic data, and, where appropriate, 
clinical data demonstrating the consequences of genetic variation.  It 
should have in place user-friendly methods to accept these data 
deposits of diverse forms and sizes.  In all cases, the data should be 
described using the standard nomenclature of the respective fields.  
The knowledge base should have reciprocal links to other established 
databases, such as GenBank, dbSNP, PDB, etc.

The knowledge base should describe gene-protein-drug-disease 
relationships, with each object layer completely represented.   
Relationships between these different data types should be displayed 
visually, and reflect the opinions and agreement of researchers working 
in these fields.  Raw data should be stored wherever possible, so that 
PharmGKB can be mined to learn of new correlations.  This is intended 
to be a hypothesis-generating tool.  Moreover, data should also be 
summarized and interpreted so that the information in the knowledge 
base is accessible to all scientist-users.  Given the long history of 
the field of pharmacogenetics, there should be a current and complete 
literature archive linked to complete publications wherever possible.  
Existing high value data sets outside of the network research groups 
should be sought to populate PharmGKB, to ensure complete and even-
handed representation across the field of pharmacogenetics.  Methods to 
establish credit and provide practical scientific incentives for 
submitters should be proposed.  

Applications to continue the knowledge Base PharmGKB should reflect the 
current status of the project, and describe how the design aspects, 
implementation, and maintenance will be continued or improved upon.  
Careful attention should be paid to issues of curation, and delineating 
who has the responsibility to format, abstract, and check the different 
kinds of data sets for completeness and accuracy.  Comparisons should 
be made to other successful ongoing database efforts.  Future major 
design directions should be presented and discussed, with prototypes.  
Discussion of accomplishments, challenges, and obstacles should be 
provided, and/or external observations and alternative strategies on 
how to overcome problem areas.  There should be evidence of the 
practical ability to work with the research groups in the network.  If 
a new database group is funded, copies of the existing datasets and 
data tables will be provided at the time of award, according to the 
prior negotiated terms and conditions regarding future portability.  
All of the data in PharmGKB are currently available to authenticated 
users for downloading by standard formats.  The name PharmGKB has been 
copyrighted by NIGMS.

Taken together, the research and database groups of the 
Pharmacogenetics Research Network and Knowledge Base should encompass a 
range of ongoing studies and original data on pharmacologically 
important genes, proteins, and pathways.  This will be accomplished by 
funding a balanced series of research groups that are studying 
different gene families, drug treatments, and diseases of significance 
to human health.  The scope of the Pharmacogenetics Research Network 
will likely continue to include enzymes of drug metabolism, small 
molecule transporters, and target receptors and pathways involved in 
drug treatment of cardiovascular diseases, asthma, cancer, and 
depression, and may broaden somewhat in reflection of the participating 
NIH institutes  interests.  

This network will be continued as a trans-NIH effort; the institutes  
specific interests are described below:

NIGMS is interested in studies identifying robust, statistically valid 
correlations between pharmacogenetic responses (phenotypes) and genetic 
variation (genotypes, haplotypes) using state-of-the-art approaches and 
technologies, and in the deposition of this knowledge into a database 
designed to be accessible by the entire research community.

NCI is interested in projects that can potentially lead to meaningful 
improvements in clinical and survival endpoints, and in studies of 
genetic variability in human populations that may influence risk of 
preneoplastic conditions or primary and secondary malignancies after 
exposure to medications, including cancer therapies.
NHLBI is interested in studies of the role of genetic polymorphisms and 
their functional consequences in modulating treatment responses in 
heart, lung, blood, and sleep diseases.

NHGRI supports research on how databases represent phenotypes, 
particularly related to genetic variation, and encourages the use and 
extension of standardized ontologies, as well as rapid data release. 

NIDA is interested in the influence of genetic variation on metabolic, 
homeostatic, neurocognitive, and physiological responses to abused 
drugs, as well as the safety and efficacy of drugs used for the 
treatment of addiction, dependence, and withdrawal, and in drug-drug 
interactions (e.g., antiretrovirals and drugs of abuse).

NIEHS is interested in identifying the response genes that are 
important to understanding genetic susceptibility to environmental 
exposures (see the Environmental Genome Project at  

NLM is interested in knowledge representation and the design and 
management of databases with medical data.

ORWH is interested in evaluating the importance of gender differences 
in genetic polymorphisms of proteins important in the pharmacokinetics 
and pharmacodynamics of drugs and drug reactions, and the role of 
hormones and other factors.  


This RFA will use the NIH U01 award mechanism.  The applicant is solely 
responsible for planning, directing, and executing the proposed 
project.  The RFA is a one-time solicitation.  The anticipated award 
date is on or after July 1, 2005.  Applications that are not funded in 
the competition described in this RFA may be resubmitted as NEW 
investigator-initiated applications using the standard receipt dates 
for NEW applications described in the instructions to the PHS 398 

This RFA uses just-in-time concepts.  It uses the non-modular budgeting 
formats.  Follow the instructions for non-modular budget research grant 
applications and submit the detailed categorical budget information on 
the PHS 398 form.  This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at

The NIH U01 is a cooperative agreement award mechanism.  In the 
cooperative agreement mechanism, the Principal Investigator retains the 
primary responsibility and dominant role for planning, directing, and 
executing the proposed project, with NIH staff being substantially 
involved as a partner with the Principal Investigator as described 
under the section "Cooperative Agreement Terms and Conditions of 
Award .  NIH makes no commitment to continue the cooperative agreement 
programs beyond the initially awarded period of performance.  

The participating ICs intend to commit up to $25 million in FY 2005 to 
fund approximately 10 to 12 new and/or 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 up to $2 million per year.  
Facilities and administrative costs for subcontracts may be excluded 
from this direct costs limit.  Because the nature and scope of the 
proposed research will vary from application to application, it is 
anticipated that the size and duration of each award will also vary. 
Although the financial plans of the ICs 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 
meritorious applications.  
You may submit (an) application(s) if your institution has any of the 
following characteristics: 
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges,             
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government 
o Foreign institutions are not eligible to apply

Foreign institutions are not eligible to apply, but foreign components 
may be included as subcontractors, where unique opportunities are 
offered.  These circumstances should be described and justified in the 


Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   

o Attendance at two Steering Committee meetings per year is required.  
These will likely rotate between the East and West coasts and central 
US.  Travel funds should be requested for this purpose for the 
Principal Investigator and for one to two other Observers.

o A plan for depositing data into PharmGKB is required.  See the 
current submission methods at  
This satisfies the NIH requirement for sharing research data for 
applications greater than $500,000 direct costs in any year of the 
proposed research.  Funds should be requested to support individuals 
capable to submitting data to PharmGKB.

o A letter should be included in the application, stating that the 
applicant research group members have read all of the existing policies 
of the Pharmacogenetics Research Network 
(  The letter should 
indicate that the group members will adhere to each of the policies and 
will contribute to the development of future policies that will guide 
the network’s actions.  

Cooperative Agreement Terms and Conditions of Award

The following Terms and Conditions will be incorporated into the award 
statement and will be provided to the Principal Investigator as well as 
to the appropriate institutional official, at the time of award.  The 
following special terms of award are in addition to, and not in lieu 
of, otherwise applicable OMB administrative guidelines, HHS grant 
administration regulations at 45 CFR Parts 74 and 92 (Part 92 is 
applicable when State and local Governments are eligible to apply), and 
other HHS, PHS, and NIH grant administration policies:

The administrative and funding instrument used for this program will be 
the cooperative agreement (U01), an "assistance" mechanism (rather than 
an "acquisition" mechanism), in which substantial NIH programmatic 
involvement with the awardees is anticipated during performance of the 
activities.  Under the cooperative agreement, the NIH purpose is to 
support and stimulate the recipients  activities by involvement in and 
otherwise working jointly with the award recipients in a partnership 
role; it is not to assume direction, prime responsibility, or a 
dominant role in the activities.  Consistent with this concept, the 
dominant role and prime responsibility resides with the awardees for 
the project as a whole, although specific tasks and activities may be 
shared among the awardees and the NIH through the Steering Committee.  

1. Principal Investigator Rights and Responsibilities

The Principal Investigator will coordinate project activities 
scientifically and administratively at the institution.  The Principal 
Investigator will have the primary responsibility for defining the 
details for projects and cores within the guidelines of this RFA, and 
for performing the scientific activities.  A Principal Investigator 
will agree to accept close coordination, cooperation, and participation 
of NIH staff in those aspects of management of the project as described 
below.  Awardees agree to accept and implement the guidelines of the 
Steering Committee regarding data release into PharmGKB.  Awardees will 
retain custody of and have primary rights to the data and software 
developed under these awards, subject to Government rights of access 
consistent with current HHS, PHS, and NIH policies.  

The Principal Investigator of a research or database group will:

o Coordinate the experimental approaches and procedures
o Set annual project milestones for the research or database group
o Report annually on progress towards the set milestones
o Accept and implement polices approved by the Steering Committee
o Submit data to PharmGKB, according to guidelines agreed upon and 
established by the Steering Committee 
o Attend Steering Committee meetings, and participate in the 
cooperative nature of the group
o Represent the views of other researchers in their research area

2. NIH Scientist Administrators Responsibilities

NIH Scientist Administrators from the participating ICs will have 
substantial programmatic involvement that is above and beyond the 
normal stewardship role in awards, as described below.  They are 
representative NIH extramural staff who will serve on the Steering 
Committee based upon their areas of scientific expertise (e.g., 
pharmacology, genetics) and actively guide development of the 
Pharmacogenetics Research Network by providing overall advice and 
coordination.  They should facilitate a partnership relationship 
between NIH and the research and database groups, and ensure that the 
directions taken remain consistent with NIH’s missions and goals.  They 
will make recommendations and provide specific guidance to aid in both 
accomplishing the existing goals and addressing emerging research 
opportunities.  Additionally, an IC program director will be assigned 
to each award and is responsible for the normal stewardship role of 
providing scientific oversight, as well as monitoring adherence to 
policies and procedures specific to the funding institutes; the 
assigned program director may also serve as an NIH Scientist 

The NIH Scientist Administrators will:

o Actively share their relevant expertise and overall knowledge
o Help to coordinate activities among the awardees, commensurate with 
their expertise
o Be information resources about ongoing NIH-supported research and 
resource collections 
o Attend Steering Committee meetings, and participate in the 
cooperative nature of the group
o Promote PharmGKB to the scientific community at large
o Assist in implementing recommendations for allocating NIH support 
among the awardees
o Work with the program director(s) to monitor adherence to policies 
and procedures of the funding ICs

3. Collaborative Responsibilities

A Steering Committee will serve as the governing board of the 
Pharmacogenetics Research Network.  Membership will include 
representation from each of the research groups and database groups, 
and NIH Scientist Administrators of the appropriate scientific 
expertise representing the funding ICs.  It may include selected 
scientists other than the awardees, when additional expertise is 
required as necessary for committee breadth and balance.  The rest of 
the Steering Committee will appoint these members by majority vote.  
NIH representation on the Steering Committee will be roughly 
proportional to the IC investment, and there may be rotating positions.  
Each full member will have one vote; however, NIH voting representation 
on the Steering Committee will not exceed one-third of the allowed 
number of votes.  Awardee members of the Steering Committee will be 
required to accept and implement policies approved by the Steering 

The Steering Committee will:

o Meet regularly and serve as the main governing board
o Be run by the Chair of the Pharmacogenetics Research Network
o Develop common policies, guidelines, and procedures
o Facilitate the process of developing and maintaining a cohesive group
o Authorize administrative and scientific subcommittees to follow 
through on its business
o Identify scientific opportunities, emerging needs, or impediments
o Interact productively with the External Scientific Panel

4. NIH Network Program Director and Administrative Coordination 

The NIH Network Program Director will assume responsibility for overall 
stewardship of the network, and for coordination of the 
Pharmacogenetics Research Network and Knowledge Base.  These tasks are 
in addition to the normal stewardship role of providing scientific 
oversight, as well as monitoring adherence to policies and procedures 
specific to the funding institutes.  The NIH Network Program Director 
will facilitate creation of the Steering Committee and will attend all 
meetings.  Logistical arrangements will be made for the Steering 
Committee meetings and other administrative duties related to the 
committee functions, such as conference calls, report mailings, 
publications tracking, etc.  These activities may be accomplished by a 
variety of arrangements, such as by adding funds to one of the research 
or database groups to support an administrative position.  

The NIH Network Program Director will appoint a Steering Committee 
Chair to serve on a year-to-year mutually renewable basis, will aid in 
outlining responsibilities on a regular basis, and will arrange 
resources necessary to accomplish the targeted administrative goals.  
The NIH Network Program Director will actively assist the Chair in 
developing the meeting agendas.  Two to three meetings will be held 
each year, and the Chair will run the Steering Committee meetings.  
Subcommittees will be established by the Steering Committee as 
necessary.  The NIH Network Program Director will ensure coordination 
of the Steering Committee’s activities and implementation of the 
group’s recommendations.  

The NIH Network Program Director will also assist the External 
Scientific Panel, which is advisory to the Pharmacogenetics Research 
Network.  The Steering Committee Chair will take the lead on 
interactions representing the network with the External Scientific 
Panel.  These groups will meet jointly approximately twice per year.  
Institutes will not handle data prior to its public release in 
PharmGKB; the awardees are responsible for providing data tracking.  If 
clinical studies are proposed, data and safety monitoring plans should 
be described.  The policies of the funding ICs must be followed 
(consult with the appropriate institute).  

5. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters 
(within the scope of the award) between award recipients and the NIH 
may be brought to arbitration.  An Arbitration Panel composed of three 
members will be convened.  It will have three members:  a designee of 
the Steering Committee chosen without NIH staff voting, one NIH 
designee, and a third designee with expertise in the relevant area who 
is chosen by the other two; in the case of an individual disagreement, 
the first member may be chosen by the individual awardee.  This special 
arbitration procedure in no way affects the awardee's right to appeal 
an adverse action that is otherwise appealable in accordance with PHS 
regulations 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 

6. External Advisory Groups

A standing External Scientific Panel (see membership at has been appointed 
to guide the Pharmacogenetics Research Network and Knowledge Base, 
following consultation with the network awardees and the funding ICs.  
Additional members may be added to this panel, through discussion with 
the NIH Network Program Director.  In its charter, the group agreed to 
twice a year meetings with the network, with written reports sharing 
evaluative advice consisting of suggestions and recommendations.  It 
will be the responsibility of the Chair of the Pharmacogenetics 
Research Network to prepare written responses to the External 
Scientific Panel, and to share copies of the report and the reply with 
the funding NIH institutes in a timely manner.

The Director, NIGMS, retains the right to call any additional meetings 
of advisors, most likely members of the National Advisory General 
Medical Sciences Council or their designees, at any time to provide 
advice on the scientific progress of the Pharmacogenetics Research 
Network and Knowledge Base.  It is anticipated that such a group of 
advisors may want to attend a meeting of the Pharmacogenetics Research 
Network as part of its fact-finding mission.  Any information or 
reports will be shared with the other ICs participating in this 

7. Milestones and Evaluations

Applicants should define yearly milestones in their applications (as 
well as in their progress reports), and the selected awardees will have 
the opportunity to modify these milestones at the time of their awards.  
The awardees  milestones may be provided to the Steering Committee.  It 
is expected that the milestones should be adjusted annually at the 
award anniversary dates, both to incorporate a group’s scientific 
accomplishments and progress in the field in general, as well as to 
reflect the recommendations of the Steering Committee and the External 
Scientific Panel.  In accordance with the procedure described above, 
the NIH Scientist Administrators may recommend augmenting any project, 
as discussed through the Steering Committee, or reducing or withholding 
funds for any project that substantially fails to meet its milestones 
or does not remain state-of-the-art. 


The next public meeting of the Pharmacogenetics Research Network will 
take place on March 8, 2004, in Los Angeles; see for more information and to 
register.  If there is sufficient interest, an informational session 
will take place late afternoon on March 7 at the meeting hotel.  
Contact staff in advance to discuss this possibility.  Frequently asked 
questions (FAQs) will be developed from this session and shared with 
all potential applicants.

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and grants 
management/financial issues:

o Direct your questions about scientific/research issues to the 
relevant IC representative:

Rochelle M. Long, Ph.D.
Pharmacology, Physiology, and Biological Chemistry Division
Building 45, Room 2AS.49G, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-1926
FAX:  (301) 480-2802

Richard A. Anderson, M.D., Ph.D.
Genetics and Developmental Biology Division
Building 45, Room 2AS.25B, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0943
FAX:  (301) 480-2228

Ken Kobayashi, M.D.
Cancer Therapy Evaluation Program
6130 Executive Blvd.
Suite 7131, MSC 7426
Rockville, MD   20852
Telephone:  (301) 496-1196
Fax:  (301) 402-0428

J. Fernando Arena, M.D., Ph.D.
Division of Cancer Control and Population Sciences 
6130 Executive Blvd., Executive Plaza North 
MSC 7395, Rm. 5104
Rockville, MD   20852 
Telephone:  (301) 594-5868
Fax:  (301) 402-4279 

Susan-Banks Schlegel, Ph.D.
Division of Lung Diseases
Rockledge Two, Rm. 10220
6701 Rockledge Drive, MSC 7952
Bethesda, MD   20817 
Telephone: (301) 435-0202
Fax:  (301) 480-3557

Dina Paltoo, Ph.D., M.P.H.
Division of Heart and Vascular Diseases
Rockledge Two, Rm. 9180
6701 Rockledge Drive, MSC 7940
Bethesda, MD   20817 
Telephone:   (301) 435-1802
Fax:   (301) 480-1336

Lisa D. Brooks, Ph.D.
Genetic Variation Program          
31 Center Dr., Rm. B2B07         
Bethesda, MD 20892-2033
Telephone:   (301) 435-5544
Fax:   (301) 480-2770  

Joni L. Rutter, Ph.D.
Division of Neuroscience and Behavioral Research
6001 Executive Blvd., Rm. 5227, MSC 9555
Bethesda, MD  20892-9555
Telephone:   (301) 435-0298
Fax:   (301) 594-6043

Kimberly Gray, Ph.D.
Division of Extramural Research and Training
111 TW Alexander Drive
P.O. Box 12233, MD EC-21
Research Triangle Park, NC 27709
Telephone:   (919) 541-0293
Fax:  (919)316-4606

Milton Corn, M.D.
Extramural Programs
6705 Rockledge Drive
Building 1, Suite 301
Bethesda, MD 20892
Telephone:  (301)496-4621
Fax:  (301) 402-2952

Lisa Begg, Dr.P.H., R.N.
Research Programs
1 Center Dr., Rm. 201, MSC 0161
Bethesda, MD 20892
Telephone:  (301) 496-7853
Fax:  (301) 402-1798

o Direct your questions about peer review issues to:

Richard Panniers, Ph.D.
Rockledge Two, Rm. 5148
6701 Rockledge Dr.,  MSC 7842
Bethesda, MD   20817
Telephone:  (301) 435-1741
Fax:  (301) 480-1988

o Direct your questions about grants management/financial matters to 
the relevant IC representative (new applicants, or renewal applicants 
funded by NIGMS should contact that institute; renewal applicants 
funded by NHLBI should contact that institute):

John Matala
PPBC/MORE Grants Management
Building 45, Rm. 2AS.55K, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-3928
FAX:  (301) 480-2554

Holly Atherton
Grants Operations Branch
Rockledge II MSC 7926
Rockledge Two, Rm. 7152
Bethesda, MD 20817
Telephone:  (301) 435-0166
Fax:  (301) 480-3310
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o 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 IC staff to estimate the potential review 
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Rochelle M. Long, Ph.D.
Pharmacology, Physiology, and Biological Chemistry Division
Building 45, Room 2AS.49G, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-1926
FAX:  (301) 480-2802


Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:
SUPPLEMENTARY INSTRUCTIONS: Applicants should use the following 
guidance, in addition to the instructions accompanying the PHS 398 

The application process should be followed for regular research grant 
_instructions.htm#Page_Limitations), with the exception that the page 
limit for the Research Plan is raised to 50.  Additionally, the 
specific instructions below must be addressed. All other instructions
(e.g., font size, limit on appendix materials) remain the same.

Abstract, Research Sites, Key Personnel (page 2):  Briefly describe the 
proposed plans and identify whether this is a research or database 
group, and a new or continuing group in the Pharmacogenetics Research 
Network.  If this group was part of a previous award in the network, 
explain the relationship.  List all key personnel significantly 
involved in the project.
Table of Contents (page 3):  Prepare a detailed Table of Contents that 
includes all elements of the application.  Use numeric pagination only.  
Organizational components should be presented in the order in which 
they appear in the application, and identified with an institutional 
location.  New components of groups previously in the Pharmacogenetics 
Research Network should be identified.

Budgets:  These must be prepared as overall composites as well as 
according to individual components with details (see below). 

Composite budget - initial budget period (page 4) and entire proposed 
Form PHS 398 to present the total budget for all requested support for 
the first year.  For each category such as Personnel, Equipment, etc., 
give the total amounts requested for each component core or project.  
prepare a budget which provides totals for each year of requested 
support.  Requests beyond the IC standard inflationary increases (3%) 
for any increases in succeeding years must be noted and well-justified 
in the individual component core and project budgets. 

Individual scientific component budgets - initial budget period (page 
4) and entire proposed period (page 5).  Detailed, itemized individual 
budgets for each scientific core and project should be prepared and 
placed immediately prior to the description of the relevant individual 
component in the Research Plan section.  This is where justifications 
and explanations should be provided.  

Note: Where there are multiple participating subcontracting 
organizations, each entity will additionally need submit a separate 
composite budget for both the initial budget period and the entire 
proposed project period.  Follow instructions for collaborations and 
included signed institutional letters.

Biographical sketches and letters of commitment:  Biographical sketches 
must be included for all key personnel and consultants, clearly 
indicating their backgrounds and expertise.  

Research Environment:  Complete the Resources page of PHS 398 for the 
overall program, including both the host institution and any other 
participating institutions.  Briefly describe the features of the 
institutional environment(s) that are relevant.

Research Plan:  There is an overall page limit of 50 pages for this 
section.  A recommended organization (Progress Report/Preliminary Data, 
Future Plans, Data Deposits, Other) is below.

Progress Report:  A Progress Report (or Preliminary Data section, if 
this is a new application) section must have an over-arching summary 
that includes discussion of major contributions to the research area, 
as well as to the overall goals of the Pharmacogenetics Research 
Network.  Specific references to successful data deposits should be 
made; these deposits must be explained well enough for the reviewers to 
understand completely.  Critical assessment of genotypes/haplotypes 
generated, and association with functional and clinical phenotypes, 
should be provided.  Tools, resources, and reagents previously offered 
for sharing should be included here, as well as a description of 
whether or how they have been utilized by others.

Future Plans:  Past experience has shown that a series of cores or 
projects works well as a format for a systematic approach to a well-
defined problem.  The plans should be organized according to these 
cores or projects, keeping in mind that a major goal of the 
pharmacogenetics research network is to make scientific correlations 
linking phenotypes to genotypes and to deposit the information into 
PharmGKB.  Again, references must be made to how the research program 
will fit into the Pharmacogenetics Research Network.  There should be 
specific descriptions of future data deposits, with estimated 
timetables; these deposits should be explained well enough for the 
reviewers to understand completely.  The applicant group’s views of 
important questions in the field, and areas that the network might 
address should be included.  Potential tools, resources, and reagents 
should again be addressed if new ones will be disseminated.  Describe 
the organizational relationships, the process for setting milestones, 
and the flow of materials and data through the cores or projects.  
Metrics for measuring progress as an individual research or database 
group, and for the network as a whole should be posed.  Discuss meeting 
schedules and plans for any external advisory groups specific to the 
proposed core or project.  Do name the relevant areas, but do not name 
the specific members of such groups if they are not yet constituted.  
Do name the members if they are already operating.  The application 
should speculate regarding ways in which the Pharmacogenetics Research 
Network can improve the state of the field and enable new research by 
impacting all pharmacogenetics researchers.  Applicants are strongly 
urged to read very carefully the Additional Criteria for Review section 
of this RFA (below). 

Data Deposits:  Plans for making future data deposits into PharmGKB 
should be explicitly addressed.  There is a Pharmacogenetics Research 
Network statement on the timing and tracking of data deposits 
(  Sufficient funds 
must be requested for properly trained personnel to make timely data 
deposits and to maintain the representative area in the database though 
any proposed curation responsibilities.  Participation in the 
Pharmacogenetics Research Network brings responsibility to represent a 
research area for development in the database.  Research groups should 
be prepared to set standards for data deposits, to oversee these areas 
in PharmGKB, and to identify others in the research community where 
PharmGKB should reach out to accumulate data.  Database groups should 
be prepared to seek valuable data sets, to oversee the deposit process, 
and to accurately estimate the demands of curation, maintenance, and 
future database development. 

Other:  The next four requirements (intellectual property, human 
subjects, collaborations with clinical networks, and community 
consultation) must be addressed if relevant to the research being 
proposed in the application. 

Plans for handling intellectual property that may be generated should 
be addressed in the application.  There is a Pharmacogenetics Research 
Network policy in this area 
The intention of the policy is to protect the rights of institutions, 
but also to encourage the rapid dissemination of results 
and open licensing of inventions for academic research purposes.  A 
letter should be included in the application, stating that the 
applicant research group members have read the existing policies of the 
Pharmacogenetics Research Network and will adhere to its policies 
and/or contribute to the creation of future policies that will guide 
network actions. 

Plans to account for data derived from human subjects should be 
addressed in the application.  A provisional letter should be provided, 
stating that that the recommended language for informed consents 
( has been 
viewed, and describing how it will be adapted for a research group’s 
use.  This letter should specify the manner in which clinical data will 
be handled for deposit into PharmGKB, when individual research data 
will be permitted, and when summary data will be required, and how 
granular that summary may be.  

Plans to interact with existing clinical networks should be addressed 
in the application.  There should be a letter(s) from any collaborators 
supplying materials for pharmacogenetics analysis, and this should 
grant permission and should also reconcile the restrictions (if any) 
and timing for deposit of the results into PharmGKB.  Typically, 
letters indicating the approval of a Steering Committee and/or a Data 
Coordinating Committee of the clinical study or network are required.

Plans to propose research studies collecting data for deposit into the 
public knowledge base PharmGKB must address in the application how the 
research group will consult with named communities involved in the 
research.  This could include racial, ethnic, cultural, or religious 
communities, as well as patient or disease-defined groups.  Funds may 
be requested for the purpose of fulfilling this goal.  Please see the 
NIH  Points to Consider  document at  It is 
important to involve representatives of populations to solicit their 
thoughts and learn of effective ways to share research results.  See 
also the recommendations of the NIGMS Populations Advisory Group at
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number 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 must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at:
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and five 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)

APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
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.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the participating ICs.  Incomplete and/or non-
responsive applications will not be reviewed.

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 CSR in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 

o 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 and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate National Advisory 
Councils and Boards. 

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 evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of the following 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
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.

SIGNIFICANCE: Does this study address an important problem? If the aims 
of the application are achieved, how will scientific knowledge be 
advanced?  What will be the effect of these studies on the concepts or 
methods that drive this field?

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

INNOVATION: Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does the project 
challenge existing paradigms or develop new methodologies or 

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?

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? 
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items (criteria for research groups and database groups, as 
USE OF VERTEBRATE ANIMALS IN RESEARCH) will be considered in the 
determination of scientific merit and the priority score.

Additional criteria for a new or renewal research group:

o Is the choice of the research area of high significance to the field 
of pharmacogenetics, consistent with top level research opportunities, 
and relevant to human health? 

o Is the scope of the research area sufficiently broad to be a program 
in pharmacogenetics, and yet sufficiently cohesive as to have a 
distinct theme uniting the activities?
o Is the overall strategic approach to the problem (phenotype-to-
genotype or genotype-to-genotype) well-justified?

o Are the specific experiments proposed consistent with a modern, 
comprehensive approach, including both adequate study design, 
statistical analyses, and technical methodologies?

o Are the study populations well-described, and of sufficient sample 
size and power? 

o Is this a multidisciplinary group, with people of the appropriate 
expertise selected, participating at a reasonable level of effort?  Is 
there evidence of their commitment to the project? 

o Is the organization (e.g., cores, projects) of the comprehensive 
research program and the team assignments practical and realistic?

o Will this research effort produce data of sufficient quantity and in 
a realistic timeframe to significantly add to the database, PharmGKB?

o If this is a new application, are meaningful data deposits planned in 
a timely manner?  If this is a renewal application, what is the group’s 
track record in making meaningful data deposits into PharmGKB?   

o Has sufficient staffing of the appropriate backgrounds been assigned 
responsibility for database deposits for the group?

o Is there interest expressed in the commitment to a research network?  
If this is a renewal application, what is the evidence of past 
involvement or service to the network?

o Will the research program make contributions beyond a single 
laboratory, and will resources for the community be generated?  Are 
there reasonable plans proposed to share the cell lines, reagents, 
specimens, software, etc?

o Does this research program have a record of participating in 
collaborative studies, and do they have a plan to stimulate collegial 
communications with the pharmacogenetics research community?

o How will research studies and their outcome eventually be shared with 
non-scientists, especially the study patient and volunteer populations 
(e.g., newsletter, website)?

o How has the research group planned for issues related to data-
gathering, including strategies to approach topics such as informed 
consents, identified populations, confidentiality, and intellectual 

Additional criteria for a new or renewal database group:

o Has sufficient thought been given to the wide variety and depth and 
overall quantity of data that will be generated by the research groups?  
Will the knowledge base be optimized to maximize its scientific value?

o Are there plans to solicit necessary pharmacogenetics information 
beyond that generated by the research groups, given knowledge of the 
field in general? 

o Does the knowledge base have the capacity for complex multi-factorial 
representations of pharmacogenetics phenotypes?

o Are the data submission methods simple, intuitive, and realistic for 
genotype and phenotype information?

o Has sufficient and skilled staffing been proposed to assist with data 
deposits from network (and non-network) scientists?  

o Has appropriate attention been paid to issues of curation and 
maintenance of datasets?

o How has the database group planned for issues related to data-
gathering, including strategies to approach topics such as informed 
consents, identified populations, confidentiality, and intellectual 

human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the 
sections on Federal Citations, below).

Previous discussions with NIH and the Pharmacogenetics Research Network 
have led to the recommendation that people of varying racial and ethnic 
backgrounds be allowed to describe themselves freely and with cultural, 
geographic, and historical references (see  
These data will be captured into PharmGKB, along with traditional, 
required OMB categories used to describe the inclusion of women and 
minorities in clinical research.

are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  


Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of 
the proposed research must include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the 
reviewers.  For this RFA, because it is central to the core mission of 
the program to deposit data into PharmGKB, reviewers will factor the 
proposed data sharing plan into the determination of scientific merit 
or priority score. 
BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.


Letter of Intent Receipt Date:  July 19, 2004
Application Receipt Date:  August 19, 2004
Peer Review Date:  Winter 2004-2005
Council Review:  May 2005
Earliest Anticipated Start Date:  July 1, 2005


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

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

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained. 

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is 
required for all types of clinical trials, including physiologic, 
toxicity, and dose-finding studies (phase I); efficacy studies (phase 
II); efficacy, effectiveness and comparative trials (phase III).  The 
establishment of data and safety monitoring boards (DSMBs) is required 
for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   NIH Policy for Data and Safety 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 
or more in direct costs in any single year are expected to include a 
plan for data sharing or state why this is not possible.  Investigators should 
seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule.  Reviewers 
will consider the data sharing plan and will factor the plan to deposit 
data into PharmGKB into the determination of the scientific merit or 
the priority score.

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

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
a complete copy of the updated Guidelines are available at 
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must 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) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 

SUBJECTS:  The NIH maintains a policy 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 is available at

NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at 
and at  
Only research using hESC lines that are registered in the 
NIH Human Embryonic Stem Cell Registry will be eligible for Federal 
funding (see   It is the responsibility of the 
applicant to provide, in the project description and elsewhere in the 
application as appropriate, the official NIH identifier(s) for the hESC 
line(s) to be used in the proposed research.  Applications that do not 
provide this information will be returned without review. 

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

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.

The Department of Health and Human Services (DHHS) issued final 
modification to the  Standards for Privacy of Individually Identifiable 
Health Information , the  Privacy Rule,  on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as  covered entities ) must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution.  The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on  Am 
I a covered entity?   Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

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.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 

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 RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92.  All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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.

NIAAA is not participating in this RFA, but is interested in studies to 
identify genetic variations contributing to increased susceptibility 
for alcohol dependence and alcoholism, and variations that modify 
efficacy, safety and toxicity of drugs for the treatment of alcohol 
dependence, alcoholism and alcohol-related disorders.

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