Expired RFA-GM-10-001: Pharmacogenomics Research Network (U01/U19)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of General Medical Sciences (NIGMS), (http://www.nigms.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov)
National Cancer Institute (NCI), (http://www.nci.nih.gov)
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov)
National Institute on Mental Health (NIMH), (http://www.nimh.nih.gov)
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov)

Title: Pharmacogenomics Research Network (U01/U19)

Announcement Type
This is a re-issue of RFA-GM-04-002.

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

March 5, 2009 - See (RFA-GM-10-002).

Request For Applications (RFA) Number: RFA-GM-10-001

Catalog of Federal Domestic Assistance Number(s)
93.859, 93.837, 93.838, 93.839, 93.393, 93.394, 93.395, 93.396, 93.279, 93.209, 93.242

Key Dates
Release Date: January 30, 2009
Letters of Intent Receipt Date: May 2, 2009
Application Receipt Date: June 2, 2009
Peer Review Date: November 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: April 1, 2010
Additional Information To Be Available Date (Url Activation Date): February 1, 2009 at www.nigms.nih.gov/initiatives/PGRN/RFAinfo
Expiration Date: June 3, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. The purpose of this funding opportunity announcement issued by NIGMS, NHLBI, NCI, NIDA, NIMH, and NICHD is to allow new and renewal applications for research groups to compete to become part of the Pharmacogenomics Research Network (PGRN), and to create network resources that serve the entire PGRN. The PGRN is a consortium of interdisciplinary groups with a core mission to conduct research into understanding the genetic basis of variable drug responses, both therapeutic and adverse. The scientific objectives of the research network include definition of the pressing problems for safe and effective use of medications, establishment of truly cross-disciplinary research groups, application of the most appropriate genetic and genomic methods to important sample collections, discovery and replication studies that identify variation in critical genes and biological pathways, elucidation of the functional consequences of genetic variation for the drugs being studied, and understanding the clinical implications of genotyping to predict drug responses.
Mechanism of Support. This FOA will utilize the U01 and U19 grant mechanisms. U01 awards will be made for research groups, and U19 awards will be made for research groups with network resource component add-ons.
Funds Available and Anticipated Number of Awards. The total amount of funding that the agencies/ICs expect to award through this announcement is approximately $30 million in FY2010; the anticipated number of U01 and U19 awards is approximately 12-14.
Budget and Project Period. The expected direct costs amount for each individual research group award is $1 to $1.5 million per year, and for each add-on network resource is $0.1 to $0.5 million per year (there may be up to two add-ons per research group); the total project period may be up to five years.
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization 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 support.
Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
Resubmissions. Resubmission applications are not permitted in response to this FOA.
Renewals. Renewal applications are permitted in response to this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
Application Materials. See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Nature of the Research Opportunity

The purpose of this funding opportunity announcement is to enable new and renewal applications to compete for support as research groups in the Pharmacogenomics Research Network (PGRN, http://www.nigms.nih.gov/Initiatives/PGRN/), and to establish network resource components that will serve the entire PGRN. The PGRN is a consortium of interdisciplinary groups with a core mission to conduct research into understanding the genetic/genomic basis of variable drug responses, both therapeutic and adverse. The proposed research programs should include efforts not only to identify the genes, pathways, and systems that produce inter-individual differences in drug responses, but also to establish the mechanistic basis of these differences. As before, research groups will be able to determine their disease and drug areas of interest, consistent with the missions of the institutes funding the research. The focus of this opportunity is to understand drug effects in humans, and while animal or model organism work may be included, it should be in support of studies correlating human genetic differences and drug responses.

Background

Pharmacogenetics research has made great strides in recent years, with the identification of gene alleles that influence drug effects in humans. In some cases, these findings now form the basis for predictive genetic tests to guide drug choice or dose. Some examples include the HLA-B alleles that mediate the hypersensitivity response to abacavir and carbamezepine; VKORC1 haplotypes and CYP2C9 alleles which, when combined with clinical factors, can be used to establish an initial dosing protocol for warfarin; a UGT1A1 allele which is responsible for reduced clearance of the activated form of irinotecan, and can lead to life-threatening diarrhea; TPMT alleles which predict rapid bone marrow suppression for homozygous individuals when 6-mercaptopurine is used in a chemotherapeutic regimen; the many CYP2D6 alleles encoding forms of the highly polymorphic cytochrome P450 enzyme responsible for biotransformation of tamoxifen to the active moiety that predicts long term survival; beta-2-adrenergic receptor polymorphisms that predict decreased efficacy of the bronchodilator albuterol; and SLC01B1 polymorphisms in the gene encoding the organic anion transporter that determines blood levels of statin drugs producing myopathies. Many of these discoveries were based upon PGRN-supported research.

While these examples are encouraging, our knowledge of all genetic predictors of drug responses is far from complete and further research is needed to clearly establish genotype-phenotype relationships. Moreover, these are simple single gene examples (with the exception of warfarin), and a true understanding and prediction of many drug responses will require knowledge of multiple genetic and non-genetic factors. Modern experimental approaches in this field anticipate multiple variants, often with smaller contributing effects, as the genome is more comprehensively and systematically examined. Hence the increased emphasis on pharmacogenomics, and the network’s name will be changed to the Pharmacogenomics Research Network to reflect this evolution within the field.

If the ultimate goal of pharmacogenomics is to guide appropriate therapeutic choices, then association studies to discover variants correlated with drug responses will not be sufficient; a functional understanding is essential to predicting how to use drugs safely and effectively in people. All relevant pathways of pharmacokinetics ( what the body does to the drug ) and pharmacodynamics ( what the drug does to the body ) must be well-understood. Variation in genes encoding proteins found in any of these pathways or effectors can lead to measurable changes in drug blood levels and/or clinical responses. This initiative requires both a genomic and mechanistic approach to understanding and solving problems related to differences in drug responses, including both optimizing drug efficacy and preventing adverse drug effects.

Collaboration and cooperation are essential for progress to be made in this complex field. It is beyond the ability of most groups to have expertise in all the areas required. Currently, the PGRN has demonstrated that it is possible to come together and collaborate, to exchange information and approaches, and to build relationships with new partners that benefit all and elevate the field as a whole. One such example is the International Warfarin Pharmacogenetics Consortium (IWPC, http://www.pharmgkb.org/views/project.jsp?pId=56), a data-sharing partnership organized by PharmGKB and selected researchers working in the area, where investigators world-wide agreed to share their genetic data and clinical parameters in order to arrive at a consensus model for genotype-guided dosing; leadership and cooperation ensured that data on variation in the CYP2C9 and VKORC1 genes could be shared in a meta-analysis. Another example of a collaboration that shows great promise is the relationship between the PGRN and RIKEN Center for Genomic Medicine (http://www.nigms.nih.gov/Initiatives/PGRN/GAP/). Several joint projects are underway with sample sets from patients well-phenotyped for drug responses, to be examined in genome-wide association studies designed to reveal possible candidate genes that can be tested for replication in future experiments.

Knowledge to be Achieved

The PGRN should perform research to identify the variability in genes and evaluate the functional consequences of that variability leading to clinical application of the knowledge. In the past, PGRN groups have been focused in the areas of cardiovascular diseases (such as arrhythmias, hypertension, coagulation, and hypercholesterolemia), cancers (including breast, gastrointestinal, and childhood leukemias), asthma, depression, addiction, and DMET (drug metabolism, elimination, and transport). These remain areas of interest, but this funding opportunity is not limited to those areas. In addition to conducting fundamental and clinical research, the PGRN research groups should work together to set and achieve network-wide scientific goals, thus contributing to the evidence base overall and planning for future translational studies in pharmacogenomics.

There are fundamental properties underlying drug responses that cross a variety of disease/drug applications, for example, the common pathways of biotransformation by the drug metabolizing and conjugating enzymes, and transport of drug molecules and their metabolites into and out of cells and the blood. Likewise, drug targets in inflammatory and signaling pathways are known to be common elements of disease susceptibility. Genetic variation in these pathways, and the mechanisms of action of drugs as well as the consequences of genetic variation at polymorphic sites, must be better understood. Pharmacogenomic variation becomes significant when a clinical outcome is altered in a predictable manner based upon functional changes in proteins and/or pathways. This information may be useful to make clear medical recommendations based upon genotyping. Robust predictive tests can then be developed and applied, in conjunction with clinical guidelines, in order for this knowledge to be utilized in the practice of medicine. Other possible useful applications of the knowledge achieved may be improved information gained from early stage trials, and enhanced design approaches for more efficient late larger-scale clinical trials for drug development.

Objectives of the Program

The scientific objectives expected of the PGRN as a whole include:

definition of the critical problems for the safe and effective use of medications;
establishment of truly cross-disciplinary research groups and teams;
application of the most cutting edge genetic and genomic methods to investigations with important specimen collections;
discovery (and replication) of the critical genes and biological pathways, and important variation in those systems;
identification of the mechanisms of action and modes of clearance of the drugs being studied;
definition of the clinical implications of genetic variant detection.

Different experimental approaches will be encouraged within the PGRN; research groups may have multiple problems under study, as long as a strategy is articulated and justified for inclusion of the projects within a research group with a cohesive focus.

It is expected that the research areas of pharmacological focus will be sufficiently complex and of broad impact, and that the genomic approaches will be cutting edge, commensurate with the substantial resources that will be allowed for each award. This initiative is not intended to fund regular R01-scale work.

Types of Research and Experimental Approaches

Consistent with the existing network, research groups will again be able to propose their drug/disease areas of interest, as they align with the sponsoring funding institutes interests (see statements below). Research groups may choose to take a phenotype-to-genotype approach for genomic discovery studies beginning with collections of sufficient numbers of very well-phenotyped patient specimens, or a genotype-to-phenotype approach to validate hits from genomic discovery studies and/or to comprehensively determine genetic variation in pathways and systems important for drug responses. It is anticipated that these two approaches will converge, and that ideal research groups will likely contain elements from both approaches. Interactions between PGRN groups will be expected when biological pathways of common interest are being studied; that is part of the value of funding in this research field as a network.

When polymorphisms have been identified in discovery studies, potentially through genome-wide association studies and/or in re-sequencing experiments, replication studies are essential, along with subsequent validation that the candidates have clinical relevance. In order for implicated variants to be established as potentially causative, mechanistic studies will be required to demonstrate how the variants change the active site or stability or regulation of the protein/drug interaction and compensatory actions; these studies may require the integration of multiple approaches (for example, alteration of DNA, RNA, or protein characteristics or functions, after exposure to drug or metabolite) and will possibly include the use of cultured cell systems or specific animal models. Finally, studies in humans should demonstrate that the hypothesized predictive nature of the genotype(s), haplotype(s), or combination thereof determines reduced or increased functional drug effects or toxicities. At times, altered disease presentation and drug responsiveness both result from genetic variation, thus phenotypes must be very carefully determined prior to embarking upon large scale experiments. Robust analytical approaches to complex problems will be expected, with careful attention paid to statistical assumptions so that conclusive results will be obtained.

Both retrospective analysis of existing sample materials and prospective studies will be considered under this funding opportunity. In all cases there must be preliminary evidence of a genetic basis for variability in patient responsiveness, clear criteria for defining drug responses consistent with clinical guidelines in the field, and access to specimens or enrollment of patients in sufficient numbers to reasonably ensure study success. There are methodological (for example, study design) and analytical (for example, statistical methods) challenges in this field, and novel approaches can be developed and are encouraged. Discovery studies in accessible populations including but not limited to large medical or pharmacy practice groups, or organizations such as the VA, and in clinical trials (including those supported by the funding institutes and by industry), should be valuable resources for these studies. The research proposed should anticipate and investigators should plan for independent replication studies. Animal and model organism components may be included to the extent that they generate leads (for example, through comparative genomic approaches), or that they are useful to test mechanisms (for example, that a particular single nucleotide polymorphism leads to a functional change in the protein being studied).

Examples of Research Topics

Some examples of problems of interest to the institutes include but are not limited to the topics below:

NIGMS: This institute is interested in research addressing mechanisms underlying drug responses and drug interactions, including pathways of drug metabolism, distribution, transport, and elimination, as well as drug targets in the cellular signaling and inflammatory responses. Primary clinical focus areas include drug action in humans (clinical pharmacology and toxicology), anesthesia, and trauma, burn, and peri-operative injury. NIGMS will also support network resource development and will broadly sponsor and coordinate the PGRN’s activities.

NHLBI: This institute is interested in retrospective and prospective clinical studies to identify and validate genes and genetic variations that play a role in modulating treatment responses in heart, lung, blood, and sleep diseases and disorders. As a next step to follow-up on the genes discovered, the institute additionally encourages the application of network, integrative, and systems approaches in these clinical populations to investigate gene functions and the biological pathways involved in drug responses, safety, and efficacy.

NCI: This institute is interested in correlative studies utilizing existing materials collected from cancer patients in the Clinical Trials Cooperative Group program and other cancer intervention trials, prospectively collecting materials from cancer patients responding or not responding to treatments and/or those experiencing adverse reactions, establishing pharmacogenomic endpoints for use in ongoing clinical trials and at the inception of future treatment trials, evaluating patients in phase II clinical trials to establish genotype profiles in order to reduce the number of patients required in phase III trials, conducting studies of the genetic and exogenous factors that influence the biotransformation of oncological agents, applying pharmacogenomic advances to improve existing trial designs and data analysis, and developing novel clinical methodologies utilizing pharmacogenomic profiling to stratify, select, treat, and follow-up cancer patients. This institute is also interested in research addressing genetic variability and genome-wide studies associated with drug responses in large, heterogeneous population-based studies, including studies of drug efficacy and toxicity discovered in clinical trial analysis.

NIDA: This institute is interested in research addressing high-throughput studies of approved treatments for drugs of abuse in human populations that will incorporate replication as well as analysis of function/mechanism. Translational approaches that apply genetic knowledge with other knowledge (such as well-characterized enzymatic assays) to define, test, and validate a sensitive and specific test for success regardless of cessation method or treatment are encouraged. Also of interest: exploring drug-drug interactions (for example, drugs of abuse combined with medications, or medications for drugs of abuse combined with other medications), pharmacogenetics of safety and efficacy in phase II and III trials, functional studies of variants and their mechanisms, and development of methods for prediction of treatment success for addiction.

NIMH: This institute is interested in research that associates responses to pharmaceutical treatments of patients with mental disorders (or at high risk for these disorders) with genomic variation. Novel approaches, including the use of biomarkers and other component or intermediate-based phenotypes correlated with the clinical disorder, are also encouraged.

NICHD: This institute is interested in research that can potentially lead to improvement of drug safety and efficacy, and new drug development for pediatric and obstetric populations. This includes studies addressing drug distribution, metabolism, elimination, receptors, and transporters and signaling pathways, as well as interactions of genes, drugs, and environmental factors underlying differences in drug responses, drug actions, and drug toxicity in children at various developmental stages and women in pregnancy.

New Program Features Network Resources

In addition to support for scientific studies, PGRN research groups may now also apply for major network resource components necessary to facilitate network-wide research goals. For example, such resources might include:

coordination of technology for high-throughput genotyping/re-sequencing applications and negotiation for capacity in support of PGRN studies;
coordination of statistical analysis and development of methods and approaches offered as a consultation service;
development of an ethical framework for study of the concerns of implementation (including economics) of pharmacogenomic discoveries;
codification of standardized phenotype definitions and relationships (ontologies), in coordination with other established government-funded efforts;
coordination of short course training, workshops, and educational materials for researchers and medical professionals in Pharmacogenomics, in cooperation with other ongoing activities;
support of the logistical functions of the network (including a PGRN website, organization of semi-annual meetings, publications tracking, support of internal fund competitions, committee coordination, communications, documentation, and other features, to be developed with direction from the NIH PGRN program director)

It will be up to applicants to develop network resource descriptions and responsibilities; funds may be requested commensurate with these activities. Any resource components will have to be available to all PGRN groups in the network. These network resources need not necessarily be service cores but should be coordination and capacity sites for the PGRN. They may not have an organ, system, or disease focus. There will be a limited number of network resources, and these components will require separate application sections, may run for the entire five year award period if needed, and are optional for any research group application. A PGRN network resource is an add-on component and cannot be applied for alone. Applicants for network resources will have to estimate and justify the need for such a component.

The NIH will decide which network resources are essential following peer review and National Advisory Council discussions. Consideration will include how the network resource is defined and whether it can accomplish its goals for the PGRN as proposed, or with alterations consistent with the cooperative agreement mechanism.

New Administrative Features Pilot and Developmental Partnerships

A new aspect of the PGRN will be funds held in reserve in anticipation of internal competitions. Pilot projects and a developmental program are expected, both as partnership projects, and funds will be internally competed and awarded periodically.

pilot partnership projects will be smaller-scale studies that were unforeseen at the time of application, that should enable new approaches to be piloted within the PGRN or formation of new relationships with individuals to bring non-PGRN members into PGRN projects;
developmental partnership projects will provide the ability to create larger-scale PGRN-wide relationships with new entities, for example, novel studies with health care systems utilizing electronic medical records, or modern discovery-based scientific approaches (such as bioinformatics, proteomics, or metabolomic analysis)

Both kinds of partnership projects will be evaluated administratively during the five year course of the PGRN funding period, and separate descriptions are not required at this time. It is expected that the scale of a pilot partnership might be up to $50,000/year for 1-2 years, and a developmental partnership might be up to $200,000/year for 2-4 years. Funds will most likely be retained at NIH until used, although other options may be utilized to allow for flexibility in planning. No funds should be requested at this time, because the purpose will be to recognize and potentially fund new opportunities not known at the time of application.

Program Formation and Governance

The PGRN will be re-formed with the most competitive groups, and weight will be given to distribution and balance across the field of pharmacogenomics. PGRN reorganization will be finalized after funding, in order to maximize the benefits from funding the research groups as a network. NIH staff will continue to have scientific administrative roles in this cooperative agreement, as outlined elsewhere in the Terms and Conditions of award.

The PGRN is governed by a Steering Committee and led by a rotating Chair, who is a PGRN member. Early after funding, the leadership of the groups will meet in a retreat to set goals and milestones for the funding period. The PGRN will continue to have working groups in areas of interest to the awardees and the funding institutes. The current working groups of the PGRN include: Cardiovascular-Pulmonary, Cancer Partnerships, Data Sharing/Consortia, Adverse Drug Reactions, Publications, Statistical Analysis, Pediatric Study Interactions, and Genotyping. A Coordinating Committee serves to coordinate the activities of the working groups and to generate and vet policies proposed to the Steering Committee.

The tasks of the working groups will include, among other responsibilities: identifying common scientific areas and adjusting projects to accommodate shared interests, identifying novel projects that may result from synergy given the awarded groups, and identifying ways to interact with other ongoing initiatives. Working groups may also propose projects to be funded as partnership projects (see above) or as independently-submitted grant award applications. Working groups may propose new research collaborations with non-network investigators and organizations, as long as all PGRN members have the opportunity to participate, according to criteria established by the Coordinating Committee. In some cases, existing working groups may evolve to become network resources as described above, although the resources may not be organ, system, or disease-based and must be available to all groups in the PGRN.

External Input to the Network

The PGRN will continue to have an External Scientific Panel (ESP), with balanced membership and leadership determined at the outset of the award period by the PGRN principal investigators, with the advice of NIH staff members on the Steering Committee and the approval of the NIH PGRN program director. The ESP will be convened to advise the network and to help the group become more than the sum of the parts and to achieve an impact on and accelerate the contributions of the field of pharmacogenomics. The PGRN Steering Committee members will meet at least annually with members of the ESP, will receive and consider a report of the ESP’s comments, and will respond with a written letter each time to be shared with the funding institutes.

Interactions with other Initiatives and Agencies

One purpose of having a network is to elevate the field for all researchers. Any group wishing to join the PGRN, new or renewal, should provide evidence of successful and significant collaborative interactions. Interest and willingness and time available to cooperate in joint interactions and committees should be demonstrated, with high priority given to proven experience related to projects that might relate productively to pharmacogenomics studies (for example, but not limited to: genome-wide studies, clinical studies and trials, electronic health records, and/or statistical consortia).

Leadership activities will be expected of the PGRN research groups. Reviewers will be asked to comment specifically on the potential for leadership in the field. PGRN investigators should plan to interact cooperatively with other ongoing, potentially related efforts. For example:

validated pharmacogenomics information should be shared with the knowledge base PharmGKB (http://www.pharmgkb.org)
clinical trials are a source of potentially appropriate specimen sets for research studies with academic, government, and industry partners (http://clinicaltrials.gov and http://www.cancer.gov/clinicaltrials)
drug response phenotype and intermediate phenotype definitions should be shared with the PhenX Toolkit (http://www.phenx.org)
research involving identification of drug responses in electronic medical records could potentially be coordinated with the eMERGE initiative (http://www.gwas.net)
relevant clinical studies might be proposed to the Clinical and Translational Science Awards, CTSAs (http://www.ctsaweb.org) or the Pediatric Pharmacology Research Units, PPRUs (http://www.ppru.org)
educational efforts could be coordinated with the Centers for Education and Research on Therapeutics program, CERTS (http://www.certs.hhs.gov/)

Likewise, the NIH, AHRQ, CDC, and FDA all sponsor multiple efforts that could interact productively for pharmacogenomics studies. These are only examples, and the goal is to leverage existing networks and to coordinate productively with other ongoing efforts supported by NIH and DHHS. Applicants should propose specific, concrete interactions with other initiatives as the opportunities present and may request funds in support of collaborations.

Commitment to Diversity

Applicants responding to this initiative must propose creative and successful ways to model diversity in their research teams. Reports from the National Science Foundation and the National Academies emphasize the need for a well-trained workforce in the sciences. They describe the continuing importance of developing and maintaining a strong, vital, scientific workforce that reflects the diversity of our nation. African Americans, Hispanic Americans, American Indians, and Natives of the US Pacific Islands are particularly underrepresented in the biomedical and behavioral sciences. NIH, through programs at NIGMS, is committed to promoting and advancing scientific workforce diversity (http://www.nigms.nih.gov/News/Reports/workforcediversity_100307.htm). The scientific teams of the PGRN research groups should reflect that resolve.

Data and Sample Sharing under this Initiative

Data sharing is an important aspect of this initiative. NIH wants valuable datasets that identify genetic contributions to health and disease, including drug responses, to be shareable to the maximum extent possible. Regardless of the amount requested, awards under this initiative must meet requirements for an NIH application in excess of $500,000 and present a data-sharing plan that utilizes existing established databases for the data types being collected. For example, data generated from genome-wide association studies must be deposited into the database of Genotypes and Phenotypes (dbGAP, http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap), for access according to its policies. Guidance for developing data-sharing plans and for IRBs evaluating those plans is provided by NIH at http://grants.nih.gov/grants/gwas/.

Sample sharing is also encouraged under this initiative. Some institutes supporting the Pharmacogenomics Research Network have invested considerable effort into disease-specific specimen collections. Applicants are urged to be as proactive as possible in planning their studies and consents to promote sharing (for example, sharing clinical specimens, cell lines, transgenic animals, and reagents), and to describe these plans fully.

Reviewers for this initiative will be asked to comment specifically on the plans to share phenotype and genotype data, as well as plans for specimen sharing and banking. Applicants should also comply with all NIH requirements for Data Safety and Monitoring Plans, as applicable. Details of all NIH policies are found in the appropriate section of this funding opportunity announcement

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the U01 and U19 cooperative agreement award mechanisms.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) 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 VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". NIH intends to allow for the possibility of reissuing this funding opportunity announcement near the conclusion of the five year award period, although plans are indefinite at this time.

2. Funds Available

the total amount of funds expected to be awarded through this announcement is up to $170 million over five years;
the anticipated number of awards is approximately 12-14 research groups (including approximately 4-6 network resource add-ons, as defined in New Program Features);
U01 applications should be submitted for research groups, and U19 applications should be submitted for research groups with network resources;
the range of maximum expected direct costs amount for each research group is $1 - $1.5 million per year;
the range of additional expected direct costs for each network resource component is $0.1 - $0.5 million per year;
a network resource is optional - only research groups may propose these add-on components, and they may not be applied for alone;
no research group may include more than 2 additional network resources;
two or more groups may work together to create an enhanced network resource - this interaction should be very clearly presented and contributions should be distinctly outlined in the appropriate sections of the pertinent applications (also, cover letters should refer to related applications);
all awards are anticipated to be up to five years in duration, where justified

The estimated amount of funds available for support of 12-14 projects awarded as a result of this announcement is $30 million total costs for fiscal year 2010. Future year amounts will depend on annual appropriations.

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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education
Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Small Businesses
For-Profit Organizations (Other than Small Businesses)

The following organizations/institutions are NOT eligible to apply independently but may be a part of an application as a research component or as a network resource:

Non-domestic (non-U.S.) Entities (Foreign Organizations)

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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 support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

Principal investigators must participate in a multidisciplinary environment or group, must have evidence of an established research program, and must plan to contribute significant time, effort, and leadership to the PGRN. The PGRN is intended to impact and elevate the field of pharmacogenomics as a whole; this is not simply intended as a mechanism to fund an association of investigators at an institution. Reviewers will be asked to comment specifically on the appropriateness of a group to be funded under this initiative, and on the commitment that a principal investigator appears able to make to leadership in this network.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are permitted in response to this FOA.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A).

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: May 2, 2009
Application Receipt Date: June 2, 2009
Peer Review Date: November 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: April 1, 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the Principal Investigator
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

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 in Section IV.3.A.

The letter of intent should be sent to:

Rochelle M. Long, PhD
Pharmacology, Physiology, and Biological Chemistry Division
NIGMS, NIH
45 Center Drive
Bldg. 45, Rm. 2As.49G
Bethesda, MD 20892
Telephone: (301) 594-3827
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity 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 a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

For cooperative agreements, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Plan Page Limitations

There is an overall page limit of 40 pages for the Research Plan for a research group in a U01 application, with the recommendation to be divided as follows:

2 pages for an Overall Research Program Summary (must stand alone and represent the entire proposed program, referring to each essential component)

2 pages for the Specific Aims

6 pages for the Background/Significance

8 pages for the Preliminary Studies/Progress Report

18 pages for the Research Design and Methods

1 page for Management within a research group (each group must also name a program coordinator and describe internal communication plans within the group, as well as state tentative areas of interest/emphasis for work within the PGRN; include the Multiple PD/PI Leadership Plan described above here, if applicable)

1 page for Data Sharing/Dissemination plans (each group must adhere to all prevailing NIH policies for data deposits in a proactive manner; include timeframes and be specific about how data transfers will take place)

1 page for a plan for Increasing Researcher Diversity (each group must propose ways to reflect NIGMS and NIH’s commitment to promoting and modeling diversity in research teams)

0.5 page for handling Research Resources and Specimen Banking (each group must plan to share valuable resources to the greatest extent possible)

0.5 page for Intellectual Property plans (an institution’s stance will ideally be consistent with advancing and not hindering future research)

There is an additional overall page limit of 10 pages for each network resource (as described in New Program Features) in a U19 application, with the recommendation to be divided as follows:

1 page for an Overall Network Resource Summary (must stand alone and define the service or focus and essential nature for the PGRN)

1 page for the Background/Significance

1 page for the Preliminary Studies/Experience with Methods

6 pages for the Resource Organization and Approach (include justification for the PGRN needs, and structure and management plans that fit with those needs)

1 page for Management of interactions with the PGRN (each resource must name a network resource liaison and describe communication plans with the PGRN)

The policies for Appendices are not changed for this funding opportunity announcement for either U01 or U19 applications; see the PHS 398 grant application instructions for details.

Budgetary Instructions:

Overall composite budgets should be provided for the entire program, and individual budgets provided for each component part (project, core, or network resource, etc.). Place these budgets at the front of the application in sequence, so that they do not interrupt the pagination and limits described above. Use roman numerals and titles to identify each component of the program and its associated budget, and make them match the entries in the Table of Contents. Place the composite budgets before the associated detailed budgets. All costs should be reflected in the composite budgets, but Facilities and Administrative costs required to set up and maintain subcontracts will not count against the upper budgetary limits for this announcement, nor will one-time equipment requests.

Composite budgets There should be a composite budget for the initial budget period (to cover all components for the first year of the program) on form page 4, and there should be a composite budget for the entire proposed period of support (typically 5 years) on form page 5. For each composite, prepare and total the amounts by each major budget category such as Personnel, Equipment, Supplies, etc. (list the amounts by component in the space allowed on the form to itemize, and place category totals in the blocks on the forms).

Individual component budgets For each project, core, or network resource, there should be a detailed, itemized budget for the initial budget period (to cover all aspects for the first year of the program) on form page 4, and a budget for the entire proposed period of support (typically 5 years) on form page 5. Complete justifications and explanations should be provided, including the rationale for continuing any component for the entire project period. Inflationary increases will be limited to the NIH-approved amounts, and in some cases individual institutes will limit increases for awards that received funding in prior years (details to be provided by the institute staff contacts listed in this announcement).

Subcontracts Where there are subcontracting organizations, each entity will need to submit separate budget pages, if they are not already presented separately according to the instructions above. They should both be included in the itemized listing described for a project, core, or network resource, and their requests must be prepared separately as a detailed, itemized budget for the initial budget period and as a budget for the entire proposed period of support.

Supplementary Instructions for all applications:

Every research group should plan for and may request funds to support the travel of the principal investigator(s) and at a minimum one co-investigator to at least two PGRN meetings per year of two days duration, to be held in a rotating location around the US. The purpose of the meetings will be to assess scientific opportunities in the field and for dissemination of technical information, as well as to hold the internal Steering Committee meetings to discuss PGRN planning and administration.

Each group should be prepared to co-organize and provide local assistance for at least one meeting during the entire five year funding period. Activities in support of a meeting should be described and charges estimated, in accord with applicable NIH cost principles. Plans should be presented for this purpose in each application, but funds should NOT be specifically requested at this time. NIH will likely choose to award funds only when it is decided that a meeting will occur, by mutual agreement with the principal investigator. NIH may also decide in the future how the funds will be awarded, or possibly coordinated with a logistical network resource (if such an award is made). Any future requests for supplements will always include a review of unobligated balances on an award, in order to consider rebudgeting funds from other categories.

Every research group should plan to support a program coordinator for adequate effort to assist with communication and coordination of PGRN activities within a research group. This person’s duties will exceed secretarial tasks and should require a background commensurate with the responsibilities. Funds to support this role may be requested in a U01 application.

Any group that applies for a network resource (as described in New Program Features) should also specifically plan to support a network resource liaison for adequate effort to assist with communication and coordination of activities between research groups in the PGRN. Funds may be requested for the role in a U19 application, and this may be the same person as the program coordinator for a research group, mentioned above, for a greater amount of effort.

Any group that applies for a network resource (as described in New Program Features) should describe any specialized activities proposed, if they are an essential part of the service proposed for the network. For example, periodic workshops could be proposed, or publication of reports. These activities must be explicitly described, estimated, and justified in the network resource plans, and the funds to support activities may be requested in accord with applicable NIH cost principles

External advisors and/or advisory committee members to be utilized by a research group on a periodic basis for scientific or technical guidance are highly encouraged; however, the advisors or committee members should be described in an application only by area of expertise. Potential members should NOT be contacted, named, or appointed until after an award is made.

Follow instructions for all other aspects of the PHS 398 paper grant application form. Ensure that all institutional letters are included and signed.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CDs only. Include five identical CDs in the same package with the application (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Many institutes participating in this FOA already support well-defined specimen-sharing programs, and their programs should be utilized and policies shall be adhered to as appropriate for the scientific area and subject area of the applications. Consult with the institute staff contacts listed in this announcement if there are questions and for more details.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIH Center for Scientific Review and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned a priority score.
Receive a written critique.
Receive a second level of review by the appropriate National Advisory Councils or Boards

The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined by peer review
Availability of funds
Relevance of the proposed project to program priorities
Geographical and program balance
Potential to contribute to a productive network
Essential nature of proposed network resources
Impact of data (and sample) sharing efforts

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Review criteria for U01 applications and research group components of U19 applications:

Overall Impact. Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims advance the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the program of research have the potential to establish new paradigms for pharmacogenomics studies? What will the significance be of understanding the genomic basis of differences in treatment responses for the selected area of research?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? What is the evidence that they work well in a collaborative environment? Do the investigative team members demonstrate the potential to be interactive and effective in the PGRN?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are the studies proposed at the cutting edge for pharmacogenomics (if appropriate), and will the activities outlined for the project period be nimble enough to stay current to the greatest extent possible, given the rapid rate of innovation in genomic technologies?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the approaches proposed the most appropriate for the field of pharmacogenomics, given the nature of the studies to be conducted, the source(s) of clinical materials available, the established knowledge in the field, and the most likely to clearly establish the genetic contributions and functional basis of drug responses in the selected area of focus?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there evidence that the environment is conducive to establishing a research program of the complexity and scope required for the PGRN?

In addition to the above, the following criteria will be applied to all applications in the determination of scientific merit and the score for overall impact:

Data and Resource Sharing. Does the applicant emphasize plans to share phenotype and genotype data, as well as sharing relevant samples and models where possible. Is the applicant s commitment to the goal of sharing data proactive, realistic, and achievable.

Leadership. Does the applicant propose leadership activities and interactions with other ongoing efforts in the field of pharmacogenomics. Is the commitment of the principal investigator(s) and his/her investigative team, adequate given the goals of this network.

Review criteria for network resource components of U19 applications:

The following review criteria will be applied, and each network resource will be given only one score an overall impact score.

Overall evaluation of a network resource. What is the evidence for the need for such a network resource? Will the provision of this resource facilitate functioning of the PGRN, accelerate the rate of discovery and understanding in the field, or provide an important contribution to the network as a whole? Are the investigators an appropriate choice to lead this resource, and are they the best-positioned to carry out the work in addition to being qualified? Is the level of innovation appropriate for the task and consistent with the best quality work in the field? Is this network resource well-defined, and can it accomplish its goals as proposed or with alterations consistent with the cooperative agreement mechanism? Is/are the institutions and their environment(s) appropriate selections, given the task of the network resource? Overall, how great of an impact will the resource have on the network?

Additional Review Criteria for both U01 and U19 applications. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations. As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Commitment to Diversity. Reviewers should comment on how well the scientific teams of the proposed research group and/or network resource reflect the NIH’s and NIGMS commitment to promoting and advancing scientific workforce diversity, and on the value and likelihood of success of the plans proposed.

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, and will factor them into the scores as described above under Resource Sharing Plan(s)

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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.

2.A. Cooperative Agreement Terms and Conditions 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 an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the 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 as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

Coordinating projects (and network resource activities, if relevant) scientifically and administratively at the institution(s); defining the details of the scientific activities and planning, conducting, analyzing, and publishing results, interpretations, and conclusions of studies;

Accepting close interaction with and participation of NIH staff in aspects of management of the network as defined below in their roles; cooperating and assisting in implementing the recommendations of the Steering Committee;

Contributing leadership in thought, ideas, and actions; working with the organization, structure, and advisors of the network, as outlined in the Program Formation and Governance section, and any subsequent modifications by joint agreement;

Attending meetings and calls on network-wide efforts, as agreed upon in the leadership retreat and working groups described under the Program Formation and Governance section; agreeing to devote sufficient time and effort in follow-up;

Reporting annually on progress within their own research groups (and network resource activities, if relevant), and additionally on specialized network activities as described in the Reporting section, below; adhering to all NIH policies in effect for the kinds of genomic studies to be supported by these awards.

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.

2. A.2. NIH Staff Responsibilities

The NIH PGRN program director will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

The NIH PGRN program director will be responsible for:

Establishing the PGRN Steering Committee and appointing its Chair and vice-Chair; planning agendas for the calls and meetings along with the PGRN Chair; handling and managing the flow of reports and responses to be archived for the PGRN;

Actively sharing relevant administrative expertise and overall knowledge about NIH programs; coordinating activities between institutes of the NIH; promoting best practices and forward-looking policies for research studies;

Working with the logistical network resource, if one is awarded, or providing an alternative means for making the provisions necessary for network meetings and calls - this may be accomplished by a variety of arrangements such as by the award of supplemental funds or by a government contract;

Working with the network resources that successfully compete for funding, to ensure that their capabilities and capacities are fairly allocated and appropriately utilized for network projects; making recommendations and/or provisions for adjustment of funding as becomes necessary scientifically;

Attending meetings and calls on network-wide efforts, as agreed upon in the leadership retreat and working groups described under the Program Formation and Governance section of this FOA;

Assisting in the renewed formation of the External Scientific Panel (ESP), which is advisory to the PGRN; representing the PGRN to the ESP by receiving advice and conveying responses in writing approximately annually following face-to-face meetings.

Additionally, institute program officials from each of the funding institutes will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notices.

2.A.3. Collaborative Responsibilities

Close interactions between the Principal Investigators and NIH PGRN program director will be expected, and they will jointly be responsible for:

Establishing the Steering Committee of the PGRN as the group described in the Program Formation and Governance section, setting up subcommittees and working groups, and making them run cohesively and productively to accomplish the purpose of this initiative;

Ensuring that NIH representation is proportional to its investment (an NIH staff person will never be the Chair or vice-Chair of the Steering Committee);

Planning regular communications by calls and meetings for the purpose of accomplishing the PGRN’s goals of identifying areas of mutual interest and specific opportunities to interact, lead, and elevate the field of pharmacogenomics;

Devising processes and procedures to compete for funds described under New Administrative Features (Pilot and Developmental Partnerships), nurturing and developing new and existing collaborations and tracking their progress;

Receiving and responding to advice in writing from the PGRN’s ESP, sharing this advice with all funding institutes, and evaluating and adjusting network goals as appropriate in an ongoing dialogue with the ESP;

Cooperating with any independent evaluations that may be planned by any of the NIH institutes funding this initiative (most likely NIGMS as the lead supporting component) and/or the designees of their National Advisory Councils.

Each full member of the Steering Committee will have one vote. The number of NIH program officials will never exceed one half of the total membership for voting purposes. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. 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 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 regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Awardees will be required to periodically submit letters detailing activities in support of PGRN-wide goals established when the network begins to meet, according to the responsibilities outlined in the Terms and Conditions of award. Awardees may also be required to report periodically on summaries of data deposits, resource sharing, major network-wide collaborations, and network resource activities described under New Program Features, as well as projects described under New Administrative Features, and other mutually agreed-upon activities.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Rochelle M. Long, PhD
Pharmacology, Physiology, and Biological Chemistry Division
NIGMS, NIH
45 Center Drive
Bldg. 45, Rm. 2As.49G
Bethesda, MD 20892
Telephone: (301) 594-3827
Email: [email protected]

Richard A. Anderson, MD, PhD
Genetics and Developmental Biology Division
NIGMS, NIH
45 Center Drive
Bldg. 45, Rm. 2As.25A
Bethesda, MD 20892
Telephone: (301) 594-0943
Email: [email protected]

Dina N. Paltoo, PhD, MPH
Division of Cardiovascular Diseases
NHLBI, NIH
2 Rockledge Center, Rm. 8220
6701 Rockledge Dr.
Bethesda, MD 20892
20817 for express mail
Telephone: (301) 435-0513
Email: [email protected]

Weiniu Gan, PhD
Division of Lung Diseases
NHLBI, NIH
2 Rockledge Center, Rm. 10164
6701 Rockledge Dr.
Bethesda, MD 20892
20817 for express mail
Telephone: (301) 435-0202
Email: [email protected]

Leah B. Sansbury, PhD, MSPH
Division of Cancer Control and Population Sciences
NCI, NIH
Executive Plaza North, Rm. 5106
6130 Executive Blvd.
Rockville, MD 20892
20852 for express mail
Telephone: (301) 435-4910
Email: [email protected]

Heng Xie, MD, MPH, PhD
Division of Cancer Treatment and Diagnosis
NCI, NIH
Executive Plaza North, Rm. 7009
6130 Executive Blvd.
Rockville, MD 20892
20852 for express mail
Telephone: (301) 496-8866
Email: [email protected]

Joni L. Rutter, PhD
Division of Basic Neuroscience and Behavioral Research
NIDA, NIH
Neuroscience Ctr., Rm. 4282
6001 Executive Blvd.
Bethesda, MD 20892
20852 Rockville, MD for express mail
Telephone: (301) 435-0298
Email: [email protected]

Zhaoxia Ren, MD, PhD
Obstetric and Pediatric Pharmacology Branch
NICHD, NIH
Rm. 4B15
6100 Executive Blvd.
Rockville, MD 20892
Telephone: (301) 402-9340
Email: [email protected]

Thomas Lehner, PhD
Neuroscience and Basic Behavioral Science Division
NIMH, NIH
Neuroscience Ctr., Rm. 7190
6001 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 443-9869
Email: [email protected]

2. Peer Review Contacts:

Richard Panniers, PhD
Genes, Genomes, and Genetics IRG
CSR, NIH
2 Rockledge Center, Rm. 2198
6701 Rockledge Dr.
Bethesda, MD 20892
20817 for express mail
Telephone: (301) 435-1741
Email: [email protected]

3. Financial or Grants Management Contacts:

Lisa Moeller
Grants Administration Branch
NIGMS, NIH
Bldg. 45, Rm. 2AN.50C
45 Center Dr.
Bethesda, MD 20892
Telephone: (301) 594-3914
Email: [email protected]

NIGMS, as the lead funding institute, will provide the grants management consultative support for new applications which will be assigned to that institute initially. For renewal applications, investigators are urged to contact grants management staff in the institutes currently funding their applications, and the name of the appropriate financial official can be obtained from the scientific/research contact individuals listed above.

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

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 (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $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 (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported 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 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. 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 differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

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 (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). 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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
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).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) 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 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 site.

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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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 http://grants.nih.gov/grants/policy/policy.htm.

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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.