Medications Development for the Treatment of Pregnant/Postpartum Women with Substance-Related Disorders and/or In Utero Substance-Exposed Neonates (R01)

Medications Development for the Treatment of Pregnant/Postpartum Women with Substance-Related Disorders and/or In Utero Substance-Exposed Neonates (R01) is sponsored by National Institutes of Health (NIH). Encourages research to develop safer and more effective pharmacological treatments for pregnant or postpartum women with substance use disorders and neonates exposed to substances in utero.

Expired PA-09-106: Medications Development for the Treatment of Pregnant/Postpartum Women with Substance Related Disorders and/or In Utero Substance Exposed Neonates (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Participating Organizations Institutes of Health (NIH), http://www.

nih. gov Participating Organizations National Institute on Alcohol Abuse and Alcoholism (NIAAA), ( http://www. niaaa.

nih. gov/ ) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ( http://www. nichd.

nih. gov /) National Institute on Drug Abuse (NIDA) ( http://www. nida.

nih. gov ) Title: Medications Development for the Treatment of Pregnant/Postpartum Women with Substance Related Disorders and/or In Utero Substance Exposed Neonates (R01) Update: The following update relating to this announcement has been issued: September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.

This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions.

If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions. March 30, 2009 - See Notice NOT-HD-09-011 Participation of NICHD. March 12, 2009 - See Notice NOT-AA-09-001 Participation of NIAAA.

Announcement (PA) Number: PA-09-106 submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants. gov ( http://www. grants.

gov ) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. BE SUBMITTED IN PAPER FORMAT. in conjunction with the application guidelines included with this announcement for Grants (hereafter called Grants.

gov/Apply). is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV .

Domestic Assistance Number(s) Opening Date: May 5, 2009 (Earliest date an application may be submitted Letters of Intent Receipt Date(s): On-time submission requires that applications be successfully submitted to Grants. gov no later than 5:00 p. m.

local time (of the applicant institution/organization). Application Due Date(s): Standard dates apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm AIDS Application Due Date(s): Standard dates apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm#AIDS . Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Anticipated Start Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward To Be Available Date (URL Activation Date): Not Applicable Expiration Date: May 8, 2012 purpose of this FOA is to foster the development of novel pharmacological strategies for the treatment of pregnant/postpartum women with Substance Related Disorders (SRDs) and/or in utero substance exposed neonates.

To that end, this FOA issued by NIDA, National Institutes of Health, will encourage applications to implement preclinical and clinical research directed towards: 1) the identification, evaluation, and development of safe and effective novel pharmacotherapies (e.g., new chemical entities or immunotherapies) for the treatment of pregnant/postpartum women with SRDs and/or in utero substance exposed neonates, and/or 2) the evaluation of the safety and efficacy of FDA approved medications (e.g., medications approved for a different indication) for the treatment of pregnant/postpartum women with SRDs and/or in utero substance of Support.

This FOA will use the NIH Research Project Grant (R01) mechanism and runs in parallel with a FOA of identical scientific scope, PA-09- 107 that encourages applications under the Exploratory/Developmental (R21) grant mechanism. Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications .

Budget and Project Period. The total project period for an application submitted in response to this funding opportunity may not exceed 5 years. Applicants for an R01 award are not limited in dollars but need to reflect the actual needs Application Research Strategy Length: The R01 application Research Plan component of the PHS398 (Item 3) may not exceed 25_pages, including tables, graphs, figures, diagrams, and charts.

See http://grants1. nih. gov/grants/funding/funding_program.

htm Institutions/Organizations. Institutions/organizations listed in Section III, 1. A.

are eligible to apply. Eligible Project Directors/Principal Investigators (PDs/PIs). Include 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 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 that each application is Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications ( NOT-OD-09-003 , NOT-OD-09-016 ).

Renewals. . Renewal applications are not permitted in response to this FOA.

Application Materials. See Section IV. 1 for application materials.

General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites: SF424 (R&R) Application and Electronic Submission Information: http://grants. nih.

gov/grants/funding/424/index. htm Electronic Submission of Grant Applications: http://era. nih.

gov/ElectronicReceipt/ Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936. Part II Full Text of Announcement Section I.

Funding Opportunity Section II. Award Information Section III. Eligibility Information 2.

Cost Sharing or Matching 3. Other-Special Eligibility Criteria Section IV. Application and Submission 1.

Request Application Information 2. Content and Form of Application Submission 3. Submission Dates and Times A.

Submission, Review, and B. Submitting an Application Electronically to the NIH C. Application Processing 4.

Intergovernmental Review Requirements and Information Section V. Application Review Information 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 2. Administrative and National Policy Requirements Section VII.

Agency Contacts 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 purpose of this FOA is to foster the development of novel pharmacological strategies for the treatment of pregnant/postpartum women with Substance Related Disorders (SRDs) and/or in utero substance exposed neonates.

To that end, this FOA issued by NIDA, National Institutes of Health, will encourage applications to implement preclinical and clinical research directed towards: 1) the identification, evaluation, and development of safe and effective novel pharmacotherapies (e.g., new chemical entities or immunotherapies) for the treatment of pregnant/postpartum women with SRDs and/or in utero substance exposed neonates, and/or 2) the evaluation of the safety and efficacy of FDA approved medications (e.g., medications approved for a different indication) for the treatment of pregnant/postpartum women with SRDs and/or in utero substance exposed neonates.

may focus on pharmacotherapies for the treatment of substance abuse/dependence and its complications during pregnancy or the postpartum period and/or the treatment of the complications associated with in utero substance exposure.

Substances of abuse include nicotine, cannabis, methamphetamine, cocaine, opioids, hallucinogens, inhalants, phencyclidine, and prescription medications such as analgesics, sedatives, hypnotics, anxiolytics, and alcohol. Preclinical and clinical research may focus on currently FDA-approved and/or novel investigational medications, including immunotherapies.

This Funding Opportunity Announcement is designed to encourage preclinical or clinical research, such as human laboratory studies as well as Phase II and Phase III Medications development for the treatment of pregnant/postpartum women with substance related disorders and/or their in utero substance exposed neonates addresses an emerging public health problem in which there is a significant gap in preclinical and clinical research.

In the Sixth Triennial Report to Congress, NIDA estimated that approximately 5. 5% of women used some illicit drug during pregnancy. It has been estimated that there are about 2.

5 million pregnant women in the United States each year. Other data from the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) show that the 12-month prevalence of any substance use disorder among pregnant women is 14. 6%.

In addition, past-year pregnant women were significantly less likely than non-pregnant women to have been diagnosed as having any substance use disorder, including alcohol and other drug use disorders and nicotine dependence, and any psychiatric disorder, but not any illicit drug use.

Though statistics in these two reports vary, both reports indicate that a significant public health problem exists in the area of pregnant/postpartum women with SRDs and/or their in utero substance exposed neonates. Substance abuse during pregnancy often occurs in the context of complex environmental factors and poly-drug exposure, as well as medical conditions which are associated with adverse neonatal consequences.

They include premature delivery, low birth weights, smaller head circumferences, and shorter body lengths, than infants not exposed in utero to substances of abuse. Women who use drugs during pregnancy are more likely to be in a financial crisis, more likely to be adversely involved with the criminal justice system, been victims of violent crime, and/or have psychiatric comorbidity.

Estimation of the full extent of the consequences of maternal drug use is difficult. Given the higher incidence of polysubstance abuse in general, determining the specific hazard of a particular drug to the unborn child is extremely challenging. Clearly, research on medication treatments for i n utero substance exposure is a public health priority.

There is a major gap between the focus of research and the needs of clinical practice in the area of substance exposed pregnant/postpartum women and their in utero exposed neonates. Research on this vulnerable substance-exposed population has primarily focused on the negative effects of substance exposure.

The research on cocaine, methamphetamine, tobacco, cannabis, and alcohol primarily focuses on the negative effects of the substance, thus leaving a gap in regard to potential pharmacotherapy treatment strategies. Much is known in regard to the negative effects of substances of abuse on the pregnant/post partum women and their substance exposed neonates but relatively little is known in regard to medication treatment strategies.

The area of opiate exposed pregnant/postpartum women and in utero opiate exposed neonates is leading this field in pharmacotherapy treatment strategies but still gaps in this research area exist. For example, research most often focuses on the negative effects of opiate exposure rather then focusing on efficacious medication treatments.

Research has demonstrated that neonatal mortality is more than four times higher for opiate exposed neonates . The incidence of Neonatal Abstinence Syndrome (NAS) has been reported to be as high as 54% to 94% of all babies who have been exposed to opiates in utero .

Opiate exposure in utero has been demonstrated to reduce the birth weight and head circumference of the affected infant, leading to long term cognitive and behavioral problems. The majority of infants exposed to opioids undergo withdrawal at different levels of severity, indicating a need for specific pharmacotherapy treatments.

A number of pharmacotherapies have been used in the management of NAS including paregoric, tincture of opium, morphine, methadone, phenobarbital, clonidine, chlorpromazine, buprenorphine, and diazepam. In current practice, tincture of opium or morphine sulfate solution are used to manage 63% of opioid and 52% of poly-drug withdrawals. In addition, methadone is used for 20% of opioid withdrawals.

Unfortunately, there are very few published studies that compare the efficacy of different medication treatments for NAS, based on severity of withdrawal. Research on the risk / benefit ratio and best practices of the most optimal treatment regimen is not conclusive at this time.

To fill this gap, new clinical and preclinical research is needed to identify more effective medication treatment strategies, including combination medication treatments and adjunctive pharmacotherapies for NAS. pregnant/postpartum women and in utero stimulant exposure research has primarily focused on adverse effects, with minimal research emphasis on pharmacotherapy treatments for these Substance Related Disorders (SRDs).

Due to this gap in research, much is known about the negative effects of stimulants on mother and child, but no standard of care exists in regard to medication treatments for stimulant exposure. For example, research indicates cocaine-exposed infants compared with unexposed controls exhibited higher rates of intrauterine growth retardation, small head circumference, neurologic abnormalities, and impaired auditory information processing.

Adverse neonatal effects associated with fetal cocaine exposure have been shown to follow a dose-response relationship such that newborns with higher levels of prenatal cocaine exposure show higher rates of impairments in fetal head growth and abnormalities of muscle tone, movements, and posture.

It has long been known that cocaine decreases uteroplacental blood flow and can cause uteroplacental in sufficiency, placental hypoperfusion, vasoconstriction of the uterine vasculature, and increases in blood pressure and heart rate. Cocaine induced vasoconstriction in the pregnant mother can cause maternal hypertension resulting in higher frequency of abruption placentae.

Certainly, research indicates that a pregnant woman and her developing fetus are at risk for numerous medical problems due to cocaine exposure and yet no standard of care exists in regard to pharmacotherapy for this vulnerable population. In addition, methamphetamine exposure throughout gestation has also been associated with decreased growth at term. Low birth weight infants have increased mortality and morbidity.

Small prenatal head circumference is associated with the detrimental neurodevelopmental outcomes. With stimulants, neonatal withdrawal symptoms are not readily determined because what appears to be withdrawal may in fact be symptomatology of the drug itself. Little is known about medication interventions for this SRD in this population.

In part this is due to the fact that there are no FDA-approved medications for the treatment of stimulant use disorders. However, pregnant/postpartum women and their infants frequently receive off-label medications for these disorders or their psychiatric co-morbidities with little or no information about their safety.

Given the health risks associated with stimulant exposure to pregnant women and their neonates, clinical and preclinical pharmacotherapy research in this area is of paramount importance. cannabis-related disorders, there is no FDA-approved pharmacotherapy to treat them.

It is known that cannabis exposure to one or more marijuana joints per day during the first trimester predicted deficits in the childrens Wide Range Achievement Test (WRAT-R) reading and spelling scores, and a lower rating on the teachers' evaluations of the children's performance. Second-trimester marijuana use was associated with problems in reading comprehension and underachievement.

Research thus far indicates a public health problem and negative effects but very little clinical and preclinical research exists in the area of medication treatment for cannabis exposed pregnant/postpartum women Much is known in regard to the negative effects of tobacco on pregnant/postpartum women and their tobacco-exposed neonates, but relatively few research studies exist in regard to medication treatment for this condition.

According to the Centers for Disease Control 2002 PRAMS Surveillance Report on Tobacco Use, cigarette smoking during pregnancy contributes to a number of adverse birth outcomes, including spontaneous abortion, stillbirth, fetal death, and sudden infant death syndrome (SIDS). An estimated 5% of all infant deaths in the United States are attributable to maternal smoking during pregnancy.

Smoking is the most important known preventable risk factor for low birth weight and small size for gestational age, both of which are leading contributors to fetal and neonatal deaths. The incidence of low birth weight of children of mothers who smoke is estimated to be about double that for non-smokers.

Cigarette smoking during pregnancy is also associated with premature rupture of membranes, abruption placentae, placenta previa, and preterm delivery. Smoking during pregnancy accounts for a 150% increase in overall perinatal mortality. Several studies indicate a dose-response effect in which mothers who smoke greater amounts during pregnancy have progressively higher rates of low birth weight and preterm deliveries.

Cigarette smoking during pregnancy is also associated with an increased risk for various birth defects, including orofacial clefts, clubfoot, hydrocephaly, and microcephaly.

Research is needed in regard to nicotine replacement therapies and other anti-smoking medications in the population of pregnant/postpartum women and Research on alcohol-exposed pregnant/postpartum women and their neonates is extensive but again, the research has yielded information primarily focused on the negative effects as opposed to pharmacotherapy treatments.

Fetal Alcohol Syndrome (FAS) is a birth defect characterized by craniofacial malformations, neurological and motor deficits, intrauterine growth retardation, learning disabilities, and behavioral and social deficits. The Alcohol Policies Project (APP) reports that FAS is estimated to occur in 1 to 2 live births per every 1,000 in the United States each year.

APP also reports that fetal alcohol effects are estimated to occur in 3 to 5 live births per every 1,000 in the United States each year. FAS is one of the most serious consequences of heavy drinking during pregnancy.

The umbrella term "Fetal Alcohol Spectrum Disorders (FASD)" is now used to characterize the full range of prenatal alcohol damage varying from mild to severe and encompassing a broad array of physical defects and cognitive, behavioral, and emotional deficits. As a very common disorder, FASD affects some 40,000 births per year, nearly one in 100.

Recent research is ongoing with regard to ligand receptor interaction to prevent teratogenesis. As with other drugs of abuse, minimal research exists in regard to pharmacotherapies for alcohol exposed pregnant/postpartum women and their alcohol exposed neonates. is clear that recent research in the area of substance exposure in pregnancy indicates significant risks for the mother and child.

The research results regarding the negative effects of opioids, cocaine, methamphetamine, tobacco, cannabis, and alcohol contrast with the relatively minimal body of research evaluating the safety and/or efficacy of medications for this vulnerable population.

This research gap indicates that further clinical and preclinical research is needed in the area of medication development for the treatment of substance exposed pregnant/postpartum women and their neonates.

In order to address this gap, NIDA seeks to expand the field of substance abuse research to focus on pharmacotherapies, also including adjunctive behavioral therapies, for pregnant/postpartum women with SRDs and in utero substance exposed neonates.

The primary goal of this FOA is to find safe and efficacious pharmacological treatments for pregnant/postpartum women with substance related disorders (SRDs) and in utero substance exposed neonates by encouraging grant applications that implement preclinical or clinical research on this topics of interest include but are not limited to: testing of new chemical entities which would act as full agonists, partial agonists, or antagonists in pregnancy animal models.

Medicinal chemistry efforts and associated pharmacological testing directed at the discovery of leads and lead optimization relevant to medications development for the treatment of substance exposure in pregnant/post partum women and in utero substance and clinical research on the effects of withdrawal and detoxification in pregnant animal models and pregnant women with SRDs.

testing of medications that may affect the interaction between cannabinoid, opioid and dopamine systems in pregnant animal models. of dosing for approved medications for SRDs by testing them in pregnant women and their in utero substance-exposed neonates.

on the safety and efficacy of various pharmacotherapies for smoking cessation applied during pregnancy (i.e., establish the risk/benefit studies on pharmacologic interventions related to specific drug exposure using cardiovascular measures, dosing and tapering protocols, and plasma concentrations of research medications in pregnant/postpartum women and substance exposed neonates.

clinical trials that specifically address the pharmacotherapy needs of substance exposed pregnant/postpartum women and in utero substance and efficacy studies of the drugs currently used in the treatment of Neonatal Abstinence Syndrome (NAS). of the effects of medications for the treatment of SRDs on the neonate.

on the elimination of agonist and partial agonist treatment medications, such as methadone or buprenorphine in the newborn at various gestational of pharmacotherapy strategies for co-morbid SRDs in pregnant women and in utero substance-exposed neonates.

of adjunctive behavioral strategies for medication treatments of SRDs and co-morbid SRDs in pregnant women and in utero substance-exposed on systematic abstinence scoring methods to determine the severity of withdrawal and the need for pharmacotherapy. and clinical effects of treatment medications on developmental outcomes of prenatal exposure to substances of abuse.

Counseling and Testing Policy for the National Institute on Drug Abuse : In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing.

NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information see http://grants.

nih. gov/grants/guide/notice-files/NOT-DA-07-013. html .

Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.

Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www. nida.

nih. gov/about/organization/nacda/CouncilStatement. html .

for Consultation and Collaboration web-based Networking Project (NNP) to encourage investigators to collaborate with other scientists to gain access to specialized expertise, unique research resources, diverse populations, or geographic locations not otherwise available. For applicants interested in identifying potential collaborators, the NNP website is available at http://nnp. drugabuse.

gov, as a source of information on the mission, focus, and leadership of NIDAs research networks. The website features an interactive map with more than 300 local network sites, a directory of close to 400 addiction researchers and practitioners, and the extensive resources of 14 NIDA-supported research networks located across the country.

If appropriate for the proposed research, NIDA encourages grant applicants to use the resources of the NNP and make reference in the grant application See Section VIII, Other Information - Required Federal Citations , for policies related to this FOA will use the (R01) award mechanism. The Project Director/Principal Investigator (PD/PI) will be for planning, directing, and executing the proposed project.

Just-in-Time information concepts (see SF424 (R&R) Application Guide ) . It also uses the modular as well as the non-modular budget formats (see http://grants. nih.

gov/grants/funding/modular/modular. htm ). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component . opportunity will use an NIH cooperative agreement award mechanism.

In the cooperative agreement mechanism, the PD(s)/PI(s) retain(s) 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 PD(s)/PI(s), as described under VI. 2.

Administrative Requirements , "Cooperative Agreement Terms and 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 and Administrative (F&A) 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 III. Eligibility Information 1.

A.

Eligible Institutions organizations/institutions are eligible to apply: Controlled Institutions of Higher Education Institutions of Higher Education Hispanic-s erving Institutions Historically Black Colleges Tribally Controlled Colleges Alaska Native and Native Hawaiian Serving with 501(c)(3) IRS Status (Other than Institutions of Higher Education) without 501(c)(3) IRS Status (Other than Institutions of Higher Education) Organizations (Other than Small Businesses) American Tribal Governments (Federally Recognized) American Tribally Designated Organizations Housing Authorities/Indian Housing Authorities U.S. Territory or Possession Indian/Native American Tribal Governments (Other than Federally Non-domestic (non-U.S.) Entities (Foreign Eligible Agencies of the Federal Government Faith-based or Community-based Organizations.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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 than one PD/PI (i.e., 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 and 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 electronic Research Administration (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 grant 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.

When considering the multiple PD/PI option, 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 . program does not require cost sharing as defined in the current NIH Grants 3. Other-Special Eligibility Criteria of Applications.

Applicants may submit more than one application, provided that each application is scientifically distinct. Resubmissions.

Applicants may submit a resubmission application, but such application must include an Introduction Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications will be permitted addressing the previous peer review critique (Summary Statement). only a single amendment (A1). See http://grants.

nih. gov/grants/guide/notice-files/NOT-OD-09-003. html and NOT-OD-09-016 .

Original new and competing renewal applications that were submitted prior to January 25, 2009 will be permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that applications are not permitted in response to this FOA. Section IV.

Application and Submission Information Appropriate registrations with Grants. gov and eRA Commons must be completed on or before the due date in order to successfully submit an application. Several of the steps of the registration process could take four weeks or more.

Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered with both Grants. gov and the Commons . All registrations must be complete by the submission deadline for the application to be considered ?

on-time? (see 3. C.

1 for more information about on-time submission). download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www. grants.

gov/Apply/ and follow the directions provided on that Web site. A one-time registration is required for institutions/organizations at both: Grants. gov ( http://www.

grants. gov/applicants/get_registered. jsp ) eRA Commons ( http://era.

nih. gov/ElectronicReceipt/preparing. htm ) PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

additional separate actions are required before an applicant can submit an electronic application, as follows: Organizational/Institutional Registration in Grants. gov/Get Registered Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants. gov registration process.

If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration. The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.

Direct questions regarding Grants. gov registration to: Business Hours: M-F 7:00 a. m.

- 9:00 p. m. Eastern Time 2) Organizational/Institutional Registration in the eRA Commons To find out if an organization is already Commons-registered, see Organizations Registered in NIH eRA Commons.

Direct questions regarding the Commons registration to: Phone: 301-402-7469 or 866-504-9552 (Toll Free) Business hours M-F 7:00 a. m. 8:00 p.

m. Eastern Time Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) The individual(s) designated as PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.

hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account. When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization.

PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons. This registration/affiliation must be done by the AOR/SO or his/her designee who is already registered in the Commons. and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants. gov and the Commons .

The NIH will accept electronic applications only from organizations that have completed all 1. Request Application Information download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants. gov/Apply .

Only the forms package directly attached to a specific FOA