and Human Services (HHS)
EXPIRED
Participating Organization(s) |
National Institutes of Health (NIH) |
National Institute of Mental Health (NIMH) |
|
Funding Opportunity Title |
National Cooperative Drug Discovery/ Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction (U19) |
Activity Code |
U19 Research Program Cooperative Agreements |
Announcement Type |
Reissue of PAR-08-238 |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
PAR-11-207 |
Companion FOA |
PAR-11-206, UM1, Multi-Component Research Project Cooperative Agreements |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.242, 93.273, 93.279 |
FOA Purpose |
The purpose of the National Cooperative Drug Discovery/Development Group (NCDDG) Program is to create multidisciplinary research groups or partnerships for the discovery of pharmacological agents to treat and to study mental illness, drug or alcohol addiction. The objectives of this program are to: accelerate innovative drug discovery; develop pharmacologic tools for basic and clinical research on mental disorders, or drug or alcohol addiction; develop and validate models for evaluating novel therapeutics for mental disorders; and support early phase human clinical testing to rapidly assess the safety and efficacy of promising drug candidates and new indications for IND-ready drugs for the treatment of mental disorders or alcohol addiction. The National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) invite applications to advance the discovery, preclinical development, and proof of concept testing of new, rationally based candidate medications to treat mental disorders or drug or alcohol addiction, and to develop novel ligands as tools to further characterize existing or to validate new drug targets. Partnerships between academia and industry are strongly encouraged. |
Posted Date |
April 22, 2011 |
Letter of Intent Due Date |
May 24, 2011; September 26, 2011; January 24, 2012; May 22, 2012; September 24, 2012; January 22, 2013 |
Application Due Date(s) |
June 24, 2011; October 24, 2011; February 24, 2012; June 22, 2012; October 22, 2012; February 22, 2013 |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
October, February, and June annually |
Advisory Council Review |
|
Earliest Start Date(s) |
April, July, December annually |
Expiration Date |
February 23, 2013 |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH s Applying Electronically website.
Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Purpose
The intent of this Funding Opportunity Announcement (FOA) is to encourage applications from academic, biotechnology, or pharmaceutical industry investigators interested in participating with the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in a National Cooperative Drug Discovery/Development Group (NCDDG) program. The objectives of this program are to advance the discovery, preclinical development, and proof of concept testing of new, rationally based candidate medications to treat mental disorders or drug or alcohol addiction and to develop novel ligands as tools to advance biological research on the function of genes, cells, and biochemical pathways implicated in the etiology and pathophysiology of mental disorders, drug or alcohol addiction, and as potential new therapeutics. Partnerships between academia and industry are strongly encouraged.
Each NCDDG program should consist of a multi-disciplinary team of scientists with appropriate expertise to further the development and evaluation of novel compounds. Scientists from both academia and pharmaceutical industry are encouraged to participate within an NCDDG; scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects (see Section III. 1. Additional Information on Eligibility for details). It is anticipated that the interaction of academic and non-profit research institutions with industry and NIH via the NCDDG model will: 1) accelerate the discovery and development of new therapeutics for mental disorders, drug or alcohol addiction; 2) increase the availability of pharmacologic research tools (including imaging agents) for basic and clinical research; 3) facilitate the development and validation of models to evaluate novel therapeutics for mental disorders; 4) increase the availability of new IND-ready compounds suitable for testing in humans; and 5) facilitate the development and validation of new clinical measures or biomarkers suitable for use in human proof of concept trials of novel therapeutics for mental disorders or alcohol addiction.
The goal of the NCDDG program is not to duplicate or compete with the private sector but to complement and accelerate the development of research tools for new molecular targets implicated in mental disorders, drug or alcohol addiction, and effective compounds for the prevention and treatment of psychiatric and addictive disorders, as well as core features of these illnesses, especially in areas of unmet medical need.
Background
Significant advances in neuroscience, genetics, and basic behavioral science, together with technological developments, have provided a rich knowledge base for understanding pathophysiology, identifying new molecular targets for drug discovery, and developing rational pharmacotherapies for the treatment of psychiatric and substance abuse disorders. With the wealth of potential new drug targets, the opportunity exists to accelerate the process of target validation and medication discovery to make great strides toward novel and effective treatments for mental disorders, drug or alcohol addiction.
NIMHs objectives and interests for the NCDDG program
NIMH’s objective for the NCDDG program is to establish public-private partnerships to conduct innovative, high impact research focused on the discovery of pharmacological agents targeting novel molecular targets implicated in the pathophysiology of mood and anxiety disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, fragile x, autism, and other mental illnesses. Research projects directed towards ameliorating clinical dimensions of psychopathology embedded in DSM diagnostic entities, but not typically identified as the primary target of current clinical therapeutics, are also encouraged. (see the Research Domain Criteria (RDOC) webpage for more details).
NIMH relevant NCDDG research projects can focus on one or more molecular targets and include two or more of the following projects or components ranging from ligand discovery and testing in preclinical models to human proof of concept studies. Examples that projects or components may focus on include, but are not limited to:
This program strongly encourages resource contributions (financial and in-kind), of the partners within the NCDDG (e.g., biotechnology, pharmaceutical, or disease foundations) for IND-directed toxicology and safety studies and for phase I and IIa studies. Private sources of funding should be identified in the application to support Good Manufacturing Practice (GMP) synthesis, formulation, and/or IND filing costs.
For proof of concept studies, priority will be given to first-time or early trials of IND-ready agents with pre-clinical profiles suggesting the possibility of therapeutic effect in human disease. Testing of novel indications for already approved agents will be considered, based on strong theoretical rationale and/or public health significance.
Specific go/no go decision-making points and quantitative milestones should be included for assessing progress and success toward the therapeutic development goal, including a proposed plan for further development of novel compounds or drug candidates; these milestones will be used by program staff in assessing yearly progress and continued funding.
NIDAs objectives and interests for the NCDDG program
NIDA's interests are in the discovery of ligands that constitute important research tools and/or medication candidates to advance the development of pharmacotherapies for drug addiction treatment. Over the past decade or so, there have been major advances in our understanding of the protein targets, neural circuitry, and behavioral phenomena associated with addiction, and in the effects of drugs of abuse on CNS processes associated with addictive behavior, such as synaptic plasticity. The initial targets for most drugs of abuse are known and have been shown to be predominantly either G-protein coupled receptors, such as the dopamine receptor, an indirect site of action for cocaine and amphetamine, or ligand gated ion channels, such as the nicotinic cholinergic receptors (nAChRs), a target for nicotine. Drug addiction also involves activation of intracellular signaling proteins that can affect the response to drugs of abuse, and there is clear evidence for the involvement of numerous, specific neurotransmitter systems in addiction. Genetic polymorphisms are likely to lead to variation in the biological activity in many of these protein targets, which may be relevant to individual variability in response to drugs of abuse and, ultimately, to vulnerability to addiction. Given that research has discovered some of the mechanisms through which addictive drugs act in the CNS, numerous potentially viable targets for medications are known and, for the most part, well characterized. Hence the opportunity exists for the development of new ligands for target validation studies and potentially for development as pharmacotherapies.
From NIDAs perspective, the NCDDG is a ligand discovery and translational initiative in which the objective is the development of molecules with a particular profile of action as prototypes for medications to treat addiction or as tools to advance research in the treatment development domain. A number of cellular and animal models are currently available for ligand discovery efforts relevant to drug addiction treatment research. It is therefore expected that groups will include a program to evaluate the efficacy of novel ligands in appropriate models. Components of NIDA-relevant NCDDG research projects could include, but are not limited to: (1) assessment of the behavioral profile of novel ligands in tests of reinforcement, relapse and withdrawal; (2) tests of the ability of novel ligands to modulate cellular processes of plasticity in reward-relevant regions of the brain; (3) assessment of ligand efficacy on G-protein coupled receptors and ligand gated ion channel activation; and 4) receptor activation effects on down-stream intracellular systems or in modulating the release of addiction-relevant neurotransmitters. Projects that propose integrating two or more of these approaches also are encouraged.
Two targets, the mu-opiate receptor and the dopamine transporter, have been extensively pursued in medication discovery efforts related to opiate and cocaine addiction, respectively. Given the clinical availability of mu-opiate agonists, partial agonists and antagonists and the large number of NIDA-supported grants already focusing on the dopamine transporter, NIDA is not interested in supporting NCDDG projects with a focus on these two targets. Applicants are encouraged to focus on the discovery of truly novel ligands through the pursuit of targets such as orexin (hypocretin) and nicotinic acetylcholine receptor subtypes. A more extensive list of targets for consideration can be found below.
NIAAAs objectives and interests for the NCDDG program
NIAAAs interests for the NCDDG program are in the discovery of novel ligands that may lead to the development of medications for the treatment of alcohol dependence and addiction, and ligands to be used as tools to research biological processes contributing to compulsive drinking. The focus of proposed research projects should follow that described above by NIMH, but should be relevant to the mission of NIAAA. Applicants are strongly encouraged to discuss proposals involving toxicity, safety and pharmacokinetic as well as proof of concept studies of novel compounds with NIAAA staff listed in Section VII - Agency Contact(s) Scientific/Research Contacts.
Compounds currently approved by the Food and Drug Administration for treating alcohol dependence have distinct mechanisms of action and target distinct behavioral aspects of problem alcohol consumption. Disulfiram (Antabuse), an aldehyde dehydrogenase inhibitor leads to a systemic build up of acetaldehyde when alcohol is ingested. This is experienced as an unpleasant intoxication and creates an aversion to consuming alcohol. Naltrexone, an opiate receptor antagonist, is thought to diminish alcohols positive reinforcing effects, particularly in people with mu opiate receptor polymorphisms. Acamprosates therapeutic mechanism of action is unclear, but it is thought that acamprosate attenuates the enhanced glutamatergic transmission during alcohol withdrawal and may work best at alleviating craving and relapse in abstinent patients. Each medication has been found to be highly effective in some patients, yet other patients fail to respond to them. Thus, there is a need for the development of medications that interact at additional targets, and that treat additional behavioral facets of alcoholism.
Current pharmaceutical strategies for treating alcohol use disorders are broadly designed towards developing agents that: a) modify alcohol intoxication, reduce the pleasurable effects of alcohol or increase the aversive effects, b) reduce craving or the urge to drink, c) reduce the signs and symptoms of acute and protracted withdrawal syndromes, and d) treat co-morbid psychiatric illnesses or reduce psychological distress which contributes to elevated alcohol consumption. Alcohols multiple biological effects, and the many physical and behavioral alterations that occur following chronic alcohol use and abuse offer opportunities for developing additional pharmacotherapies.
NCDDG is an opportunity to identify and develop compounds towards both existing and new molecular targets having the potential to treat alcohol use disorders, or to facilitate and enhance basic and clinical research on identifying the neurobiological and behavioral processes that contribute to the transition from voluntary to compulsive drinking. Aspects of alcohol consumption and alcohol-seeking are modulated through the actions of neurotransmitter receptors and transporters, ion channels, neuromodulators, hormones, and intracellular signaling networks. Thus, there are a number of potential target sites for which new pharmaceutical agents may be developed, such as effectors of opioid, serotonin, dopamine, glutamate, GABA, cannabinoid, and adenosine receptors, modulators of neuropeptide systems (NPY, CRF, substance P), and agents that alter signal transduction pathways (such as protein kinase effectors, protein phosphatase inhibitors, G-protein regulators and calcium signaling disruptors).
Cellular models may be used as initial screening tools to evaluate the molecular properties of candidate compounds. However, it is further expected that the more promising compounds will be tested and evaluated in established animal models of behavioral aspects of alcoholism, such as drinking, dependence, craving and reinstatement models (see Drug Discovery Today: Disease Models 2: 313, 2005). As no single compound is expected to address all of the behavioral aspects and consequences of alcoholism, projects that propose integrating two or more behavioral testing paradigms are especially sought.
The identification and pursuit of agents towards novel targets previously un-recognized or understudied for the treatment of alcohol abuse disorders are especially encouraged. In particular, NIAAA encourages applications focusing on agents that alleviate craving and dysphoria during protracted abstinence, and agents effective in patients who have co-morbid psychiatric illnesses (e.g., schizophrenia, bipolar disorder). Applications that essentially propose to further extend the testing of established or well-studied compounds and strategies are not appropriate for this FOA.
Summary
In summary, the NCDDG Program will support broad, innovative, multidisciplinary, multi-project approaches to the discovery of new, rationally based treatments and research tools for mental disorders, drug or alcohol addiction. Since the creative talents in the required scientific disciplines are rarely available in a single institution, a multi-institutional, group approach involving academic, nonprofit, commercial, and/or industrial institutions is envisioned. Academic and pharmaceutical scientists are strongly encouraged to form partnerships that take full advantage of their combined intellectual and material resources for drug discovery, lead optimization, model development, and clinical testing. Further, the interaction of academic and non-profit research institutions with pharmaceutical industry and NIH is expected to facilitate subsequent development and marketing of new pharmacologic treatments, although these latter activities are not within the scope of this FOA. Molecular targets for drug discovery, and the sources and types of chemical entities to be investigated, will be selected by the applying group. Both novel mechanism of action and disease-oriented approaches are of interest.
Research Scope
The objective of this FOA is to establish NCDDG Groups to conduct innovative, high impact research focused on the discovery and testing of chemical entities for novel molecular targets implicated in the pathophysiology of mental disorders, or drug or alcohol addiction. The NCDDG serves as a vehicle for pharmaceutical and academic scientists to pool intellectual and material resources for the translation of basic science findings into the conceptualization, discovery, and evaluation of new chemical entities. Groups are encouraged to select molecular targets for drug discovery based on recent findings in basic and clinical neuroscience, genetics, and proteomics relevant to the understanding of mental disorders, drug or alcohol addiction.
Molecular targets that applicants may wish to consider include, but are not limited to, the following. Receptors: adenosine; adrenergic: alpha 1, alpha 2; cannabinoid: CB1, CB2; corticotropin releasing hormone: CRF R1, CRF R2; dopamine: D1, D3, D4, D5; estrogen; GABA A subunits; GABA ion channel; GABA B; glutamatergic, glycine site; metabotropic glutamate subtypes and other glutamate receptor subtypes; muscarinic subunits; neurokinin receptors: NK1, NK2, NK3; heteromeric neuronal nicotinic receptor subunits; NMDA subunits; opioid receptors: mu, delta, kappa; serotonin: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, 5-HT7; orexin (hypocretin); oxytocin; vaspressin receptors; intracellular targets;
Potential ligands of interest to NIMH, NIDA and NIAAA might be identified by their receptor properties (e.g., allosteric modulators, partial agonists, agonists, or antagonists), solubility, pharmacokinetics, oral or CNS bioavailability, or other characteristics to support their use as research tools or candidates for drug development.
The identification of lead compounds and refining them for medication development are important goals of this initiative. Generally this can involve classical approaches of medicinal chemistry using structure-activity relationship (SAR) rationales. The use of chemical libraries, structural biology and computer modeling of molecular targets to screen for compounds with activity at selected targets are also examples of appropriate approaches. If applicants do choose to conduct library screening, they are encouraged to focus on targeted libraries rather than random structural screening. Screening of existing libraries (e.g., G-protein receptor-focused) that will not require significant synthetic resources is encouraged. Note that the pharmaceutical industry has reduced its reliance on combinatorial chemistry approaches due to general lack of success. Although NIDA, NIMH and NIAAA will not rule out the use of combinatorial chemistry in NCDDG projects, applicants proposing them should provide appropriate justification that this approach to compound synthesis is desirable.
It is anticipated that the interaction of academic and non-profit research institutions with NIH and pharmaceutical industry will facilitate timely evaluation and development of preclinical and clinical research tools, models, and novel therapeutics. Applicants should outline proposed plans for further development of promising compounds or clinical candidates that are generated by the NCDDG program.
Note: The development of analogs of established or well-studied agents for the treatment of mental disorders, drug or alcohol abuse is not appropriate for this FOA. Cost-sharing for IND-directed toxicology and safety, first in human, and proof of concept studies is encouraged. Private sources of funding should be identified in the application to support GMP synthesis, formulation, and/or IND filing costs. For applicants seeking additional sources of support for preclinical development activities such as toxicology and safety pharmacology assessment, bulk synthesis, GMP manufacturing, or formulation development, the NIH Rapid Access to Interventional Development (NIH-RAID) (PAR-09-027) program offers investigators access to preclinical development resources on a competitive basis.
Funding Instrument |
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities. |
Application Types Allowed |
New The OER Glossary and the PHS398 Application Guide provide details on these application types. |
Funds Available and Anticipated Number of Awards |
The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. |
Award Budget |
Application budgets are not limited, but need to reflect actual needs of the proposed project. |
Award Project Period |
The total project period for an application submitted in response to this FOA may not exceed five years. |
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.
Higher Education Institutions:
Nonprofits Other Than Institutions of Higher Education
For profit Organizations
Governments
Non-domestic (non-U.S.) Entities (Foreign Organizations) are
not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed. [ Changed to Non-domestic (non-U.S.) Entities (Foreign Organizations) are not permitted. Foreign (non-U.S.) components of U.S. organizations are allowed per NOT-MH-11-011 ].
Common Fund/Roadmap text, Collaborative Research, or Projects Greater than 5 years Duration: See instructional documents in the NIH Guide Publishing System for the text to insert.
Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (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 for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.
Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.
It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
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.
By the date listed in Part 1. Overview Information, 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 PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity
The letter of intent should be sent to:
Linda Brady, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7204, MSC 965
Bethesda, MD 20892-9645
Rockville, MD 20852-9645 (for express/courier service)
Telephone: (301) 443-3563
Email: lbrady@mail.nih.gov
Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application,
including the checklist, and three signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
At the time of submission, two additional paper copies of
the application and all copies of the appendix files must be sent to:
Jean G. Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-3367
FAX: (301) 443-4720
Email: jnoronha@mail.nih.gov
All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:
Special Instructions/Research Strategy Page Limitations
In addition to the details described here for U19 applications, applicants also need to be aware of information described in Section III.3 - Additional Information on Eligibility of this FOA.
Applications received in response to this FOA can propose a NCDDG group consisting of scientific collaborators focused on two or more Research Projects with Scientific and Administrative Core components. Applications focusing on one or two Research Projects should respond to the companion FOA utilizing the UM1 mechansim (see PAR-11-206).
Applicants are encouraged to organize the application by initially presenting the face page, the abstract page with key personnel, a table of contents, summary budget pages for the entire application, and other documentation pertaining to the entire project (i.e., the Special Requirements). This should be followed by the Overall Research Strategy section of no more than twelve pages that provides an Overall Research Strategy (see A. Overall Research Strategy of the NCDDG for details) of the NCDDG. The content requirements of this section are described below.
Following the General Description(s), each component (the Research Project(s) and Cores, if any, should be presented individually with its accompanying individual budget and justification, biographical sketches, other support pages, 1-page specific aims and research plan.
A. Overall Research Strategy of the NCDDG. The section must not exceed 12 pages, (excluding the 1 page introduction for a resubmission or revision) and should provide the following details:
B. Specific Instructions for Individual Research Projects. For each Research Project there should be a 1-page Specific Aims section, followed by the Research Strategy (limited to 12 pages) as indicated in the form PHS 398. A 1 page introduction may be included for each core in a resubmission, to address the prior summary statement, and a revision application to address the relationship to the parent.
For each individual Research Project, the Research Strategy needs to address:
C. Specific Instructions for Cores (U19). For each Core component, there should be a 1-page specific aims page followed by the research strategy, limited to 6-pages. A 1 page introduction may be included for each core in a resubmission application, in order to address the prior summary statement and a revision application to address the relationship to the parent. If cores are required, the applicant must describe how each Core will contribute to the goals of the overall NCDDG as well as how each individual Research Project will draw upon a particular Core. The description of each Core should clearly indicate the facilities, resources, services and professional skills that the facility will provide. Moreover, clearly described information must be provided about how the collective operation of the Cores will be effected in a coherent manner.
D. Instructions for NIH Intramural Researchers. An NIH intramural researcher collaborating on an NCDDG must obtain the approval of his/her NIH Institute Scientific Director for participating under the terms and conditions of the FOA. A copy of that letter of approval must be provided in the application.
NIH intramural researchers submitting an Individual Research Project as a part of an NCDDG, must follow the procedures for Individual Research Projects as described below:
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide, with the following modifications:
Appendix
Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.
Part I. Overview Information contains information about Key Dates.
Information on the process of receipt and determining if
your application is considered on-time is described in detail in the PHS398
Application Guide.
Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy
Statement.
Pre-award costs are allowable only as described in the NIH Grants
Policy Statement.
Applications must be received on or before the due dates in Part I. Overview Information. If an
application is received after that date, it will not be reviewed.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the PHS398 Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Reviewers will provide an overall impact/priority 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 review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific 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 NCDDG 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 change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? To what degree does the proposed plan for discovery and testing of novel drugs, research tools, and/or preclinical models support the needs for the targeted disease? What is the likelihood that it will produce a new candidate drug for development?
Investigator(s)
Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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? Have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise required for the project? Has the PD/PI demonstrated leadership in development, implementation, and management of comprehensive research programs?
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? Is the target under investigation for drug discovery novel? Will new paradigms for drug discovery or models emerge?
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 scientific disciplines represented in Research Projects and Scientific Cores adequate to
achieve the NCDDG Program objectives? Is there a sound scientific rationale for
the proposed molecular or clinical targets? Are targets, screens, and
preclinical models relevant to drug discovery for mental disorders and/or drug
or alcohol addiction? If pharmaceutical partnerships are proposed, how will
they facilitate the development and evaluation of candidate drugs, tools for
clinical research, and model validation for testing therapeutics?
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 of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? Does the clinical research team demonstrate a track record in successfully recruiting subjects into clinical trials and research studies and completing proposed studies within projected timelines?
Interaction. Are there adequate plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PD/PI, Research Project Leaders, and NIH Project Scientists? Do the investigators state their willingness to collaborate extensively and share information fully?
Review Criteria for Research Projects
Criterion scores will not be assigned for individual Research Projects.
Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Approach: Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project? Are the scientific disciplines represented in Research Projects adequate to achieve the objectives? Does the applicant acknowledge potential problem areas and consider alternative tactics? Is the plan to optimize lead structures adequate to ensure that the most efficacious drug will result? If pharmaceutical partnerships are proposed, how will they facilitate the discovery and development of drugs and evaluation of research tools or models?
Innovation: Does the Research Project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new tools, methodologies, or technologies?
Investigator(s): Are the Research Project Leader and key personnel appropriately trained and well suited to direct or carry out this work? Is the Project Leader's time commitment sufficient to achieve the goals? Is the work proposed appropriate to the experience level of the key personnel and other researchers? Have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise required for the project?
Environment: Does the technical and scientific environment in which the work will be done contribute to the probability of success? Does the proposed work take advantage of unique features of the technical and scientific expertise and employ effective collaborations?
Management of the Group: Does the PD/PI have previous experience or the ability to manage an integrated scientific enterprise? Do other members of the Group have experience that will facilitate achieving the desired research outcomes?
Review Criteria for Cores (U19)
Criterion scores will not be assigned for Individual Cores.
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, 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. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.
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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not for recommended approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.
Applications from Foreign Organizations
Not Applicable.
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).
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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NIMH , in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Councils of the participating ICs. The following will be considered in making funding decisions:
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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.
Any application awarded in response to this FOA will be subject to the DUNS,
CCR Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants website.
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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
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.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist(s) interacts scientifically with the Group and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, presenting experimental findings to the Group from published sources or from relevant contract projects, participating in the design of experiments agreed to by the Group, participating in the analysis of results, and advising in management and technical performance. The Project Scientist(s) will be a member(s) of the Steering Committee. However, the total membership by NIH staff will not exceed one-third (1/3) of the membership of the Steering Committee. In all cases, the role of NIMH, NIDA, or NIAAA will be to assist and facilitate and not to direct activities.
The NIMH or NIAAA Project Scientist(s) can recommend to their Institutes to utilize their drug development resources (e.g., CNS receptor screening, chemical synthesis, and toxicology services) in support of the NCDDG Group research activities if such resources are required on an occasional basis. The following is a list of resources that are readily available and may be supplied if they become desirable during performance. It is not anticipated that requests of services will be considered as a continuing need.
Phase I and IIA projects may be reviewed by the appropriate NIH Institute's Data and Safety Monitoring Board (DSMB) to ensure the safety of participants and the validity and integrity of the data. The study protocol(s) and consent form(s) will be reviewed by the DSMB prior to initiation of the project. The DSMB will review study reports from the NCDDG group on a regular basis to monitor subject enrollment and retention, safety, quality of data collection, and integrity of the study. Based on its review, the DSMB has the authority to stop the study after it has started.
Additionally, an NIMH, NIDA, or NIAAA Program Official will be responsible for the normal programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.
Participation of NIH Intramural Scientists.
An NIH intramural scientist may not serve as the PD/PI of an NCDDG but may
participate in a Group as a Project Leader, Scientific Core Leader,
collaborator, or consultant. However, an Intramural scientist may not receive
salary, equipment, supplies, or other remuneration from awards resulting from this
FOA. The Intramural scientist must obtain written approval of his/her NIH
Institute Scientific Director for the amount of resources that may be allocated
to the project. The approval must also specify that the conduct of the project
will comply with the DHHS regulations for research involving human subjects (if
applicable) and with the PHS policy on vertebrate animal research. The
participation of an intramural scientist is independent of and unrelated to the
role of the NIMH, NIDA and/or NIAAA Project Scientist. For NCDDG applications
that include NIH intramural components, the intramural resource level will be
included in the total cost of the overall application. The involvement of
Intramural scientists needs to be consistent with NIH Policy. http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm
Areas of Joint Responsibility include:
A governing Steering Committee composed of the PD/PI, Research Project Leaders, Core Directors, NIH Project Scientist(s), and NIH Program Official will be established in each NCDDG to assist in monitoring and developing the scientific content and direction of the program. The Steering Committee members will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings, not fewer than two per year, will be determined by the PI/PD who will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes (two or three pages) which will be delivered to the members of the Group within 30 days of the meeting.
a. The principal end products of NCDDG activities for NIMH and NIAAA are expected to include: 1) the discovery and testing of new chemical entities, optimization of lead compounds, IND-directed toxicology, safety pharmacology to support phase I studies, identification of clinical candidates for the treatment of mental disorders or alcohol addiction, and/or phase II efficacy studies; 2) research tools; and 3) preclinical models to evaluate novel therapeutics. Cost-sharing is encouraged for IND-directed toxicity and safety studies of drug candidates. Private sources of funding should be identified for GMP synthesis, formulation, IND filing costs, and toxicology and safety studies exceeding 28 days in duration.
b. The principal end products of NCDDG activities for NIDA are expected to include: 1) the discovery of ligands for target validation studies and potentially for development as pharmacotherapies for drug addiction, 2) as research tools to advance research in the treatment development domain, and 3) preclinical models to evaluate novel therapeutics. Studies required for IND-targeted preclinical development (GMP synthesis, formulation, toxicology) are generally beyond the scope of this FOA for NIDA. Such development through the NIH RAID program or private venture capital is encouraged.
c. NIMH and/or NIAAA will retain the option to cross-file or independently file an application for an investigational clinical trial (e.g., an IND application to the United States Food and Drug Administration) of any clinical research tool or invention resulting from these NIH supported cooperative agreements. Reports of data generated by the Group or any of its members required for inclusion in IND applications and for cross-filing purposes shall be submitted promptly by the Principal Investigator to the NIH Institute Project Scientist upon request. Such reports shall include background information, methods, results, and conclusions.
Dispute Resolution:
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 Dispute Resolution. A Dispute Resolution 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 dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
Intellectual Property and Patent Rights for New Chemical Entities
Since the discovery of new pharmacological treatments for mental disorders, drug or alcohol addiction is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and may be facilitated by the existence of appropriate patent coverage, it is essential that applicants provide plans to address the handling of intellectual property for new chemical entities for the treatment of mental disorders, drug or alcohol addiction under this FOA.
Successful applicants are required to supply the following confidential materials to the NIMH, NIDA and/or NIAAA Program Officials listed under Section VII. Agency Contacts.
1. Each applicant Group must provide a detailed description of the approach to be used for handling intellectual property and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents [http://grants.nih.gov/grants/intell-property.htm].
2. A formal statement of Intellectual Property among all Group members and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, must be signed and dated by the organizational official authorized to enter into intellectual property arrangements for each Group member and member institution. The signed agreement must be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.
3. A plan must be developed for disposition of combinatorial and compound libraries generated in Research Projects focused on discovery of new chemical entities as clinical candidates for drug development in conformance with Section VI.2.A - Cooperative Agreement Terms and Conditions of Award, listed below. The signed document must be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.
4. Prior to the award, the PD/PI and each Project Leader must provide a signed statement of acceptance of the participation of NIMH, NIDA or NIAAA staff during performance of the award as outlined under "NIH Staff Responsibilities" in Section VI.2.A - Cooperative Agreement Terms and Conditions of Award.
Note: Do NOT submit documents 1-4 above with the application. However, awards will not be made until these documents are received and approved by NIMH, NIDA or NIAAA.
When multiple years are involved, 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.
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.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov
Questions about preclinical drug and tool discovery for mental disorders, toxicology and safety studies, and phase I human studies should be directed to:
Linda Brady, Ph.D.
National Institute of Mental Health
Telephone: (301) 443-3563
Email: lbrady@mail.nih.gov
Questions about proof of concept studies for novel interventions or IND-ready therapeutics for mental disorders in adult populations should be directed to:
Mi Hillefors, M.D., Ph.D.
National Institute of Mental Health
Telephone: (301) 443-2738
Email: hillefom@mail.nih.gov
Questions about proof of concept studies for novel interventions or IND-ready therapeutics mental disorders in children and adolescents should be directed to:
Margaret Grabb, Ph.D.
National Institute of Mental Health
Telephone: 301-443-3563
Email: mgrabb@mail.nih.gov
David Shurtleff, Ph.D.
National Institute on Drug Abuse
Telephone: (301) 435-0891
Email: dshurtle@mail.nih.gov
Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism
Telephone: (301) 594-6382
Email: megli@mail.nih.gov
David Armstrong, Ph.D.
National Institute of Mental Health
Telephone: (301) 443-3534
Email: armstrda@mail.nih.gov
Rebecca Claycamp, M.S., CRA
National Institute of Mental Health
Telephone: (301) 443-2811
Email: rclaycam@mail.nih.gov
Pam Fleming
National Institute on Drug Abuse
Telephone: (301) 443-6710
Email: pfleming@mail.nih.gov
Judy Fox
National Institute on Alcohol Abuse and Alcoholism
Telephone: (301) 443-4704
Email: jfox@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
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 Part 52 and 45 CFR Parts 74 and 92.
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NIH Funding Opportunities and Notices
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