Notice Number: NOT-NS-18-073
Key Dates
Release Date: August 23, 2018
PA-18-591
Issued by
National Institute of Neurological Disorders and Stroke (NINDS)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Drug Abuse (NIDA)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Library of Medicine (NLM)
National Center for Complementary and Integrative Health (NCCIH)
Office of Research Infrastructure Programs (ORIP)
Office of Research on Women's Health (ORWH)
Purpose
This Notice is part of the NIH Helping to End Addiction Long-Term (HEAL) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis.
The validation of a biological target for the treatment of pain, i.e. the proof of its suitability for treating a specific or group of pain disorders, is critical to the development of new nonaddictive therapeutics. Therefore, NINDS and other participating Institutes and Centers (ICs) are inviting investigators to submit administrative supplements to PA-18-591 to expand existing ongoing pain target discovery research to add rigorous multimethod validation studies, and ultimately provide the validation of the pain therapeutic target necessary to accelerate the development of non-addictive treatments.
Background
Chronic pain is one of the most prevalent, costly, and disabling health conditions in the United States, and among the most complex to manage. Currently available drugs for acute and chronic pain have considerable limitations such as undesirable side effects, lack of data on long-term usefulness, and significant addiction and overdose potential.
This Notice is part of the NIH Helping to End Addiction Long-Term (HEAL) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Novel non-addictive targets are urgently needed that could be used for the development of small molecule drugs, biologics, or natural products. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management.
Once identified, pain treatment targets require rigorous validation to justify the significant investment in therapeutic development. Rigorous approaches to target validation include the use of multiple approaches, such as the validation of targets in animal models, unidentifiable human tissue, and/or validation of key experiments in other laboratories.Applicants with ongoing NIH funded research to identify novel pain targets are encouraged to submit an administrative supplement application to add rigorous target validation studies. These studies should have the goal of definitively determining the utility of a potential target for future therapeutic development.
Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.
Due Date: Supplement requests must be received by November 1, 2018.
Eligibility: Active R01s and equivalents and R21s with an end date through March 30, 2020 (for 1-year requests) or March 30, 2021 (for 2-year requests), not including no cost extensions. As administrative supplements, the work proposed needs to be within the scope of the research that is already supported.
Entry Criteria:- Projects should aim to validate novel targets that can lead to significant improvements over existing therapeutics for pain and have limited abuse liability.
- Projects funded through this opportunity must have a strong biological rationale for acute or chronic pain conditions.
- Applicants must include a strong rationale for the intended approach for validation, including preliminary data or literature-based evidence supporting the feasibility of the approach.
- Applicants are encouraged to use at least 2 different techniques of validation in their experimental design to validate their target.
- Preliminary data should be from well-designed experiments that include appropriate controls and statistical analyses.
- Applicants should discuss "druggability" of the target, which is based in part on the structure and accessibility of the target; and consideration to target distribution and specificity, which may contribute to undesirable on-or off- target effects.
- Relevance for therapy development: Projects should aim to validate targets that will address pain condition(s) in human patients. Applicants must discuss where their target fits in the larger pain landscape and which patients are likely to benefit.
- Target validation using animal models
- Validation of the target in human tissue, i.e. human DRGs, human iPSCs
- Testing the reproducibility of the validation assay in another laboratory
- We will also support activities in order to prepare for validation:
- Preparation and design of genetic probes (RNAi, CRISPR/Cas9 etc.)
- Creation and/or verification of genetically modified animals or cells
- If necessary for purposes of validation: Execution of small scale screening of possible probe compounds to be used to interrogate the target.
- Preparation of PET ligands for use in animal pain models
- For a genetic animal or cell model, ensuring that the target was successfully up/down regulated
- Rigorous evaluation of the effects of genetically or pharmacologically manipulating the target in a cellular assays (primary neurons or human iPSCs for example) or animal models.
- Validation of targets that are anticipated to have abuse liability
- Development of assays or probes to support basic understanding of disease or other basic research that doesn't have a clearly articulated path toward the development of a therapeutic
- Development of devices, surgical procedures, diagnostics, and rehabilitation strategies
- Clinical testing of candidate therapeutics, or any clinical studies that fit the NIH definition of clinical trials. See this link for a description: https://grants.nih.gov/policy/clinical-trials/definition.htm
- Identification of new targets
Application Instructions:
Investigators should submit applications as responses to the parent active administrative supplement PA: https://grants.nih.gov/grants/guide/pa-files/PA-18-591.html and include a reference to this notice NOT-18-073 in the cover letter.
As part of the application, investigators should submit a detailed description (up to 3 pages) of the proposed research plan to validate a novel non-addictive target for the development of pain treatments. The first page should be a summary of goals and rationale of the validation experiments proposed in the supplement, similar to the format of a Specific Aims page of other NIH funding applications.
In addition to this 3-page research plan description, applicants should also include a detailed budget that explains how the supplement funding will be used (up to 3 pages). Sufficient detail of the budget should be included to give a rationale of the funds that are requested. Individual requests can be no more than $250,000 direct costs per year exclusive of Facilities and Administrative costs on sub-contracts. Requests may be for up to two years of support, for a total of $500,000 direct costs.
In addition to the research plan and budget, price quotations from vendors, letters of support or biosketches for new key personnel may be included.
Though supplement requests are not limited to one per parent grant, we will consider substantial additional funding to an award as beyond its scope.
Before submitting a supplement request, principal investigators are strongly encouraged to contact their program officers in the Institute, Center or Office supporting their award to discuss whether the proposed supplement is within its scope.
As mentioned in NOT-OD-18-181,Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.
Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.
All instructions in the SF424 (R&R) Application Guide must be followed.
Cost Matching Requirement for For-profit Applicants
Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA. The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.
Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
a) Costs borne by another Federal grant or sub award;
b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
(d) Program income; and
(e) Patient incentives.
The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details .
Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.
Rigor and Sex as a Biological Variable: There is a crucial need to address sex influences in pain research since many pain disorders disproportionately affect women. Inclusion of the description of sex as a biological variable in all the validation experiments is encouraged. Successful projects will be well-designed and meet the NINDS RIGOR guidelines (Landis et. al. Nature 2012, 490:187-91; NOT-NS-11-023 and the NIH Rigor website).Letters of Support
For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources.Review Process:
NINDS will review each supplement application in conjunction with representatives from other ICs. NINDS will make funds available for up to 8 awards.
Criteria:
- Is the work proposed within the scope of the active award?
- Is there strong biological rationale for the target?
- Is the premise for validation experiments strong? Are the validation experiments rigorous? Has consideration for biological variables, such as sex, been demonstrated?
- Is the target therapeutically relevant and does it have a low addiction liability?
- Is the target novel? Is it likely to lead to significant improvements over existing therapeutics for pain?
- Has thought been given to the feasibility or 'druggability of the target?
Inquiries
Please direct all inquiries to:
Michael Oshinsky, PhD.
National Institute of Neurological Disorders and Stroke
Telephone:301-496-9964
Email: michael.oshinsky@nih.gov
Ann O'Mara, PHD, RN
National Cancer Institute (NCI)
Telephone: 240.276.7050
E-mail: omaraa@mail.nih.gov
Houmam Araj, PhD
National Eye Institute (NEI)
Telephone: 301.451.2020
E-mail: arajh@nei.nih.gov
Coryse St. Hillaire-Clarke, PhD
National Institute on Aging (NIA)
Telephone: 301.827.6944
E-mail: sthillaireclacn@mail.nih.gov
Abraham Bautista
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301.443.9737
E-mail: bautista@mail.nih.gov
Soundar Regunathan, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301.443.1192
E-mail: regunathans@mail.nih.gov
Charles Washabaugh, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301.594.5055
E-mail: washabac@mail.nih.gov
Susan Marden, PhD, RN
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-435-6838
E-mail: mardens@mail.nih.gov
Kristopher Bough, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-9800
Email: Boughk@nih.gov
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301.827.4655
E-mail: yolanda.vallejo@nih.gov
Teresa L.Z. Jones, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301.435.2996
E-mail: teresa.jones@nih.gov
Martha Matocha, Ph.D.
National Institute of Nursing Research (NINR)
Telephone: 301.594.2775
E-mail: matocham@mail.nih.gov
Ron Wertz
National Institute of Nursing Research (NINR)
Telephone: 301-594-2807
Email: wertzr@mail.nih.gov
Yisong Wang, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301.480.9483
E-mail: yisong.wang@nih.gov
Hua-Chuan Sim, MD
National Library of Medicine (NLM)
Telephone: 301.594.4882
E-mail: simh@mail.nih.gov
Ronald Adkins, PhD
Division of Comparative Medicine, Office of Research Infrastructure Programs (ORIP)
Telephone: 301.435.4511
E-mail: Ronald.adkins@nih.gov
Tatjana Atanasijevic, PhD
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301.451.6873
E-mail: atanasijevict@mail.nih.gov
and Human Services (HHS)
