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