Scientific Advisory Board Accepting Applications For Up To $4 Million in Research Funding

Funding Opportunity for Innovative Preclinical, Translational, and Clinical Research on the Prevention, Treatment, Rehabilitation and Return-to-Play of Hamstring Injuries

This funding opportunity is now closed. Please check back for future updates and funding opportunities.

Program Description: Executive Summary

Over 850 lower body soft tissue strains occur across the NFL each year, with the majority of these injuries to the hamstring. The burden of lower extremity strains in terms of the amount of time players miss from football activities, including games, is second only to ACL tears. Recurrence of these injuries is a significant problem, as well, both in terms of time loss and financial impact to players and Clubs.

The National Football League (the "NFL") has developed a funding program (the "Program") for the purposes of inviting research proposals and providing funding for innovative preclinical, translational and clinical research being conducted by leading investigative teams related to the prevention, treatment, rehabilitation, and return-to-play following injury to the hamstring muscle group.

The goal of this Program is to provide funding support for research proposals from leading investigative teams in the field of the biology and rehabilitation of muscle injury, specifically hamstring strains. The Program will evaluate proposals that focus on either biologic therapies or primary and secondary prevention, rehabilitation, and return-to-play following hamstring strains.

This Program's funding opportunity is intended to facilitate the following five lines of potential inquiry: 1) Original or ongoing basic translational research activities involving the use of biologic formulations (e.g. PRP, stem cell therapies, pharmacologics) in the treatment of muscle injury using the hamstring musculature as the injury model; 2) Evidence-based clinical research exploring the use of biologic agents in the treatment of sport-related muscle injuries; 3) Development of improved prevention and injury risk mitigation strategies specific to hamstring injury; 4) Design of rehabilitation and return-to-play strategies following hamstring injury that reduce the risk of injury recurrence (secondary prevention); and 5) Innovation (e.g. micro-sensor and wearable technology, cellular-based therapies and growth factors (e.g., mesenchymal stem cells [MSCs], adipose-derived stem cells, and platelet-rich plasma [PRP]).

The NFL's intent through this Program is to demonstrate the potential for translational breakthroughs by leveraging innovative research, emerging science, current data sets and archival material related to the prevention, treatment, rehabilitation, and return-to-play following muscle injury, specifically, to the hamstring muscle group. This Program is designed to support multidisciplinary investigative teams with strong track records of collaboration and accomplishment in the field. New collaborations of strong research teams will be strongly considered as well.

Funding Opportunity

The anticipated total amount to be funded for this Program is $4,000,000. The number of winning investigative teams, and the total amount to be funded, will be determined initially based on the quality of the proposals submitted and by recommendations from the Scientific Advisory Board (SAB) (see below). The NFL will make the final decision as to which proposals are funded and to what degree based on the number of proposals recommended by the SAB.

Scientific Advisory Board

The NFL has established a Scientific Advisory Board (the "SAB"), consisting of leading independent content experts, physicians, and scientists. The SAB will evaluate all Submissions (as defined below) and make funding recommendations for both the specific research proposal(s) and amounts to be funded by the NFL using objective guidelines established by the National Institutes of Health (NIH).

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Proposal Submission and Review Process

The process for submission (each such research proposal, a "Submission"; each such investigative team, a "Submitter"), review process and how funding will be determined for each investigative team is defined below:

• Pre-Proposal: Each Submitter shall prepare a short executive summary that outlines: the general goals of the research project, the qualifications of the team members, research progress made to date (if any), defined pre-clinical and/or clinical endpoints, and an anticipated timeline with expected milestones (See details below). Pre-Proposals must be submitted by completing the form at playsmartplaysafe.com/SABfunding between September 17, 2020 at 6:00 P.M. (Eastern Time) and November 30, 2020 at 6:00 P.M. (Eastern Time). Limit one (1) Pre-Proposal per investigative team. Further details regarding the submission process for Pre-Proposals can be found below.
• Formal Proposal and Oral Presentation: The SAB will evaluate each Pre-Proposal according to the guidelines set forth by the NIH Scoring Guidance (available at https://grants.nih.gov/grants/policy/review/rev_prep/scoring.htm). Selected Submitters will be invited to prepare a more detailed research proposal and will be asked to present their proposal orally (the "Oral Presentation") to the SAB during the week of March 15, 2021 (See details below). The requirements for submitting a Formal Proposal and the requirements and limitations of the Oral Presentation of the Formal Proposal shall be provided by the SAB upon notification of the invited Submitters to submit their Formal Proposal.
• Funded Proposals: The SAB will review and score all Formal Proposals and Oral Presentations using the NIH's Scoring Guidance and shall recommend to the NFL those Submissions selected for funding and the recommended amount of funding. Based on those recommendations, the NFL will determine which, if any, of the recommended Formal Proposals shall receive funding (the "Funded Proposals") and to what degree they will be funded.

Principal investigators leading the Funded Submissions will be required to attend an annual NFL conference to report their findings and progress as it pertains to the milestones outlined in their Formal Proposal.

Timeline

(subject to change by the NFL and/or the SAB)

Updated as of January 8, 2021

Official Rules

All investigative teams will be required to adhere to the official rules available on the Program Website (as defined below).

Pre-Proposal Format

All Pre-Proposals should be considered as an Executive Summary of the intended research plan. All Pre-Proposals must be submitted on 8½" x 11" paper, using Times New Roman, 12-point font, single spaced, with 1" margins. All Pre-Proposals should be limited to 3 (three) pages and contain the following sections:

• Project title with affiliations of the research team members
• Specific aims of the research project
• Experimental design (limit to 1 [one] paragraph)
• Qualifications of the research team members
• Research progress made to date (if any)
• Defined pre-clinical and/or clinical endpoints
• Innovation and Deliverables
• Anticipated timeline with milestones

Formal Proposal Format

All Formal Proposal submissions must be submitted on 8 ½" x 11" paper, using Times New Roman, 12-point font, single spaced, with 1" margins. All Formal Proposals should contain the following sections, each of which is limited as set forth below:

• Title page with affiliations of the research team members
• Background and significance
• Specific aims
• Innovation and Deliverables*

** How does the proposed research eliminate a critical barrier to success; address a gap in research/evidence; or address a critical or urgent need. What are the tangible deliverables (data, device, or protocol)?

• Experimental methods and statistical analyses (limit to two [2] pages)*

* References should be included but are not included in the page count of the experimental design. Up to 5 figures are permitted. The figures must be included in an Appendix and will not count towards the page count. Technical project milestones are encouraged and should be specific, measurable, achievable, relevant, and time-bound.

• Biosketch (one [1] paragraph for principal investigator, total limit of two (2) pages for all researchers).
• Facilities and associated resources (limit to ½ page)**

** Associated resources refer to the utilization of any physical (equipment, a unique product/reagent, tissue line, etc.) or theoretical (expertise, people, skills, new results etc.) resource, data set, ongoing research or other entity to further the proposed research.

• Related prior and current grants (limit to one [1] page)
• Team management plan detailing the contribution of each member of the research team
• Budget proposal with justification for all costs (both personnel and non-personnel) (limit to one [1] page)
• Please specify if the amount funded by the NFL will be in addition to other funding sources.
• Allowable personnel expenses include salary and applicable fringe benefits for: the principal investigator, co-investigator(s), postdoctoral and graduate students if employees receiving a stipend and other professional and technical staff.
• Only equipment essential to the conduct of this project is allowed for funding consideration. A detailed description must be provided with an explanation as to how it directly relates to this project and is not otherwise available.
• No more than ten percent (10%) of any amount funded by the NFL to any investigative team may be allocated for indirect costs (e.g., facilities and administrative overhead costs) of institutions to which investigative teams belong or are affiliated.
• NOTE: Funding will NOT be provided for the following:

1. Travel funds for students
2. Tuition
3. Dues and membership fees
4. Honoraria or travel expense for lectures
5. Maintenance/Service Contracts
6. Faculty/Staff recruiting /relocation expenses
7. Entertainment/Social Expenses

Examples of Proposal Topics

Investigative teams with scientific inquiry related to innovative translational research on the cellular mechanisms of muscle injury and repair, muscle physiology, and biologic therapies for musculoskeletal injury and disease are encouraged to submit a proposal. Example study objectives suggested, but are not limited to:

• Develop assays to characterize the composition and activity of biologic formulations - A fundamental issue with biologic formulations is their inter-individual heterogeneity. Optimal protocols are needed for measuring the composition and biologic activity of various formulations (e.g., PRP, cell preparations, other blood-based products). The critical quality attributes of these different formulations specifically intended for muscle injury need to be determined. Sentinel markers of "potency" or "quality" of these materials must also be identified that can be implemented clinically in a reliable, valid, and practical fashion. Ideally, a rapid, point-of-care test that can be done at the time of administration will be devised to assess the composition and "quality" of these formulations.
• Identify "biologic targets" for different conditions - The desired activity of these biologic agents must be established. These formulations may work by increasing tissue vascularity, increasing cellular migration, stimulating matrix synthesis, inhibiting inflammation, and/or stimulating cell differentiation. Therefore, it is imperative to determine which, if any, of these activities is necessary for the treatment of muscle cell injury.
• Identify quantitative, reproducible objective measures of treatment outcome(s) for muscle injury - Biologic treatments may be symptom-modifying but there is little evidence that these modalities are structure-modifying. Optimized imaging protocols must be developed to provide objective data in a non-invasive fashion that evaluates the outcome of treating muscle injuries with the use of biologic agents. The specific demographic, anatomic, and injury conditions that predict treatment outcome of hamstring muscle injuries should also be established.
• Identify patient factors that may affect the composition and activity of biologic formulations - Athletes frequently use non-steroidal anti-inflammatory drugs (NSAID), which can affect platelet function via inhibition of cyclo-oxygenase (COX-1 and COX-2) activity. There is little information available pertaining to the effect of NSAIDs, diet, co-morbidities, exercise, blood flow restriction therapy, and other potential factors on the composition and biologic activity of PRP and other blood products.
• Optimize preparation protocols and dosing regimens for PRP, bone marrow aspirate, and lipoaspirate - The specific preparation protocols for these biologic formulations (i.e. relevance and confirmation of platelet activation, ideal centrifugation speed and times, dosing intervals, etc.) need to be further defined with specificity for the treatment of muscle injury.
• Investigate the safety profiles of biologic formulations used to treat musculoskeletal injuries - Biologic agents have been widely used for musculoskeletal injuries and conditions. Research efforts, thus far, have been devoted primarily to the assessment of the optimal preparation and biologic effect(s) of these agents. There is limited data pertaining to the safety of these formulations on both healthy and damaged tissues.
• Develop approaches for the use of wearable micro-technologies (i.e. GPS, accelerometers, garments) to provide field-based measures of running and mechanics to help guide hamstring rehabilitation and return-to-play progression - A graduated return to high-speed running is a critical component of rehabilitation and return-to-play following hamstring injury. Current practice focuses on metrics related to distance covered at or above certain absolute or relative running intensities as well as moderating the intensity of acceleration and deceleration. With the advancement of wearable micro-technologies, an opportunity presents for the development of methodologies to provide further insights into running and its mechanics. The ultimate aim is that methodologies that are developed can be integrated as a tool to better understand the progression of running mechanics in hamstring injury and can provide meaningful information to assist the return-to-play decision making process.
• Develop strategies and progression criteria that can safely accelerate tissue loading and high-speed running exposure throughout hamstring injury rehabilitation to cause meaningful changes in muscle structure and function, reduce rehabilitation time and reduce injury risk - Following hamstring strain injury there is a there is a delicate balance between expeditious return-to-play and the provision of an appropriately progressed rehabilitation protocol of sufficient duration to maximize convalesces and minimize reinjury risk. Truncated rehabilitation following hamstring injury may be risk factor for subsequent reinjury therefore work exploring rehabilitation protocols that can maximize adaptation and minimize return-to-play times without a consequent increase in re-injury risk is needed.

• Identify novel imaging protocols and techniques to assist in the determination of return-to-play and aid in reducing reinjury risk. - Advances in quantitative imaging techniques provide a measure of muscle tissue properties that may overcome the limited value of conventional qualitative imaging in predicting time away from sport and injury recurrence. Characterizing skeletal muscle microstructure and tissue properties following hamstring strain injury and their relation to clinical outcome is an important initial step to assess the potential value of these imaging techniques. Additional efforts are needed to evaluate how changes in these quantitative imaging metrics relate to the associated neuromuscular and functional changes following rehabilitation.
• Establish evidence-based rehabilitation progression criteria and return-to-play criteria for hamstring strain injury that show edema on imaging compared to those that do not show edema, with consideration of structural, functional, and patient reported outcomes. - Established classifications of hamstring strain injury incorporate findings from imaging performed shortly after the time of injury with the goal of improving prognostic ability and rehabilitation approach. The absence of edematous findings on MRI are classified as MRI-negative or grade 0 indicating no pathology to the muscle-tendon complex. Despite the absence of pathology, MRI-negative injuries comprise a considerable portion of time loss hamstring string injuries, and are managed the same as MRI-positive injuries. Considering the gross differences in structural damage between MRI-negative and MRI-positive injuries, there is a need to develop rehabilitation strategies and return-to-play criteria specific to each.

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