Disorders of consciousness (DoC) – including coma, vegetative state, and minimally conscious state – are highly prevalent with estimates in the United States (2018)1 of:
The landscape of DoC management is fraught with challenges. Diagnosis is difficult, with no laboratory nor imaging tests to detect consciousness. Published estimates of misdiagnosis among people with DoC are around 40%. No treatments are available to prevent secondary effects of primary brain injury. There is only one proven post-acute treatment available with narrow indications – amantadine hydrochloride.
A 2020 Symposium from the Curing Coma Campaign2 laid out research targets across six areas: defining endotypes/phenotypes, biomarkers, proof-of-concept clinical trials, prognostication, long-term recovery, and large data sets. Advances in our understanding of brain pathophysiology and biotechnology offer new avenues to improve diagnosis and treatment through research. The below table lists potential areas of exploration for applicants to consider. It is not an exhaustive list, and applicants are not limited to the below topics.
| Knowledge Gap | Area of Exploration |
|---|---|
| Infrastructure for clinical trials and observational studies | Establish infrastructure such as a multicenter DoC network or Model System, focused on a specific research question |
| Poor understanding of neurobiological mechanisms underlying consciousness/DoC | Connectomics / Circuit mapping |
| Patient classification | Phenotyping / Endotyping |
| Long-term outcome | Trajectory modeling |
| Lack of biomarkers | Validation of diagnostic, prognostic, response biomarkers |
| Prognostication | Modeling, large datasets, machine learning |
| Effective treatments for neuroprotection & post-acute recovery | Focus on innovative proposals, from proof-of-concept to comparative effectiveness drug (re-purposed agents) and device (DBS, tDCS, TMS, VNS, LIFUP) studies |
1Giacino et al. “Comprehensive systematic review update summary: disorders of consciousness.” Neurology, 2018 Sept. 4; 91(10:461–470)
2Claassen J, Akbari Y, Alexander S, et al. Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness. Neurocrit Care. 2021;35(Suppl 1):4-23. doi:10.1007/s12028-021-01260-x
Domestic, non-profit organizations are eligible to receive this grant, including Higher Education Institutions, Nonprofits with 501(c)(3) IRS Status, and Nonprofits without 501(c)(3) IRS Status. Non-domestic (non-U.S.) Entities (Foreign Institutions) may participate in projects as members of consortia or as subcontractors only but are not eligible to apply as primary applicants.
Applications must include at least one team member at Mass General Brigham (MGB). Preference will be given to interprofessional, multi-institutional projects, and to teams that include at least one member from Spaulding Rehabilitation.
Projects should explicitly describe plans for engaging impacted constituency groups, with both ‘patient partners’ (inclusive of those with lived experience, family and caregivers, and organizations representative of the brain injury population) as well as professional partners such as clinicians, payers, administrators, and policy makers1. Applicants should consider level of engagement, and opportunity to place those with lived personal experience in partnership and shared leadership roles with decision-making authority2.
This award funds projects that create infrastructure to enable prospective multicenter RCTs (including adaptive platform trials) and/or evaluate biologically plausible treatments. Acquisition of pilot data for larger multicenter studies is a key aim of this initiative. Retrospective and meta-analyses are not eligible proposals.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Principal Investigator is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are especially encouraged to apply.
1PCORI Engagement Rubric. PCORI (Patient-Centered Outcomes Research Institute) website. http://www.pcori.org/sites/default/files/Engagement-Rubric.pdf. Published February 4, 2014. Updated October 12, 2015. Accessed November 21, 2023.
2Carman KL, Dardess P, Maurer M, et al. Patient and family engagement: a framework for understanding the elements and developing interventions and policies. Health Aff (Millwood). 2013;32(2):223-231. doi:10.1377/hlthaff.2012.1133
Applying for this opportunity is a two-step process. Applicants must first submit a Letter of Intent (LOI). Applicants will then be advanced to the next round and invited to submit a full proposal.
Applicants are asked to submit a letter of intent through the CoLab on-line application system that includes the following information:
The online application is equivalent to approximately three pages.
Selected applicants will be asked to submit full proposals through the CoLab on-line application system that include the following information:
The on-line application is equivalent to approximately 12 pages.
Includes a team member from Mass General Brigham? (Yes/No)
Includes a team member from Spaulding Rehabilitation? (Yes/No)
Project Narrative (20 points)
Specific Aims (20 points)
Proposed Activities (30 points)
Potential Impact of Proposed Work (30 points)
Background & Significance (20 points)
Project personnel/expertise and institutional resources (10 points)
Research methods & study design (60 points)
Operational management (10 points)
Shonali Gaudino
sgaudino@mgb.org
(617) 952-6509
