Cohen Veterans Bioscience

Brain health tools & technologies:in order to fast-track precision diagnostics and targeted therapeutics and wellness approaches for maintenance and restoration of brain health, cvb is leveraging innovation and technology to build tools and platforms that enable discovery and development across brain diseases. These tools & platforms allow researchers from academia and industry to access and utilize best-in-class practices and allow efforts to be scaled with rigor and reproducibility. (see schedule o for full detail of our programs)platform efforts focus on capacity that enables reliable discovery of biomarkers and biological pathways that are translationally relevant for the development of diagnostics and therapeutic targets for drug and other medical interventions. Each platform is creating research tools (e.g. Animal models, data standards, computational models, reference databases, etc.) That will accelerate/foster these discoveries.within this framework, cvb has established both intramural (research conducted by, or including, cvb staff or contractors) and extramural research programs (research conducted via grants or in collaboration with external academic, industry, foundation and government partners) and also operates several public-private partnerships. These cooperative alliances organize and fund a network of partners who each contribute complementary and synergistic data, capabilities, or expertise to support a common roadmap for identifying diagnostic biomarkers, building predictive brain disease models, developing robust standardized translational tools, and catalyzing pharmaceutical drug development. The emphasis is on team science with Cohen Veterans Bioscience serving as its hub.our platform programs currently include the braincommons (cloud-based data & analytics), earlysignal (wearable and home sensors for monitoring health status), rapid-dx (establishing best practices for discovery and validation of biomarkers), amp-it-up (for preclinical discovery and translation) and tap (target advancement program).braincommons:the braincommons (bc) is a cloud-based research and discovery platform for the brain health community which features data, tools, and community access in a secure, scalable, and sustainable environment. It is designed to further democratize data and enable greater collaboration globally among brain scientists working in a variety of settings.we are in a new era of brain research, where powerful data acquisition technologies are generating multimodal data at increasing scales. To enable disease modeling efforts, as well as the discovery and replication of biomarkers, there is a critical need for a platform that can house multi-modal data types, across diagnostic categories, in conjunction with data pipelines to ensure reproducible analysis, and with an ability to apply state-of-the art machine-learning algorithms. In 2022, the braincommons was launched to our first community of research partners in ptsd, tbi and parkinson's.in 2023, we have launched a new user interface for the braincommons and have uploaded our national normative neuroimaging library data to the platform to be shared with the research community with accompanying pipelines for data processing.earlysignal:the aim of our digital health program, early signal, is to record and analyze a range of data directly related to the well-being of patients living with brain disorders. Behavioral, cognitive, physiological and other information are collected through our integrated technology platform.wearable and sensor technologies hold promise in the assessment and continuous monitoring of patients in order to better screen and diagnose, monitor disease progression, and observe intervention response or lack thereof. Digital health monitoring also allows us to study brain health and disease in unprecedented ways, by tracking variables such as sleep, physical activity, stress and cognition, we may be able to better understand what changes over time - and to develop earlier and preventive diagnostics and treatments to make a difference in patients' lives. Medical-grade data is needed for fda approval of such platforms for use in medical decision making and data integration is necessary for clinicians' workflow. This program supports multiple partners to test and validate wearables, sensors, apps and other digital health technologies for use in monitoring brain health. In 2022, cvb, in partnership with university of Pennsylvania, completed a study to test and validate the performance of wearable and sensor devices for the assessment of sleep compared to gold standard poly-somnography, using cvb-designed secure automated deidentified data collection and cvb's study manager tool to support conduct of the trial. In 2022, we completed the development of our "trial-in-a-box" fully automated clinical trial solution for the collection and automated processing and analysis of digital health data in traditional, hybrid, and fully decentralized trial formats. In the fully decentralized setting, this allows study sponsors to send wearable and home sensor technology study kits directly to eligible study participants without requiring them to visit a study center, enabling a more diverse and often less-studied population to participate. The provided devices are paired with a downloadable study app on the participant's own device to collect related subjective outcomes such as traditional scales of depression, function, and activity as well ecological momentary assessments.in 2023, we launched and completed the 40 winks sleep study a cutting-edge, voluntary wearables research study aiming to improve and simplify how we measure sleep. The goal of the 40 winks study is to evaluate and improve methods of measuring sleep at home, which may help inform the development of diagnostics and treatments that are user-friendly, cost-effective, and reliable. The study recruited healthy adult volunteers, or adults self-reporting insomnia, including Veterans in both groups.rapid-dx: research alliance for precision therapeutics, innovation and diagnostics rapid-dx is cvb's flagship biomarker discovery collaborative - fast-tracking the advancement of objective diagnostics for brain diseases.a biomarker is a characteristic that is objectively measured and evaluated as an indicator of a normal or pathologic biological process or a response to a therapeutic intervention. Developing biomarker-based diagnostics is essential to shifting diagnosis and treatment of psychiatric and neurologic conditions (such as ptsd and tbi) from a symptom-based approach to a biological, mechanistically-based one that targets the effects of trauma at their molecular roots. Many potential brain-related biomarkers published in the literature have not been independently replicated or advanced through a qualification process for regulatory approval and use.rapid-dx is a public-private partnership program including government, foundations, and leading academic centers established for collecting data and performing studies necessary to discover and replicate biomarkers and qualify successful and relevant candidates for development as clinical diagnostics.through this program cvb has established the cvb biorepository in partnership with Indiana university. The goal of the biorepository is to establish a centralized resource for tissue and biosample storage for enabling biomarker discovery, replication, and validation across a number of brain conditions, including post-traumatic stress disorder ("ptsd"), traumatic brain injury ("tbi"), suicide, dementia, major depressive disorder and other mental health disorders, among others.the cvb brain biorepository houses blood and saliva samples that were collected as part of biomarker studies directly sponsored by Cohen Veterans Bioscience or through key partnership programs. Our biorepository banks a variety of biologic samples including, plasma, serum, and saliva, and will encourage future collaborations with researchers from academia, industry, government, and foundations.brain trauma programs: post traumatic stress disorder and traumatic brain injury. This cvb program was founded in 2015 to establish a national research roadmap for ptsd, tbi and related conditions (e.g. Suicidality). Brain trauma blueprint - state of the science summits:the brain trauma blueprint httpswwwbraintraumablueprintorg is a framework to establish roadmaps to advance precision diagnostics and therapeutics for survivors of brain trauma by outlining research goals & priorities, establishing consensus around failure modes & knowledge gaps, and developing strategies to move the field forward for trauma-related conditions by fostering collaboration and resource allocation across the broader stakeholder community.

Standardized advanced neuroimaging scans on 3,000 adult volunteers, the resulting imaging data, along with demographic information and the results of neurocognitive assessments, is forming a library documenting population variation in brain structure and function as measured by these advanced imaging methods.through this imaging database, it is our goal to advance neuroimaging to dramatically improve the identification of affected individuals and allow physicians to objectively and efficiently diagnose conditions such as tbi, dementia and other brain disorders where brain structure is detected via mri.in 2022, we continued recruitment into the library, reaching over 1,800 enrolled subjects and also added blood sample collection for newly recruited individuals. Computational modeling & data sciences:cvb has established an intramural data sciences program to build machine-learning and artificial intelligence based predictive models of disease. These programs build on our original orion ms bio-modelling program and focuses on models of ptsd, tbi, parkinsons and dementia and other conditions.post-traumatic stress disorder ("pstd") 1.0:our main priority is to build a multi-modal model of ptsd using deeply-phenotyped cohorts such as the best study and Cohen Veterans center studies. In 2022, we have built analysis pipelines for epigenetic, eeg, inflammatory marker and clinical data and we are on track to build our first model by year end.parkinson's progression markers initiative ("ppmi") data science modeling group:existing diagnoses for complex brain disorders such as parkinson's disease focus on understanding clusters of major symptoms. In order to drive progress in the development of new treatments, it is important to understand the role of specific biological processes in determining patient outcomes. In this program, we model the michael j. Fox foundation ("mjff") sponsored parkinson's progression model initiative study. The study has evaluated participants' clinical status while collecting imaging, behavioral, 'omics and other assessments longitudinally since 2010. In our aligned missions to advance brain health, mjff selected cvb's data science team to leverage this cohort together with a multi-disciplinary approach to quantitatively explore, evaluate, and predict disease trajectory, risk factors, and subtypes. Given the breadth and depth of the ppmi data and rich opportunities to develop impactful disease models, the team use their subject matter expertise across translational science to generate insights from 'omics, imaging, genetic and clinical data by integrating techniques across advanced statistics, machine learning, and computational modeling to facilitate pd biomarker discovery and deepen our understanding of disease progression.multiple sclerosis ("ms") 1.0:the orion bionetworks flagship program successfully piloted the establishment of a multiple sclerosis bionetwork comprised of academic (neuroscience institute of the brigham and women's hospital), advocacy (accelerated cure project for ms), computational (gns healthcare, metacell, thomson reuters), informatics (converge by deloitte, rancho biosciences, exaptive), and online patient community partners (patientslikeme [plm]). De-identified hippa-compliant data from three databases were curated and loaded into a cloud-based data knowledge management system. The integrated repository includes 9,000 subjects with ms and related conditions. The alliance developed a roadmap for joint execution with specific scientific aims. The alliance has generated multiple models based on the data repository using different algorithmic approaches: phenotypic prognostic model and two molecular prognostic models.ptsd and tbi preclinical modeling program:animal models of psychiatric disorders offer a complementary research modality that supports clinical research. In order to achieve a satisfactory degree of validity and reliability, animal models of complex and intricate psychiatric disorders, such as ptsd, must fulfill certain criteria: pathogenic processes must be observable and measurable, and must reliably reflect clinical symptomatology, and pharmacological agents that are known to affect symptoms in human subjects, should modulate these processes. Cvb has established the alliance for models of ptsd, innovative technologies and uniform practices ("amp-it- up") to support preclinical model development. Multiple sub-grant awards completed and published their finding this year in support the mission of this program.peers - the platform for the exchange of experimental research standards:peers is a platform that enables sharing of information on parameters that affect the robustness of preclinical data. Peers is like a wiki on how to design, conduct and analyze experiments to increase data robustness. Peers allows users to search for factors and parameters that are of relevance to their experiments and gives guidance and advice on how to leverage these factors to increase the quality, robustness and reproducibility of research. Peers allows users to: (1) search for factors and parameters that are of relevance to their experiments (2) find recommendations and best practices on experimental design, execution and data analysis for specific in vitro methods or in vivo models (3) share experiences and knowledge to help others build high-quality, reproducible data sets (4) cite contributions (5) increase the quality, robustness and reproducibility of research.addressing sex as a biological variable in preclinical research:differences between males and females extend well beyond reproduction, with significant implications for human health and disease. This is particularly the case in the field of neuroscience, where differences in basic biology between men and women can lead to sex differences in the prevalence, progression, and responses to treatment of many brain disorders.this video training series was developed and launched by Cohen Veterans Bioscience in 2022, to ensure that early-stage research is conducted to the highest and most rigorous standards possible. One solution is to ensure that the research community - including graduate students, postdocs, and other early career researchers - have the tools they need to enable the implementation of best practices across the experimental process. The goal of the video training series, which contains three modules, was to provide practical guidance to preclinical researchers on how to navigate the nih's 2015 policy on incorporating sex as a biological variable into their current and future research.global preclinical data forum:the global preclinical data forum ("gpdf") is a jointly sponsored u.s. and european initiative that encourages global collaboration to address the challenge of ensuring that preclinical research is reproducible, robust and translatable to support disease research utility for clinical research & development ("r&d"). It supports best research practices, the development and implementation of data quality standards, preclinical data & technological platforms, and training programs for the neuroscience community with the goal of enhancing the data utility derived from preclinical models.this is our fifth year supporting, with the european college of neuropharmacology ("ecnp"), the world's first negative data prize as an incentive for preclinical researchers to publish "negative data" results to ensure all neuroscience studies properly advance knowledge. The prize is awarded to the researcher or research group whose neuroscience study best exemplifies data where the outcomes do not confirm the expected results or working hypothesis. The preclinical award was presented during the 2020 virtual ecnp conference.in 2023 we continued to award the best negative prize awards program to clinical researchers whose neuroscience study best exemplifies data where the outcomes do not confirm the expected results or working hypothesis.eqipd quality system:the gpdf and Cohen Veterans Bioscience are both major contributors to the european union innovative medicine initiative-funded consortium called eqipd (eqipd.org). The eqipd consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The eqipd quality system was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. Eqipd defines research quality as the extent to which research data are fit for their intended use.

The state of the science summits are the basis for building the roadmaps and are designed as retreats for 100 to 200 stakeholders to come together to realize true impact. The stakeholders encompass a broad swath of the community from academic institutions to government agencies, foundations supporting translational research, industry and individuals with lived experience.each summit serves as a launchpad for ongoing working groups to develop evidence-based strategies and recommendations on how to fill those gaps, identify new gaps as others are filled, and disseminate these findings back to the community at large through white papers and proceedings.the inaugural state of the science summit ("soss"), held in 2018, focused on diagnosis of trauma-related brain disorders with a major focus on post-traumatic stress disorder. The trauma-related brain disorders research community has identified a need to establish a mechanism-based taxonomy for these conditions to advance biomarker discovery as well as diagnosis and therapeutic development. A shift from a syndromic classification system to a mechanistic one necessitates a review of the current scientific knowledge, adoption of new scientific models, and identification of research and knowledge gaps. The soss brought together multidisciplinary stakeholders with deep scientific and clinical expertise to address this pressing need.the theme of the second state of the science summit, held in 2019 was paths to treatment for traumatic brain injury(s) with a focus on the taxonomy and nosology of the chronic sequelae, challenges and opportunities in clinical practice and development, and etiology and mechanism of persistent symptoms. As measurement tools advance, research has been able to focus on different types of injury, beyond the mild, moderate, and severe classifications of tbi. To augment and support the many efforts across fields and organizations over the past decade, in 2020 we worked with thought leaders across tbi to prepare a consensus blueprint to drive translational science for tbi. In 2021, we published recommendations in support of the national tbi precision research roadmap.in 2022, we launched the tbi action alliance in support of a national tbi precision research roadmap. The roadmap, based on recommendations from the brain trauma expert community, outlines a series of critical projects with specified milestones that will materially advance progress towards the stated goals of "advancing a first generation of tbi diagnostics and treatments".the tbi precision research roadmap focuses on 7 lines of effort:1. Injury burden: identify the burden of disease across all populations and injury severities as determined by incidence, prevalence and long-term trajectories of patients suffering from tbi.2. Disease models: develop an array of translationally valid disease models (preclinical and computational) based on biological understanding of trauma pathogenesis and disease phenotypes that support evaluation of novel therapies.3. Precision diagnosis: identify, develop and validate diagnostic, prognostic and predictive biomarkers fortbi to develop first generation diagnostic tests.4. Targeted therapeutics: validate therapeutic targets & fast track a first-generation of tbi (wellness, device, digital, drug) therapeutics targeted to the right person at the right time.5. Clinical practice implementation: accelerate adoption of best practices, clinical practice guidelines, and precision therapeutic approaches to optimize brain health outcomes.6. Translational infrastructure and enablingtechnologies: identify and address infrastructure,incentives, regulatory and technology gaps to advance the tbi roadmap.7. Awareness and advocacy: place tbi at the top of the u.s. public policy agenda and raise awareness to reduce stigma of brain injury, encourage treatment-seeking, and enable access and reimbursement of care.in 2023 we launched the tbi action alliance to support the execution of the national tbi roadmap through a public-private partnership model that engages multiple sectors to advance the objectives outlined in the roadmap. (tbiaction.org)rapid-diagnostics (rapid-dx) - research studies:best biomarker ptsd study:despite the efficacy of psychotherapy as first-line treatment for ptsd, large inter-individual differences in outcomes exist, with roughly 50% of patients responding to treatment and fewer than that fully remitting. This grant supported the development of a response diagnostic test based on preliminary findings for a combination cognitive/imaging marker resulting from cvb's investment in the Cohen Veterans center study at nyu/stanford. The program included a clinical study at two centers of over 200 subjects to replicate the initial finding, and is seeking qualification via the food and drug administration ("fda") guidance to support the commercialization and/or availability of the test for clinical practice and research and development. This study completed recruitment in december 2019 and seminal results which demonstrate that an eeg based biomarker can predict treatment response for individuals with ptsd or mdd were published in 2020 and 2021.in 2023, we have completed our analysis of c biomarker assays on blood samples collected in the best study program to look for genetic and inflammatory markers that may be predictive of response and/or disease and initiated dissemination of these results at multiple conferences.ptsd genetics program:the psychiatric genetics consortium-ptsd working group - broad institute collaboration is supporting the largest global genome wide association study ("gwas") of ptsd to date with data from over 200,000 individuals analyzed. The main goal is to uncover the genetic underpinnings of ptsd risk and publish all results. Seminal findings of the first ptsd genetic risk loci from this program were published in nature communications in october 2019.in 2022, the gwas program has expanded to include over 350,000 individuals with trauma and 2 million health controls yielding over 95 identified genetic risk loci.in 2023, the results for this analysis were published.prism2 (psychiatric ratings using intermediate stratified markers 2):in 2021, we joined the innovative medicines initiative and european federation of pharmaceutical industries and associations (efpia) as a funder and collaborator in the prism2 study program. Building on the success of innovative research by the prism project, the innovative medicine initiative 2, a joint undertaking between the eu and the efpia, has backed the program with funding for a new project to explore the underlying biology of alzheimer's disease, schizophrenia and major depressive disorder (mdd). The new prism 2 (psychiatric ratings using intermediate stratified markers 2) project aims to identify quantitative biological features common across the diseases, opening the possibility of developing targeted treatments irrespective of traditional diagnosis.prism was a pan-european research project that ran from 2016 to 2021 and received $16.5 million in funding from the innovative medicines initiative 2 joint undertaking, supported by the european union's horizon 2020 research and innovation programme and efpia. The results of prism constitute the foundation for the current prism 2 project.the prism2 project launched in 2022, including patient enrollment of individuals with schizophrenia, dementia or major depression across three centers in europe.study recruitment for prism2 is targeted for completed in 2023.national normative neuroimaging library program:cvb has created an imaging reference library essential to the development of effective clinical imaging tools for diagnosing and managing patients with brain disorders. Advanced neuroimaging can now detect microscopic changes in brain structure caused by trauma or disease. These advanced imaging approaches include diffusion tensor imaging ("dti"), functional connectivity, perfusion weighted imaging, and volumetric imaging. Despite their promise, these advanced approaches are currently primarily confined to research use. The numerical nature of the information these advanced imaging approaches yield is difficult to translate from the study of groups of individuals to a single patient without a reference. The imaging database is based on the results of a national study of normative individuals, sponsored by cvb at university of Virginia, baylor university and university of Utah and two military sites.

Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the eqipd quality system is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The eqipd quality system proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. In 2023, eqipd was awarded a major grant (istand) by the innovative medicines initiative in europe. There is currently no established framework readily available outside of selected companies and research organizations that apply internally-developed standards and criteria to support adequate research rigor that is commensurate with the purpose and appropriately achievable. The grant program will establish and test such a framework to support the processes of generating and reporting nonregulated research results, and to systematize decision-making based on such results. It could be applied to nonregulated research in any domain (i.e., research not conducted under good practice gxp standards such as glp), including the development of biomarkers.policy & advocacy initiatives:we are committed to advocating for policy reforms at the federal level that build upon evidence-based precision medicine approaches and have the power to bring new solutions for ptsd and tbi in years, not decades. As part of our advocacy efforts, we co-founded the coalition to heal invisible wounds (the "coalition"), a collaborative initiative aimed at advocating for policy reforms to widen and expedite the pipeline for new therapies and diagnostics for ptsd and tbi - which can both drastically increase the risk of suicide among Veterans. In 2023, we continue to grow membership in the alliance as well as contribute to the advancement of seminal legislation to support Veterans and brain research.