Converging evidence also points to impaired SN-mediated switching between the DMN and executive networks, contributing to persistent self-focus and insufficient recruitment of cognitive control. Together, these findings support a systems-level imbalance an architectural problem in network coordination rather than a purely local neurotransmitter deficit.

At Salience Clinical, we operate at the intersection of systems neuroscience, clinical development strategy, biomarker integration, and translational positioning. Our focus is not theoretical neuroscience; it is applied architecture. We help teams translate emerging network science into concrete decisions about development pipelines, endpoint strategy, and evidence generation.

AAV-mediated delivery of enzymes, neurotransmitter-modulating proteins, or neurotrophic factors has been extensively explored in Parkinson’s disease. While early studies suggested biological activity, several randomized controlled trials failed to meet primary clinical endpoints, highlighting the challenges of placebo effects, target engagement, and disease heterogeneity.

CNS disorders are now being reclassified by molecular signatures, circuit-level dysfunction, and digital phenotypes. This is not a technological upgrade; it is a strategic reset. Sponsors who continue to build programs around blunt diagnostic categories and legacy endpoints will increasingly fail, not because their science is weak, but because their development logic is obsolete.

Healthcare systems face a growing economic crisis: more than 13 million patients suffer from chronic wounds each year, yet traditional health-economic models capture only a fraction of the true burden. Current accounting focuses on product prices and episode-level costs while missing the far larger impacts of delayed healing, lost productivity, caregiver strain, and preventable complications.

Real-world evidence (RWE) has emerged as an essential complement to clinical trials, offering continuous insights into implant durability, safety, effectiveness, and economic value across actual care settings. This white paper reviews the importance of RWE in orthopedics, key data sources including national registries and the Orthopedic Coordinated Registry Network (Ortho-CRN), regulatory context, advanced analytical methods, and future directions involving AI and federated data networks. Strategic guidance is provided for manufacturers aiming to integrate RWE into product development, regulatory compliance, market access, and innovation.

In an era where regulatory expectations, technological complexity, and global harmonization are accelerating, cross-functional excellence determines whether a device reaches patients on time—and with the safety and performance they deserve. Organizations that treat plans as living documents, invest early in collaborative risk management, and unify engineering, clinical, regulatory, and quality perspectives transform development complexity into meaningful patient impact.

Healthcare systems face a growing economic crisis: more than 13 million patients suffer from chronic wounds each year, yet traditional health-economic models capture only a fraction of the true burden. Current accounting focuses on product prices and episode-level costs while missing the far larger impacts of delayed healing, lost productivity, caregiver strain, and preventable complications.

Real-world evidence (RWE) has emerged as an essential complement to clinical trials, offering continuous insights into implant durability, safety, effectiveness, and economic value across actual care settings. This white paper reviews the importance of RWE in orthopedics, key data sources including national registries and the Orthopedic Coordinated Registry Network (Ortho-CRN), regulatory context, advanced analytical methods, and future directions involving AI and federated data networks. Strategic guidance is provided for manufacturers aiming to integrate RWE into product development, regulatory compliance, market access, and innovation.

Orthopedic implants are long-term, often lifelong, interventions that require rigorous evidence demonstrating sustained safety and performance. Traditional RCTs with limited follow-up and narrow populations cannot fully capture the complex real-world environment, especially given the variability in surgical techniques, patient comorbidities, and health system factors. As payer and regulatory expectations evolve, RWE has become indispensable for demonstrating lifetime device value and supporting continuous improvement.

Musculoskeletal regenerative medicine is approaching a commercial inflection point. What was once a speculative frontier cell therapies, bioengineered scaffolds, gene-modified constructs is now advancing first-generation clinical programs.