Advances in CNS trials: Key 2025 milestones and 2026 outlook 

Introduction 

Looking back to 2025, it was a year of great progression in technological advancements and CNS clinical trial regulations. 2025 took leaps beyond our predictions in bringing transformative milestones by resetting procedural priorities and regulations. Set by leading bodies and standardising approval boards, the standards and approaches now accepted within CNS clinical trials has changed, moving research and clinical trial processes regarding design, execution and approval into new, more applicable territory. We look forward to seeing these changes bring about innovation, collaborations and discoveries.  

Main events of 2025 

The GCP guidelines saw an upgrade when its formal adopted version was published in early January 2025. The newer version of the GCP guidelines contains some more regimental additions and some more exploratory and creatively inviting regulations. From more robust documentation standards for trial conduction and management when on site, to more exploratory and creative protocol design opportunities for achieving and reaching successful primary and secondary endpoints.  

The updated SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 Statement was published in April 2025. The update was built through a formal process including a scoping literature review, a three-round Delphi consensus survey with hundreds of experts and a consensus meeting to ensure that the new recommendations reflect best practices. This demonstrates a new approach to protocol standardisation reflecting more accurately the reality of scientific procedure.  

The main aim of SPIRIT 2025 is to improve the completeness, transparency, and usefulness of trial protocols. Compared with the 2013 version, SPIRIT 2025: 

ADNI’s policies on standardised neuroimaging protocols and open data sharing have become a model for multisite CNS research, enhancing comparability and enabling translational biomarkers in dementia trials. In 2025 ADNI underwent updates to their open sharing protocols by conducting “ANDI-4 implementation”, in which they carried out cohort expansion, increased diversity and new standardised imaging/biomarker protocols across sites. Alongside releasing their most up to date imaging, biomarkers and genetic large-scale datasets on their most recent trials.  

Why these 2025 updates matter: 

The 2025 update of the Regulatory Science Research Needs (RSRN) was publicly noted in September 2025 and implemented into EMA. The Regulatory Science Research Needs initiative forms part of the EMA’s strategy to advance regulatory science through targeted research that fills knowledge gaps and supports medicine development and regulatory decision-making. In overview, they focused on improving clinical research, improving regulatory system evolution, and fostering technologies for specific medicine development (European Medicines Agency (EMA) Regulatory science and research). 

This reflects EMA’s interest to adapt regulatory systems for future science, including analytic science and data-driven decision-making. 

The NIH issued a formal revision to its Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research via Notice NOT-OD-25-131, released July 17, 2025. This update did not repeal sex as a biological variable (SABV) but altered key phrasing and reporting expectations: 

Terminology shift: The policy now uses “sex” instead of “sex/gender” in alignment with updated federal definitions (HHS Sex-Based Definitions and Executive Order 14168). 

Reporting expectations expanded: Inclusion plans and progress reports must explicitly address sex, race/ethnicity, and age categories in data collection and results reporting. 

How this has changed research conduction:  

In grant proposals: A clear plan explaining how biological sex is factored into study design, sample selection, and analyses. Justifications if only one sex is studied (e.g., scientifically justified exceptions).   

In progress reports or outputs: Disaggregated results by sex, with analyses demonstrating any differences or explaining lack thereof. Reporting of sex-based data alongside other demographic variables. 

These updates are a great leap for scientific conduction in that gender-based differences are required to be considered and justified. This increases patient specificity in drug and treatment methods.   

In 2025 we saw a large number of pharma and tech platforms presenting early CNS digital endpoint data at major 2025 scientific meetings, demonstrating advanced metrics and utility for the use of digital biomarkers and wearables in CNS trials, enhancing feasibility and data collection sensitivity. The trend of digital biomarkers being incorporated into clinical trial protocol design earlier, with wearables supporting decentralised data collection and patient-centric monitoring is carrying on into 2026 and continues to grow in its technology and uses.  

The International Neuroinformatics Coordinating Facility (INCF) continues to function as a community-led standards organisation promoting open science and FAIR data principles for neuroscience research. INCF develops, endorses, and disseminates standards and best practices that make neuroscience data and tools more interoperable, reusable, and transparent — crucial for reproducibility and cross-site data comparison in both basic and clinical studies. Their updates improved standards around data sharing and reproducibility, FAIR compliance, supporting advanced data integration, and bridged standards with infrastructure. More specifically the changes the INCF implemented in 2025 are as listed below:  

Enhancing Data Sharing & Reproducibility: Standardised identifiers (RRIDs) help ensure that datasets from CNS biomarker studies, imaging trials, and preclinical workflows cite resources consistently, facilitating cross-trial comparability and reproducibility (International Neuroinformatics Coordinating Facility, 2025). 

Improving FAIR Compliance: Training and community engagement events improve researchers’ ability to apply FAIR principles to their data generation, management, and sharing, which is increasingly expected by funders and journals.  

Supporting Advanced Data Integration: Expanded standards like BIDS extensions, e.g., Magnetic Resonance Spectroscopy – Brain Imaging Data Structure (MRS-BIDS) allow richer modalities to be stored and shared using a common organisational framework — critical for multimodal CNS trials involving MRI, spectroscopy, EEG, etc (Bouchard, A.E., et al. 2025). 

Challenges faced in 2025 

Blood–brain barrier (BBB) and drug delivery: Delivering effective doses to the brain remains scientifically difficult. The BBB continues to block many high potential therapeutic candidates. This unresolved barrier continues to drive higher clinical trial failure rates for novel CNS drugs. (Drug Target Review, The future of CNS drug development). 

Lack of validated biomarkers: Across many CNS conditions, there’s still a shortage of reliable biomarkers for early detection, progression tracking, or therapeutic response — slowing study design and increasing uncertainty of outcomes.  

Disease heterogeneity: Many CNS disorders, including Alzheimer’s and multiple sclerosis, have multiple root causes. Consequently, patients suffering from these conditions generally require more personalised treatments, complicating drug development and lengthening development time. This heterogeneity also affects the ability to produce consistent results in clinical trials, as study groups sharing the same symptoms and disease progressions are hard to find.  

Decentralised & fragmented data flows: While decentralised clinical trials (DCTs) promise more accessibility, in 2025 they introduced challenges around data fragmentation, inconsistent tech literacy, and difficulties ensuring data quality across remote participants. 

Operational errors leading to regulatory setbacks: Recent evaluations indicate that trial submission failures for CNS applications frequently stem from safety concerns, inconsistent efficacy data, or weaknesses in study planning — meaning even “completed” trials can fail to progress through review. 

What we predict for 2026 

For 2026, our predictions are going to be very different than the ones made in 2024 for 2025. This greatly demonstrates the scale and speed at which the industry and landscape for CNS trials is changing and evolving to meet the need of its target population. Within a 2-year time period, we can state greatly different predictions for what is to come in the industry of CNS clinical trials.  

As we start 2026, there are already heavy weight challenges and opportunities coming our way that those in the field of CNS clinical trials will have to find ways of overcoming and integrating into their pipelines, in order to stay above the level of transformation and competitive innovation that is currently taking place within CNS based therapeutic research.  

Our predictions for 2026:  

The landscape of CNS clinical trials in the world, particularly across the US and the UK is evolving and dynamically transforming to meet the potential of new technologies, AI, and updated regulatory policies. These changes greatly change how researchers, CROs and sponsors approach and carry out early phase clinical trials and execute clinical trials. These changes should transform the speed and success at which novel compounds and therapeutic intervention can be offered to target populations. We look forward to seeing what innovative approaches and outcomes arise from these changes.  

2026 looks to be a year of exploring uncharted territory in the field of CNS trials and holds the promise of providing exciting advancements to the field of clinical neuroscience.  

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