Operationalizing Imaging in CNS Clinical Trials: Delivering Scientific Rigor with a Scalable Operational Footprint

Introduction

While neurological disease is one of the leading causes of ill health and disability worldwide, significant gaps in the availability of and access to effective treatments and therapeutic approaches remain. Despite complicated designs, many compounds fail clinical trials in the Central Nervous System (CNS) space. This is due, in part, to lack of understanding of disease mechanisms, uncertainty regarding drug delivery mechanisms (i.e. blood-brain-barrier), safety issues, not selecting the right patient population and execution of trials to realize the study endpoints.

Successful imaging in CNS clinical trials demands a tightly integrated approach where scientific rigor and operational excellence work together to successfully execute the clinical study protocol. To explore how this balance is achieved, Perceptive’s Dr. Elif Sikoglu and Renee Tschopp offer their expert perspectives, highlighting how Perceptive Imaging delivers scientific rigor with scalable operations in CNS clinical trials.

Why are CNS Clinical Trials so Complex and How Does Imaging Come to Play?

From a scientific standpoint, CNS trials pose challenges which set them apart from many other therapeutic areas. “The brain is extraordinarily complex, and there are still significant unknowns in CNS disease pathophysiology,” explains Sikoglu. “Disease mechanisms often arise from an interplay of genetic predisposition, comorbidities, and environmental influences- all adding layers of complexity to therapeutic discovery and evaluation. Understanding the therapeutic impact in CNS frequently depends on invasive procedures (e.g. CSF collection) that can be hard to harmonize, costly, and demand significant expertise.”

Here, imaging can offer objective markers, including:

• Confirming target engagement and brain penetration
• Helping the understanding of mechanism of action of the potential therapeutic
• Supporting safety monitoring
• Tracking disease progression.

In another words, if utilized within a thoughtful framework and with operational excellence, imaging can be considered the cornerstone of CNS drug development – bridging gaps in mechanistic understanding, de‑risking early‑stage decision‑making, and anchoring therapeutic interpretation in objective CNS biology.

Operational Challenges at Scale

Operationally, CNS clinical trials present another unique set of challenges, particularly when studies are large-scale and rely on multiple imaging modalities. CNS clinical trials require complex endpoint assessments and associated data harmonization and data quality challenges.

Everything starts with alignment,” explains Tschopp. “Ensuring early alignment with sponsors on scope and expectations is key. From there, we’re working toward targeted first-patient-in dates, which first requires finalizing study-specific imaging documentation, building databases, and ensuring sites are trained and ready to appropriately acquire and transfer data per study requirements.”

The Perceptive team monitors the imaging centers throughout the study and we pride ourselves on the close and collaborative relationships we’ve built, which enables us to keep  a keen eye on  proactive quality control. Protocol adherence, data quality checks, and early issue identification are crucial in ensuring scientific intent is realized throughout execution.

“As scientists, we naturally want to include as many markers as possible to understand complex mechanisms,” says Sikoglu. “However, we have to keep the patient and the site in mind. The goal is to find the optimal balance between uncovering the answers while working within the agreed framework of the clinical trial.”

“If utilized within a thoughtful framework and with operational excellence, imaging can be considered the cornerstone of CNS drug development – bridging gaps in mechanistic understanding, de‑risking early‑stage decision‑making, and anchoring therapeutic interpretation in objective CNS biology.”

The Imaging Data Lifecycle

Perceptive has extensive experience successfully managing large, global CNS clinical trials, and can quickly pivot approaches to support client needs while firmly maintaining integrity with our processes within the given regulations. Images, no matter the modality, should be acquired by the approved acquisition protocol and the specific parameters of each imaging center. The images are then transferred to Perceptive for quality control, where we review them for completeness and protocol adherence and work with sites to resolve any queries. From there, the data moves onto visual neuro-radiology reads and/or quantitative analysis and then are entered into validated databases and prepared for delivery back to the sites and/or sponsor.

Perceptive works with clinical site teams to ensure everyone understands the expectations of the trial, including turnaround times. “Sponsors want things fast, and we strive to meet their timelines without compromising on quality. We regularly meet or beat turnaround times, which supports clients with meeting their timelines,” says Tschopp.

Web-based platforms facilitate easy image upload and provide the internal team with visibility into the data’s life cycle and potential issues. Technology supports exporting reports for clients, covering image status, data in-house, and site setup status, ensuring the study is conducted according to regulations and scope. “We continue to leverage advanced technology, actively building tools to improve turnaround times by utilizing automatization and advanced analytics, allowing the science to thrive.”

Compliant and Scalable

Once contracted to support a study, Perceptive assigns a project manager and members of the scientific delivery team, who work together closely to ensure the study is executed according to scope, study protocols and well-defined and regulatory approved processes, maintaining clear internal and external communication. “During one large-scale, high-priority phase 3 Alzheimer’s clinical trial, we had to set up imaging centers as quickly as possible,” explains Tschopp. “Through effective cross-team communication, within a few months we were able to set up almost 300 imaging centers to start receiving data and effectively managed the influx of over 5,000 screening scans, which contributed to the drug’s eventual FDA approval in July 2024.”

Despite the inherent complexity of CNS trials, the field continues to advance rapidly. Researchers are driving meaningful progress in CNS drug development, through novel approaches including AI-guided molecular optimization, multi-target small molecules, and molecular engineering, all showing significant promise, making it an exciting prospect for pharmaceutical sponsors.

Behind every data point is a real patient navigating the uncertainties of their neurological condition. While scientific rigor enables meaningful clinical insights, operational excellence ensures participants are effectively supported throughout the trial lifecycle, amid complex regulatory and logistical demands. With an extremely talented team whose combined expertise would be an asset to any CNS clinical trial, and established relationships with CNS KOLs, and constantly advancing technological capabilities, Perceptive Imaging supports CNS clinical trial success, driving alignment between scientific rigor and operational excellence, and having first-hand experience supporting the successful CNS drug approval process.