Key Takeaways:
- Early engagement with imaging vendors during protocol development can prevent costly delays and amendments
- Preclinical imaging data should inform clinical trial design, especially for ocular assessments
- Standardized image acquisition protocols are essential for data quality and consistency across sites
- For GLP-1 studies, comprehensive baseline ocular assessments are crucial given known associations with conditions like NAION
- Strategic planning for imaging requirements can mitigate staffing shortages and logistical challenges
The Growing Importance of Imaging in Clinical Trials
Imaging has become crucial for evaluating efficacy and safety in GLP-1 and neurology clinical trials. However, challenges associated with imaging are often overlooked until they affect trial timelines, costs, and outcomes.
Early identification of imaging risks can prevent costly delays and ensure data integrity throughout your study. The stakes are particularly high in therapeutic areas like GLP-1 drugs and neurology, where imaging endpoints provide critical safety and efficacy data.
Understanding Imaging Types and Requirements
Clinical trials typically utilize two main categories of imaging:
- Type One Imaging: Quantitative at the point of acquisition (examples: QCT, DEXA, OCT)
- Type Two Imaging: Qualitative images that require quantitative measurements for clinical trial endpoints (examples: X-ray, basic CT, photographs)
"The patient acquisition protocol is absolutely critical," explains Dr. Colin Miller of The Bracken Group, a medical imaging expert. "Without proper setup, positioning, or calibration, endpoints may be missed entirely."
Precision becomes paramount for meaningful longitudinal measurements. While baseline measurements require high accuracy, follow-up assessments demand high precision to ensure changes detected reflect therapeutic effects rather than imaging inconsistencies.
Preclinical Imaging Considerations
Many ocular assessment procedures in preclinical studies mirror those in human trials, but important limitations exist, particularly around subjective measures like visual acuity.
"In humans, we can say 'my vision is blurry' or 'I have double vision,' but unfortunately, these types of assessments we cannot do in preclinical trials because we deal with animals," explains Dr. Simone Iwabe, a Senior Veterinary Ophthalmologist at Altasciences.
For CNS studies, functional analyses like pupillometry (measuring pupil constriction speed and magnitude) or electroretinography (ERG) can detect potential effects on visual pathways, even when structural changes aren't visible during standard examinations.
"Sometimes you do not see any change on ophthalmic examination. However, the function can be compromised," notes Dr. Iwabe. "Functional analysis is very important to detect microscopic changes that you cannot easily detect with regular eye examination."
GLP-1 Receptor Agonists and Ocular Risks
GLP-1 receptor agonists have been associated with certain ocular events, most notably, non-arteritic anterior ischemic optic neuropathy (NAION), a rare but serious condition that is irreversible and untreatable.
"This is a rare condition... painless, develops somewhat rapidly, sadly irreversible, untreatable," explains Dr. David Nguyen, General Manager and Medical Director at Altasciences. Recent observational studies have found that once-weekly semaglutide doubles the risk of developing NAION in type 2 diabetics.
The Danish health registry conducted a five-year observational study with nearly half a million diabetic patients, confirming this association despite controlling for various external factors.
Comprehensive baseline ocular assessments are essential for study participants, especially since early-phase GLP-1 studies increasingly recruit individuals with obesity or metabolic disorders who may already have underlying vascular changes.
Operational Challenges in Clinical Trial Imaging
Several operational challenges can impact trial success:
- Limited availability of specialists: With approximately 19,000 active ophthalmologists in the US (one for every 17,000 patients) and growing demand, securing timely appointments becomes difficult.
- Query rates: Poor-quality images requiring retakes can cascade into missed windows, patient transportation issues, and timeline delays.
- Standardized protocols: Equipment like OCT can have hundreds of different settings—simply specifying "OCT image" is insufficient without detailed acquisition protocols.
- Exam form considerations: Even basic assessments like visual acuity can use different measurement standards (ETDRS vs. Snellen), complicating data aggregation and analysis.
“If you're doing a Phase 3 and have 50 US sites, each could have an individual imaging provider. How do you know there will be quality across all of them?" This question, proposed by Jessica McKenzie, Vice President of Life Sciences at 20/20 Onsite, highlights the complexity of maintaining consistency across multi-site trials.
Strategic Recommendations
Based on expert insights, consider these strategic approaches for managing imaging in your GLP-1 and neurology studies:
- Engage imaging vendors early during protocol development rather than after finalization.
- Develop detailed image acquisition guidelines that specify equipment settings, technique, and measurement standards.
- Consider site capabilities during selection. If appropriate imaging support isn't available, high-enrolling sites may need to be declined.
- Evaluate preclinical findings to determine which clinical assessments provide the most meaningful safety and efficacy data.
- Budget realistically for fair market value compensation that will incentivize specialists to participate.
"It helps the site as well," notes McKenzie. "Once you've identified the site, we're going to go through almost word by word what the protocol's saying. Something as simple as saying 'this will be evaluated by an ophthalmologist versus an optometrist' raises questions about whether you truly need an ophthalmologist or if an optometrist would suffice."
By proactively addressing imaging requirements in GLP-1 and neurology clinical trials, sponsors can reduce risk, maintain data integrity, and avoid costly delays—ultimately protecting trial timelines and participant safety.
Conclusion
A proactive, strategic approach to imaging in GLP-1 and neurology studies is imperative. Engaging imaging vendors early on and implementing standardized acquisition protocols prevents costly delays and protocol amendments and ensures the accurate capture of quantitative and qualitative data. In this context, translating preclinical insights into meaningful, consistent clinical assessments—especially comprehensive baseline ocular evaluations—is essential to mitigating risks such as NAION and ensuring robust trial outcomes.
Addressing operational challenges—from specialist availability to equipment calibration—fortifies data integrity across multiple study sites. As imaging continues to play a critical role in evaluating safety and efficacy, these best practices transform it from a routine technical task into a strategic asset that drives better trial performance and ultimately enhances patient safety and trial success.
Planning a trial with imaging components?
Book a call with 20/20 Onsite to ensure expert support, standardized protocols, and risk mitigation from the start. Let our experts help you overcome imaging challenges and safeguard your data integrity—book your call today.
This article is based on a 20/20 Onsite webinar, “Critical Imaging Risks in GLP-1 and Neurology Studies.” Presenters included Jessica McKenzie (Vice President, Life Sciences, 20/20 Onsite), Dr. David Nguyen, MD, MBA (General Manager and Medical Director, Altasciences), Dr. Simone Iwabe, DVM, PhD, DACVO (Senior Veterinary Ophthalmologist, Altasciences), and Dr. Colin Miller (Founder, The Bracken Group).