Findings
Variability in imaging acquisition, display, and interpretation methods across different clinical sites can increase endpoint measurement errors, potentially compromising a trial’s ability to achieve its objectives.
Standard imaging procedures used in routine medical practice are often insufficient for clinical trials, which require greater standardization to reduce variability and ensure the interpretability of results.
In open-label trials, site-based image interpretation is vulnerable to bias because knowledge of a patient’s clinical status can influence assessments.
Technical factors such as equipment upgrades, software changes, and inconsistent image quality can introduce errors and undermine the consistency of imaging data collected in multicenter trials.
Lack of consistency in image reader training and performance can lead to significant variability in endpoint measurements, reducing the precision of the treatment effect estimate.

Recommendations
Sponsors should develop and implement trial-specific imaging process standards, detailed in a document called an imaging charter, that go beyond routine medical practice.
Use a centralized image interpretation process to enhance the credibility of image assessments, ensure consistency, manage reader performance, and reduce variability.
Image readers should be blinded to treatment assignments and, in most cases, to other clinical data to prevent bias in the primary endpoint assessment.
Standardize all critical imaging procedures, including equipment settings, subject preparation, image acquisition protocols, site qualification processes, and ongoing quality control monitoring.
Establish clear procedures for image data transfer, quality assessment, locking, and archiving to maintain data integrity and ensure a verifiable audit trail.

Regulatory Considerations
Sponsors are encouraged to submit the imaging charter to the FDA for review, as compliance with the charter is an important part of verifying the trial’s data integrity.
The use of investigational imaging equipment, software, or interpretation tools in a clinical trial must comply with all applicable FDA regulations, including investigational device exemption (IDE) requirements.
Imaging source data and records must be retained for a minimum of two years after a marketing application is approved or an investigation is discontinued, as specified in 21 CFR 312.
The final report submitted to the FDA for review should thoroughly document all imaging processes that took place during the trial, from acquisition and interpretation to data transfer.
The clinical protocol and consent forms must describe all imaging-related risks to subjects, such as radiation exposure, for review by institutional review boards (IRBs).