In April 2018, the FDA issued an industry guidance for Clinical Trial Imaging Endpoint Process Standards. While the guidance was intended to clarify process standards for sponsors collecting imaging data as part of their clinical trials, it also brought up a new question: what type of imaging standard is right for my trial?
To make the correct decision, sponsors need to explore the two types of imaging process standards and determine when the use of each is appropriate.
Standard of Care/Medical Practice Standards
Sponsors can use existing medical practice standards in their clinical protocols when they anticipate a limited amount of variability in the imaging process, including acquisition, display, interpretation, and archiving. If the measure or outcome of an imaging endpoint does not significantly vary across clinical sites and is readily apparent on an image, then medical practice imaging process standards are likely acceptable for that trial.
If a sponsor intends to use medical imaging processes in their standards, they should state so in their clinical protocol.
If a trial’s image endpoint quantification process is complex or highly variable, it’s more likely that medical practice standards will not apply. In those cases, sponsors need to consider trial-specific process standards.
Trial-Specific Imaging Process Standards
The FDA guidance indicates that the regulatory body believes that trial-specific imaging process standards should be employed when primary or secondary endpoints are based on imaging data. Sponsors should look into developing and implementing these standards when considering the potential factors that can introduce variability and inaccuracy in the endpoint.
According to the FDA, factors that should cause a sponsor to develop trial-specific imaging process standards include:
- Availability of imaging modality and performance variation across trial sites
- Qualifications and training of imaging technologists
- Phantom requirements and machine calibrations
- Image quality control
- Image display
- Image interpretation
- Image data archivation
If a clinical study requires central review – a rigorous, standardized process of evaluation with an audit trail – then trial-specific imaging process standards are likely required.
Choosing an Imaging Standard – Why It Matters
According to the FDA, imaging process standards help sponsors ensure:
- Imaging data is acquired in compliance with a trial’s protocol
- Imaging data quality is maintained within and among clinical sites
- A verifiable record of the imaging process is created
It’s important that sponsors communicate with the FDA to discuss the appropriateness of their imaging protocols for achieving their desired endpoint. Choosing the right imaging process standards makes it easier for a study to accurately detect a drug’s impact or effect on a patient, whether positive or negative.
If following discussions with the FDA, a sponsor chooses to develop trial-specific standards, they can describe those standards in the body of their trial protocol, assuming the standards are not complex. However, if the trial-specific standards are expansive, sponsors should create a separate imaging charter to describe their plans.
Overall, standardizing processes reduces variability and ensures interpretability of imaging results, two factors essential to the success of a clinical trial.
Tim Kulbago is Vice President, Imaging at ERT and Robert Ford, MD is the Principal and Founder of Clinical Trials Imaging Consulting, LLC.