The evolution of diagnostic imaging technologies across medicine has been rapid, and a number of companies seeking approval for novel drugs and devices have been using and want to use imaging data as study endpoints in clinical trials. To assist these companies, the U.S. Food and Drug Administration (FDA) recently released a new draft guidance on the use of images in clinical trials. The new draft document, “Clinical Trial imaging endpoint process standards: Guidance for industry,” if enacted as written, will have important implications for the conduct of ophthalmic clinical trials.
Designed to provide a clear path for clinical trial sponsors who want to use images as an endpoint in drug and device clinical trials, the guidance focuses on creating standards for image acquisition, display, archiving, and interpretation, all of which the FDA considers key elements when imaging is used in determining whether a drug or device has met its primary endpoint.
Imaging process standards aim to help trial sponsors ensure that images are obtained in a uniform manner that complies with a trial’s protocol and that allows fair comparison with images obtained with different devices by different people and at different centers; the guidance also calls for a verifiable audit trail to document the accuracy and reliability of the imaging process. Uniformity in image gathering, transmission, and interpretation is a critical aspect of ensuring a clinical trial’s ability to establish treatment effects and detect potential safety concerns.
Published in March 2015, the FDA draft guidance would revise the Standards for Clinical Trial Imaging Endpoints issued in August 2011. A number of key points have been clarified, including the need, in some cases, for an “imaging charter” that would detail trial-specific imaging process standards that would have to be in place prior to patient enrollment.
Trial-specific standards are particularly important in specialties like ophthalmology, where there are few specialty-wide standards for imaging.
One important aspect of this is that the draft guidance would require that any software used in image interpretation be FDA-approved or cleared, or undergo the arduous investigational device exemption (IDE) process. “If interpretation tools are to be used,” the guidance states, “the [imaging] charter should specify the use of FDA-approved computer-assisted interpretation tools. Alternatively, an unapproved (investigational) tool justified for use with a given imaging modality can be used in some situations if it is compliant with all applicable FDA regulations, including the investigational device exemption requirement” (p. 26, ll. 1048-52).
What this means is that sponsors of trials with imaging endpoints would have three options for compliance: use software already approved or cleared by the FDA-for ophthalmic image management and interpretation (currently, the only such software is EXCELSIOR™ by EyeKor, LLC); develop their own software and ensure that it meets the standards set in the IDE process; or use a single manufacturer’s already approved software, which may have limited capability to analyze data across multiple technology platforms—and ophthalmic trials regularly use data from multiple platforms.
As a draft guidance, the document will evolve, and the FDA must still decide whether the proposal will be adopted in whole, in part, as amended, or not at all. But, for now, sponsors are strongly encouraged by the FDA to follow the guidance as closely as possible to make sure that their clinical trials don’t hit regulatory snags down the road.