The role of an Imaging Core Lab is to acquire the best imaging data which supports the protocol safety, efficacy or exploratory endpoints for submission to the regulatory bodies. A significant component of this is the development of an imaging charter.
The complexity of global clinical trial designs represents operationalization challenges and, as result, a number of imaging documents and SOPs have been created to ensure the imaging lab gets the work done correctly. Here, we review the contents of an imaging charter, which clinical trial sponsors are encouraged to develop and adhere to in order to optimize the quality of imaging data obtained in clinical trials.
The Food and Drug Administration (FDA) released a series of imaging- and endpoint-related guidance documents between 2004 – 2018, and the most recently released guidance document (issued in April 2018) entitled: “Clinical Trial Imaging Endpoint Process Standards Guidance for Industry” explains that “…this guidance is to assist sponsors in optimizing the quality of imaging data obtained in clinical trials…” and “…on imaging acquisition, display, archiving, and interpretation process standards.”1-6
“There is no standard format or content recommended for a charter”2. Imaging Charters may be created as a single document or collection of individual documents tailored to the clinical trial and should include the following headings or subheadings:
Executive Summary of the Trial Design and the Role of Imaging in the Trial:
This highlights the role of imaging variables (data) collected for the analysis of endpoints and provides a summary of the image interpretation and reader design paradigms.
Standards for Imaging Acquisition:
- Details on: clinical site personnel; equipment standardization and qualification including the use of phantoms (if required);
- Clinical site training on the study protocol, imaging requirements and imaging platform used to transfer images to the core lab;
- Imaging acquisition parameters (imaging protocol);
- Imaging associated drug(s) (e.g., sedatives, pharmacologic stress agents, contrast agents, radiopharmaceuticals, etc.) used during subject imaging;
- Handling of “off protocol” non-required study images;
- Imaging risks such as exposure to contrast media or radiation dose;
- Handling of incidental findings if likely to be observed in the trial;
- Image quality control monitoring and data storage/transfer processes.
Standards for Imaging Interpretation:
This document is primarily used when images will be reviewed at a centralized core lab. However, there is value in site-based read standardization as discussed in several of our past imaging blogs. This document focuses on core lab processes such as:
- The selection of images for review (anatomic regions, image sequences, etc)
- Image display (blinding and anonymization)
- Reading queue processes
- Reader selection, replacement, and qualifications
- Reader training on the goals and unique requirements/criteria used for interpretations
- Reader paradigm and adjudication design
- Computer software and eCRFs including analysis tools; image transfers, and read systems
Charter Modifications Before Imaging:
Aligned with the principles of Good Clinical Practice, the charter should include instructions on modification processes should these be necessary to correct deficiencies or add new analyses or image assessments during the trial. In general, though, changes are not common and the FDA guidance strongly recommends that the details and appropriateness of the protocol-defined imaging endpoint in a Phase 3 trial be firmly established either in previous trials or through legacy use of a criteria.
Imaging Data Transfer Process to the Sponsor:
The charter should describe the data handling and transfer processes for the study endpoints/variables.
Archiving of Imaging and Imaging Interpretations:
Imaging endpoints that are critical to support regulatory approval are treated in the usual manner as source data collected by the clinical site and core lab. The charter should describe the process for archiving, storing and back up of imaging information.
Verification of Fidelity of Charter Documents with the Clinical Protocol and Statistical Analysis Plan:
The charter should include a summary of the review steps used to ensure the clinical study protocol imaging endpoints align with the charter and associated technical documents.
Configuring an effective imaging management solution that generates high quality endpoint data and ensures compliance with process, quality and regulatory standards starts with developing the right imaging documentation for your study. The effective development of this document involves many individuals (technical or functional groups) and requires close communication and alignment of study stakeholders. It is from this critical document foundation that all other aspects of your imaging study are derived.
- Clinical Trial Imaging Endpoint Process Standards Guidance for Industry issue date 04/26/2018
- New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products: Guidance for Industry issue date 12/31/2009
- Developing Medical Imaging Drug and Biological Products Part 1: Conducting Safety Assessments issue date 06/17/2004
- Developing Medical Imaging Drug and Biological Products Part 2: Clinical Indications issue date 06/17/2004
- Developing Medical Imaging Drug and Biological Products Part 3: Design, Analysis, and Interpretation of Clinical Studies issue date 06/17/2004