Three key questions this article answers:
- What is an Independent Reading Center (IRC) and what do they do?
- Why are IRCs important for imaging clinical trials?
- What do Sponsors gain from IRCs?
WHAT IS AN IRC AND WHAT DO THEY DO?
An IRC is a contract research business providing unbiased, independent image analyses to assist a sponsor in conducting an imaging clinical trial. IRCs work with multiple stakeholders including Sponsors, CROs, and imaging sites to support global, multi-site clinical trials.
What IRCs Do
IRCs provide expert readers who analyze medical images for use in clinical trials. Readers examine images from a wide range of diseases, then diagnose and classify diseases based on the images. Readers may also provide measurements or scores of disease progression.
IRCs train readers on specific imaging protocols to reproducibly evaluate images. Standardized training leads to more accurate disease descriptions and diagnoses and more positive clinical trial outcomes.
IRCs Provide Standardized Imaging Procedures
One of the most essential aspects of an IRC is its use of Standardized Operating Procedures (SOPs) for imaging. These procedures are followed from study startup, throughout conduct of the study, and at the end of the study.
Pre-study/startup SOPs include:
- Certification of technicians and/or instrumentation at the sites
- Procedures for reading the images
- Procedures for the quality control of each project
- Reading workflow, such as double reading with adjudication
- Configuring data collection forms (custom-built databases or others)
Study conduct SOPs include:
- Procedures for clinical sites to anonymize, label, and submit images
- Acknowledgement to the site of the receipt of images by the reading center
- A process for getting the images ready for reading (i.e., uploading, file conversion, display requirements, etc.)
- Quality evaluation of data submissions from sites to resolve anomalies and prepare data for storage and reading
- Query resolution and data corrections to resolve discrepancies/inconsistencies
- Data storage, backup, and protection
End of study SOPs include:
- Data lock and unlock
- Closeout procedures
WHY ARE IRCS IMPORTANT FOR IMAGING CLINICAL TRIALS?
IRCs play a vital role in imaging clinical trials by providing imaging protocol standardization, improved data quality, reduced bias and variability, and a regulatory approval pathway.
Imaging Protocol Standardization and Improved Data Quality
Through imaging protocol standardization using imaging charters and SOPs, IRCs empower valid comparison of outcomes across multiple time points at an individual participant level. IRCs also promote a high-level of data quality through training, certification, and monitoring of clinical site data collection. IRCs help reduce image quality issues, which are a common source of variability and missing data in clinical trials. Thus, inclusion of central reads helps ensure optimal quality.
Reduction of Bias and Variability
IRCs also help reduce bias and variability. For example, IRCs can reduce or remove potential reader bias that can exist in site-based (local) reviews. IRCs can also reduce bias through uniform image evaluations across clinical sites by evaluators who are masked to treatment assignment and other clinical information. Finally, IRCs minimize inter-reader and intra-reader variability through rigorous reader training and oversight.
Pathway for Regulatory Approval
Perhaps most importantly, IRCs provide a pathway for regulatory approval. Phase III (and some Phase II) trials require an IRC for regulatory approval. The 2018 FDA Guidance “Clinical Trial Imaging Endpoint Process Standards: Guidance for Industry” suggests that a masked, centralized image interpretation process may:
- Enhance the credibility of image assessments
- Better ensure consistency of image assessments
The FDA Guidance further states that some imaging modalities may be vulnerable to site-specific image quality problems and that centralized image assessment may minimize these problems. Centralized image interpretation also may help control image quality and provide the actual imaging-based endpoint measurements.
WHAT DO SPONSORS GAIN FROM IRCS?
Sponsors gain FDA compliance, enhanced detection of drug treatment effects, improved data quality and cost savings, and early phase trial benefits.
Compliance and Enhanced Detection of Drug Treatment Effects
2018 FDA Guidance “Clinical Trial Imaging Endpoint Process Standards: Guidance for Industry” states that imaging process standards help Sponsors ensure that imaging data are obtained in a manner that complies with a trial’s protocol. Imaging process standards also help ensure that the quality of imaging data is maintained within and among clinical sites. Standardization also ensures a verifiable record of the imaging process is created. Finally, minimizing imaging process variability may enhance ability to detect drug treatment effects.
Improved Data Quality Leads to Cost Savings
Not only does high quality data and interpretation help meet rigorous regulatory requirements, it can also provide cost savings. Sponsors may avoid the cost of reanalyzing or re-collecting imaging data due to poor quality. Re-collecting or re-imaging may lead to unforeseen expenditures and lost time, which could have a potential negative impact on the valuation and viability of trial Sponsors.
Early Phase Trial Benefits
While the need for, and benefit of, IRCs in Phase II and III trials is well understood, early phase collect and hold studies with an IRC can benefit Sponsors, too. For example, access to all study images may help support additional exploratory analyses. Sponsors may also be able to study different levels of treatment response or combinations of response, which may enhance understanding of the clinical benefits of their investigational products. When to perform centralized image review and collection depends on the therapeutic area and the risk-benefit for the sponsor. In the long term, central review may help insure the value of a development program asset.
Learn more about MERIT’s Collect & Hold services
As a contract research business, IRCs provide unbiased, independent image analyses to assist a Sponsor in conducting an imaging clinical trial. IRCs supply expert readers who analyze medical images from a wide range of diseases, then diagnose and classify diseases based on the images. One of the most crucial aspects of an IRC is its use of standardized procedures for imaging. IRCs play an important role in imaging clinical trials by providing imaging protocol standardization, improved data quality, reduced bias and variability, and a regulatory approval pathway. By employing an IRC, Sponsors gain FDA compliance, enhanced detection of drug treatment effects, improved data quality and cost savings, and early phase trial benefits.
MERIT is an innovative, global clinical trial endpoint services provider and recognized leader in medical imaging. We partner with CROs, pharmaceutical, and biotech companies to deliver reliable IRC services in clinical trials. Together our work advances and accelerates the improvement of therapeutic options for patients worldwide.
Partnerships with MERIT provide the following advantages:
- Expertise in managing and evaluating images
- Standardization of data, readers, and interpretation
- Technology platform for stakeholders to work together with data transparency and accessibility
- Collaborative approach with nimble and attentive service for Sponsors