Medical imaging has been used for decades in the evaluation and development of pharmaceuticals and medical devices. This is due to imaging’s ability to provide unique data on the structure and function of biological systems.
From Early Diagnostics to Surrogate Markers
Medical imaging shares a long history with clinical research dating back to the introduction of diagnostic X-ray technology in 1895. By the late 1980s, academic imaging labs were routinely conducting clinical research studies on behalf of the pharmaceutical and medical device industries. By the early- to mid-1990s, many of these academic labs had helped spawn an emerging niche industry—the imaging service providers, comprised of Imaging Core Labs (ICLs) or Imaging Contract Research Organizations (iCROs).
Medical imaging is routinely employed in a wide range of therapeutic areas and clinical trial phases, and includes both morphological and functional imaging modalities. When measuring the effects on humans of various medical interventions, medical imaging endpoints are often predictive of clinical outcomes. Imaging endpoint data is therefore a viable surrogate for standard clinical observation. This represents not only a potential to improve or shorten patient involvement in clinical studies, but also significant savings in time and money overall.
An independent central review (ICR) of medical image data is used as a verification of imaging endpoints in clinical trials. The primary reasons for using a central review are to remove the potential for reader bias that can exist in site-based (local) reviews, and to minimize inter-reader and intra-reader variability by maintaining consistency and rigor of training and oversight. Additionally, most Phase III trials, and even some large Phase II trials, require an ICR for regulatory approval. The inclusion of a central read paradigm can be the right design to ensure optimal quality.
With the introduction of more complex mechanisms of action or more subtle pharmacological effects, some image-based studies require centralized review, because of the specific reader training, or if an expert reader is required for the specialized image interpretation.
Regulatory Oversight of Imaging Trials
Since the release of the Food and Drug Administration Modernization Act (FDAMA) of 1997, imaging data have been included in regulatory submissions at a rapidly growing rate. In March 2004, the FDA launched the Critical Path Initiative (CPI), which included imaging among the scientific and technological tools that could be used to predict the safety and efficacy of potential new drugs and medical devices. In August 2011, FDA released its draft guidance document Clinical Trial Imaging Endpoint Process Standards, which was finalized in April 2018. This document outlines the imaging processes that clinical trial sponsors should address when using imaging endpoints in a clinical trial to support the approval of a proposed new drug. This includes specific guidelines for the review, or reading, of medical images.
According to the FDA imaging guidelines, the usefulness of a central review “is determined by the role, variability, and susceptibility to bias of imaging within the trial as well as modality-specific image quality considerations and overall trial design features.”
Precision and Quality Drive Effective Decision Making
Ultimately, a central image review process can provide a more precise estimate of treatment effect, based on high-quality images, standardized reader training, and uniform review criteria on a validated platform. It’s worth noting that a central review also provides a single repository of critical data. This becomes increasingly important under new guidelines for good clinical practice, including ICH E6(R2).
As clinical trial sponsors navigate the waters of increasing regulatory oversight, they must ensure that their data is of the highest quality and that the interpretation of that data will meet the rigorous requirements for approval by regulatory agencies. The cost of reanalyzing or re-collecting imaging data due to poor quality or loss, is extreme. This is reflected not only in unforeseen expenditures, but also in lost time. These can have an immense negative impact on the valuation and long-term viability of many trial sponsors, as well as their ability to improve the lives of patients.
Getting It Right
Whether you are a large pharma company, a biotech, a CRO, or an academic institution, Keosys Medical Imaging can help you with your imaging needs. We understand that each project has its own sets of unique challenges and requirements, and we offer a range of services to provide speed, flexibility, and peace of mind. Whether you’re conducting an early-stage project or a multicenter international trial, our team of experts is here to guide you.
No matter which service package is right for your trial needs, they all provide central collection with automatic quality assurance and de-identification of the data before it’s uploaded on our Imagys imaging management platform.
Collect & Hold (Silver Tier)
This service is convenient for any company running an early phase clinical trial using internal image review. Image data is collected and centrally archived without a Quality Control check.
It’s now ready to transfer or review at a later date without delay or risk of loss. A single license to our Imagys online review platform is provided and central reads can be performed by you internally or by readers managed directly by your team.
This tier offers lower costs (all paid upfront with no hidden fees) and provides flexibility in how you use your data. It will not allow you to generate regulatory-compliant data, however, since it provides no quality control or Imaging Acquisition Guidelines.
Collect, Control, & Hold (Gold Tier)
Our Gold Tier service provides central collection and automatic QA and deidentification of the data but also includes imaging site qualification and training for image acquisition and data transfer according to the Image Acquisition Guidelines developed specifically for your study.
We provide ongoing support and communication to assure the highest quality data is acquired. A subset of images are quality controlled by one of our trained technicians to make sure sites are compliant with the Imaging Acquisition Guidelines.
Two licenses to our online Imagys review platform are provided and central reads can be performed by you internally or by readers managed directly by your team.
The cost structure for our gold tier is based on the same structure as the silver but also includes a one-time payment for the Imaging Acquisition Guidelines as well as invoicing for the training of investigator sites and imaging technicians. This tier allows you to make sure the imaging data produced by sites is homogeneous but does not allow you to fully control the quality of the images throughout the trial. Data produced using this tier could not be used for a regulatory submission.
Advanced Collect, Control, & Hold (Platinum Tier)
Our Platinum Tier service builds on the Gold Tier and offers additional QC oversight of your data acquisition as well as site coordination from our project team for the entire length of the project. This service is ideal for multi-site trials spanning global regions and/or studies with complex or multiple imaging endpoints that don’t require an initial central review but may lead to a regulatory submission.
Multi-site coordination is provided, and image data is quality controlled by our pool of highly competent technicians so it’s ready for regulatory review without further cleaning. Five licenses to our online image review platform are provided.
Our Platinum offer therefore includes the cost of our quality control services as well as study site coordination. Unlike the Silver and Gold packages, our Platinum and Full-service offers are based on a pay as you go system.
Collect, QC, Read, & Hold (Full Service)
Our Full-Service offering provides the most advanced approach to clinical trial imaging support and assures the highest quality image acquisition and central image review. This service is ideal for studies of any complexity that require a central review of data. With this approach, we provide not only the highest quality data collection and transfer, but also the highest quality review thanks to our pool of physicians specialized in different therapeutic areas, plus upfront consultation and ongoing project management and communication.
Upfront consultation is provided to help you design your imaging study to achieve your goals, maintain timelines and budgets, and meet all regulatory requirements for data integrity.
Ongoing project management, a communications plan, Image Acquisition Guidelines, reader training and monitoring, and an Image Review Charter ensure that your study glides along without a hitch.
You’ll also benefit from ongoing reading of images in real time (or by batch depending on the study design) and an unlimited number of licenses to our Imagys online image review platform.
Our Full-service package is invoiced on a monthly basis based on study activity. This offer has the same set-up as our Platinum Tier, but also includes the costs for each medical image read, which is invoiced per timepoint. Project Management fees include study coordination and site monitoring which are invoiced on a monthly basis.
Whether you need full-service support with imaging endpoint consultation, an Image Review Charter, Project Management, and Independent Centralized Review, or a simple collect and hold system, Keosys can provide you with the most advanced online imaging platform, automated quality assurance and quality control to provide you with the highest quality imaging data possible for your clinical trials.