Imaging in clinical trials has seen tremendous growth over the past two decades. And, imaging data is increasingly used to support the primary endpoint for some trials. Here, ERT’s VP of Imaging, Tim Kulbago, discusses the drivers behind these trends and how advanced technology is helping trial sponsors meet regulators’ growing interest in clinical trial imaging.
What’s driving the growing need for imaging in clinical development?
As regulators seek as much safety and efficacy evidence as possible, they’re increasingly requesting imaging endpoints. Since imaging is capable of providing data that’s highly relevant to clinical research, it’s no surprise regulators are requesting it more often. Also, the pharmaceutical industry is exploring new treatment pathways and more sophisticated medicines, which leads regulators to request additional information in order to reliably evaluate the product’s safety and efficacy.
What challenges do sponsors face when incorporating imaging into their clinical development plans?
For some trial sponsors, the addition of imaging in their clinical trials creates yet another layer of complexity, produces new regulatory challenges and raises workflow compliance concerns. For example, a given trial can have any number of images from a variety of modalities that require review by clinical expert readers (e.g., radiologists, pathologists, dermatologists, cardiologists), typically at multiple sites. The more variables present, the more opportunities exist for error(s), compliance missteps and subjective — often biased — data. To position trials for success, sponsors need to evolve their imaging strategies to overcome the issues associated with traditional approaches to imaging, including inconsistencies, image transfer issues, the likelihood of subjective assessments, as well as incomplete data and timeline delays.
How are imaging data typically collected and analyzed in clinical trials?
Traditional image collection, evaluation and management are outdated, often based on images burned to CDs and not reviewed for acceptability until the end of a trial when site issues cannot be resolved. They typically follow a “one-size-fits-all” workflow that causes compliance and data quality issues throughout a clinical trial. Additionally, lost images, missing time points and manually assessed images with arbitrary scoring generates subjective and variable data, which requires additional time for reconciliation, in turn extending clinical trial timelines and cost.
What’s the role of technology in clinical research imaging?
Technological advancements are delivering significant improvements to the collection, evaluation and submission of clinical trial imaging data. Technology-enabled imaging – specifically, image analysis software – brings myriad benefits to clinical studies, including data accuracy, consistency, adaptability and compliance. For example, image analysis software can be implemented to direct and guide a reader through the analysis of each imaging time point and can even pre-process and segment anatomical structures of interest in lock-step with the study’s imaging charter and Independent Review Manual (IRM). This minimizes protocol deviations and ensures that each reader’s unique (and unconscious) bias does not creep into the analysis process by focusing the reader on targeted endpoints whose workflows are outlined in the trial-specific IRM.
Software-guided reads are becoming an important part of trial design and the development of the trial’s IRM to help ensure all images are read uniformly and consistently, minimizing inter-/intra-reader variability and the potential for imaging-related queries.
Why should sponsors consider a more high-tech approach to imaging?
A technology-driven imaging solution empowers quantitative and objective image analysis that is more accurate and verifiable than subjective and time-consuming scoring systems. Image analysis software can adapt to each study protocol to minimize cost, time, risk, subjectivity and data variability, while instilling greater confidence in data quality. Imaging technology reduces the risk of typical human bias and delivers data that is:
- Streamlined: Combined software-based image analysis and clinical expert readings remove time, cost and variability, while strengthening data quality
- Harmonized: Protocol development, qualification and training harmonize image quality across global sites
- Definitive: Quantitative, reproducible and objective data enables definitive safety and efficacy endpoints that are achieved correctly the first time around
The bottom line is that technology-driven image analysis software gives sponsors more confidence that the safety and efficacy conclusions they’re drawing from imaging results will meet regulators’ expectations.
What is the current thinking around computer technologies becoming the primary source of image interpretation?
Although we’re often surrounded by examples of computers taking over in our daily lives, for example, IBM Watson and self-driving cars, in clinical research they’re only one part of the solution. To get optimal imaging results, sponsors also need human expertise for over-read of imaging analysis. ERT’s approach to imaging is based on a combination of best-in-class technology and a global network of qualified and trained clinical expert readers that ensure optimal imaging results and meet regulators’ expectations. We’re encouraged by the interest sponsors are taking in this more advanced approach and think it signals that they, too, are willing to move away from decades-old methods and step into the 21st century.
What does the future of imaging look like and what does that mean for clinical study imaging? How can sponsors prepare now?
Sponsors will see continued pressure from regulators to show the safety and efficacy of drugs through imaging. We’ve already seen explosive growth in imaging since the early 2000’s, and expect this to continue, albeit at a slower pace. Each clinical study with a primary, secondary and/or exploratory imaging endpoint will have many image observations and measurements to sift through. The larger the study, and the more complex the therapeutic area and indication, the more sponsors and CROs risk acquiring a potentially overwhelming number of imaging data points, which can lead to problems if the study team is not well prepared. Tech-driven imaging more conclusively demonstrates outcomes that will support research hypotheses and is acceptable in the market.
With imaging increasingly needed, trial leaders need to be ready to meet the challenge. There’s no need to inject unnecessary risk in trials, so sponsors who take steps to ensure accuracy and compliance will mitigate delays, added expense, and regulatory issues down the road. They’ll be well-positioned to keep trials moving ahead.
Chris Neppes is Product Marketing Director, Respiratory, Imaging & Site Optimization at ERT