Physicians, pharmaceutical companies and sponsors designing and implementing clinical trials of experimental therapies for inflammatory bowel disease (IBD) face unique challenges, including the use of a video component for assessing mucosal healing and the trend toward centralization of endoscopic evaluations. Furthermore, study design in IBD trials can vary significantly with regard to reader paradigms, approaches for assessing reader variability, and adjudication processes. Imaging core labs are focused on overcoming these challenges, offering services and expertise to facilitate centralized and standardized assessments for IBD clinical trials.
Two of BioClinica's scientific experts, Harris Ahmad, MD and Hui Jing Yu, PhD, along with leaders in the GI space, have co-authored a recent report titled Central Endoscopy Reads in Inflammatory Bowel Disease Clinical Trials-The Role of the Imaging Core Lab. I recently sat down with Dr. Harris Ahmad, Director of Medical Affairs and Therapeutic Area Lead for Gastroenterology and Rheumatology at BioClinica to talk more about medical imaging in IBD clinical trials. Here's what he had to say.
What are some of the key challenges facing sponsors of IBD trials?
The most common and reliable primary endpoint used in IBD trials is mucosal healing. Historically, this has been accomplished using still images of the small and large bowel. However, the increased use of full length videos from colonoscopies and sigmoidoscopies creates technical challenges for sponsors and clinical sites including proper video acquisition, segmental annotation, and standardized transmission of large files from clinical sites.
Additionally, with a trend towards centralization of endoscopic evaluations, sponsors rely on the interpretation of endoscopic findings by both a local physician and a central reader. Without regulatory guidance for central read design in the IBD space, sponsors must devise reader paradigms and approaches to find the optimal methodology for their study. This results in a multitude of paradigms to choose from without standardization across studies.
How are Imaging Core Labs (ICLs) helping to overcome these challenges?
In the pharmaceutical industry, imaging core labs have played a critical role in the development and approval of a wide variety of new therapies. For IBD trials, ICLs are taking on the important role of managing complex video data from colonoscopies and sigmoidoscopies. They provide services and expertise for standardizing and optimizing video acquisition at clinical sites, verifying a site's ability to record and submit high quality video. ICLs also provide a solution for electronic transmission of video data to a central database. Once uploaded, video data is analyzed for quality and resolution prior to independent review by an expert central reader familiar with the imaging protocol and scoring system used in the study.
You focus on read paradigms for GI trials in your paper. Can you tell us a little more about read paradigms and why they are so important?
Read paradigms are crucial for clinical trials as they define the flow of data and the process for analyzing data throughout the course of a trial. Factors that can influence the selection of reader design include sponsor budgets and timelines, local read bias, and patient enrollment. Different paradigms are considered for eligibility studies versus efficacy studies. In general, read paradigms will differ in the number and type of readers used (i.e. local vs central readers), the use of reader variability monitoring (inter and intra- reader variability), and the methodology for adjudication (resolving differences between readers). In the paper, we provide additional detail for the most common paradigms used for eligibility and efficacy, denoting the advantages and pitfalls of using each. We hope to engage and spark collaborative discussions between the academic community, sponsors, and regulatory authorities on the best approach for standardizing IBD trials
Do you think that the use of an ICL for IBD clinical trials will continue to grow?
Absolutely. ICLs are already making their mark in the GI space, developing tools and resources for standardizing and managing video data in support of new treatments. They have the expertise to provide expert central readers helping to eliminate bias and improve enrollment efficiency for clinical trials. Their experience with regulatory agencies will also prove to be invaluable for helping to standardize reader paradigms in this area.
To read Dr. Ahmad's paper in Gastroenterology Report, click here.
For more information on imaging core lab services for IBD trials, click here.