Role of Central Reading Centres in Ophthalmology Clinical Trials
06 Apr 2023
A Central Reading Centre (CRC) specializes in the standardized evaluation of images to determine the presence and severity of various ocular diseases such as diabetic retinopathy and age-related macular degeneration. This standardization and uniformity ensures consistency in clinical trial data. FDA has released a draft guidance titled "Clinical Trial Imaging Endpoint Process Standards" in August 2011, which describes the standards that sponsors need to ensure for the clinical trial imaging data such that it complies with trial protocol, while maintaining imaging data quality within and among clinical sites with verifiable records. (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) 2018)
Clinical trials for retinal diseases have a range of imaging modalities such as such as OCT, fluorescein angiography (FA), ultra-widefield fundus photography, among many others for evaluation of the endpoints by the central reading centers.
Image interpretation is the key function of the central reading centers, which follows a defined workflow starting from certification of imaging technicians and equipment to standardization of the imaging procedures. Every study image is monitored for quality throughout the study and the image interpretation is carried out by certified and trained graders who are masked to treatment assignment and other clinical information.
There is a fundamental difference between assessment by Ophthalmologists and CRCs. An Ophthalmologist is aware of the medical history of the patient, whereas CRCs provide standardized and objective grading of study images by trained graders who are not aware of the patient characteristics or treatment arm assignment. This unbiased assessment using standardized grading protocols and reliable image quality is a major benefit of the CRC in clinical trials.
Standardization also encompasses the equipment standards as it is crucial to ensure comparability of the imaging modalities. Retinal thickness measurements vary with the choice of OCT device. These differences are a result of segmentation algorithms used in each OCT device, and variations where the segmentation boundaries are drawn. Thus, if different types of OCT devices are used such as older time domain OCT or current spectral domain OCT or swept source OCT, then this would result in different retinal thickness among patients from various sites.
An example of standardized employment of the imaging modality was the EVEREST study which was the first multi-centre randomized controlled trial for polypoidal choroidal vasculopathy. Every site in this study utilized the Heidelberg retinal angiograph (Heidelberg Engineering, Heidelberg, Germany) instrument. This defined imaging modality enabled the assessment of two of the study diagnostic criteria - the presence of a branching vascular network and pulsation of the polyps. ---
Another aspect in the evaluation of the images involves the use of software which assist the graders in interpretation of the images. The software maintains continuity of grading with the preservation of the historical data sets and minimizes variability within studies.
With advancement of technology in clinical trials, software ensures privacy of data, import and export of images, statistical evaluation, data storage and archival, preservation of eCRF form, validation of software with new requirements, access rights to specific users, audit trail for industrial compliance and much more.
References:
Tan, Colin S, Wei Kiong Ngo, Jian Ping Chen, Nikolle W Tan, and Tock Han Lim. 2015. "EVEREST Study Report 2: Imaging and Grading Protocol, and Baseline Characteristics of a Randomised Controlled Trial of Polypoidal Choroidal Vasculopathy."
The British Journal of Ophthalmology 99 (5): 624-28. https://doi.org/10.1136/bjophthalmol-2014-305674.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). 2018. "Clinical Trial Imaging Endpoint Process Standards Guidance
for Industry." https://www.fda.gov/media/81172/download
What Lambda Therapeutic Research LimitedOffers
Lambda Therapeutic Research
is a leading CRO, with 20+ years of experience in clinical trials and centres spread out across the world.
We provide comprehensive services for interpretation and analyses of images from Optical Coherence Tomography (OCT), to Color
Fundus Photographs (CFP) and Fluorescein Angiography (FA).
Our current service support in Ophthalmic Clinical Research is mainly in the field of retina. We are exploring further research areas in Ophthalmology.
Our Central Reading Centre ensures...
Compliance with Good Clinical Practice (GCP), Good Documentation Practices and harmonization with the Global Regulatory Requirements
Defined Standard Operating Procedures (SOP) and guidelines:
- Image Acquisition guidelines for certification and actual study
- Independent Review Charter
- Site operation manuals
- User manuals for QC and Grader
Rigorous quality control by...
- Certification and Training of the study-site personnel
- Self-developed software with a secured online platform for image upload, review, and grading
- Staffed with graders who have expertise in evaluating ophthalmic images
Sophisticated functional and imaging analysis to ensure the highest quality and insight derived from clinical trials
