Critical Challenges to the Management of Imaging in Clinical Trials
06 Apr 2023
Clinical trials enable the development and access of new drugs to patients. Imaging is considered a valuable tool which forms the basis of robust response and progression criteria to assess the drug in clinical trial participants. As highlighted by recent Food and Drug Administration guidance (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), imaging has become an integral part of the research.
Clinical trials are conducted across multiple sites. Therefore, standardisation of the imaging parameters and interpretation criteria to ensure endpoints are accurately measured is extremely important. Imaging in clinical trials can differ from the imaging at each clinical trial site. Hence, the logistics necessary for the capture and transfer of the imaging data play a vital role. Failure to comply with the imaging requirements can lead to unusable data, repeat imaging, or the removal of patients from the trial.
This requirement of standardisation brings forth the importance of the Central Reading Center (CRC), which focuses on collecting high-quality data through training, certification, and monitoring of clinical site data collection.
However, there are several key challenges to the successful execution of the clinical trial imaging faced
by the CRCs at the investigational sites:
- One of the most common challenge is unavailability of trained staff with experience in implementing the requirements of study imaging. Most clinical trials require training of the imaging guidelines. These training sessions can sometimes be lengthy to ensure in-depth understanding of the imaging requirements. Site staff who are new to imaging or a site with temporary staff availability would require frequent training sessions to familiarize themselves to capture accurate images as per the study requirement. For example, Response Evaluation Criteria in Solid Tumours (RECIST) is a commonly used assessment parameter in oncology trial. RECIST-compliant CT imaging parameters are relatively trivial to implement for sites equipped with trained staff. However, a common error in terms of failure to comply with the mandatory requirement of 5 mm CT scan slice thickness is observed at sites with staff who are new to study imaging. This circumstance becomes critical, resulting into retraining and reupload of the images which may impact or slow down the patient's recruitment and follow-up.
- The next most common challenge is the wrong patients' data being uploaded for review by the central reading center. Sites which have a high patient inflow or with a certain number of patients scheduled for follow up on the same day, can sometimes inadvertently mix the study images and upload the wrong patient's data for review. There is also a chance that the follow up visits of the same patient may get intermixed. This results into image rejections, delay in receiving and reviewing the images which ultimately impacts the study endpoints.
- The next most common challenge is the wrong patients' data being uploaded for review by the central reading center. Sites which have a high patient inflow or with a certain number of patients scheduled for follow up on the same day, can sometimes inadvertently mix the study images and upload the wrong patient's data for review. There is also a chance that the follow up visits of the same patient may get intermixed. This results into image rejections, delay in receiving and reviewing the images which ultimately impacts the study endpoints.
- An imaging clinical trial is completely based on the images received from site; hence the quality of images holds a paramount importance. The factors affecting the quality of images range from participant factors such as non-cooperation by the participant at the time of imaging to site staff that lack hands-on training required for image capture as per the study. This leads to repeat imaging which can cause inconvenience to the participant, additional delay in upload of images, difficulty in grading with an overall impact on the final evaluation and outcome.
- When issues or discrepancies arise during the review by CRC, queries are put forward to the site. However, some sites fail to remain updated on the mails received from the CRC and hence, a delay in response from the site directly affects the eligibility review and subsequent patient enrollment. Additionally, majority of the time, the queries related to missing data, demographics, acquisition para meters or patient positioning for scans are avoidable if the sites ensure a thorough review of the imaging manuals, reference guides and data forms provided by the CRC to the sites.
- The CRC receives only patient scans for review while the investigator reviews the patient's condition based on medical history, scans, and other supporting documents. Thus, the sites need to understand that there can be differences between the grader review and investigator's assessment and additional queries directed to the grader review by the site team can impact the overall time taken for patient enrollment
These challenges are critical and failure to address them can cause protocol deviations, patient withdrawal from the study and even affect the integrity of the trial
References:
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
How does Lambda Therapeutic Research Limited address the challenges:
Lambda Therapeutic Research Limited (LTR) is a leading CRO, with centers spread worldwide and having 20+ years of experience in clinical trials.
The Central Reading Center at Lambda has an experience of over 10 years with multiple studies in the field of oncology, ophthalmology, and bone specific diseases.
The CRC at LTR acknowledges the issues which can occur at the site and addresses each issue systematically in the following ways:
- It is recommended that sites should have a separate research team of experienced imaging technicians with appropriate domain knowledge.
- Sites are assessed for infrastructure and other imaging requirements prior to site selection to ensure availability of the necessary resources for the study.
- Multiple training sessions are conducted which provide a robust understanding of the imaging requirements in the study. These trainings can be remote or onsite and include a detailed knowledge of the imaging methodology, software requirements for data upload, use of study specific equipment which eventually ensures timely submission of correct data to the CRC.
- All the queries to the sites are directly notified via email and followed up telephonically to bridge the communication gap between the site and CRC.
- Regular follow-up with sites to rectify and resolve queries related to the imaging protocol for the study thus increasing the efficiency and accuracy of study related imaging.
- Investigators meetings are conducted which ensures a uniform understanding of the protocol, guidelines and the applicable regulations among the investigators which thus improves the overall execution of the clinical trial.
The CRC at LTR provides unreserved support to the site and thus covers guidance for all aspects of imaging in a clinical trial. Every project is spearheaded by industry experienced team of certified graders and imaging research associates. We also offer a full range of central review services and consultation for a wide range of therapeutic segments for its sponsors.