Starting a trial can be very challenging. There are many actors involved and many questions to consider. When it comes to imaging, key questions can be narrowed down to three. In this blog, we will give guidance to help sponsors and CROs answer each one.
Local read or central read?
During a trial, when imaging is acquired, the question to ask yourself is should images be read locally at the site or centrally by readers blinded to clinical information and not otherwise involved in the trial.
Local reads are carried out at sites where the physician has access to all clinical information on the subject, including past imaging and biological reports. Different readers may read different time points, depending on the radiologist working on the day. This can cause variability in the reads. Therefore, having only local reads in a trial is primarily recommended for small, early phase trials to obtain preliminary efficacy results.
Central reads, however, are carried out in a controlled environment by experienced readers specifically trained on the study and read criteria. During the reads, central readers follow rigorous methodology defined in the Imaging Review Charter, and their performance is regularly monitored. Reports are thus more consistent, measurements more accurate, and results more robust. Centralized image interpretation is often critical, especially for open-label, phase III trials where imaging is a primary endpoint.
Costs should be taken into account when making this choice. A cost-effective solution is to collect and hold images read locally and, depending on local findings, trigger a retrospective central read to confirm results.
Single read or double read?
In a single read design, only one radiologist will interpret all the images for a given patient. These designs are cost effective solutions when imaging endpoints are secondary or exploratory endpoints in phase I or II trials. Indeed, even if the study is an early phase trial, imaging can thus still be centrally assessed to obtain robust results while keeping cost down.
In a double read or 2+1 read design, two primary readers will evaluate each imaging time point. Discordance on the main point of assessment is adjudicated by a third reader, who selects the evaluation of one of the two primary readers he or she agrees with the most. 2+1 designs are required as per FDA recommendations when results of image measurements are essential for the assessment of efficacy endpoints, particularly in large phase II and phase III trials. With this, design errors, bias, and, therefore, variability in results are limited. (FDA, Clinical Trial Imaging Endpoint Process Standards Guidance for Industry, April 2018.)
On-going reads or batch reads?
Images can be centrally read in an on-going mode in a short turnaround time after they are acquired. On-going modes are recommended when central read results have an impact on subject management, such as confirmation of progression. However, with on-going reads, intra-reader variability tends to increase, as central readers would read a time point every 2 or 3 months.
Consequently, batch reading is recommended whenever possible as compared to ongoing reads because it reduces intra-reader variability. Batches ideally consist of all completed visits for a given subject. The goal should be for the reader to assess all the time points for a given patient in one sitting.
More questions? We’re here for you
Whenever you have any questions about medical imaging in clinical trials, you can turn to us at Keosys with confidence. For more information any time, reach out to our sales team at firstname.lastname@example.org.