February 23, 2021

Managing a Breakthrough: Navigating the Operational Challenges of Breakthrough Trial Imaging

Here we review some of the operational challenges that can be expected during the FDA’s accelerated review process and present a case study of how the need for medical imaging escalated, practically overnight, when Breakthrough Therapy designation was granted for a novel oncology compound.

Study oversight takes on new meaning when Breakthrough Therapy designation is granted – especially in clinical development programs that require medical imaging. This occurs throughout three key phases:

  • Imaging Charter: Created quickly at the very outset of the study. The imaging charter defines the logic and basis for the independent analysis methodology, and the duties and responsibilities of the individuals conducting the analysis.
  • Patient Recruitment: Imaging can be used to enrich and speed patient recruitment, ensuring that sites only enroll patients that are appropriate for the study. For example, determining if a tumor is measurable on CT scan.
  • Image Management: Images are expeditiously collected, quality-control checked, and provided to expert independent readers who will evaluate the images based on the analysis criteria defined in the Charter.

“An experienced imaging provider can be valuable in breakthrough therapy trials, from consulting on imaging charters / modalities to suggesting optimal sites, readers, and investigators”

– Elizabeth Dalton, Calyx

Pivoting Quickly: A Breakthrough Trial Imaging Case Study

It was no surprise to Calyx’s Medical Imaging team when this sponsor received Breakthrough Therapy designation on its novel oncology compound. Even non-scientific staff noticed tumors disappearing from CTs and MRIs, indicating this compound could change cancer treatment significantly.

The sponsor initially didn’t know if they needed a comprehensive imaging solution so our imaging experts proposed a simple study design and provided data that was used for preclinical evidence. When the sponsor achieved the coveted Breakthrough Therapy designation our team immediately pivoted this simple phase 1 trial to the design of an advanced phase 3 trial (Figure 1).

In less than three months, Calyx’s Medical Imaging team:

  • Wrote a charter
  • Coded and released an application with three criteria (RECIST 1.1, iRECIST, and volumes)
  • Selected and onboarded 10 radiologists and clinical oncologists
  • Began supporting the enrollment of over 1200 patients
  • Supported multiple rolling reviews

Calyx’s scalable infrastructure enabled us to pivot quickly in order to meet the trial’s accelerated timelines. The sponsor was awarded Breakthrough Therapy approval, delivering a novel cancer treatment to patients whose lives depended on it.


Having supported so many accelerated approvals, Calyx has translated that experience into proven methods to support our customers facing the specific challenges of Breakthrough Therapy trials. Part of our approach is to truly partner in support of the sponsor, from providing consulting on imaging charters and advising on optimal modalities to suggesting experienced and high-quality sites, readers, and principal investigators.

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