Accurate cardiac imaging and monitoring support

ICON delivered ECG and ECHO modality imaging for a top 10 pharmaceutical company, contributing to the achievement of an important milestone in breakthrough pulmonary arterial hypertension treatment (PAH), a rare but fatal condition. ICON Medical Imaging and Cardiac Safety Solutions, (previously Biotel) began collaborating with the developer on the phase 2 study to ensure consistency and reproducibility to protect data quality and integrity within inherently variable conditions of the study. The sponsor added four more large late phase projects to the scope, including this phase 3 registrational study, which resulted in the first FDA-approved activin signalling inhibitor therapy for PAH – a novel therapeutic option for patients.

PAH is an inherently challenging and complex condition with a selectively confirmed, very sick patient population for each study. The intrinsic functional variability of imaging the heart posed one of the greatest challenges to the study and required mitigation for consistency and accuracy across this large later-stage trial. Because ECHO does not involve still imaging there is greater potential for variability between the sonographers reading the data. It was important therefore to ensure consistent training for high-quality ECHO execution and reproducible, accurate reads from 583 geographically dispersed sites to minimise the margin of variability.

The ICON team advised on study protocol and ECHO parameters to streamline operational efficiency in both the imaging and reading execution, providing continuity for the studies from phases 2 through 3. Sites were trained on the same methodology and provided with custom Image Acquisition Guidelines to facilitate consistent data collection and reads.

ICON’s industry-leading experts provided two-tier reviews where sonographers initially read ECHOs for quality control and specialist echocardiologists reviewed the measurements. All sonographers employed for this study were required to pass stringent qualifications including test images. To mitigate risks in variability between sonographers or echocardiogram technologists, senior scientists reviewed data from sites to flag abnormal trends that would trigger further training or quality controls.
 

ICON’s consultation on protocol and imaging modality parameters, consistent training across sites, adherence to methodology and strict quality controls successfully mitigated the variability in the sponsor’s PAH studies. The concise, accurate data results were reproducible, which decreased the number of patients required for subsequent studies from a statistical point of view, reducing pressures on a rare disease population and increasing regulator confidence in the clinical results. As a primary endpoint, the success of ECHO imaging directly contributed to the ultimate approval of this breakthrough PAH therapy.