Case Study-Year One: Clinical Performance Evaluation carried out on the Biocartis Idylla NRAS – BRAF assay to support CE IVD marking
Carrying out a Clinical Performance Evaluation is a critical step in the development of a new IVD device and applying CE-IVD marking before entering the EU / EEA market. Engaging with skilled partners can significantly reduce the cost and time of carrying out such studies. The Newcastle Molecular Pathology Node is able to provide excellent access to a wide range of real-world clinical samples and pathology expertise in sample preparation and demanding techniques such as microdissection. In collaboration with the Newcastle Device Evidence Co‑operative (DEC) and partners, the Node successfully took part in a Clinical Performance Evaluation (CPE) study being carried out by Biocartis NV as part of their requirements for CE‑IVD marking.
The Idylla™ IVD platform, is a rapid and self-contained real-time PCR molecular diagnostic system, and as part of an expansion in the range of IVD assays offered for oncology, the company has recently developed a combination NRAS – BRAF mutation test which it wishes to bring to the market.
To fulfil the requirements of the EU IVD directive 98/79/EU, before applying CE marking to an IVD device, a formal CPE study must be carried out and the necessary technical files created, documenting evidence which supports the performance claims made by the device manufacturer under the anticipated conditions of use.
The objective of the CPE study was to demonstrate the overall agreement of the Idylla™ NRAS – BRAF mutation test in comparison with fair comparator tests, in tumour samples obtained from patients with malignant metastatic colorectal cancer. The study was performed in accordance with the requirements of quality standard EN-13612 (2003), ‘Performance evaluation of in-vitro diagnostic medical devices’ and was unblended, observational and retrospective in design.
Tumour samples were obtained from the pathology departments of the Newcastle upon Tyne Hospitals NHS Foundation Trust, UK (n = 95) and Aarhus University Hospital, Denmark (n = 156).
Idylla™ units were placed in laboratories at NewGene, an industry partner of the Newcastle Node, and Aarhus Institute of Pathology and assay results produced by these systems and comparator assays (NewGene – Agena MassARRAY®, Aarhus – Roche Cobas®) evaluated. Replicate tumour samples from the Aarhus collection were also analysed by NewGene using the MassARRAY® system.
In this study, the Newcastle Pathology Node were responsible for identifying suitable samples for inclusion in the Newcastle cohort; defining pathology processes and assessing samples for parameters such as proportion of tumour cells and the extent of necrotic and mucinous material. Pathology Node staff performed sample macro-dissection where appropriate. Robust pathology processes were essential to generate a high quality sample collection that could be analysed in this study and the resulting data showed an extremely high degree of concordance between results from the Idylla™ system and the comparator test platforms. This was greater than the 97% minimum concordance level set out in the study protocol as necessary for the study to be regarded as a success, with no further requirement for additional sample analyses.
With these results, Biocartis are now able to complete the required technical documentation and self-certify the Idylla™ NRAS – BRAF assay as fulfilling the requirements of the EU IVD directive 98/79/EU. A comprehensive publication describing this study and containing a detailed analysis of the results generated is currently in preparation.