Development of a strategy to obtain CE marking for MarginGuide

Abstract

The most frequent type of head and neck cancer is oral cavity squamous cell carcinoma (OCSCC). Surgery is the mainstay of treatment and aims for complete resection of the tumor with adequate margins, while sparing healthy tissue as much as possible. Adequate margins lead to higher survival and a marked reduction in local recurrence in OCSCC patients. However, recent studies have shown that adequate resection margins are often only achieved in the minority (15-26%) of the oral cavity cancer cases. Achieving adequate margins is difficult due to the complex anatomy and that surgeons solely rely on visual inspection, palpation and preoperative imaging.

Therefore, SurGuide B.V., Erasmus MC, RiverD International B.V. and art photonics GmbH joined forces to develop MarginGuide: an objective, fast, easy to use, intraoperative tool based on Raman spectroscopy for intraoperative assessment resection margins (IOARM) in soft tissue OCSCC specimens. The team is currently taking steps to further develop MarginGuide into a commercially available product by obtaining CE-marking. The goal of this thesis is to develop and partially carry out a strategy to obtain CE-marking for MarginGuide.

A strategy that will demonstrate MarginGuide’s compliance to the General Safety and Performance requirements from the In Vitro Diagnostic Medical Device Regulation (IVDR) was developed. The strategy includes 1) a review of literature, investigating the performance of the current standard of care for IOARM in OCSCC surgery and diagnostic alternatives (predicate devices), 2) a risk analysis, and 3) the design of studies to evaluate MarginGuide’s performance.

The literature review showed that 1) the most frequently used method for IOARM in OCSCC, i.e. frozen section, is prone to sampling errors since only a fraction of the resection surface can be assessed and 2) there are two marketed devices that use spectroscopy for IOARM in breast cancer surgery, but they did not meet the criteria of a predicate device. This indicates the need to generate new safety and performance data with MarginGuide.

The risk analysis was performed to identify the risks associated with MarginGuide for patients, operators and bystanders. All identified risks were mitigated by control measures, of which the new control measures were added to the requirements of MarginGuide.

To evaluate MarginGuide’s performance, the following studies were designed: 1) a pilot study to investigate the accuracy of MarginGuide in measuring resection margins in OCSCC specimens at specific measurement locations with a precision better than 1 mm, 2) a usability study to evaluate a designed measurement protocol for IOARM, and 3) an observational study to demonstrate the non-inferiority of MarginGuide to IOARM as performed in Erasmus MC in predicting margin status.

A performance evaluation plan containing the performance of the current methods for IOARM, the risk analysis and the designed studies (including a post-market follow up plan) should be forwarded to the Notified Body (NB). The studies will be carried out after the NB gave permission. The results should be reported in a performance evaluation report, that will be assessed by a NB to determine whether MarginGuide receives CE-marking.