In WP1 (Diagnostic device development) DPGx tested both NanoString chemistries, Standard and Fusion Elements, in order to select the best one in terms of functionality, specificity and sensitivity. After several tests the Standard chemistry was chosen for the device development because Fusion Elements showed cross-reactivity, high background and lower sensitivity.
In the same WP the NanoString Standard Chemistry codeset (probes panel) has been upgraded and a commercially available human RNA has been identified as a possible positive reaction control for the device and tested in all runs.
In WP3 (Design & development of the analysis software) BM studied the regulations about software certification as a medical device, NanoString technology and output and requirements provided by DPGx. Then BM together with DPGx defined the first draft of calculation algorithms that have to “translate” the NanoString raw data into information suitable for a medical report.
Other activities performed by BM in this WP for the development of the software prototype are: database design, technology selection and definition of user interfaces and reporting.
In WP4 (External validation of the diagnostic device and the associated analysis software) GL staff was trained on NanoString pre-analytic and analytic procedure.
The WP5 (Collection of clinical samples) has been carried out by DPGx with the support of two Subcontractors: Laboratory of Biosciences, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (IRST) and Laboratory of Molecular Pathology, Azienda Ospedaliera Universitaria Pisana, Pisa (AOUP).
During the first 6 months the procedure for the submission of the clinical trial application data for an Ethics Committee opinion and the preparation of supporting documents have been performed.
The clinical study has been approved by CEIIAV and CEAVNO Ethics Committees on December 2015.
Afterwards 51 NSCLC patients have been selected: 6 from IRST, 45 from AOUP, both positive and negative for ALK/ROS1/RET rearrangements. IHC-ALK slides, FISH-ALK/ROS1/RET digital images and sets of FFPE tissue sections for RNA extraction have been collected for 12 samples, FISH-ALK digital images have been collected for most of them
In WP6 (Data mining and correlation) for the quantification of tissue features and morphology DPGx provided IHC-ALK slides and FISH-ALK/ROS1/RET digital images to the subcontractor Definiens, that was in charge of developing a software solution. So far the development of three FISH translocation analysis algorithms (ALK, ROS1 and RET) have been completed. Development of ALK-IHC analysis algorithm is work in progress.
For WP8 (Project Management) a Consortium agreement has been signed and a Steering Committee, a Technical Board and a Project Management Team have been settled.
Three general meetings took place for activities alignment, problems troubleshooting and update about the project progress.
A Project Plan for monitoring the progression of all WPs and tasks and a Quality Assurance Plan defining quality assurance & risk assessment topics have been prepared and shared among partners.
Regarding the administrative management a cost breakdown structure has been created in order to support the correlation of costs per WP and all the guidelines and documents for costs and time management have been prepared.
Communication with EU and Project officer has been implement and maintained as well.
