Validation of a Software and the Follow-up of Anteropoterior Migration of Stent

Control and quality assurance will be applied in the investigation site. The monitor mandated by the sponsor Nurea will ensure the follow-up and the proper completion of the study, the collection of data in writing, their documentation, recording and report, in accordance with the procedures in place and in accordance with good clinical practice as well as the laws and regulations in force.

Quality control visits realised at regular intervals will be realised by the monitor. During those visits, the following elements could be demanded:

• Informed consent forms, information note
• Respect of the plan of the study and the procedures defined in it
• Quality of the data collected in the Case Report Form (CRF): accuracy, missing data, consistency of data with the "source" documents (medical file, appointment book, originals of laboratory results).
• Management of any products
• Security data All contacts made will give rise to a specific written report

Three type of visits (quality control) will be realised:

• The initiation visit (realised in person) will concern every person potentially involved in the investigation. This visit will be about presenting the plan, redefine inclusion objectives, recall everyone's responsibility and the regulation, as well as answering question.
• The monitoring visits will be realised by the monitor after the first inclusion to ensure the respect of the plan and the regulation, as well as the quality of the collected data. Those visits will be realised every 2weeks, but the frequency can vary regarding the complexity of the study, of the number and the pace of inclusions. Therefore, there will be at least one visit per month.
• The close-out visit will be realised after the last data have been collected. The purpose of this visit is to verify the quality of the collected data, to update the documents before archiving.

In addition to these on-site travels, a regular monitoring over the phone will be realised in order to best support the participating physicians throughout the study.

These quality controls are supplemented by regular follow-up audits in order to evaluate the quality of collected data and to crop the study. An audit may be conducted at any time by persons appointed by the sponsor and independent of the persons conducting the research. Its purpose is to verify the participants' safety and respect for their rights, compliance with applicable regulations and the reliability of data.

An inspection can also be carried out by a competent authority (ANSM for France or EMA in the context of a European study, for example).

The audit, as well as the inspection, can be applied at all stages of the research, from the development of the protocol to the publication of the results and the classification of the data used or produced as part of the research.

Data management Access to data Only participating physicians and the monitor (or clinical research staff) will have access to source files during the monitoring visits.

During quality control visits, the principal investigator must make the following documents available:

• informed consent,
• briefing notes,
• observation notebooks,
• source documents (medical records, appointment books, etc.) In accordance with the law in force, patients have a right of access to their medical file. According to the law of January 2002, patients will be told where they can inquire about the results of the study.

Guidelines for collecting data The term "Case Report Form (CRF)" designates any document whatever its support (for example paper, optical, magnetic or electronic) intended to collect in writing all the information required by the protocol concerning each person who is suitable for research and to be sent to the sponsor.

All the information required by the protocol must be recorded in case report forms and an explanation must be provided for any missing data. The data will have to be collected as and when they are obtained and transcribed in these notebooks in a clear and legible way.

It is the responsibility of the investigator to complete the CRF, but he may delegate this task to the clinical trial technicians or to the research nurse, provided that he has previously completed a task delegation form.

Data collection will be done using e-CRF that will include patient characteristics and study data. The patient will be identified by an alphanumeric code and the data concerning him/her will be anonymized in the form. The code will be reported on all pages of the observation book.

Modification of e-CRF data Corrections of errors which have occurred in an e-CRF will be carried out via the correction module thereof, and must be dated, initialed, and justified.

The copies of the observation notebooks will be kept for at least 15 years on the investigation site while the original copy, once the quality control has been carried out, will be archived by the sponsor for the same duration.

Standard operating procedures Investigators will determine whether patients meet the inclusion criteria, and whether the use of one or the other device will bring them beneficial results.

Screening / pre-selection The selection of the patients is realised by the principal investigator. A first screening of the patient that could be included in the study is realised.

To be pre-included, those patients shall:

1. respect the selection criteria (inclusion and exclusion criteria),
2. have given their consent form by non-opposition
3. Have been treated and /or followed by the hospital

The discrimination of the group of patients is carried out according to the list above.

Reception of the consent form / inclusion The consent form is obtained by non-opposition. The information note and consent form are sent to the pre-selected patient. After one month without any manifestation (refusal) from the patient, the consent is considered as acquired.

The inclusion is validated when all data (cited above) are registered in the e-CRF.

When the consent of the patient has been received, the following data are registered in the e-CRF:

• Demographic data: age, gender
• Scan references: scan manufacturer, contrasted or not, pre- or post-operation scan, scan date
• Investigation data: Patient number, date of signature of the consent
• Images data: Pre-operation scan, post-operation scan The inclusion is validated when all data (cited above) are registered in the e-CRF.

Sample size assessment

The number of patients needed is calculated to answer the main objective of this study which is the validation of the de vice PRAEVAorta® 2. The study realised on the first version of the medical device PRAEVAorta® has shown a proportion of 93% of patient with measures calculated by the software in adequation with the measures realised following the standard method of analysis (ratio ≥ 90%). Because the new version of the software PRAEVAorta® 2 has been improved, we expect to observe the same proportion.

Patient number calculation:

Hypotheses are the following:

H0: The proportion of patients with an absolute mean discrepancy > 5mm is 90% H1: The proportion of patient with an absolute mean discrepancy ≤ 5mm is strictly over 90% For this statistical analysis, variables are quantitative: aorta measurements. We consider over here the proportion of patients per sub-group who have as less or greater than 90%.

Comparison of two proportions: a theoretical proportion with an observed proportion The theoretical proportion ϕ0 is 90%

n=([1,96(φ0(1-φ0))^0,5 +u2β(φ(1-φ))^0,5]^2)/([φ0-φ]^2)=32

For security reasons and to anticipate any problem we choose to include approximately 25% more subjects. Therefore, the total of patient is 40. We add 15 additional patients to meet the ancillary objective of evaluating anteroposterior migration of stents. The total is then 65 patients.

Patients will be devided in 4 groups related to the type of scan analysed

Images' analysis Pseudonymised pre-operation and post-operation thin-sliced CT images in DICOM format will be analysed.

This study is design in two parts:

Part 1: Validation of the software PRAEVAorta® 2 on 40 patients (principal objective).

The automatic measurements are compared to the physician measurements.

Procedure to follow:

Step 1. Inclusion and exclusion criteria validation Step 2. Demographic data and scanner references collection Step 3. CT scans (in DICOM format) collection Step 4. First Randomisation of the subjects' order Step 5. Determination of the measures by the physician with the standard method Step 6. Second randomisation of the subjects' order Step 7. Software analysis of the images with PRAEVAorta® Suite and Physician trust opinion In step 7, physicians will have to indicate if, based on the report generated by PRAEVAorta® 2, they trust the software measures or they do not, in order to validate clinical safety.

All data will be written in the e-CRF. The comparison of data will be done during the statistical analysis. The occurrence of device deficiencies will also be notified in the e-CRF.

A Mid-term report will be written by the end of part 1.

Part 2: Post-op follow-up of antero-posterior migration of stents and evaluation of the risk of endoleaks (secondary objective) The antero-posterior migration of stents will be analysed thanks to the software analysis.

This part is realised on post-op CT scan of 50 patients who have undergone a EVAR surgery. The 50 patients are composed of the 25 patients with an AAA, included in part 1 with 25 more in order to have more significant results.

Step 1. Inclusion and exclusion criteria validation for the 25 more patients Step 2. Demographic data and scanner references collection Step 3. CT scans (in DICOM format) collection Step 4. Software analysis of the images with PRAEVAorta® Suite All data will be written in the eCRF. The comparison of data will be done during the statistical analysis. The occurrence of device deficiencies will also be notified in the eCRF.

The final report will be written when both part of the study are realised.

Statistics:

Aggregated data analysed as treated and per subgroup. Descriptive analysis

• Pearson's coefficient correlation
• Absolute mean discrepancy per measurements
• Global mean and standard deviation per measurement endpoint
• Ratio for a measure
• Maximum aortic diameter ratio
• Computational analysis time The duration of the semi-automatic segmentation manually corrected by the 2 surgeons was reported and compared to the fully automatic method.
• Detectable and non-detectable error rate for safety evaluation
• Calculation of false positive, false negative, sensibility, specificity, positive predictive values, negative predictive values and likelihood ratio (LR+ and LR-). Inferential analysis Objective: comparing an observed proportion p1 with a theoretical proportion p0 p1: proportion of adequate data p0: theoretical proportion: 90% A one-sided right test will be realised to evaluate the comparison

Evaluation criteria:

Principal criteria:

• 90% of the patients shaw 90% of adequacy.

Secondary criteria:

Evaluation of the measurements and the segmentations:

• The mean discrepancy shall be ≤ 5mm
• Pearson correlation shall be ≥ 90%

Evaluation of risks:

• Unanticipated risks should not be critical Evaluation of the security
• The detectable error rate shall be ≥ 95%
• The non-detectable error rate shall be ≤ 5% Evaluation of PRAEVAorta® Web
• No critical bug No critical unanticipated risks