(870 days)
The everlinQ® endoAVF System is indicated for the creation of an arteriovenous fistula (AVF) using the ulnar artery and ulnar vein in patients with minimum artery and yein diameters of 2.0 mm and less than 2.0 mm separation between the artery and vein at the fistula creation site who have chronic kidney disease and need hemodialysis.
The everlinQ® endoAVF System (everlinQ®) consists of two single-use disposable magnetic catheters: a venous catheter and an arterial catheter, both of which are 6 Fr in diameter. The venous catheter contains an electrode for delivery of radiofrequency (RF) energy while the arterial catheter contains a ceramic backstop that serves as a mechanical stop for the electrode. The everlinQ® is used with a commercially available electrosurgical unit (ESU) and electrosurgical pencil.
The EverlinQ® endoAVF system is a percutaneous catheter system indicated for the creation of an arteriovenous fistula (AVF) in the arm of patients with chronic kidney disease who need hemodialysis. The device's performance was evaluated through a pivotal study (NEAT Study) and a supportive Global Analysis, encompassing data from multiple clinical studies and commercial use.
Acceptance Criteria and Reported Device Performance
The primary effectiveness endpoint for the device was the percentage of patients with fistula maturation/usability at 3 months post-procedure. This was defined as an endoAVF that is free of stenosis or thrombosis, with brachial artery flow of at least 500 ml/min and at least 4 mm vein diameter (as measured by duplex ultrasound) OR the patient was dialyzed using 2 needles. The performance goal for this endpoint was set at 57.5%, derived from historical surgical AVF failure rates.
The primary safety endpoint was the percentage of patients who experienced one or more serious study device-related adverse events during the first 3 months following AVF creation, as adjudicated by an independent Clinical Events Committee (CEC). There was no formal hypothesis test associated with this safety endpoint.
Here's a table summarizing the acceptance criteria and reported device performance from the NEAT Study:
| Acceptance Criteria Category | Specific Metric | Acceptance Criterion (Hypothesis/Goal) | Reported Device Performance (NEAT Study) |
|---|---|---|---|
| Effectiveness | Primary effectiveness endpoint: Fistula maturation/usability at 3 months post-procedure | Lower bound of 90% CI for proportion of patients with fistula maturation/usability > 57.5% | 91.2% (52/57 subjects met the criteria) |
| (82.4%, 96.5%) - Exact 90% Confidence Interval. Hypothesis Rejected (Performance Goal Met) | |||
| Safety | Primary safety endpoint: Percentage of patients with one or more serious device-related adverse events at 3 months post-procedure | Not a formal hypothesis test; evaluated for acceptable risk profile. | 1.67% (1/60 subjects experienced a serious device-related event) |
| (0.04% - 8.94%) - Two-sided 95% exact binomial confidence interval. |
Study Details Proving Device Meets Acceptance Criteria
The primary study used to demonstrate the device meets acceptance criteria was the Novel Endovascular Access Trial (NEAT Study), supplemented by a Global Analysis that pooled data from NEAT, FLEX, EU PMCF, and EASE studies, as well as commercial use data (COMM).
2. Sample Size and Data Provenance
- Test Set (Clinical Studies):
- NEAT Study (Pivotal): 60 "study cohort" subjects and 20 "roll-in" subjects. The primary effectiveness and safety analyses were performed on the 60 study cohort subjects.
- Global Analysis (Supportive):
- Pooled Safety Analysis Population: 125 subjects (from NEAT (N=60), FLEX (N=33), EU-PMCF (N=32)).
- Pooled Effectiveness Analysis Population: 157 subjects (from NEAT (N=60), FLEX (N=33), EU-PMCF (N=32), EASE (N=32)).
- COMM (Commercial data set): 79 subjects (not included in pooled safety/effectiveness due to data unavailability).
- Data Provenance: The clinical studies were conducted in multiple countries:
- NEAT: Canada, Australia, and New Zealand.
- FLEX: Paraguay.
- EU PMCF: Germany, England.
- EASE: Paraguay.
- COMM: England, Germany, Netherlands, Switzerland.
- Retrospective/Prospective: All mentioned clinical studies (FLEX, NEAT, EU PMCF, EASE) were prospective, single-arm, multi-center studies. The commercial use data (COMM) was collected retrospectively from treating physicians.
3. Number of Experts and Qualifications for Ground Truth (Clinical Test Sets)
- Clinical Events Committee (CEC): An independent CEC adjudicated all safety events (Serious Adverse Events and Significant Events).
- Number of Experts: The CEC consisted of three independent physicians.
- Qualifications of Experts: The physicians comprising the CEC had expertise in vascular surgery, interventional nephrology, and/or interventional radiology. Specific years of experience are not mentioned.
4. Adjudication Method for the Test Set
- CEC Adjudication: The document states that "All procedural safety data and relevant post-procedure events were adjudicated by an independent CEC." The CEC Charter describes the event definitions and the adjudication process. It also mentions that "Each event was classified with respect to: 1. Relationship to the study device, 2. Relationship to the procedure, 3. Relationship to coil embolization, if used, 4. Relationship to a brachial artery closure device, if used, 5. Whether the event was an Unanticipated Adverse Device Effect, 6. Whether the event met the definition of a Significant Event."
- The exact voting mechanism (e.g., 2+1, 3+1) is not explicitly stated beyond stating it was an "independent CEC." However, given the three-expert composition, it is highly likely that a consensus or majority vote mechanism was used.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was performed. This device is a medical device for creating a fistula, not an AI/imaging diagnostic tool. Therefore, a comparative effectiveness study evaluating human readers' improvement with vs. without AI assistance is not applicable to this submission.
6. Standalone Performance (Algorithm Only)
- Not Applicable. The EverlinQ® system is a physical medical device, not an algorithm or software. The document explicitly states: "The everlinQ® endoAVF System does not contain software." Therefore, standalone algorithm performance was not relevant or assessed.
7. Type of Ground Truth Used (Clinical Test Sets)
The "ground truth" for the clinical effectiveness and safety endpoints was primarily based on:
- Clinical Assessments and Measurements:
- Duplex Ultrasound: Used for measuring brachial artery flow (ml/min) and vein diameter (mm) for the primary effectiveness endpoint.
- Direct Observation/Confirmation: Fistulography or duplex ultrasound verification confirmed successful endoAVF creation for procedural success.
- Clinical Usability: Patient was dialyzed using 2 needles (part of the primary effectiveness endpoint and functional cannulation assessments).
- Adjudicated Events: Safety events (SAEs, significant events) were adjudicated by the independent CEC based on medical records and definitions.
- Outcome Data: Patency rates (primary, assisted primary, secondary, functional) and CVC exposure were tracked based on clinical outcomes.
8. Sample Size for the Training Set
- Not Applicable/Not Explicitly Defined in this Context. The device is a physical medical device, not an AI/ML model that undergoes "training" on a "training set" in the computational sense. The "training" referred to in the document relates to the training of physicians in the proper use of the device, which occurred after initial study completion and was evaluated in a smaller, subsequent cohort.
9. How Ground Truth for Training Set was Established
- Not Applicable. As noted above, there is no "training set" in the AI/ML sense to establish ground truth for. The "training" in the document refers to physician training on device usage. The impact of this physician training was observed in a small cohort, demonstrating a numerical reduction in SAEs related to brachial artery access. This outcome acted as an observed result rather than a "ground truth" derived for a training dataset.
§ 870.1252 Percutaneous catheter for creation of an arteriovenous fistula for hemodialysis access.
(a)
Identification. This device is a single use percutaneous catheter system that creates an arteriovenous fistula in the arm of patients with chronic kidney disease who need hemodialysis.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must evaluate:
(i) The ability to safely deliver, deploy, and remove the device;
(ii) The ability of the device to create an arteriovenous fistula;
(iii) The ability of the arteriovenous fistula to attain a blood flow rate and diameter suitable for hemodialysis;
(iv) The ability of the fistula to be used for vascular access for hemodialysis;
(v) The patency of the fistula; and
(vi) The rates and types of all adverse events.
(2) Animal testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be assessed:
(i) Delivery, deployment, and retrieval of the device;
(ii) Compatibility with other devices labeled for use with the device;
(iii) Patency of the fistula;
(iv) Characterization of blood flow at the time of the fistula creation procedure and at chronic followup; and
(v) Gross pathology and histopathology assessing vascular injury and downstream embolization.
(3) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Simulated-use testing in a clinically relevant bench anatomic model to assess the delivery, deployment, activation, and retrieval of the device;
(ii) Tensile strengths of joints and components;
(iii) Accurate positioning and alignment of the device to achieve fistula creation; and
(iv) Characterization and verification of all dimensions.
(4) Electrical performance, electrical safety, and electromagnetic compatibility (EMC) testing must be performed for devices with electrical components.
(5) Software verification, validation, and hazard analysis must be performed for devices that use software.
(6) All patient-contacting components of the device must be demonstrated to be biocompatible.
(7) Performance data must demonstrate the sterility of the device components intended to be provided sterile.
(8) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
(9) Labeling for the device must include:
(i) Instructions for use;
(ii) Identification of system components and compatible devices;
(iii) Expertise needed for the safe use of the device;
(iv) A detailed summary of the clinical testing conducted and the patient population studied; and
(v) A shelf life and storage conditions.