(90 days)
Immunoassay for the in vitro quantitative determination of neutrophil gelatinase-associated lipocalin (NGAL) in human urine.
Determination of NGAL is intended to be used in conjunction with clinical evaluation in pediatric patients (≥ 3 months to
The ProNephro AKI™ (NGAL) Reagent Kit contains Reaction Buffer Reagent (R1) and Immunoparticle Suspension Reagent (R2). The R1 reagent is a ready-to-use tris-buffer solution containing murine protein and preservative. The R2 reagent is a ready-to-use suspension of polystyrene microparticles coated with mouse monoclonal antibodies to NGAL that also contains preservative. The ProNephro AKI Reagent Kit provides enough reagents for 100 tests on the Roche cobas c 501 clinical chemistry analyzer. The finished kit will also include a labeled Roche cassette and two funnels for transferring the reagent into the Roche cassette.
The reagents must be transferred to a Roche cassette prior to the cobas c 501. This is done by pouring the R1 reagent into Position B of the cassette and R2 reagent into Position C. The operator will load the cassette onto the instrument and run the ProNephro AKI™ (NGAL) test per the instructions for use.
The ProNephro AKI® (NGAL) Calibrator Kit consists of five (5) individual ready-to-use calibrator solutions (1 mL each) comprised of different concentrations (50-3000 ng/mL) of recombinant human NGAL in a HEPES buffer and a preservative.
The ProNephro AKI™ (NGAL) Control Kit contains ready-to-use High (500 ng/mL target concentration) and Low (200 ng/mL target concentration) Controls comprised of recombinant human NGAL in HEPES buffer and a preservative. There are three (3) 1 mL bottles of each level included with the kit.
Here's a breakdown of the acceptance criteria and study information for the ProNephro AKI™ (NGAL) device, based on the provided text:
Acceptance Criteria and Device Performance
The direct acceptance criteria for the clinical performance are not explicitly stated in a quantifiable manner (e.g., "Sensitivity must be >= X%"). Instead, the document presents the device's performance metrics from the validation study, implying these met the internal criteria for acceptance. The table below summarizes the reported clinical performance.
Table 1: Acceptance Criteria (Implied) and Reported Device Performance
| Performance Metric | Implied Acceptance Criterion (from Predicate) | Reported Device Performance (ProNephro AKI™ (NGAL)) - Overall Study Population (n=514) | Reported Device Performance - Group 1 (n=422) | Reported Device Performance - Group 2 (n=92) |
|---|---|---|---|---|
| Sensitivity (CI 95%) | 90-93% (83-99%) / 76% (60-91%) | 72.3% (57.4-84.4%) | 61.1% (35.8-82.7%) | 79.3% (60.3-92.0%) |
| Specificity (CI 95%) | 45-49% (39-54%) / 51% (41-60%) | 86.3% (82.8-89.3%) | 88.6% (85.1-91.5%) | 71.4% (58.7-82.1%) |
| Positive Predictive Value (PPV) (CI 95%) | 26-27% (21-33%) / 31% (21-42%) | 34.7% (28.5-41.4%) | 19.3% (10.1-31.9%) | 56.1% (39.8-71.5%) |
| Negative Predictive Value (NPV) (CI 95%) | 96-97% (93-100%) / 88% (79-96%) | 96.9% (95.1-98.0%) | 98.1% (96.1-99.2%) | 88.2% (76.1-95.6%) |
Note: The "Implied Acceptance Criterion" is derived from the performance ranges of the predicate device (NEPHROCHECK® Test System) presented in Table 2 of the document. The device performance for ProNephro AKI™ (NGAL) is directly reported.
Study Information
Here's a breakdown of the requested study information:
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Sample size used for the test set and the data provenance:
- Test Set Sample Size: 514 evaluable subjects for the overall clinical performance validation, comprising 422 subjects in Group 1 and 92 subjects in Group 2.
- Data Provenance: Multi-center prospective clinical study ("GUIDANCE") conducted at 15 sites across the US.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: At least two independent clinical experts.
- Qualifications of Experts: Not explicitly stated in the document. They are referred to as "independent clinical experts."
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Adjudication Method: "The clinical data for each subject were captured and provided to at least two independent clinical experts for adjudication." This implies a consensus-based adjudication, but the exact method (e.g., needing agreement from both, or a tie-breaker if they disagree) is not detailed.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a quantitative immunoassay for a biomarker (NGAL), not an imaging AI diagnostic that assists human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the clinical performance results presented (Sensitivity, Specificity, PPV, NPV) represent the standalone performance of the ProNephro AKI™ (NGAL) test. It is intended to be used "in conjunction with clinical evaluation," meaning the result from the test (NGAL concentration) is an input for the clinician's overall assessment, rather than the device itself being a "human-in-the-loop" AI system.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Ground Truth Type: Expert consensus for "moderate to severe acute kidney injury (Stage 2 to 3 AKI) 48 to 72 hours after the time of assessment," based on clinical data. The text states: "The clinical data for each subject were captured and provided to at least two independent clinical experts for adjudication."
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The sample size for the training set:
- Training Set Sample Size: The clinical cutoff of 125 ng/mL was established using a multi-center prospective clinical study called EARNEST with 257 pediatric patients (203 evaluable subjects). This study served as the "training" or "cutoff establishment" cohort before validation.
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How the ground truth for the training set was established:
- The ground truth for the EARNEST study (which established the cutoff) was defined as "moderate to severe acute kidney injury (Stage 2 to 3 AKI) 48 to 72 hours after the time of assessment." The specific method for establishing this ground truth (e.g., based on KDIGO criteria, expert adjudication) is not explicitly detailed for the EARNEST study in the same way it is for the GUIDANCE validation study, but it is implied to be clinical assessment.
§ 862.1220 Acute kidney injury test system.
(a)
Identification. An acute kidney injury test system is a device that is intended to measure one or more analytes in human samples as an aid in the assessment of a patient's risk for developing acute kidney injury. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must detail an appropriate end user device training program that will be offered while marketing the device as part of your efforts to mitigate the risk of incorrect interpretation of test results.
(2) As part of the risk management activities performed as part of your 21 CFR 820.30 design controls, you must document the appropriate end user device training program provided in your premarket notification submission to satisfy special control 21 CFR 862.1220(b)(1) that will be offered while marketing the device as part of your efforts to mitigate the risk of incorrect interpretation of test results.
(3) Robust clinical data demonstrating the positive predictive value, negative predictive value, sensitivity and specificity of the test in the intended use population must be submitted as part of the premarket notification submission.