(187 days)
The IDS-iSYS Aldosterone assay (IS-3300) is a device intended for use in clinical laboratories for the quantitative determination of Aldosterone in human EDTA plasma on the IDS-iSYS Multi-Discipline Automated System. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of Aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hyperaldosteronism, edematous states and other conditions of electrolyte balance.
The IDS-iSYS Aldosterone Control Set (IS-3330) is intended for use as assaved quality control samples to monitor the accuracy of the IDS-iSYS Aldosterone assay on the IDS-iSYS Multi-Discipline Automated System.
The IDS-iSYS Aldosterone Calibration Verifiers (IS-3335) are intended for medical purposes for use in the quantitative verification of calibration of the IDS-iSYS Aldosterone assay on the IDS-iSYS Multi-Discipline Automated System.
The IDS-iSYS Aldosterone assay is based on chemiluminescence technology. A biotinylated monoclonal anti-Aldosterone antibody is incubated with the sample, after an incubation step an Aldosterone acridinium conjugate is added and after a further incubation step streptavidin coated magnetic particles are added. Following a third incubation step the particles are "captured" using a magnet. After a washing step and addition of trigger reagents, the light emitted by the acridinium label is inversely proportional to the concentration of Aldosterone in the original sample.
Here's an analysis of the provided text to extract the requested information about acceptance criteria and the supporting study:
The provided document is a 510(k) Summary for the IDS-iSYS Aldosterone assay, control set, and calibration verifiers. It focuses on demonstrating substantial equivalence to a predicate device, as required for FDA clearance. The document details performance characteristics but does not explicitly state acceptance criteria in a pass/fail format typical of formal acceptance criteria documents. Instead, it reports performance values found during validation studies.
Here's the breakdown of the information you requested, based on what's available in the document:
1. Table of Acceptance Criteria and Reported Device Performance
As mentioned, explicit "acceptance criteria" are not listed in a single table. However, the performance characteristics are reported, and implicitly, these values are considered acceptable for demonstrating substantial equivalence. The table below compiles the reported performance data from the document.
Note: The document does not provide a column for "Acceptance Criteria" as a separate, pre-defined target. The "Reported Device Performance" is the outcome of the studies aiming to demonstrate acceptable performance.
| Performance Characteristic | Implicit or Explicit Acceptance Threshold (Not explicitly stated as "acceptance criteria" but implied targets from regulatory guidance or industry standards) | Reported Device Performance (IDS-iSYS Aldosterone Assay) | Source of Data |
|---|---|---|---|
| Precision (CV%) | Implied: Generally low CV% indicating good reproducibility (e.g., 0.98 or >0.99) indicating a strong linear relationship. | R² = 1.00 | Text (p.9) |
| Regression Equation (y=mx+b) | Implied: Slope (m) close to 1, intercept (b) close to 0. | y = 1.00x - 1.24 (slope = 1.00, intercept = -1.24) | Text (p.9) |
| Limit of Blank (LoB) | Implied: Low value to correctly identify absence of analyte. | 2.0 ng/dL | Table (p.11) |
| Limit of Detection (LoD) | Implied: Low value to correctly detect presence of analyte. | 3.2 ng/dL | Table (p.11) |
| Limit of Quantitation (LoQ) | Implied: Low value with acceptable precision (e.g., typically ≤20% CV). | 3.9 ng/dL (at 20% CV) | Table (p.11) |
| Interference (Concentration Bias) | Explicitly stated criterion in study: ≤10% concentration bias to the unspiked sample. | All tested interferents met this criterion. | Text (p.11) |
| Cross-Reactivity | Implied: Low percentage for non-target analytes, 100% for target analyte. | Aldosterone: 100%. Other analytes: 0.0003% to 3.1% (3α, 5β-Tetrahydroaldosterone: 3.1%) | Table (p.13) |
| Method Comparison (Slope vs. Predicate) | Implied for substantial equivalence: Slope close to 1, intercept close to 0, high R². | Linear Regression: Slope = 1.053, Intercept = 0.09 ng/dL, R² = 0.980 | Text (p.14) |
| Passing-Bablok: Slope = 1.070, Intercept = -0.29 | Text (p.14) |
2. Sample Size Used for the Test Set and Data Provenance
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Precision/Reproducibility:
- Sample Size: Six EDTA plasma samples (9 "samples" were run over 20 days, generating 80 replicates per sample concentration).
- Data Provenance: Not explicitly stated, but clinical laboratory setting is implied. The phrase "two sites using three analyzers" could suggest multi-center testing, potentially from different locations/countries, but this is not specified. The studies were performed for the manufacturer for regulatory submission.
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Linearity/Assay Reportable Range:
- Sample Size: One high plasma sample diluted with a low sample to create 11 dilution samples. Run in quadruplicate.
- Data Provenance: Not specified, likely internal laboratory data for the manufacturer.
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Detection Limit (LoB, LoD, LoQ):
- Sample Size:
- LoB (Lot 1): One zero-aldosterone plasma sample, 10 replicates for 5 days (total 50 replicates).
- LoD/LoQ (Lot 1): 7 samples, 2 replicates per sample, once per day for 8 days.
- LoB (Lot 2): One zero-aldosterone plasma sample, 6 replicates for 5 days (total 30 replicates).
- LoD (Lot 2): 8 samples, 2 replicates per sample, once per day for 5 days.
- LoQ (Lot 2): 7 samples, 2 replicates per sample, once per day for 5 days.
- Data Provenance: Not specified, likely internal laboratory data for the manufacturer. Two different sites and two different analyzers were used.
- Sample Size:
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Analytical Specificity (Interference and Cross-Reactivity):
- Sample Size:
- Interference: Two base plasma samples ("Low" and "High" Aldosterone concentrations), spiked with various potential interferents. For each interferent, 26 replicates for blank and spiked samples were compared.
- Cross-reactivity: Stock solutions of various compounds diluted serially to create 7-point standard curves for each substance.
- Data Provenance: Not specified, likely internal laboratory data for the manufacturer.
- Sample Size:
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Method Comparison:
- Sample Size: 161 samples (including 12 altered samples).
- Data Provenance: Not specified, implied to be clinical or patient samples. Whether these were retrospective or prospective, or their country of origin, is not mentioned.
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Reference Range Study (Expected Values):
- Sample Size: 228 Caucasian adult samples.
- Data Provenance: Collected in the US, prospective (samples collected under specific conditions: 7-10 am after overnight fasting, upright/supine positions).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This type of information is generally NOT applicable to in vitro diagnostic (IVD) devices like the Aldosterone assay described. For IVD assays, "ground truth" is typically established by:
- Reference methods/predicate devices (e.g., Diasorin Liaison Aldosterone assay for method comparison).
- Gravimetric preparation of standards and calibrators for traceability.
- Defined sample characteristics (e.g., "zero aldosterone plasma," "high plasma sample").
There were no human experts assessing images or making diagnoses that would require adjudication.
4. Adjudication Method for the Test Set
Not applicable, as this is an IVD assay, not a device requiring human interpretation of results in a diagnostic context that would call for adjudication of different interpretations.
5. 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
Not applicable. This is an IVD assay for quantitative determination of a biomarker; there are no "human readers" interpreting results in the way an MRMC study would be designed for an imaging AI device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies conducted (Precision, Linearity, LoD/LoQ, Analytical Specificity, Method Comparison) represent the standalone performance of the IDS-iSYS Aldosterone assay system. The device quantifies aldosterone in plasma samples directly, without human interpretation of results being a variable in its core analytical performance.
7. The Type of Ground Truth Used
The ground truth used for various studies includes:
- Reference materials: Aldosterone (≥95% HPLC; A9477Sigma-Aldrich) dissolved in Dioxane, with concentration calculated by UV quantitation using molar extinction coefficient (for calibrators and traceability).
- Predicate device results: The Diasorin Liaison Aldosterone assay (K130321) for method comparison.
- Spiked samples: For linearity, interference, and cross-reactivity studies, known concentrations of analyte or interferents were added to base samples to create "true" concentrations.
- Patient samples: For method comparison and reference range studies, patient samples were used. Their "truth" for method comparison was established by the predicate device. For reference ranges, the "truth" was the measured value distributed among a healthy population.
8. The Sample Size for the Training Set
The document describes performance studies (validation) but does not explicitly mention a "training set" in the context of machine learning. For an IVD assay, the development process involves reagent optimization, calibration curve fitting, etc., which conceptually use data, but this is not typically termed a "training set" like in AI/ML.
However, the "Master curve" and "two-point calibration" system is mentioned. The "logistic parameters of the Master calibration curve" are generated using "data of 20 runs Internal Reference Calibrators" (p.9). This could be considered analogous to a training process for establishing the core measurement algorithm, but it's not a training set for an AI inference model.
9. How the Ground Truth for the Training Set Was Established
If we consider the generation of the "Master calibration curve" as a "training" process:
- Ground Truth: The "Internal Reference Calibrators" referenced (p.9) would serve as the ground truth. These calibrators are traceable to gravimetrically prepared Aldosterone standards using high-purity Aldosterone and UV quantitation (p.9).
- Establishment Method: The "new kit calibrator sets are run as 'unknowns' in duplicate in at least 20 assays on one analyser" (p.9). "The data of 20 runs Internal Reference Calibrators are used to generate the logistic parameters of the Master calibration curve by using Prism software package" (p.9).
§ 862.1045 Aldosterone test system.
(a)
Identification. An aldosterone test system is a device intended to measure the hormone aldosterone in serum and urine. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by the excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.(b)
Classification. Class II.