(57 days)
The Access AMH assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and lithium heparin plasma using the Access Immunoassay Systems as an aid in the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). The Access AMH is intended to be used in conjunction with other clinical and laboratory findings such as antral follicle count, before starting therapy. The Access AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
The Access Anti-Mullerian Hormone Assay, Access Anti-Mullerian Hormone Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay System for the quantitative determination of Anti-Mullerian Hormone levels in human serum and lithium heparin plasma using the Dxl 9000 Access Immunoassay system.
The provided text describes the performance of the Access AMH assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to a predicate device (Access AMH assay on Access 2 Immunoassay System).
Here's an analysis of the acceptance criteria and study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a single table outlining acceptance criteria for all aspects, but rather describes them within the "Summary of Studies" section. Based on the text, here's a reconstructed table:
| Test Parameter | Acceptance Criteria | Reported Device Performance (Access AMH on Dxl 9000) | Result |
|---|---|---|---|
| Method Comparison | Not explicitly stated (implied to be comparable) | Slope: 1.02 (95% CI: 1.00 - 1.03) | |
| Intercept: 0.011 (95% CI: -0.013 - 0.067) | |||
| Correlation Coefficient (R): 1.00 | Comparable to predicate device; estimated bias at reference limits hasn't changed appreciably. | ||
| Imprecision | Within-laboratory (total) %CV for AMH concentrations > 0.16 ng/mL | Within-laboratory (total) %CV ranged from 2.2% to 5.4% for AMH concentrations > 0.16 ng/mL. | |
| Maximum Total Error (TE) of 16% (meets acceptance criteria) | Meets acceptance criteria for total error and bias. | ||
| Linearity | Linear throughout the analytical measuring interval. | Linear on the Dxl 9000 Immunoassay System throughout the analytical measuring interval (0.08 - 24 ng/mL (0.57 - 171 pmol/L)). | Meets acceptance criterion. |
| Limit of Blank (LoB) | ≤ 0.01 ng/mL | Determined to be 0.001 ng/mL. | Meets acceptance criterion. |
| Limit of Detection (LoD) | ≤ 0.02 ng/mL | Estimated to be 0.002 ng/mL. | Meets acceptance criterion. |
| Limit of Quantitation (LoQ) | ≤ 0.08 ng/mL (0.57 pmol/L) for 20% within-laboratory (total) CV | The 20% CV LoQ estimate is 0.003 ng/mL (0.02 pmol/L). | |
| The LoQ at 20% within-laboratory (total) CV estimate is ≤ 0.08 ng/mL (0.57 pmol/L). | Meets acceptance criterion. | ||
| Reproducibility | SD ≤ 0.042 ng/mL for values ≤ 0.16 ng/mL | ||
| CV ≤ 13.0% for values > 0.16 ng/mL | The study (data not explicitly presented in detail beyond the conclusion) shows that the Access AMH assay meets design input requirements for reproducibility on Dxl 9000 with an SD ≤ 0.042 ng/mL for values ≤ 0.16 ng/mL and CV ≤ 13.0% for values > 0.16 ng/mL. | Meets design input requirements. |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison:
- Sample Size: N = 126
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). The "Concentration Range" is specified as "Access 2 values," suggesting that these are samples previously run on the predicate device.
- Imprecision:
- Sample Size: 88 for each of the 9 samples tested (total 9 x 88 = 792 individual measurements).
- Data Provenance: Not specified.
- Linearity, LoB, LoD, LoQ, Reproducibility:
- Sample Size: Not explicitly stated for these individual studies, beyond the "N" values in the imprecision table.
- Data Provenance: Not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document describes performance characteristics of an in vitro diagnostic (IVD) assay quantifying AMH levels. Ground truth in this context typically refers to the true concentration of AMH in a sample, often established by a reference method or highly accurate assay.
- The text does not mention the use of human experts (e.g., radiologists) or their qualifications to establish ground truth for the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility).
- For these types of IVD studies, the "ground truth" is often established by comparing the device's results to a recognized reference method or the established predicate device, or by using validated calibrators and controls with known analyte concentrations.
4. Adjudication Method for the Test Set
Given that this is an in vitro diagnostic device assessing analytical performance rather than diagnostic imaging interpretation, an adjudication method (like 2+1 or 3+1) is not applicable and therefore not mentioned. The evaluation relies on quantitative measurements against analytical criteria or a comparative method.
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
- No, an MRMC comparative effectiveness study was not done.
- This device is an in vitro diagnostic test for Anti-Müllerian hormone (AMH) levels, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of improving human reader performance with AI assistance is not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, the provided studies describe standalone performance of the assay.
- The Access AMH assay is an automated chemiluminescent immunoassay run on an analyzer (Dxl 9000 Access Immunoassay Analyzer). The performance metrics (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility) are inherently standalone, reflecting the analytical capabilities of the device itself without direct human interaction in the measurement process (beyond operating the instrument and collecting/inputting samples).
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- For the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility), the ground truth is implicitly defined by:
- Reference method/Predicate device comparison: For the method comparison study, the "Access 2 values" (from the predicate device) serve as the reference point for comparison.
- Known concentrations: For imprecision, linearity, LoB, LoD, LoQ studies, ground truth is established using samples (e.g., controls, calibrators, spiked samples) with known or carefully characterized AMH concentrations. This is a common practice in IVD analytical validation.
- It is not based on expert consensus, pathology, or outcomes data, as these are typically used for clinical diagnostic accuracy studies or imaging interpretation.
8. The Sample Size for the Training Set
The document describes performance validation studies, not development studies involving a training set in the context of machine learning.
- Therefore, the concept of a "training set" in this context is not applicable as this is an immunoassay, not an AI/ML algorithm that requires training data.
9. How the Ground Truth for the Training Set was Established
As mentioned above, the concept of a "training set" is not applicable. Therefore, there is no discussion of how ground truth for a training set was established.
§ 862.1092 Anti-mullerian hormone test system.
(a)
Identification. An anti-mullerian hormone test system is an in vitro diagnostic device intended to measure anti-mullerian hormone in human serum and plasma. An anti-mullerian hormone test system is intended to be used for assessing ovarian reserve in women.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) An adequate traceability plan to minimize the risk of drift in anti-mullerian hormone test system results over time.
(ii) Detailed documentation of a prospective clinical study to demonstrate clinical performance or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(A) Results must demonstrate adequate clinical performance relative to a well-accepted comparator.
(B) Clinical sample results must demonstrate consistency of device output throughout the device measuring range that is appropriate for the intended use population.
(C) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the proposed indications for use(s), and results of all statistical analyses.
(iii) Reference intervals generated by testing an adequate number of samples from apparently healthy normal individuals in the intended use population.
(2) The labeling required under § 809.10(b) of this chapter must include a warning statement that the device is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy, and that the device should be used in conjunction with the antral follicle count.