(132 days)
This in vitro immunoassay is intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer using ADVIA IMS CA125 II Assay on a Bayer ADVIA® IMS™. CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostics procedures. The CA125 II Assay is also indicated as a one-time test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone firstline therapy and would be considered diagnostic second-look procedures. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.
The Bayer ADVIA® IMS™CA 125 II Assay is an in vitro diagnostic device intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer. The CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostic procedures. The CA 125 II Assay is also indicated as a one-time test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. An assay value of greater than 35 UlmL is predictive of residual disease, provided that alrernate causes of elevated CA 125 II Assay values can be excluded. It is recommended that the assessment and treatment of patients with ovarian cancer and the use of this CA 125 II Assay be under the order of a physician trained and experienced in the management of gynecologic cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.
This in vitro immunoassay is intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer using ADVIA IMS CA125 II Assay on a Bayer ADVIA® IMS™.
The provided documents detail the performance evaluation of the Bayer ADVIA® IMS™ CA 125 II Assay, particularly by comparing it to a predicate device (Immuno 1 CA125 II Assay). This is a technical summary for a 510(k) submission, focusing on establishing substantial equivalence rather than a typical clinical study with acceptance criteria for a new AI device or a novel diagnostic. As such, some of the requested information, such as the number of experts used for ground truth, adjudication methods, or AI-specific details (MRMC, standalone algorithm performance, training set details), are not applicable or provided in this type of submission for an immunoassay.
Here's an interpretation of the available information against your request:
Acceptance Criteria and Device Performance for CA 125 II Assay
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a 510(k) submission for an immunoassay, the "acceptance criteria" are implied by showing the device's performance is comparable to a legally marketed predicate device (Immuno 1 CA125 II Assay) and within acceptable limits for a clinical laboratory test. The document does not explicitly state "acceptance criteria" for each metric in a pass/fail format but rather presents the results of equivalence studies. We can infer the "acceptance criteria" were met because the 510(k) was cleared.
| Performance Metric | Implied Acceptance Criteria (relative to predicate) | Reported Device Performance (ADVIA IMS) |
|---|---|---|
| Imprecision (Total CV%) | Comparable to predicate device (Immuno 1) | Level 1: 3.0%; Level 2: 1.9%; Level 3: 2.5% |
| Linearity Recovery | Acceptable range (e.g., 90-110%) and comparable to predicate | 96.7% (met specifications, in concordance with Immuno 1) |
| Parallelism Recovery | Acceptable range and comparable to predicate | 95.6% to 109.7% (in concordance with Immuno 1) |
| Correlation (vs. Immuno 1) | High correlation (R value close to 1), small Syx | R = 0.994, Syx = 13.74 U/mL (Regression: Y = 1.047 * X - 3.94) |
| Longitudinal Monitoring (Sensitivity) | Clinically relevant sensitivity for detecting change | 94.7% (95% CI: 74.0% to 99.9%) |
| Longitudinal Monitoring (Specificity) | Clinically relevant specificity for detecting no change | 22.2% (95% CI: 2.8% to 60.0%) |
| Interfering Substances (Recovery Bias) | No clinically significant bias | All tested substances showed no clinically significant recovery bias (e.g., Hemoglobin -2.3%, Lipids 0.9%, Bilirubin -2.6%, etc.) |
| Analytical Range | Defined and clinically relevant | 0.5 - 550 U/mL |
| Minimum Detectable Concentration | Low enough for clinical utility and comparable to predicate | 0.5 U/mL (Immuno 1: 0.9 U/mL) |
2. Sample Size and Data Provenance for Test Set
- Correlation Study (Serum): N = 45 (compared to Immuno 1). The document does not specify the country of origin. This appears to be retrospective, using existing samples for method comparison.
- Longitudinal Samples Evaluation: Two examples of serial patient monitoring studies are shown graphically. The table for sensitivity/specificity for clinical status changes has N=28 (total specimens, implies 28 instances of clinical change/no change being assessed). Data provenance (country, retrospective/prospective) is not specified.
- Interfering Substances: Low serum pools were spiked. The number of samples for each interference test is not explicitly given, but typically involves a few replicates for each substance. Data provenance is not specified.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable for this immunoassay submission. For this type of device, "ground truth" is established by the reference measurement method (the predicate device, Immuno 1) or by the expected analytical performance characteristics for laboratory tests, rather than expert interpretation of images or clinical cases.
- The longitudinal evaluation references "guidelines by Bast et al," which suggests clinical experts defined what constitutes disease progression (doubling of CA125 II values) and response to therapy (50% decrease). However, no specific number or qualifications of experts involved in the study's ground truth assessment are provided.
4. Adjudication Method for the Test Set
- Not applicable for this immunoassay submission. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments (e.g., image-based diagnosis) where multiple readers provide initial interpretations. For an immunoassay, the result is a quantitative value, and comparisons are made against a reference method or clinical outcome definitions, not expert reconciliation of interpretations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, not performed. An MRMC study is not relevant for an immunoassay that produces a quantitative numerical result. This type of study assesses human reader performance with and without an AI assistant, which is not applicable here.
6. Standalone (Algorithm Only) Performance Study
- Yes, in essence. The entire submission describes the standalone performance of the ADVIA® IMS™ CA 125 II Assay. It is an automated in vitro diagnostic device, and its performance characteristics (imprecision, linearity, correlation, etc.) are intrinsically "algorithm only" in the context of it being a laboratory instrument and assay, without a human-in-the-loop interacting with its fundamental measurement principle. The output is a quantitative value, not a diagnostic interpretation that would then be reviewed by a human.
7. Type of Ground Truth Used
- Reference Method/Predicate Device: For analytical performance (imprecision, linearity, parallelism, correlation), the Immuno 1 CA125 II Assay served as the primary reference for comparison, indicating "substantial equivalence" as the ground truth.
- Clinical Definitions: For longitudinal monitoring, "ground truth" for clinical status change (progression, response) was based on established guidelines (Bast et al.) related to CA125 II value changes correlating with disease progression or response to therapy.
- Spiking/Known Concentrations: For interfering substances and analytical range, ground truth was based on known concentrations of spiked substances or samples with pre-determined high/low CA125 levels.
8. Sample Size for the Training Set
- Not applicable. This is an immunoassay, not an AI/machine learning device that requires a "training set" in the conventional sense. The assay's chemical and mechanical parameters are developed through standard laboratory procedures and optimization, not machine learning model training.
9. How Ground Truth for the Training Set Was Established
- Not applicable. As above, there is no "training set" or "ground truth" for it in the context of an AI/ML algorithm. The assay's development involves optimizing reagent formulations, instrument settings, and calibration processes, which are guided by established analytical chemistry principles and empirical testing.
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.