(79 days)
The Nichols Advantage Hyperglycosylated Human Chorionic Gonadotropin (H-hCG) Assay (or simply: Nichols Advantage® H-hCG Assay) is intended for use with the Nichols Advantage® Specialty System for the quantitative measurement of hyperglycosylated human chorionic gonadotropin (H-hCG), a placental hormone in human serum, or for the qualitative determination of H-hCG in urine as an aid in the detection of pregnancy. These diagnoses should be made with appropriate additional clinical evidence. Clinical considerations and professional judgment should be applied to any test device result as with this Nichols H-hCG chemiluminescent immunoassay.
The Nichols Advantage® H-hCG Assay is used in conjunction with two H-hCG calibrators which are used to calibrate the assay and are provided separately to the reagent cartridge. The control is used for the monitoring of the accuracy and precision of the Nichols Advantage H-hCG Assay and successful calibration is confirmed using three H-hCG controls also provided separately to the calibrators and reagent cartridge.
The Nichols Advantage Hyperglycosylated Human Chorionic Gonadotropin Assay (i.e., Nichols Advantage® H-hCG Assay) is a two-step, two-site immunochemiluminometric assay for use with the Nichols Advantage® Specialty System, for the measurement of H-hCG as an aid in the detection of pregnancy. This new Nichols Advantage® H-hCG Assay Jas with the predicate of the Diagnostic Products Corporation (= DPC) termed: the DPC IMMULITE® hCG Immunoassay (K990222; cleared 2/26/99)] is a two-step, two-site immunochemiluminometric assay for use with the Nichols Advantage® Specialty System.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance for Nichols Advantage® H-hCG Assay
1. Table of Acceptance Criteria and the Reported Device Performance
| Feature / Metric | Acceptance Criteria (Target) | Reported Device Performance (Nichols Advantage H-hCG Assay) |
|---|---|---|
| Precision/Reproducibility | ||
| Total (Average CV) | No more than 2% higher than the predicate IMMULITE 2000 hCG Assay (Predicate was up to 7.22% C.V.) | 6.7% C.V. (This meets the implicit criteria as 6.7% is less than 7.22%) |
| Within-Run (CV) | Not greater than 5% at a dose > 10 ng/mL Serum | Not greater than 5% at a dose > 10 ng/mL Serum |
| Total (CV) (at >10 ng/mL Serum) | Not greater than 10% at a dose > 10 ng/mL Serum | Not greater than 10% |
| Linearity/Reportable Range | Linear regression correlation for critical values with predicate (r > 0.9, P dynamic range). | |
| Method Comparison (Serum) | ||
| Concordance | Achieve high concordance with predicate (e.g., >95%) | 99.1% |
| % Agreement Positive | Achieve high positive agreement with predicate (e.g., >95%) | 100.0% |
| % Agreement Negative | Achieve high negative agreement with predicate (e.g., >95%) | 96.8% |
| Method Comparison (Urine) | ||
| Concordance | Achieve high concordance with predicate (e.g., >95%) | 97.2% |
| % Agreement Positive | Achieve high positive agreement with predicate (e.g., >95%) | 99.0% |
| % Agreement Negative | Achieve high negative agreement with predicate (e.g., >85-90%) | 89.6% |
2. Sample sizes used for the test set and the data provenance
- Precision/Reproducibility: Patient or patient pool samples were evaluated. An "accelerated format of the NCCLS EP-5 protocol" was used, involving two replicates of each specimen run on each of four assays per day over a 10-day period, yielding 80 data points.
- Linearity/Assay Reportable Range:
- n = 61 "apparently pregnant and health female subjects" reporting 0-2 weeks of gestation.
- Detection Limit/Assay Cut-off (Non-pregnant subjects): n = 81 "non-pregnant apparently health female subjects."
- Method Comparison (Serum): n = 659 total samples (479 pregnant, 180 non-pregnant).
- Method Comparison (Urine): n = 777 total samples (632 pregnant, 145 non-pregnant).
- Expected Values/Reference Range (Cut-off establishment):
- n = 178 serum samples (apparently healthy and non-pregnant adult women, age 17-64).
- n = 85 random urine samples (apparently healthy and non-pregnant adult women, age 17-71).
- Both groups were "ambulatory, free-living, southern California community-dwelling."
- Expected Values (Pregnant women): n = 357 first trimester serum samples from "apparently healthy pregnant women" (categorized by gestational weeks/LMP).
- Data Provenance: The document explicitly states that samples for establishing expected values/reference ranges were from "southern California community-dwelling adult women." For other studies, data provenance is not explicitly stated but is implied to be clinical samples from similar populations as tested by the predicate device. The samples for determining cross-reactivity of various hCG forms were provided by Columbia University or Sigma Chemical Co. All clinical data presented appears to be retrospective, derived from collected clinical samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not explicitly state that experts were used to establish the ground truth for the test set. Instead, the ground truth for pregnancy status (pregnant vs. non-pregnant) relies on:
- Clinical reporting: "apparently pregnant and health female subjects [i.e., those reporting 0 to 2 weeks of gestation]" and "apparently healthy pregnant women."
- Comparison to a predicate device: The DPC IMMULITE® hCG Immunoassay (K990222) is used as the reference standard for method comparison, implying its results are the accepted ground truth for hCG levels and pregnancy status.
- Lack of specific mention: There is no mention of radiologists, pathologists, or other clinical experts adjudicating cases for ground truth.
4. Adjudication method (for the test set)
There is no explicit mention of an adjudication method (like 2+1, 3+1, none) for establishing ground truth from multiple experts. The ground truth appears to be based on:
- Self-reported gestational status.
- Comparison with a well-established predicate device, implying its results serve as a form of reference standard.
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 MRMC comparative effectiveness study was done or mentioned. This device is an immunoassay (laboratory test system), not an AI-assisted diagnostic imaging or clinical decision support system that would involve human "readers" or AI assistance. The comparison is between two laboratory assay methods.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the device operates as a standalone algorithm/system without human-in-the-loop performance influencing the assay results. The Nichols Advantage® H-hCG Assay itself is a laboratory instrument that quantitatively measures H-hCG. Interpretation of results (e.g., positive for pregnancy) is based on defined cut-off values (e.g., >= 1.0 ng/mL), which are determined by the assay and not subject to real-time human interpretation for each primary result. Clinical considerations and professional judgment are applied after the objective result is obtained, suggesting the assay itself is standalone.
7. The type of ground truth used
The primary ground truth used is a combination of:
- Clinical status (self-reported/historical): "apparently pregnant" or "non-pregnant" status of individuals.
- Predicate device results: The DPC IMMULITE® hCG Immunoassay results serve as a comparative ground truth/reference standard for establishing correlation and agreement. For linearity, the DPC values were used to correlate with the NID values.
- Derived cut-off values: For the "detection limit" studies, the ground truth was derived from statistical analysis of H-hCG levels in known non-pregnant individuals.
8. The sample size for the training set
The document does not explicitly differentiate between "training" and "test" sets in the context of machine learning. For an immunoassay, the concept of a training set is typically represented by the samples and data used to develop the assay, establish its calibration, and set initial performance parameters. The document focuses on the validation or performance characteristic studies. For the purposes of this request, if we consider "training" analogous to the data used to define the assay's operational parameters and reference ranges, then:
- For establishing reference ranges/expected values: n=178 serum samples (non-pregnant) and n=85 urine samples (non-pregnant) were used to determine the decision threshold. n=357 first trimester serum samples (pregnant) were used to establish expected values by gestational week.
9. How the ground truth for the training set was established
For the data used to establish assay parameters and reference ranges:
- The ground truth (pregnant or non-pregnant status) was established based on the clinical status of the subjects (e.g., "apparently healthy and non-pregnant adult women," "pregnant women"). This likely involves a combination of medical history, last menstrual period, and potentially other clinical assessments not detailed in the summary.
- Analytical measures: The "ground truth" for linearity and method comparison was provided by the predicate device's quantitative results, allowing for a direct comparison and correlation study. The predicate device's established performance served as the benchmark.
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.