(168 days)
The Chemtrue® hCG urine or Combo test is a rapid lateral flow immunoassay for the visual qualitative detection of human chorionic gonadotropin (hCG) in human urine or serum as an aid in the early determination of pregnancy. The Dipstick/Cassette and Combo Tests are for prescription use only, including at physician's offices or other Point-Of-Care sites (POC).
The Chemtrue® hCG urine test is designed in Dipstick and Cassette formats. The hCG Combo (Serum/Urine) test is available in Cassette format only. Each test device consists of one (1) individual test strip and each test strip in the device consists of:
- A conjugate pad contains colloidal gold conjugated with monoclonal anti-hCG antibody specific to the beta subunit of hCG.
- A nitrocellulose membrane which is striped with the specific goat anti-hCG in the test line (T line) and goat anti-mouse antibody in the control line (C line serves as an internal quality control of the system and appears as a colored band during the test regardless of the hCG level in the test sample.
All the configurations have the same membrane format, reagents and gold conjugate pad, as well as the same flow characteristics, except the test line in the nitrocellulose membrane for hCG Combo test is striped with polyclonal goat anti-hCG antibodies.
Devices are packaged one device per foil pouch and 25 devices in each kit.
Here's a breakdown of the acceptance criteria and study information for the Chemtrue® Human Chorionic Gonadotropin (hCG) Pregnancy Test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a bulleted list prior to presenting results, but rather demonstrates performance against the intended claims (e.g., cutoff levels, agreement with predicate). Based on the performance data, the implicit acceptance criteria are that the device demonstrates comparable sensitivity and specificity to the predicate devices, and consistent performance across lots, sites, and operators.
Chemtrue® hCG Pregnancy Urine Dipstick Test & Cassette Test (Cutoff: 20 mIU/mL)
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Table 1-a, 1-b) |
|---|---|---|
| Sensitivity Study | 100% detection at 20 mIU/mL and above; 0% detection at 0 and 10 mIU/mL | 20 mIU/mL (Cutoff): 15/15 positive (100%) for all lots/formats |
| 40 mIU/mL: 15/15 positive (100%) for all lots/formats | ||
| 80 mIU/mL: 15/15 positive (100%) for all lots/formats | ||
| 0 mIU/mL: 0/15 positive (0%) for all lots/formats | ||
| 10 mIU/mL (-50% Cutoff): 0/15 positive (0%) for all lots/formats | ||
| 15 mIU/mL (-25% Cutoff): 3/15 positive for all lots/formats | ||
| Method Comparison (vs. Predicate K990578) | High agreement (e.g., >95%) with predicate in detecting positive and negative samples. | Dipstick (Table 8): Sensitivity 100% (150/150), Specificity 100% (150/150), Total Agreement 100% (300/300) |
| Cassette (Table 9): Sensitivity 100% (149/149), Specificity 99.3% (150/151), Total Agreement 99.7% (299/300) | ||
| Reproducibility (Cutoff: 20 mIU/mL) | Consistent results across sites and operators, especially at and around cutoff. | 20 mIU/mL (Cutoff): 27/27 positive at all 3 sites and for both Dipstick and Cassette formats (100% agreement). |
| 15 mIU/mL (-25% cutoff): Dipstick: 3/27 positive; Cassette: 2/27 positive. (Shows expected variability below cutoff). | ||
| Within Site Agreement: 100% (Site 1, 3), 99.5% (Site 2) | ||
| Between Sites Agreement: 99.8% | ||
| High Dose Hook Effect | No false negatives at high hCG concentrations. | No hook effect observed up to 500 IU/mL (500,000 mIU/mL). (Table 14) |
| Analytical Specificity / Cross-Reactivity | No significant interference from tested substances at specified concentrations. | No cross-reactivity with hLH, hFSH, hTSH, or other common interfering substances (Tables 13, 14-a, 15-a, 15-b). No interference from hCGBcf up to 1,000,000 pmol/mL. |
| pH and Specific Gravity | Consistent performance across physiological pH and specific gravity ranges. | No interference observed for pH 2.0-9.0 and SG 1.003-1.030. |
Chemtrue® hCG Combo (Serum/Urine) Cassette Test (Cutoff: 25 mIU/mL)
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Tables 2-a, 2-b) |
|---|---|---|
| Sensitivity Study | 100% detection at 25 mIU/mL and above; 0% detection at 0 and 10 mIU/mL (urine) / 0, 10, 20 mIU/mL (serum) | 25 mIU/mL (Cutoff): 15/15 positive (100%) for all lots/formats |
| 50 mIU/mL: 15/15 positive (100%) for all lots/formats | ||
| 100 mIU/mL: 15/15 positive (100%) for all lots/formats | ||
| 0 mIU/mL: 0/15 positive (0%) for all lots/formats | ||
| 10 mIU/mL (-60% Cutoff): 0/15 positive (0%) for all lots/formats | ||
| 20 mIU/mL (-20% Cutoff): 3/15 positive (Urine), 3/15 positive (Serum) | ||
| Method Comparison (vs. Predicate K964461) | High agreement (e.g., >95%) with predicate in detecting positive and negative samples. | Serum (Table 10): Sensitivity 100% (150/150), Specificity 100% (150/150), Total Agreement 100% (300/300) |
| Urine (Table 11): Sensitivity 100% (150/150), Specificity 100% (150/150), Total Agreement 100% (300/300) | ||
| Reproducibility (Cutoff: 25 mIU/mL) | Consistent results across sites and operators, especially at and around cutoff. | 25 mIU/mL (Cutoff): 27/27 positive at all 3 sites and for both Urine and Serum formats (100% agreement). |
| 20 mIU/mL (-20% cutoff): Urine: 5/27 positive; Serum: 5/27 positive. (Shows expected variability below cutoff). | ||
| Within Site Agreement: 100% (Site 1, 3), 99.5% (Site 2) | ||
| Between Sites Agreement: 99.8% | ||
| High Dose Hook Effect | No false negatives at high hCG concentrations. | No hook effect observed up to 500 IU/mL (500,000 mIU/mL). (Table 15) |
| Analytical Specificity / Cross-Reactivity | No significant interference from tested substances at specified concentrations. | No cross-reactivity with hLH, hFSH, hTSH, or other common interfering substances (Tables 13, 14-a, 15-a, 15-b). No interference from hCGBcf up to 1,000,000 pmol/mL. |
| pH and Specific Gravity | Consistent performance across physiological pH and specific gravity ranges. | No interference observed for pH 2.0-9.0 and SG 1.003-1.030. |
2. Sample Size Used for the Test Set and Data Provenance
-
Sensitivity (Cutoff Characteristics) Study:
- Sample Size: For each device format (Dipstick, Cassette, Combo Urine, Combo Serum), 3 lots were tested. For each lot, 6 hCG concentration levels (0, 10, 15, 20, 40, 80 mIU/mL for urine tests; 0, 10, 20, 25, 50, 100 mIU/mL for combo tests) were used with 5 replicates each.
- Total for Urine tests: 3 lots * 6 concentrations * 5 replicates = 90 tests per urine format (Dipstick, Cassette)
- Total for Combo tests: 3 lots * 6 concentrations * 5 replicates = 90 tests per Combo format (Urine, Serum)
- Data Provenance: Spiked hCG urine/serum pools from non-pregnant donors. The origin of the donors/samples is not specified (e.g., country), but they are described as "human urine pool from non-pregnant donors" and "non-pregnant human serum and urine pools." This is a prospective spiking study.
- Sample Size: For each device format (Dipstick, Cassette, Combo Urine, Combo Serum), 3 lots were tested. For each lot, 6 hCG concentration levels (0, 10, 15, 20, 40, 80 mIU/mL for urine tests; 0, 10, 20, 25, 50, 100 mIU/mL for combo tests) were used with 5 replicates each.
-
Reproducibility (Precision) Study:
- Sample Size:
- For each device format (Dipstick, Cassette, Combo Urine, Combo Serum), 3 lots were tested.
- 7 hCG concentration levels for urine (0, 10, 15, 20, 25, 30, 35 mIU/mL) and 6 for serum (0, 15, 20, 25, 30, 35 mIU/mL).
- Tested over 3 non-consecutive days with 3 operators per site across 3 sites. Each operator tested each control level (implied that 1 replicate for each level was run by each operator per day).
- Calculation per device format and concentration level: 3 lots * 3 sites * 3 operators = 27 data points.
- Data Provenance: Spiked hCG urine/serum controls, calibrated against WHO 5th IS, confirmed with Abbott i2000 instrument. The study was conducted at "three (3) POL sites." The geographical location of these POL sites is not explicitly stated. This is a prospective spiking study.
- Sample Size:
-
Method Comparison Study:
- Sample Size:
- Urine: 300 clinical urine samples (150 hCG negative, 150 hCG positive).
- Serum: 100 clinical serum samples (50 hCG negative, 50 hCG positive).
- Data Provenance: Clinical samples from women who were suspected to be pregnant or non-pregnant women of childbearing age (including peri-menopausal). The study was conducted at "three (3) POL sites... in Shanghai China." The data is retrospective clinical samples (but prospective testing with the device).
- Sample Size:
-
Analytical Specificity (Cross-reactivity) Study:
- Sample Size: For each device format, 3 lots were tested. hLH, hFSH, hTSH, and other interfering substances were spiked into hCG negative and 50 mIU/mL controls (number of replicates not explicitly stated for all, but typically done in replicates).
- hCGBcf interference: For each device format (Dipstick, Cassette, Combo Urine, Combo Serum), 3 lots were tested. 5 and 50 mIU/mL hCG controls were spiked with 4 hCGBcf concentrations. 10 replicates for each condition were tested (e.g., 3 lots * 2 hCG concentrations * 4 hCGBcf concentrations * 10 replicates = 240 tests for Dipstick, and similarly for other formats).
- Data Provenance: Spiked samples.
-
High Dose (Hook Effect) Study:
- Sample Size: For each device format (Urine Tests: Dipstick, Cassette; Combo Tests: Urine, Serum), 3 lots were used. 5 hCG concentrations (50, 100, 200, 300, 500 IU/mL) were tested with 5 replicates per lot.
- Total for Urine tests: 3 lots * 5 concentrations * 5 replicates = 75 tests per urine format.
- Total for Combo tests: 3 lots * 5 concentrations * 5 replicates = 75 tests per combo format.
- Data Provenance: Spiked non-pregnant urine and serum pools.
- Sample Size: For each device format (Urine Tests: Dipstick, Cassette; Combo Tests: Urine, Serum), 3 lots were used. 5 hCG concentrations (50, 100, 200, 300, 500 IU/mL) were tested with 5 replicates per lot.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth for the test sets (except method comparison and analytical specificity, discussed below) was established by spiking known concentrations of hCG into negative samples, and these concentrations were "quantitatively confirmed by Abbott i2000 instrument." This means there were no human experts establishing ground truth for the spiked studies.
For the Method Comparison Study:
- The "hCG positive serum samples were quantitatively confirmed by Abbott i2000 instrument." This establishes a quantitative ground truth for positive samples.
- The "150 hCG negative urine samples (collected from women of childbearing age, including peri-menopausal)" and "50 hCG negative serum samples" implicitly had their negative status confirmed, likely through prior testing or knowledge that they were from non-pregnant individuals.
- For the comparison itself, the predicate devices (Genzyme Diagnostics OSOM® Card hCG Urine Test (K990578) and Teco Diagnostics One-Step Urine/Serum Combo Pregnancy Card Test (K964461)) served as the reference standard against which the new devices were compared. The predicate devices themselves would have been cleared based on their own performance against a ground truth. No specific "experts" are mentioned as establishing ground truth for this comparative study beyond the established performance of the predicate and quantitative instrumentation.
For Analytical Specificity (Cross-reactivity): The "ground truth" was the known presence of specific interfering substances and the known absence or presence of hCG at specific concentrations.
4. Adjudication Method for the Test Set
- Sensitivity, Reproducibility, High Dose, Analytical Specificity, and pH/SG studies: The results were interpreted at 5 minutes by the "same operator" who performed the test in the reproducibility study. In the sensitivity study, "three (3) operators" tested the samples. These studies used objective criteria (presence/absence of a line) and known hCG concentrations, so an explicit adjudication method beyond visual interpretation by the operator (or in some cases, multiple operators) is not described or typically required for this type of qualitative assay performance testing using spiked samples.
- Method Comparison Study: "Each specimen was evenly split into three aliquots. Each site tested 100 samples with a unique set of blind codes for each device formation." The test device's result was then compared to the predicate device's result. Discrepancies are noted (e.g., "One discrepant result in this table was from a single sample with a hCG concentration near the cut-off"). No explicit multi-reader adjudication method (like 2+1) is mentioned, as the comparison is against an established predicate device.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, a formal MRMC comparative effectiveness study was not explicitly done in the sense of comparing human readers with and without AI assistance. This document describes a traditional in-vitro diagnostic (IVD) device (a lateral-flow immunoassay) which is interpreted visually by a human. The studies performed are standard IVD performance characteristic studies.
The "Method Comparison Study" involved multiple operators (9 operators across 3 sites in Shanghai, China), but this was comparing the device's performance to a predicate device, not comparing human reader effectiveness with and without AI. It demonstrated that human readers could use the new device to achieve results comparable to predicate devices. Therefore, the concept of "effect size of how much human readers improve with AI vs without AI assistance" is not applicable here.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes, in essence, the fundamental performance characteristics (Sensitivity/Cutoff, Analytical Specificity, High Dose, pH/SG, Stability) of the device itself were tested in a standalone manner by evaluating its ability to correctly identify various concentrations of hCG or detect interfering substances, independent of human variability in clinical settings. These are tests of the device's inherent analytical performance.
However, since this is a visually-read qualitative immunoassay, the final "output" is inherently derived from human observation. The "Reproducibility (Precision) Study" assessed the consistency of this human observation across multiple users and sites, ensuring that the human-in-the-loop interpretation provided reliable results.
7. The Type of Ground Truth Used
- For Sensitivity/Cutoff, Reproducibility, Analytical Specificity, High Dose, pH/SG studies: The ground truth was known concentrations of hCG or other substances that were quantitatively confirmed by a reference instrument (Abbott i2000) or laboratory standards (WHO 5th IS 07/364). This is considered an analytical ground truth based on spiked samples.
- For Method Comparison Study: The ground truth for clinical samples was established by comparison against legally marketed predicate devices (Genzyme Diagnostics OSOM® Card hCG Urine Test and Teco Diagnostics One-Step Urine/Serum Combo Pregnancy Card Test). For serum samples, the hCG positive status was also quantitatively confirmed by an Abbott i2000 instrument. This is a comparative ground truth against an existing, cleared device, supported by quantitative confirmation for positives.
8. The Sample Size for the Training Set
The document describes the submission as a premarket notification (510(k)) for a new device. It does not explicitly mention a "training set" in the context of machine learning algorithms. This device is a lateral flow immunoassay, which does not typically involve training a computational algorithm. The studies described are performance validation studies for the finished device.
9. How the Ground Truth for the Training Set was Established
As there is no mention of a "training set" in the context of a machine learning algorithm, this question is not applicable. The device's fundamental design is based on immunological principles, not learned from a dataset.
§ 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.