(451 days)
The Altest Pregnancy Rapid Combo Test Cassette is a rapid chromatographic immunoassay for the qualitative detection of human chorionic gonadotropin in urine or serum to aid in the early detection of pregnancy. The test is for health care professionals use including professionals at point of care (POC).
The Alltest Pregnancy Rapid Combo Test Cassette measures the presence of the hormone Human Chorionic Gonadotrophin (HCG) in human urine or serum for the early detection of pregnancy. During pregnancy, HCG is produced by the placenta shortly after the embryo attaches to the uterine lining. The test device is used as a single cassette device.
The provided document is a 510(k) summary for the Alltest Pregnancy Rapid Combo Test Cassette, which is a rapid chromatographic immunoassay for the qualitative detection of human chorionic gonadotropin (hCG) in urine or serum to aid in the early detection of pregnancy. The device is intended for prescription use by healthcare professionals, including those at the point of care.
Here's an analysis of the acceptance criteria and the studies performed:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" in a separate section with predefined thresholds. Instead, it presents performance data from various studies. Based on the "Performance Characteristics" section, the implicit acceptance criteria are that the device should demonstrate:
- High precision and accuracy around the cut-off values.
- Stability over an extended period.
- Specificity, with no significant interference from related hormones or common substances.
- No high-dose hook effect.
- Performance comparable to a legally marketed predicate device.
The reported device performance aligns with these implicit criteria, indicating successful validation.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision/Cut-Off | Establish accurate cut-off values (10 mIU/mL for serum, 20 mIU/mL for urine) with consistent positive/negative results across sites, lots, and operators. | * Serum: At 8 mIU/mL (below cut-off), 75.6% positive. At 10 mIU/mL (cut-off), 100% positive. At 0, 3, 5 mIU/mL, 100% negative. At concentrations >= 10 mIU/mL, 100% positive. |
- Urine: At 15 mIU/mL (below cut-off), 48.9% positive. At 17.5 mIU/mL (below cut-off), 80% positive. At 20 mIU/mL (cut-off), 100% positive. At 0, 5, 10 mIU/mL, 100% negative. At concentrations >= 20 mIU/mL, 100% positive.
- Conclusion: Cut-off values of 10 mIU/mL for serum and 20 mIU/mL for urine are verified. |
| Stability | Demonstrate stability for an appropriate shelf life under specified storage conditions. | Stable at 2-30°C for 24 months based on an accelerated stability study at 55°C. |
| Specificity (High Dose Effect) | No hook effect at high hCG concentrations. | No hook effect observed with hCG concentrations ranging from 500 to 2,000,000 mIU/mL. |
| Specificity (ß-core fragment) | No significant interference from hCG ß-core fragment up to certain concentrations. | No interference observed except for false positives above 100 pmol/L ß-core fragment hCG. (Note: The document doesn't provide the expected range of ß-core fragment in actual samples or how this level of interference compares to clinical relevance, but states "No difference was observed for different lots and different operators.") |
| Specificity (Glycoprotein Hormones) | No interference from LH, FSH, TSH at physiological/elevated levels. | No interference observed at LH concentrations up to 500 IU/mL, FSH concentrations up to 1000 mIU/mL, and TSH concentrations up to 1000 uIU/mL. |
| Interference (Common Substances) | No interference from a specified list of common exogenous and endogenous substances at given concentrations. | All tested compounds (Acetaminophen, Acetoacetic Acid, Ascorbic Acid, Atropine, Acetosalicylic Acid, Albumin, Bilirubin, Caffeine, Codeine, Ephedrine, EDTA, Ethanol, Gentisic Acid, Glucose, Hemoglobin, Methadone, Phenylpropanolamine, Phenothiazine, Pregnanediol, Salicylic Acid, ß-hydroxybutyrate, Benzoylecgonine, Cannabinol, Methanol, Estriol-17-beta, Thiophene, Ampicillin, Tetracycline, Ketone, Total cholesterol, Triglycerides, High-density lipoprotein) showed no interference at the stated concentrations for both negative and positive hCG samples. |
| Effect of Urine Specific Gravity & pH | No interference across physiological/pathological ranges of urine specific gravity and pH. | No interference from pH ranging from 4 to 9 and specific gravity ranging from 1.001 to 1.035. |
| Method Comparison | Demonstrate substantial equivalence (high agreement) with a legally marketed predicate device. | * Urine: 100% agreement between the new device and the predicate (53 positive, 52 negative). - Serum: 100% agreement between the new device and the predicate (58 positive, 49 negative). |
2. Sample Size Used for the Test Set and Data Provenance
-
Precision/Reproducibility/Cut-Off Value Study:
- Test Set Size (Serum): 90 replicates for each hCG concentration level (3 sites x 30 replicates per concentration). In total, 9 concentrations were tested, so 90 x 9 = 810 tests.
- Test Set Size (Urine): 90 replicates for each hCG concentration level (3 sites x 30 replicates per concentration). In total, 9 concentrations were tested, so 90 x 9 = 810 tests.
- Data Provenance: Not explicitly stated, but the testing was conducted at "three testing sites" by "six different operators." It's likely these were internal or contract labs, possibly within China (where the manufacturer is located) or the US (where the submitter's contact is). The data is from controlled experimental studies.
- Retrospective/Prospective: Prospective (experimental spiking of samples).
-
Method Comparison Study:
- Test Set Size (Urine): 105 urine samples.
- Test Set Size (Serum): 107 serum samples.
- Total Test Set Size: 212 samples (from 212 women).
- Data Provenance: Samples collected from 212 women from "three testing sites." Ages ranged from 20 to 49 years. "About half of them were pregnant, early stage at less than 5 weeks." Not explicitly stated, but implies clinical samples used for comparison. The country of origin is not specified.
- Retrospective/Prospective: Likely prospective clinical sample collection for the purpose of the study.
-
Other Analytical Performance Studies (Specificity, Interference, pH/Specific Gravity):
- Sample sizes vary but generally involve spiking negative and positive samples with various concentrations of the interferent/condition and testing with 3 different lots by 3 different operators. Exact total sample counts for each condition are not explicitly provided but involve multiple replicates across lots and operators.
- Data Provenance: Controlled experimental studies with spiked samples.
- Retrospective/Prospective: Prospective (experimental spiking of samples).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Precision/Reproducibility/Cut-Off Value Study: The "ground truth" for the test set was established by precisely spiking known concentrations of hCG (traceable to the 5th WHO international Standard) into negative serum or urine specimens. This is an analytical truth rather than an expert interpretation. Six different operators performed these tests; their qualifications are not specified but would typically be laboratory technicians.
- Method Comparison Study:
- The "ground truth" for the comparison study was the result obtained from the predicate device (K132834, Clarity Diagnostics Clarity hCG Pregnancy Combo Test Cassette). This means the predicate device itself served as the reference standard, and the new device's agreement was measured against it.
- There is no mention of independent experts establishing a "true" pregnancy status. The comparison is between two devices.
- The tests were performed by "different health professionals," but their specific number or qualifications (e.g., radiologist with 10 years of experience) are not provided.
4. Adjudication Method for the Test Set
- Precision/Reproducibility/Cut-Off Value Study: No adjudication method as the ground truth was analytically determined (spiked concentrations). Results were recorded and analyzed statistically.
- Method Comparison Study: No adjudication method mentioned for comparing the predicate and new device results against a separate "true" outcome. The comparison itself uses the predicate device as the reference.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This document describes the performance of an in-vitro diagnostic (IVD) test, not an imaging device or AI-powered diagnostic that would typically involve human readers interpreting cases with and without AI assistance. Therefore, an MRMC comparative effectiveness study was not performed, and there is no effect size reported for human readers improving with AI vs. without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, in essence. The studies present the analytical performance of the device itself (the "algorithm" or immunoassay), reporting its ability to detect hCG in various conditions. While "health professionals" perform the tests, the core performance characteristics (sensitivity, specificity, cut-off accuracy, interference) are inherent to the device's design and chemical reactions, operating in a standalone manner once the sample is applied. The "Method Comparison Study" directly evaluates the standalone performance of the device against another device.
7. Type of Ground Truth Used
- Analytical Studies (Precision, Specificity, Interference, pH/Specific Gravity): The ground truth was based on known, precisely controlled concentrations of hCG, interferents, or specific pH/gravity conditions, established through spiking or preparing samples. This is a form of analytical truth.
- Method Comparison Study: The ground truth for this study was the results obtained from a legally marketed predicate device. The predicate device's results were accepted as the reference against which the new device was compared.
8. Sample Size for the Training Set
This document primarily describes analytical validation and comparison studies. For an IVD device like this, there isn't typically a "training set" in the machine learning sense. The device's performance is driven by its biochemical design and manufacturing process, not trained on data. Development may involve iterative testing and refinement, but a formal "training set" size as understood in AI/ML is not applicable or provided here.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the context of AI/ML is not applicable for this type of immunoassay device. The device's operational parameters (like antibody conjugates, membrane properties, and cut-off thresholds) are established through research, development, and analytical validation studies, not by training on a labeled 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.