(262 days)
The Distinct® Early Detection Pregnancy Test is an aid for the early detection of pregnancy intended for home use. The device is a chromatographic immunoassay that performs qualitative detection of human chorionic gonadotropin (hCG) in urine. This test can help determine pregnancy as early as 6 days before the day of the missed period (5 days before the day of the expected period).
The Distinct® Early Detection Pregnancy Test is a rapid chromatographic immunoassay for in vitro qualitative detection of human chorionic gonadotropin in urine to aid in the early detection of pregnancy. It is for self-testing. The test strip and absorbent tip are assembled in a plastic housing. The test strip contains monoclonal anti-hCG antibodies and goat anti-mouse polyclonal antibodies. The test result is shown in the result window and read visually after 3 minutes of urine application.
A blue sign of plus (+) at the test window indicates that hCG has been detected (pregnant). Absence of the plus (+) and only a blue line (-) in the Test Window suggests no hCG has been detected. To serve as a procedural control, a blue line will always appear in the Control Window indicating that proper volume of specimen has been added and membrane wicking has occurred.
The provided information describes the validation study for the "Distinct® Early Detection Pregnancy Test." Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a separate section with specific thresholds. However, based on the studies performed, the implied performance criteria for this qualitative immunoassay are high agreement with a predicate device and high sensitivity (low detection limit for hCG).
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity (Detection Limit) | Detect 10 mIU/mL hCG with 100% positivity | 100% of samples were positive at 10 mIU/mL hCG and higher. |
| Accuracy (Lay User vs. Professional) | >99% agreement with predicate device (professional use) | Urine Stream Method: 100% agreement (51 Pos, 51 Neg by both, 0 disagreement). |
| Urine Dipping Method: 100% agreement (52 Pos, 51 Neg by both, 0 disagreement). Overall accuracy >99%. | ||
| Cross-Reactivity | No cross-reactivity with FSH, TSH, LH up to 1000 mIU/mL/µIU/mL | No cross-reactivity observed with 1000 mIU/mL FSH, 1000 µIU/mL TSH, and 1000 mIU/mL LH. |
| Interference | No interference from common endogenous/exogenous substances | None of the tested endogenous or exogenous substances interfered with expected results. |
| pH Effects | No interference from urine pH 4-9 | Urine pH range of 4 to 9 did not interfere with performance. |
| Specific Gravity Effects | No interference from urine specific gravity 1.003-1.035 | Urinary specific gravity over the range of 1.003 - 1.035 did not influence results. |
| High Dose Hook Effect | No false negatives at high hCG concentrations up to 1,000,000 mIU/mL | No hook effect observed at hCG concentrations up to 1,000,000 mIU/mL. |
| hCG ß-Core Fragment Effects | No false negatives due to high ß-Core Fragment concentrations | No hook effect observed at ß-Core Fragment concentrations up to 1,000,000 pmol/L. |
| Early Pregnancy Detection | Detect pregnancy at various days before expected period (comparable to predicate) | EMP: 100% positive; EMP-1 day: 100% positive; EMP-2 days: 100% positive; EMP-3 days: 96.9% positive; EMP-4 days: 93.8% positive; EMP-5 days: 75.4% positive; EMP-6 days: 49.2% positive; EMP-7 days: 20.3% positive; EMP-8 days: 10.0% positive. |
| Negative Predictive Value (Non-Pregnant Women) | No false positives in non-pregnant women across age groups | No positive results observed for any of the 300 non-pregnant subjects across three age groups. |
| Ease of Use (Laypersons) | Can be performed correctly and is easy to use by laypersons | Study results indicate it can be performed correctly by laypersons and is easy to use. |
2. Sample Size Used for the Test Set and the Data Provenance:
- Precision/Reproducibility Study:
- Sample Size: 30 negative urine specimens spiked with hCG at various concentrations (3, 5, 6, 7.5, 8, 8.5, 10, 12, 15, and 25 mIU/mL).
- Data Provenance: Not explicitly stated, but implies laboratory-prepared samples. Retrospective (spiked samples).
- User Performance Study:
- Sample Size: 205 laypersons.
- Data Provenance: Not explicitly stated, but implies U.S. or similar country where FDA approval is sought. Prospective (lay users testing their own urine).
- Device Performance in Different Age Groups:
- Sample Size: 300 subjects (100 for each age group: 18-40, 41-45, and 55+).
- Data Provenance: Not explicitly stated. Prospective (subjects providing samples).
- Detection of hCG in Early Pregnancy Clinical Samples:
- Sample Size: 65 non-pregnant women expecting to become pregnant.
- Data Provenance: Not explicitly stated. Prospective (daily urine collection from women).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
- Precision/Reproducibility Study: The ground truth (hCG concentration) was established by spiking negative urine specimens with known concentrations of WHO 5th International hCG standard. No human experts were explicitly mentioned for interpreting the spiked samples' "true" status, as it's a controlled analytical test.
- User Performance Study: The ground truth for comparative results was established by professional testing with the predicate device using the same samples tested by laypersons. The qualifications of these professionals are not specified beyond "professional" use.
- Device Performance in Different Age Groups: The ground truth for "non-pregnant" status was assumed based on the study design for non-pregnant women. No experts were mentioned for establishing ground truth; it was based on the absence of hCG.
- Detection of hCG in Early Pregnancy Clinical Samples: The ground truth of pregnancy status was inferred from positive hCG results over time relative to the expected menstrual period. It's not explicitly stated that an "expert" individually established the ground truth for each sample. The study assesses the device's ability to detect hCG in early pregnancy, with the "truth" being the presence or absence of a detectable hCG level over time.
4. Adjudication Method for the Test Set:
- The document does not describe a formal adjudication method (e.g., 2+1, 3+1 consensus) for establishing ground truth from multiple human readers for any of the studies.
- In the User Performance Study, the comparison was between the layperson's interpretation of the candidate device and a professional's interpretation of the predicate device (or presumably, professional interpretation of the candidate device in parallel, though the wording specifies "compared to results from the same sample performed with the predicate device"). This implies a direct comparison rather than an adjudication process involving multiple readers for consensus.
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 involving AI assistance for human readers was not done. This device is a rapid chromatographic immunoassay (a traditional dipstick-style pregnancy test) and does not involve AI or digital image analysis by human readers. The "reader" is directly the lay user who visually interprets the test line.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- No, a standalone algorithm performance study was not done. The device is a visual qualitative test designed for direct human interpretation. There is no algorithm involved in interpreting the results.
7. The Type of Ground Truth Used:
- Analytical Performance Studies (Precision, Cross-Reactivity, Interference, Hook Effect, etc.): The ground truth was primarily based on known concentrations of spiked hCG and other substances (e.g., WHO 5th International Standard for hCG, known concentrations of interfering substances).
- User Performance Study: The ground truth for comparison was established by professional use of a predicate device on the same samples.
- Device Performance in Different Age Groups: Ground truth was based on the confirmed non-pregnant status of the subjects.
- Detection of hCG in Early Pregnancy Clinical Samples: Ground truth for pregnancy detection over time was based on the presence/absence of hCG in urine samples collected prospectively from women trying to conceive, with "positive" samples validated by the test itself and monitored over time relative to the expected period.
8. The Sample Size for the Training Set:
- This device is a traditional immunoassay, not an AI/ML device. Therefore, the concept of a "training set" for an algorithm is not applicable. The device itself (the physical test strip) is manufactured based on established principles of immunoassay development.
9. How the Ground Truth for the Training Set Was Established:
- As stated above, there is no training set as this is not an AI/ML device. The "ground truth" in the development of such assays typically comes from established scientific principles, calibrated reference materials (like WHO standards), and extensive R&D to ensure the antibodies and reagents perform as expected for hCG detection.
§ 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.