(218 days)
The iHealth® Early Pregnancy Test is an OTC in vitro diagnostic test used to assess early pregnancy by detecting the presence of the hCG (human chorionic gonadotropin) hormone in urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the missed period, i.e., as early as five (5) days before the day of the expected period.
The iHealth® Early Pregnancy Test Strip is an OTC in vitro diagnostic test used to assess early pregnancy by detecting the presence of the hCG (human chorionic gonadotropin) hormone in urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the missed period, i.e., as early as five (5) days before the day of the expected period.
The iHealth® Early Pregnancy Test is a lateral flow immunoassay technique device designed for the qualitative determination of human chorionic gonadotropin (hCG) concentration in human urine samples, and is indicated for use as an aid in early detection of pregnancy. The iHealth® Early Pregnancy Test is designed to detect as early as six (6) days before the day of the missed period, i.e., as early as five (5) days before the day of the expected period. Test result is displayed to the user as two lines for a 'Pregnant' result and one line for a 'Not Pregnant' result.
The iHealth® Early Pregnancy Test are in two different formats: Stick and Strip format. Two test formats use identical strips and each test strip in the device consists of: Sample pad, colloidal gold binding pad, nitrocellulose membrane, absorbent paper and PVC board, colloidal gold binding pad coated with hCG monoclonal antibody 1, test line(T Line) coated with hCG-monoclonal antibody 2 and control line(C Line) coated with goat anti-mouse IgG antibody.
Two formats have the same performance specifications. The difference is that Stick format is designed to be tested in dip or midstream method, and Strip format is tested in dip method only.
The provided document describes the iHealth® Early Pregnancy Test and iHealth® Early Pregnancy Test Strip, which are over-the-counter in vitro diagnostic devices used to detect human chorionic gonadotropin (hCG) in urine for early pregnancy detection.
Here's a breakdown of the acceptance criteria and the studies performed:
1. A table of acceptance criteria and the reported device performance:
The document doesn't explicitly state "acceptance criteria" in a separate table. However, based on the performance characteristics presented, the key acceptance criteria for this type of device would typically revolve around its analytical sensitivity (detection limit) and its ability to accurately classify pregnant and non-pregnant states. The sensitivity of hCG detection is a critical performance metric for early pregnancy tests.
Table 1: Key Performance Metrics for iHealth® Early Pregnancy Tests
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity (hCG detection) | Detect 10 mIU/mL hCG with 100% positivity. | 100% positive at 10 mIU/mL hCG for all formats and lots tested. |
| Specificity (False Positive Rate) | No false positives in non-pregnant individuals. | 0% false positives in 300 urine samples from non-pregnant premenopausal, peri-menopausal, and postmenopausal women. |
| Hook Effect | No hook effect at high hCG concentrations. | No hook effect observed up to 1,000,000 mIU/mL. |
| Shelf-Life Stability | 24 months at 2°C - 30°C. | 24 months met at 36°F - 86°F (2°C - 30°C). |
| Cross-Reactivity (hLH, hFSH, hTSH) | No cross-reactivity at specified concentrations. | No cross-reactivity observed with 500 mIU/mL hLH, 1000 mIU/mL hFSH, 1000 µIU/mL hTSH. |
| Effect of hCG β-core fragment | No effect on performance at specified concentrations. | No effect observed up to 1,000,000 pmol/L. |
| Interfering Substances | No interference from common substances. | No interference effect observed at tested concentrations of numerous substances listed (e.g., Acetaminophen, Glucose, Hemoglobin). |
| Urine pH effect | No effect on performance across physiological pH range. | No effect observed for pH ranging from 4.0 to 9.0. |
| Urine Specific Gravity effect | No effect on performance across physiological specific gravity range. | No effect observed for specific gravity ranging from 1.000 to 1.035. |
| Method Comparison (Conformity with Predicate) | 100% conformity with predicate device. | 100% conformity between candidate and predicate for both positive and negative samples. |
| Lay User Study (Conformity with Professional) | 100% conformity with professional results. | 100% positive and 100% negative conformity observed. |
| Lay User Spiked Standard (10 mIU/mL) | 100% positive detection by lay users. | 100% positive for 10 mIU/mL hCG. |
| Lay User Spiked Standard (0, 2, 3 mIU/mL) | 0% positive detection by lay users. | 0% positive for 0, 2, 3 mIU/mL hCG. |
2. Sample sizes used for the test set and the data provenance:
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Analytical Sensitivity (Precision):
- Test Set Sample Size: 405 individual tests for each hCG concentration (0, 3, 5, 7.5, 10, 12.5, 15, 25 mIU/mL) for each device format (Strip, Stick-dip, Stick-midstream), totaling 8 concentrations x 405 tests = 3240 tests per device type. The total number of individual readings is significantly higher due to multiple lots and operators. For the 5 mIU/mL the total samples are 170 negative and 235 positive in the Strip format.
- Data Provenance: Not explicitly stated, but the study was performed "at three sites" by "nine operators," suggesting a multi-site internal study. The samples were "Not-pregnant female urine was spiked with hCG traceable to the 5th WHO international standard".
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Specificity Study:
- Test Set Sample Size: 300 urine samples (100 from premenopausal, 100 from peri-menopausal, 100 from postmenopausal women).
- Data Provenance: Not explicitly stated, but implies collected urine samples.
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Hook Effect Test:
- Test Set Sample Size: Not explicitly quantified, but performed on urine samples spiked with hCG at 0, 10, 1,000, 10,000, 100,000, and 1,000,000 mIU/mL.
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Cross-Reactivity & Interfering Substances:
- Test Set Sample Size: Not explicitly quantified. Performed on negative and 10 mIU/mL hCG positive urine samples spiked with various substances.
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Method Comparison Study:
- Test Set Sample Size: 204 pregnant and non-pregnant subjects. 109 positive samples and 95 negative samples in total across both formats. iHealth® Early Pregnancy Test Strip: 103 samples (54 positive, 49 negative). iHealth® Early Pregnancy Test Stick: 101 samples (55 positive, 46 negative).
- Data Provenance: Not explicitly stated, but implies collected samples from subjects.
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Lay User Study (Conformity with Professional):
- Test Set Sample Size: 204 pregnant and not pregnant women subjects. iHealth® Early Pregnancy Test Strip: 103 subjects (54 positive, 49 negative). iHealth® Early Pregnancy Test Stick: 101 subjects (55 positive, 46 negative).
- Data Provenance: Women subjects with diverse educational and professional backgrounds and ages between 18 and 55 years old who tested their own urine samples.
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Lay User Spiked Standard Study:
- Test Set Sample Size: 100 women.
- Data Provenance: Women with diverse educational and professional backgrounds (18-55 years old) who performed testing using spiked samples.
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Detection of hCG in Early Pregnancy Clinical Samples:
- Test Set Sample Size: 83 subjects for each day relative to expected missed period (-8 to +1).
- Data Provenance: Early pregnancy urine samples collected from subjects.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Analytical Sensitivity (Precision): The results were generated by "nine operators." Their specific qualifications are not detailed, but their involvement across three sites suggests trained personnel in a laboratory or clinical setting.
- Method Comparison and Lay User Studies: The "professional testing" serves as the reference standard against which the lay user and candidate devices were compared. The number and qualifications of these "professionals" are not specified in the document.
- Detection of hCG in Early Pregnancy Clinical Samples: The "early pregnancy urine samples" themselves imply a clinical diagnosis of pregnancy, which would typically be established by medical professionals. However, the number and qualifications of these professionals are not explicitly stated.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
The document does not describe an explicit adjudication method for reconciling conflicting results, such as 2+1 or 3+1. For the analytical studies, the results are presented as counts of positive/negative outcomes, implying a direct outcome rather than expert adjudication. For the comparison studies, results are compared to a "professional" result, which acts as a gold standard, so an adjudication process for discrepancies would implicitly fall under how the "professional" result was determined.
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:
This is not applicable to the device described. The iHealth® Early Pregnancy Test is an in vitro diagnostic (IVD) device that provides a visual result (lines on a stick/strip) for human interpretation. It is not an AI-assisted diagnostic tool for human readers interpreting complex medical images or data. Therefore, an MRMC study assessing AI assistance is not relevant here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
This is not applicable. The device provides a visual output that is then interpreted by the user (human-in-the-loop). Even the "professional testing" involves human interpretation of the device's output. The device itself is not a standalone algorithm that provides a diagnosis without human interaction/interpretation of the visual signal.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Analytical Sensitivity (Precision): The ground truth was established by spiking not-pregnant female urine with known concentrations of hCG traceable to the 5th WHO international standard. This is a scientific, controlled ground truth.
- Specificity: The ground truth was based on urine samples from normal, non-pregnant women. Clinical status (non-pregnant) served as the ground truth.
- Method Comparison and Lay User Studies: The ground truth for these studies was the result obtained by professional testing using the candidate device or the predicate device. This implies a reference method result, likely also interpreted by professionals.
- Detection of hCG in Early Pregnancy Clinical Samples: The ground truth for "early pregnancy urine samples" implies a clinical diagnosis of pregnancy based on medical assessment, which is outcomes data (known pregnancy status) rather than just a subjective expert consensus on the device's result.
8. The sample size for the training set:
The document describes performance studies (analytical and clinical comparisons) but does not mention a training set sample size. This is expected as the iHealth® Early Pregnancy Test is a lateral flow immunoassay, which is a chemical/biological test, not a machine learning model that requires a "training set."
9. How the ground truth for the training set was established:
Since there is no "training set" in the context of a machine learning model for this device, this question is not applicable. The device's performance is intrinsically linked to the chemical properties of the antibodies and reagents used, validated through the performance studies described.
§ 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.