(398 days)
One Step Pregnancy Test is an over-the-counter lateral flow immunoassay for the qualitative detection of human chorionic gonadotropin (hCG) in urine. The visual test is intended for home use as an aid in early detection of pregnancy. The test is indicated for use from 4 days before the day of the expected period (5 days before the day of the missed period).
The One Step Pregnancy Test is an over-the-counter, visual pregnancy test with sensitivity of 25mIU/mL hCG (human chorionic gonadotropin) and is indicated for use up to 4 days before the expected period (5 days before the missed period). The device eeeploys an immunochromatographic sandwich assay to detect hCG on a lateral flow test strip housed in a cassette. Following sample application using the supplied pipette, the user is required to visually interpret the results displayed as lines in a result window.
This document describes the validation of the "One Step Pregnancy Test," an over-the-counter lateral flow immunoassay for qualitative detection of human chorionic gonadotropin (hCG) in urine.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criterion | Description | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity | The lowest concentration of hCG at which the device reliably produces a positive result (detects pregnancy). | 25 mIU/mL: The study demonstrated that at 25 mIU/mL hCG, 100% of the devices (180/180) returned a "Pregnant" result. |
| Analytical Specificity (Interfering Substances) | The ability of the device to correctly identify the absence of pregnancy in the presence of various potentially interfering substances (e.g., common medications, urine constituents). | No interference was observed at tested concentrations of a wide range of substances including Acetylsalicylic acid, Acetone, Albumin, Ampicillin, Ascorbic acid, Atropine, Bilirubin, Blood, Caffeine, Cannabinol, Clomiphene citrate, Cotinine, Ethanol, E3G, Glucose, Gentisic acid, Haemoglobin, Hydrochloric acid, Ibuprofen, Leukocytes, Oxytetracycline, Paracetamol, P3G, Phenylpropanolamine, Semen, Sodium hydroxide, Tetracycline, Urea, and Uric acid. |
| Analytical Specificity (Cross Reactants) | The ability of the device to correctly identify the absence of pregnancy in the presence of other hormones that might be structurally similar to hCG. | Specificity of ≥99% was demonstrated when tested with Follicle – Stimulating Hormone (FSH) (1000 mIU/mL), Luteinizing Hormone (LH) (500 mIU/mL), and Thyroid – Stimulating Hormone (TSH) (1mIU/mL). The performance was also not affected by high concentrations of hCG ß-core fragment. |
| Precision/Reproducibility | Consistency of results when tested by different operators, on different days, and with different batches of devices. | The study (180 devices from 4 batches, tested by 3 operators over 3 non-consecutive days at 8 hCG concentrations) indicated that results were not significantly affected by operator, day of testing, or batch across the tested standards. At 25 mIU/mL and above, 100% pregnant results were consistently observed across all batches. |
| High Dose Hook Effect | The absence of a "hook effect," where very high concentrations of the analyte can lead to a false negative result. | No hook effect was observed at tested hCG concentrations up to 1,000,000 mIU/mL. |
| Stability | The device maintains its performance over its claimed shelf life. | The claimed shelf life is 24 months when stored in sealed pouches at room temperature. Real-time stability studies are ongoing. (Note: This criterion is met, but the details of the study proving it are not fully described, only that it's ongoing). |
| Effect of Urine pH | The device's performance is robust across a physiologic range of urine pH. | The device continued to return a correct result when tested with urine samples in the pH range of 4 - 9. |
| Effect of Urine Specific Gravity | The device's performance is robust across a range of urine specific gravity. | The device continued to return a correct result in response to changes in specific gravity within the range from 1.000 to ≤1.035. |
| Agreement with Predicate Device | The device performs equivalently to a legally marketed predicate device. | 100% agreement with the QUIK-CHECK™ Home Pregnancy Test when testing 150 pregnant and 150 non-pregnant urine samples. |
| Lay User Performance | The device can be used and interpreted correctly by intended lay users (over-the-counter use). | 100% agreement between lay-user volunteer results and their clinical status with the One Step Pregnancy Test (n=120, 21 pregnant, 99 not pregnant). Also, 100% agreement between lay-user volunteer results and technician results. A separate lay user study on biobank samples (n=79, 70 pregnant, 9 not pregnant) also showed 100% agreement between volunteer results and the clinical status of the biobank sample. This demonstrates that volunteers were able to use the product following the IFU to obtain a valid result. |
| False-Positive Rate | The rate at which the device incorrectly identifies pregnancy in non-pregnant individuals, especially in specific demographics like peri- and post-menopausal women where hCG levels might fluctuate. | 0% false positives observed (100% specificity): |
- Peri-menopausal (n=150) and Post-menopausal (n=150) women: 100% specificity.
- Pre-menopausal (18-40 years) non-pregnant women (n=133) from the comparison study: 100% specificity. |
| Early Pregnancy Detection | The ability of the device to detect pregnancy accurately at various stages relative to the missed period, as claimed in the indications for use (from 4 days before the day of the expected period). | At 4 days before the expected period (-4 days relative to missed period), the device detected 91.7% of pregnancies (121/132). Performance increased closer to the missed period, reaching 100% on the day of the missed period (Day 0). This supports the claim for use from 4 days before the expected period. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Analytical Performance (Precision/Reproducibility/Sensitivity):
- Sample Size: 1440 devices tested (180 devices per hCG standard concentration x 8 concentrations). Each concentration had 45 devices from each of 4 batches.
- Data Provenance: Not explicitly stated, but implied to be generated in a controlled laboratory setting (likely in the UK, given the applicant's address). This was a prospective study where samples were spiked with known concentrations of hCG.
-
High Dose Hook Effect Study:
- Sample Size: 75 devices (5 replicates per concentration x 3 batches x 5 concentrations).
- Data Provenance: Laboratory setting, spiked samples.
-
Interfering Substances Study:
- Sample Size: 2 (urine standards) x Number of interfering substances (approx. 20-30 substances) x 5 devices x 3 batches. So, potentially 300-450 devices per interfering substance.
- Data Provenance: Laboratory setting, spiked samples.
-
Cross Reactants Study:
- Sample Size: 3 cross reactants x 2 (urine standards) x 5 devices x 3 batches = 90 devices. The hCG ß-core fragment study involved 165 devices (11 conditions x 5 devices x 3 batches).
- Data Provenance: Laboratory setting, spiked samples.
-
Urine pH and Specific Gravity Studies:
- Sample Size: 6 pH conditions x 2 (urine standards) x 15 devices = 180 devices for pH. 5 SG conditions x 2 (urine standards) x 15 devices = 150 devices for SG.
- Data Provenance: Laboratory setting, adjusted urine samples.
-
Comparison Study with Predicate Device:
- Sample Size: 300 urine samples (150 pregnant, 150 not pregnant). Each sample was tested on the subject device and the predicate device.
- Data Provenance: Not explicitly stated, but refers to "urine samples from pregnant women and not pregnant women," implying real patient samples. Retrospective (samples collected and then tested).
-
Early Pregnancy Detection Clinical Samples:
- Sample Size: 1197 One Step Pregnancy Test devices used. The table shows varying numbers of samples per day relative to missed period, totaling 1197.
- Data Provenance: Early pregnancy urine samples collected from days 0 to -9 relative to the day of the missed period. Implied to be real patient samples. Retrospective.
-
Lay User Study (Own Urine Sample):
- Sample Size: 120 volunteers (21 pregnant, 99 not pregnant). Each volunteer tested their own urine sample.
- Data Provenance: Prospective, real-world (home-use simulation). Participants were "pregnant and not pregnant women volunteers with diverse educational and professional backgrounds." The "clinical status" was the ground truth.
-
Lay User Study on Biobank Samples:
- Sample Size: 79 volunteers (70 pregnant, 9 not pregnant). Each volunteer tested a single biobank sample.
- Data Provenance: Prospective, using "biobank samples" with "confirmed clinical pregnancy status."
-
Specificity Study (False-Positive Rate - Peri/Post-menopausal):
- Sample Size: 300 urine samples (150 from peri-menopausal women, 150 from post-menopausal women).
- Data Provenance: Real patient samples from specific demographic groups. Retrospective.
3. Number of Experts and Qualifications for Ground Truth
- For the Analytical Performance studies (sensitivity, specificity, precision, hook effect, pH, SG), the ground truth was established by the precise spiking of hCG to known concentrations or the verified absence of hCG in negative urine, as well as the addition of known interfering/cross-reacting substances. No human "experts" were needed for interpretation of these analytical measurements; the results were quantitative (concentration) or verified qualitative properties.
- For the Comparison Study, Early Pregnancy Detection Clinical Samples, and False-Positive Rate Study (Peri/Post-menopausal), the ground truth was "clinical status" or "clinical pregnancy status." It is implied that this clinical status was established by medical professionals or standard clinical diagnostic methods. The document does not specify the number or qualifications of these experts, as the device is being compared to a clinical status rather than an expert's interpretation of an image.
- For the Lay User Studies, the ground truth was the "clinical pregnancy status" of the volunteers' own urine samples or the "confirmed clinical pregnancy status" of the biobank samples. Again, the number and specific qualifications of the medical professionals establishing this clinical status are not detailed.
4. Adjudication Method for the Test Set
- Adjudication, in the sense of multiple experts reviewing and reaching consensus on an image or case, is not applicable here. This is a diagnostic immunoassay that provides a binary (Pregnant/Not Pregnant) visual result.
- For the analytical studies, the "ground truth" was established based on the controlled preparation of the samples (e.g., precise spiking of hCG).
- For the clinical studies, results were compared against an established clinical status of the urine samples or volunteers.
- In the lay user studies, volunteer interpretations were compared against their clinical status and/or technician interpretations. The document states "100% agreement" implies a direct comparison without a complex adjudication process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done in the context of human readers improving with AI assistance. This device is a standalone over-the-counter visual test, not an AI-assisted diagnostic tool interpreted by medical professionals.
- The "Lay User Study" can be considered a form of human performance evaluation, showing that lay users can correctly interpret the test without assistance, but it is not an MRMC study and does not involve AI assistance.
6. Standalone Performance
- Yes, standalone performance was done. The entire analytical performance section (Precision/Reproducibility/Sensitivity, High dose hook effect, Analytical specificity, Effects of urine pH/SG) evaluates the device's performance independently of human interpretation bias. In these studies, trained technicians performed the tests, ensuring correct execution of the device's mechanism.
- The comparison to the predicate device and the early pregnancy detection studies also represent the device's standalone performance in a clinical context.
7. Type of Ground Truth Used
- Expert Consensus: Not applicable in the typical sense for medical image interpretation.
- Pathology: Not applicable.
- Outcomes Data: The "clinical pregnancy status" (e.g., pregnant or not pregnant) serves as the ultimate ground truth for the clinical and lay user studies. This is an outcome, based on medical assessment.
- Spiked Samples/Known Concentrations: For analytical studies, the ground truth was the precisely known concentrations of hCG or other substances added to the urine samples.
8. Sample Size for the Training Set
- Not applicable. This document describes a traditional in-vitro diagnostic (IVD) device, not an AI/Machine Learning model. Therefore, there is no "training set" in the computational sense. The device's performance is determined by its inherent chemical and physical properties, which are developed through R&D and manufacturing processes.
9. How Ground Truth for the Training Set Was Established
- Not applicable, as there is no training set for this type of medical device.
§ 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.