(30 days)
HIGHTOP Pregnancy Rapid Test Cassette is intended for the qualitative detection of human chorionic gonadotropin (hCG) in urine, as an aid in early detection of pregnancy.
HIGHTOP Pregnancy Rapid Test Strip is intended for the qualitative detection of human chorionic gonadotropin (hCG) in urine, as an aid in early detection of pregnancy.
HIGHTOP Pregnancy Rapid Test Midstream is intended for the qualitative detection of human chorionic gonadotropin (hCG) in urine, as an aid in early detection of pregnancy.
HIGHTOP Pregnancy Rapid Test measures the presence of the hormone Human Chorionic Gonadotrophin (HCG) in human urine for the detection of pregnancy. The test devices are in three different formats: Strip, Cassette and Midstream. Each test kit contains a test device sealed in a desiccated aluminum pouch and a package insert. The cassette format also contains a dropper.
Here's an analysis of the acceptance criteria and supporting studies for the HIGHTOP Pregnancy Rapid Test devices, based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Analytical Sensitivity (Detection Limit) | 25 mIU/mL (All three formats - Strip, Cassette, Midstream - achieved 100% positivity at 25 mIU/mL and 100% negativity at 18.75 mIU/mL in the sensitivity study.) |
| Hook Effect | No hook effect observed (No hook effect was observed at hCG concentrations ranging from 3125 to 2,000,000 mIU/mL.) |
| Specificity/Cross-Reactivity | No interference (No interference observed from 500 mIU/mL LH, 1000 mIU/mL FSH, 1000 mIU/L TSH, and 2,000,000 pmol/L hCG ß-core fragment for both negative and positive urine samples.) |
| Interfering Substances | No interference (No interferences observed from a comprehensive list of exogenous compounds at specified concentrations, changes in pH (4-9), or changes in specific gravity (1.002-1.032) for both negative and positive hCG urine samples.) |
| Method Comparison with Predicate Device | High Agreement (Over 96% agreement with the predicate device (WONDFO One Step HCG Urine Pregnancy Test - K043443) for all three formats. Specifically: |
- Strip: 57 positive, 0 false positive, 1 false negative, 62 true negative.
- Cassette: 56 positive, 0 false positive, 2 false negative, 62 true negative.
- Midstream: 57 positive, 0 false positive, 1 false negative, 62 true negative.) |
| Lay Person Readability & Usability | 100% positive and negative conformity with professional results. (Lay person results showed 100% agreement with professional testing. Questionnaire results indicated consumers found the test easy to use and understood labeling/results.) |
| Shelf-Life Stability | 24 months (Based on accelerated testing at 4-30°C in a sealed foil pouch. Real-time stability studies are ongoing.) |
Study Details
2. Sample size used for the test set and the data provenance
-
Analytical Performance (Sensitivity):
- Test Set Sample Size: For each hCG concentration level (0, 12.5, 18.75, 22.5, 25, 50, 100, 200 mIU/mL), 50 replicates per lot across 3 lots = 150 total tests per hCG concentration. This was performed for each of the three device formats (Strip, Cassette, Midstream).
- Data Provenance: Negative urine was spiked with hCG standard. The specific origin of the negative urine or hCG standard is not explicitly stated beyond "traceable to the 5th WHO." This is an in-vitro study setup.
-
Hook Effect Test:
- Test Set Sample Size: Not explicitly stated as a count, but "Negative urine samples were spiked with varying hCG concentrations (3125, 6250, 62500, 125000, 250000, 500000, 1000000 and 2000000 mIU/mL)." Each concentration was tested to observe the effect.
- Data Provenance: In-vitro study setup using spiked urine samples.
-
Specificity and Cross-Reactivity:
- Test Set Sample Size: "Negative and positive urine samples (10 mIU/mL and 25 mIU/mL) were spiked with various concentrations of glycoprotein hormones LH, FSH, TSH and hCG ß-core fragment." The number of replicates is not specified.
- Data Provenance: In-vitro study setup using spiked urine samples.
-
Interfering Substance Test:
- Test Set Sample Size: "Urine samples containing 10 mIU/mL and 25 mIU/mL hCG were spiked with the interfering substance to obtain the desired test concentration" for a long list of substances, as well as pH and specific gravity variations. The number of replicates is not specified.
- Data Provenance: In-vitro study setup using spiked urine samples.
-
Method Comparison Study (with predicate device):
- Test Set Sample Size: 120 urine samples from women ("approximately half... suspected to be pregnant and most of them are in the early stage of less than 5 weeks").
- Data Provenance: Prospective collection from "women presenting to test for pregnancy at OB/GYN Physician's offices." The country of origin is not specified but implied to be where the offices are located. All samples were processed and tested after collection.
-
Lay Person Study:
- Test Set Sample Size: 300 women.
- Data Provenance: Prospective collection. "Women with varying educational and occupational backgrounds from three sites were chosen for the study." The country of origin is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Analytical Performance (Sensitivity): Ground truth was established by spiking known concentrations of hCG into negative urine. No human experts were involved in establishing this ground truth. However, "Tests were performed by three different operators" for reproducibility. Their qualifications are not specified.
- Hook Effect Test, Specificity, Interfering Substances: Ground truth was established by spiking known concentrations of substances into urine. No human experts were involved in establishing this ground truth.
- Method Comparison Study: Ground truth was established by the predicate device. "All samples were tested by ten different health professionals at the 3 OB/GYN Physician's offices with the proposed and the predicate devices." The qualifications of these "health professionals" are not specified beyond their title.
- Lay Person Study: Ground truth was established by "professional testing with the candidate device." It is implied that "professional" here refers to trained personnel, likely the "health professionals" mentioned in the method comparison study. The qualifications of these professionals are not specified.
4. Adjudication method for the test set
- Analytical Performance: The document describes "Total result" columns for '-' and '+' readings, implying a summation of results from different lots and operators. It doesn't describe an adjudication process for discordant results during the initial replicates, but the final % Negative / % Positive is presented as an aggregated outcome.
- Method Comparison Study: No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for resolving discrepancies between the proposed and predicate devices, or among the ten health professionals. The results are presented as direct comparison counts between the proposed device and the predicate device.
- Lay Person Study: No explicit adjudication method is mentioned. Lay person results were compared to "professional testing with the candidate device," and a 100% conformity indicates no discrepancies needed adjudication, or any discrepancies were resolved outside of what is reported.
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 study was not done, and this device is not an AI/CAD device. The studies described are for an in vitro diagnostic (IVD) pregnancy rapid test, which is a chemical assay read visually. There is no AI assistance involved with this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, in essence, standalone performance was assessed though the term "standalone" is more common for AI algorithms. The analytical performance studies (sensitivity, hook effect, specificity, interfering substances) evaluate the device's inherent capability to detect/react to hCG under various conditions. The human role in these initial analytical tests is typically procedural (e.g., proper execution of the test, accurate reading of the results). The method comparison study and lay person study, while involving human readers (health professionals and lay users), assess the device's performance in the hands of users compared to another device or professional reading, rather than as an algorithm versus human.
7. The type of ground truth used
- Analytical Performance Studies (Sensitivity, Hook Effect, Specificity, Interfering Substances): Spiked samples with known concentrations. This is a highly controlled, synthetic ground truth established in a lab setting.
- Method Comparison Study: Ground truth was established by the predicate device (WONDFO One Step HCG Urine Pregnancy Test - K043443). This relies on the established accuracy of another legally marketed device.
- Lay Person Study: Ground truth was established by professional testing with the candidate device. This relies on the deemed accurate interpretation by trained professionals using the same device.
8. The sample size for the training set
- Not applicable. This device is a rapid diagnostic test based on immunochromatography, not an AI or machine learning model that requires a training set. The term "training set" is not relevant to the development and validation of this type of IVD.
9. How the ground truth for the training set was established
- Not applicable. (See point 8 above).
§ 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.