(111 days)
Pan Probe Blotech (PPB), Inc. LiveSure™ Human Chorionic Gonadotropin (LiveSure™ hCG) Rapid Urinary Pregnancy Test Strip and Test Card Immunoassay Devices are in vitro diagnostic (IVD) qualitative screening lateral flow chromatographic immunoassays that are designed for rapid detection of placental hCG related to pregnancy at an expected value cut-off level of 20 mlU of hCG/ml of human urine. These LiveSure™ IVD immunoassay devices for urinary hCG pregnancy screening are neer non to give visual, qualitative results and are intended for professional use only. The PPB LiveSure™ hCG Test Strip and Test Card Devices are not intended for quantitative results, nor over-the-counter sales, but provide only professional use preliminary screening data for use to aid in the diagnosis of pregnancy. A clinical diagnosis by a medical professional must be obtained in order to confirm any analytical result, and to rule c: I any non-pregnancy diseases that can also result in elevated hCG. Clinical considerations and professional judgment should be applied to any test result, particularly when preliminary positive results are indicated.
The PPB LiveSure™ hCG Screen (i.e., LiveSure™ hCG) Test Strip and Test Card Devices are rapid qualitative lateral flow chromatographic IVD immunoassays and are intended for professional IVD use only. The Pan Probe Biotech LiveSure™ hCG Test Strip & Test Card Devices provide only preliminary analytical data for use to aid in the diagnosis of pregnancy. A clinical diagnosis by a medical professional must be obtained in order to confirm any analytical result. Each test device consists of a sample reaction unit, a pink colored colloidal gold conjugate unit pre-labeled with hGC-spec fic mouse-monoclonal antibody, and a chromatographic membrane was precoated with mouse-antialpha-hCG capture antibodies at the test band region and goat-antibody at the process control band region. During the test, the human urine specimen is allowed to react with hCG-specific mouse-monocloral antibodycolloid gold conjugate, which has been predried on the test component of each device. The mixture then moves chromatographically upward on the capillary action. For a pregnancy-positive specimen, gold conjugate complex binds to hCG at a level of 20 mlU/ml or greater, forming an antibody-antigen complex. This complex binds to hCG antibody as captured regents on the Test Region and produces a colored band when hCG concentration is equal to or greater than 20 mlU/ml. Absence of this colored band in the Test Region suggests a negative result Summarizing, negative urine will produce only one pink colored band in the control region, while positive urine will produce two pink colored bands, in both the control and test regions.
Here's an analysis of the provided text to extract the requested information concerning the acceptance criteria and the study proving the device meets them:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Relative sensitivity with positive pregnancy tests | 100% (against clinical lab diagnoses and predicate devices, both in-house and external lab) |
| Relative specificity with negative pregnancy diagnoses | 100% (against clinical lab diagnoses and predicate devices, both in-house and external lab) |
| Overall accuracy | >99% (against clinical lab diagnoses and predicate devices, both in-house and external lab) |
| Sensitivity of positive EIA results | 100% (against quantitative Abbott's Axsym™ hCG ElA assay at external lab) |
| Specificity of negative EIA results | 95.0% (153/161) (against quantitative Abbott's Axsym™ hCG ElA assay at external lab). The document states this was due to low EIA values below 15 mIU/ml, which were considered false negatives by EIA as patients were clinically pregnant. Therefore, from a clinical pregnancy standpoint, the device achieved 100% agreement for positive cases. |
| Overall statistical accuracy (vs. EIA) | 96.8% (244/252) (against quantitative Abbott's Axsym™ hCG ElA assay at external lab) |
| Substantial equivalence | Confirmed against predicate ABI's SureStep™ and Quidel's QuickVue™ hCG test devices (both positive and negative diagnoses). Achieved 95% or better in equivalency to quantitative Axsym™ EIA assay results for negative diagnoses, and 100% for positive diagnoses. |
| Expected Value cut-off level | 20 mU of hCG/ml of urine (device is designed for rapid detection at this level or greater) |
Study Details
1. Sample sizes used for the test set and the data provenance:
- External Clinical Lab: 252 urine samples with clinically confirmed diagnoses.
- Data Provenance: Retrospective (implied, as samples had "clinically confirmed diagnoses" prior to testing).
- In-house Testing: 136 urine samples with clinically confirmed diagnoses.
- Data Provenance: Retrospective (implied, as samples had "clinically confirmed diagnoses" prior to testing).
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document states "clinical lab data on diagnoses of pregnancy" and "clinically confirmed diagnoses." It also mentions testing performed "by several licensed technologists" at the external lab.
- Number of experts: At least "several licensed technologists" were involved in running tests and presumably contributing to or validating the "clinical lab data on diagnoses of pregnancy." The exact number of specialists (e.g., physicians, pathologists) who established the initial clinical diagnoses is not specified, but it implies medical professionals.
- Qualifications of experts: "Licensed technologists" for performing tests, and "medical professional" for clinical diagnosis. Specific specializations (e.g., radiologist, obstetrician) are not provided.
3. Adjudication method for the test set:
- The document implies that the ground truth was established by "clinically confirmed diagnoses" or "clinical lab data on diagnoses of pregnancy." The test results from the LiveSure™ hCG devices (and predicate devices) were then compared against this established clinical truth. There is no explicit mention of an adjudication method like 2+1 or 3+1 among multiple readers for the test results themselves, rather the device's accuracy was assessed against a pre-existing clinical ground truth.
4. 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, this was not a multi-reader multi-case (MRMC) comparative effectiveness study. The device is a rapid diagnostic immunoassay intended for professional use, but it does not involve human readers interpreting complex images or data assisted by AI. The comparison was device-to-device and device-to-clinical diagnosis.
5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The LiveSure™ hCG device itself is a "standalone" rapid test strip/card. It produces a visual result (one or two pink bands). While a "professional" interprets the result, the device's performance metrics (sensitivity, specificity, accuracy) are reported for the device purely based on its output against the ground truth. It's an "algorithm only" in the sense that the chemical and physical reactions within the strip determine the outcome, without complex human interpretation of raw data. However, it requires a human to visually read the result. Therefore, it's a "device only" performance study.
6. The type of ground truth used:
- The ground truth was primarily based on expert clinical diagnoses of pregnancy.
- Additionally, quantitative Abbott's Axsym™ hCG ElA assay determinations served as a comparative ground truth for analytical performance, though the document explicitly states clinical pregnancy diagnoses superseded some EIA results (e.g., when EIA gave low negative values for clinically pregnant patients).
7. The sample size for the training set:
- The document does not specify a separate training set size. The described studies focus on testing the finished device against clinical samples. This type of immunoassay development typically involves extensive internal R&D, calibration, and optimization (which can be considered analogous to "training") with internal controls and characterized samples, but a distinct "training set" in the machine learning sense is not detailed in this submission summary.
8. How the ground truth for the training set was established:
- As no explicit training set is described in the provided summary, the method for establishing its ground truth is also not specified. Device development and calibration would have relied on characterized hCG samples and known positive/negative clinical samples, but these are not formally presented as a "training set" in this context.
§ 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.