(287 days)
The Trinity Biotech Captia™ Herpes Simplex Virus (HSV) 2 Type Specific IgG kit is an Enzyme-linked Immunosorbent Assay (ELISA) intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human serum. In conjunction with the Trinity Biotech Captia™ Herpes Simplex Virus (HSV) I Type Specific IgG kit, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. Due to the implications of positive results, it is recommended they be confirmed in a low prevalence population with Western blot. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, for testing of immunocompromised patients, or for use with automated equipment. The user is responsible for establishing assay performance in these populations and with automated equipment.
The CaptiaTM HSV 2 IgG Type Specific kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to Herpes simplex Type 2 antigen. The Captia™ HSV 2 IgG Type Specific assay may be used as an aid in the diagnoses of Herpes infection. Purified recombinant HSV gG2 antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present, it will bind to the antibody attached to the antigen on the well. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present, the substrate will undergo a color change. After an incubation period, the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
The provided document details the performance characteristics of the Captia™ HSV 2 IgG Type Specific ELISA Test Kit. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve X% sensitivity and Y% specificity"). Instead, it presents the performance of the device against a predicate device (Western Blot) and an alternate ELISA. The reported performance is summarized below from different study populations. The predicate device used for comparison is the Western Blot (WB) from a Pacific Northwest university.
| Performance Metric | Study Population | Reported Device Performance (Captia™ HSV 2 IgG ELISA) | 95% Confidence Interval (CI) |
|---|---|---|---|
| % Agreement Positive to WB | Expectant Mothers | 100.00% (43/43) | 91.8-100.0% |
| % Agreement Negative to WB | Expectant Mothers | 91.52% (151/165) | 86.2-95.3% |
| % Agreement Positive to WB | Sexually Active Adults | 96.72% (59/61) | 88.7-99.6% |
| % Agreement Negative to WB | Sexually Active Adults | 90.30% (121/134) | 84.0-94.7% |
| % Agreement Positive to WB | Low Prevalence Population | 100.00% (4/4) | 39.8-100.0% |
| % Agreement Negative to WB | Low Prevalence Population | 91.06% (163/179) | 85.9-94.8% |
| % Agreement Positive to Culture | Culture Positives | 100.00% (56/56) | 93.6-100.0% |
| % Agreement Positive to WB | Culture Positives | 100.00% (55/55) | 93.5-100.0% |
| % Positive Agreement vs. Alternate ELISA | Prospectively Collected, Sequential Sera | 97.14% (68/70) | 90.1-99.7% |
| % Negative Agreement vs. Alternate ELISA | Prospectively Collected, Sequential Sera | 92.13% (117/127) | 86.0-96.2% |
| % Agreement vs. Alternate ELISA | Prospectively Collected, Sequential Sera | 92.50% (185/200) | 87.9-95.7% |
| Type-specificity relative to WB | HSV 1 WB Positive, HSV 2 WB Negative Sera | 90.75% (265/292) | 86.8-93.8% |
| Type cross-reactivity relative to WB | HSV 1 WB Positive, HSV 2 WB Negative Sera | 8.0% (23/292) | 5.06-11.6% |
2. Sample Size Used for the Test Set and Data Provenance
The document describes several distinct test sets:
- Expectant Mothers:
- Sample Size: n = 210
- Data Provenance: Consented, coded, unselected, banked, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
- Sexually Active Adults:
- Sample Size: n = 198
- Data Provenance: Consented, unselected, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
- Low Prevalence Population:
- Sample Size: n = 184
- Data Provenance: Unselected, banked, and masked sera. The reference method (Western Blot) was from a Pacific Northwest university. This suggests retrospective data.
- Culture Positives:
- Sample Size: n = 56
- Data Provenance: Unselected, retrospective, and masked sera from patients at least six weeks but not more than one year post clinical presentation and culture HSV 2 positive. Reference methods (culture and Western Blot) were from a Pacific Northwest university.
- Prospectively Collected, Sequential Sera (vs. Alternate ELISA):
- Sample Size: n = 200
- Data Provenance: Prospective, unselected, sequentially submitted specimens. Collected by an outside investigator at a Pacific Northwest University.
- Type Specificity with HSV 1 Western Blot Positives:
- Sample Size: n = 292
- Data Provenance: HSV 1 Western Blot positive and HSV 2 Western Blot negative sera from the above described populations (expectant mothers, sexually active adults, low prevalence persons, and HSV 1 culture positives). Collected by an outside investigator at a Pacific Northwest University. This is a retrospective analysis of previously collected samples.
In general, the data seems to be from the United States (Pacific Northwest university) and is predominantly retrospective (banked, unselected, masked, retrospective sera), with one prospective study for comparison against an alternate ELISA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly mention "experts" in the context of establishing ground truth. The ground truth for comparative studies is established by reference methods, primarily:
- Western Blot (WB): From a "Pacific Northwest university." No specific detail on the qualifications of the individuals performing or interpreting the Western Blot.
- Culture (for Culture Positives set): Implies standard laboratory procedure for viral culture, not explicitly associated with "experts" in this context.
Therefore, the specific number and qualifications of experts beyond the unspecified standard practices of a university lab for performing Western Blots and cultures are not detailed in the provided information.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method (e.g., 2+1, 3+1). The comparisons are directly between the Captia™ ELISA and the reference method results. There's no mention of a process where multiple readers or experts review discordant results to reach a 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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (ELISA test kit) and does not involve human readers interpreting images or results, nor does it incorporate AI. Its performance is measured directly against laboratory reference standards.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented describe the standalone performance of the Captia™ HSV 2 IgG Type Specific ELISA Test Kit. This is an enzymatic immunoassay (ELISA) performed in a laboratory setting, and its efficacy is measured by comparing its outputs directly against established reference methods (Western Blot, culture, or another ELISA). There is no "human-in-the-loop" component in the performance evaluation described, beyond the technical execution of the tests themselves.
7. The type of ground truth used
The primary type of ground truth used across the various studies is:
- Reference Standard (Western Blot): The Western Blot (WB) method from a Pacific Northwest university served as the gold standard for serological detection of HSV 2 IgG antibodies in most studies.
- Culture: For the "Culture Positives" group, the ground truth for actual infection was established by HSV 2 culture positivity.
- Alternate ELISA: In one study, another commercially available HSV 2 type-specific IgG ELISA was used as a comparative reference.
8. The sample size for the training set
The document provides performance data based on comparative studies with clinical samples. It does not mention a "training set" in the context of machine learning or algorithm development. This is a traditional IVD device, not an AI-driven algorithm. The performance evaluation focuses on the device's accuracy against established reference methods using specific test populations.
9. How the ground truth for the training set was established
As there is no explicit "training set" described for the development of a machine learning algorithm, this question is not applicable. The device's underlying mechanism is a biochemical ELISA, not an algorithm that learns from data. Its "ground truth" for development would relate to the antigen/antibody interactions it's designed to detect.
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).