(41 days)
The LIAISON® Toxo IgG II assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer for the qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum. The results of this assay can be used as an aid in the assessment of the patient's serological status to infection with Toxoplasma gondii and in the determination of immune status of individuals including pregnant women. This assay has not been cleared/approved by the FDA for blood/plasma donor screening. U.S. Federal Law restricts this device to sale by or on the order of a physician.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants.
The LIAISON® Control Toxo IgG II (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Toxo IgG II assay on the LIAISON® XL Analyzer.
The method for qualitative determination of IgG antibodies to Toxoplasma gondii (anti-Toxo IgG) is an indirect chemiluminescence immunoassay (CLIA). The principal components of the test are magnetic particles (solid phase) coated with Toxoplasma gondii and a conjugate of mouse monoclonal antibodies to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, Toxoplasma gondii antibodies present in diluted calibrators, samples or controls bind to the solid phase. During the second incubation, the monoclonal antibody conjuqate reacts with anti-Toxo IgG that is already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and therefore, the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of anti-Toxo IqG in calibrators, samples or controls.
All assay steps and incubations are performed by the LIAISON® XL Analyzer.
The DiaSorin LIAISON® Toxo IgG II assay is intended for the qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum using chemiluminescent immunoassay (CLIA) technology on the LIAISON® XL Analyzer. The results aid in assessing a patient's serological status to Toxoplasma gondii infection and in determining the immune status of individuals, including pregnant women.
The study supporting this device's acceptance focused on comparative clinical studies against a predicate device and a CDC panel study.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state "acceptance criteria" in a quantitative format for clinical performance (e.g., minimum sensitivity/specificity thresholds). However, substantial equivalence is claimed based on agreement with a predicate device and a CDC panel. The performance data presented indicates the device aims to accurately identify positive and negative Toxoplasma gondii IgG samples.
Here's a summary of the reported device performance from the studies:
| Study Population | Performance Statistic | Reported Value |
|---|---|---|
| Prospective US Population | Agreement for Negative | 100.0% (Exact 95% CI: 98.0-100.0%) |
| (vs. Comparator Assay) | Agreement for Positive | 100.0% (Exact 95% CI: 84.5-100.0%) |
| Prospective European Population | Agreement for Negative | 94.3% (Exact 95% CI: 90.9-96.6%) |
| Toxoplasma IgG Pregnant Population | Agreement for Negative | 100.0% (Exact 95% CI: 98.0-100.0%) |
| (vs. Comparator Assay) | Agreement for Positive | 85.7% (Exact 95% CI: 60.1-96.0%) |
| Retrospective Population | Agreement for Positive | 100.0% (Exact 95% CI: 91.8-100.0%) |
| (Pre-selected positive samples) | ||
| CDC Panel Study | Sensitivity (True Positive) | 100% |
| (vs. CDC confirmed status) | Specificity (True Negative) | 100% |
2. Sample Sizes and Data Provenance
- Prospective US Population Test Set:
- Sample Size: 204 individuals
- Data Provenance: Prospective, US subjects sent to the lab for Toxoplasma gondii IgG testing.
- Prospective European Population Test Set:
- Sample Size: 600 individuals
- Data Provenance: Prospective, European subjects sent to the lab for Toxoplasma gondii IgG testing.
- Prospective Pregnant Population Test Set:
- Sample Size: 202 females
- Data Provenance: Prospective, pregnant women.
- Retrospective/Pre-Selected Population Test Set:
- Sample Size: 42 individuals
- Data Provenance: Retrospective, samples from individuals with a positive Toxoplasma gondii IgG result by the comparator assay.
- CDC Panel Study Test Set:
- Sample Size: 100 frozen blind specimens (70 true positive, 30 true negative)
- Data Provenance: CDC Toxoplasma 1998 Human Serum Panel.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test sets derived from the comparative clinical studies (US, European, Pregnant, Retrospective populations). The comparison was made against a "comparator assay" (Diamedix Is-Toxoplasma IgG ELISA). For the CDC panel study, the results were submitted to the "CDC (Reference Immunodiagnostic Lab, Biology and Diagnostic Branch Division of Parasitic Diseases) for data analysis," implying that CDC's established ground truth, likely based on expert consensus and/or confirmatory testing, was used.
4. Adjudication Method
The document does not describe a formal adjudication method for discrepancies in the comparative clinical studies. It presents agreement percentages between the new device and the comparator assay. For the CDC panel, the results were submitted to and analyzed by the CDC, which inherently implies an adjudication (or definitive classification) by that reference lab.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is an automated in vitro diagnostic assay, not an imaging or interpretive AI device that would typically involve multiple human readers.
6. Standalone Performance
Yes, a standalone performance study was done. The "Comparison to Predicate Device" section and the "Performance Data: Comparative Clinical Studies" detail the performance of the LIAISON® Toxo IgG II assay (the algorithm/device only) in comparison to a predicate device and a CDC reference panel. The results (e.g., percent agreement, sensitivity, specificity) demonstrate its performance independent of human interpretation other than reading the instrument's output.
7. Type of Ground Truth Used
- For Comparative Clinical Studies (Prospective and Retrospective populations): The ground truth was established by a "comparator assay," specifically the Diamedix Is-Toxoplasma IgG ELISA (K981498). This is a form of expert consensus or reference standard based on an FDA-cleared predicate device.
- For CDC Panel Study: The ground truth was based on the "CDC Toxoplasma 1998 Human Serum Panel," which had true positive and true negative samples validated by the CDC Reference Immunodiagnostic Lab. This represents a highly authoritative, verified ground truth.
8. Sample Size for the Training Set
The document does not specify a separate "training set" sample size. For in vitro diagnostic assays, the development process (which might involve internal optimization, calibration, and iterative testing) is usually distinct from the formal clinical validation studies submitted for regulatory clearance. The provided data focuses on the validation/test sets.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned with details on its ground truth establishment, this information is not available in the provided text. The performance data presented relates to the validation of the finalized device, not its developmental training.
§ 866.3780
Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).