(132 days)
The Copalis® Rubella IgM assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle aggregation-based immunoassay for the qualitative detection of IgM antibodies to Rubella virus in human serum and EDTA, heparin or sodium citrate plasma using the Copalis® I Immunoassay System. The test is indicated for the presumptive diagnosis of primary rubella infection.
The Copalis® Rubella IgM assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle aggregation-based immunoassay for the qualitative detection of IgM antibodies to Rubella virus in human serum and EDTA, heparin or sodium citrate plasma using the Copalis® I Immunoassay System. The test is indicated for the presumptive diagnosis of primary rubella infection.
KIT DESCRIPTION: Coupled Particle Light Scattering (Copalis®) technology Coupled Particle Light Scattering (Copalis®) technology provides a rapid method for the measurement of antibodies to specific viral or protozoan pathogens.
The Copalis® Rubella IgM Assay is based on the principle of antibody-dependent particle aggregation as detected by measurement of changes in light scattering. The serum or plasma sample is manually pre-diluted in Sample Diluent to remove IgG and IdA antibodies. Polystyrene microparticles present in the Copalis® Test Cup are coated with Rubella viral antigen (HPV 77 strain). These microparticles aggregate in the presence of the pre-diluted human serum/plasma containing IgM antibodies to Rubella virus. After 10 minutes of agitation, the levels of aggregation are determined by measurement of the number of reacted and unreacted particles as they flow past a detector. Reactivity is assessed by the level of aggregation relative to a cutoff value. The Copalis® Rubella IgM Assay detects the presence of Rubella IgM-specific antibodies. Two levels of controls are used to monitor system performance.
Here's a breakdown of the acceptance criteria and study details for the Copalis® Rubella IgM Assay, based on the provided text:
Acceptance Criteria and Device Performance
The core of the performance evaluation rests on the agreement with a predicate device, the Abbott IMx Rubella IgM test. While specific numerical acceptance criteria (e.g., "agreement must be >95%") are not explicitly stated as distinct criteria, the results presented in the tables demonstrate the agreement levels achieved. The study implicitly shows that the observed agreement percentages were deemed sufficient for demonstrating substantial equivalence.
| Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|
| Overall Agreement with Predicate Device (Abbott IMx Rubella IgM) | Acute Adult Population: 98.2% (108/110) [93.6 - 99.8%] |
| Obstetric Adult Population: 100.0% (50/50) [92.9 - 100.0%] | |
| Seronegative Population: 100.0% (97/97) [96.3 — 100.0%] | |
| Pediatric Population: 100.0% (20/20) [83.2 - 100.0%] | |
| Reproducibility (Across Sites and Within-Run %CV for Control and Panel Samples) | |
| Neg Control: Low %CV | %CV (Total): 1.7%, %CV (Within Run): na |
| Pos Control: Moderate %CV | %CV (Total): 8.0%, %CV (Within Run): na |
| NRM01-01: Low %CV | %CV (Total): 3.0%, %CV (Within Run): 2.2% |
| NRM01-02: Low %CV | %CV (Total): 2.7%, %CV (Within Run): 1.4% |
| PRM01-01: Moderate %CV | %CV (Total): 12.4%, %CV (Within Run): 8.9% |
| PRM01-02: Moderate %CV | %CV (Total): 9.8%, %CV (Within Run): 6.9% |
| PRM01-03: Low %CV | %CV (Total): 5.1%, %CV (Within Run): 3.8% |
| PRM01-04: Moderate %CV | %CV (Total): 18.5%, %CV (Within Run): 12.3% |
| Plasma Reproducibility (Comparison of Serum to EDTA, Heparin, and Citrate Plasma) | Various %CVs reported for Serum, EDTA, Heparin, and Citrate plasma across different sample levels (N1, N2, HP, LP1, LP2). All generally indicate acceptable precision for the different sample types. For example, N1 serum total %CV is 2.57, while N1 EDTA plasma total %CV is 2.43. |
Study Details
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Sample sizes used for the test set and the data provenance:
- Acute Adult Population: 114 samples were analyzed, but agreement was calculated on 110 (excluding 4 EQ results from the IMx Rubella IgM).
- Obstetric Adult Population: 50 samples.
- Seronegative Population: 99 samples were analyzed, but agreement was calculated on 97 (excluding 1 EQ result from the IMx Rubella IgM).
- Pediatric Population: 20 samples.
- Reproducibility Panel: 6 serum samples were tested in duplicate for 5 days (total N=30 per sample ID).
- Plasma Reproducibility: 6 sets of serum/multiple plasma paired samples (EDTA, heparin, sodium citrate) were tested in duplicate for 3 days.
- Data Provenance: The studies were conducted at 3 sites: 1 hospital clinical laboratory, 1 state laboratory, and at DiaSorin itself. The country of origin of the data is not specified but implicitly within the US given the submission to the FDA. The study is prospective in nature as it evaluates the performance of the new device against a predicate.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):
The ground truth in this study is established by comparison to a legally marketed predicate device, the Abbott IMx Rubella IgM test. Therefore, "experts" in the traditional sense of human readers adjudicating images are not directly applicable. The "ground truth" is the result provided by the established predicate device. -
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable, as the "ground truth" is determined by a comparative analysis against a predicate device, not by expert human adjudication of discrete findings. -
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 MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic tool that would involve human readers interpreting results with or without AI. The evaluation focuses on the assay's performance against a predicate device. -
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, the performance data presented is for the Copalis® Rubella IgM Assay as a standalone device. The results are from the assay directly, without human interpretation influencing the reported agreement percentages. The device's output is compared to the predicate device's output. -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The primary "ground truth" used for clinical performance comparison is the results from a legally marketed predicate device (Abbott IMx Rubella IgM test). For reproducibility and plasma studies, internal controls and panel members with known characteristics are used to assess the device's precision. -
The sample size for the training set:
The document describes clinical trials for performance evaluation and reproducibility studies. It does not mention a separate "training set" in the context of machine learning. For an immunoassay, the development typically involves assay optimization and validation, rather than a distinct machine learning training phase. Therefore, no specific training set sample size is provided. -
How the ground truth for the training set was established:
As there is no explicit mention of a training set in the machine learning context, the method for establishing its "ground truth" is not applicable based on the provided text. The "ground truth" for the overall assay validation is based on the predicate device.
§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.