(71 days)
The Varelisa ReCombi CTD Screen EIA kit is designed for the qualitative determination of ten antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), drug-induced lupus, scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/dermatomyositis. The Varelisa ReCombi CTD Screen detects antibodies against dsDNA, RNP (RNP70,A,C), Sm (B,B',D), SS-A/Ro(52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B, Histone, Ribosomal P Protein and Jo-1 in a single microwell.
The new device is an enzyme-linked immunosorbent assay (ELISA) using microtiter plates as the solid phase. The plate wells are coated with antinuclear antigens, which allow anti-nuclear antibodies (sample) to react with the immobilized antigens. The conjugate is rabbit anti-human IgG horseradish peroxidase (HRP), which uses 3, 3'5, 5' tetramethylbenzidine dihydrochloride (TMB) as substrate. The kit contains calibrator and negative control. The kit also contains sample diluent, wash buffer concentrate and stop solution.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Varelisa ReCombi CTD Screen, organized according to your requested information:
Device Acceptance Criteria and Performance Study
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined quantitative acceptance criteria (e.g., "sensitivity must be > X%" or "specificity must be > Y%") for the Varelisa ReCombi CTD Screen. Instead, the study aims to demonstrate laboratory equivalence and substantial equivalence to a predicate device (Varelisa® ReCombi ANA Screen K993108). The performance metrics reported are focused on the agreement between the new device's results and clinical definitions of samples, compared to the predicate device.
| Performance Metric | Varelisa ReCombi CTD Screen Performance | Predicate Device Performance | Difference (New Device - Predicate Device) | 95% Confidence Interval for Difference |
|---|---|---|---|---|
| Agreement for Positive Cases | 87.4% | 85.2% | 2.2% | [-1.7%, 5.0%] |
| (CTD samples clinically defined as positive) | ||||
| Agreement for Negative Cases | 79.0% | 84.0% | -5.0% | [-11.8%, -0.2%] |
| (Control samples clinically defined as negative) |
Implicit Acceptance Criteria (based on the provided information):
- Substantial Equivalence: The primary "acceptance criterion" is to demonstrate substantial equivalence to the predicate device. This is achieved through comparability in intended use, assay principle, and performance characteristics.
- Comparable Performance: The agreement rates for both positive (CTD) and negative (control) samples should be comparable to the predicate device, with differences falling within acceptable confidence intervals (though specific thresholds for these intervals are not explicitly stated as acceptance criteria). The presented data suggests the differences are deemed acceptable for substantial equivalence.
- "Performs according to state-of-the-art expectations": This is a qualitative statement in the summary implying that the device's overall performance is considered modern and effective for its purpose.
2. Sample Sizes Used for the Test Set and Data Provenance
- Test Set Size:
- Clinical Samples: 183 CTD (Connective Tissue Disease) samples.
- Control/Negative Samples: 100 disease controls, plus "samples from apparently healthy subjects (normal population)" (specific number not given for the normal population, but the "100 disease controls" are used for the negative agreement calculation).
- Total: At least 283 samples (183 CTD + 100 disease controls). The text also mentions "clinically defined sera and for international reference sera" and "samples from apparently healthy subjects (normal population)," suggesting the reported numbers might be a subset of a broader validation set.
- Data Provenance: Not explicitly stated, but the manufacturer is based in Germany, implying the study could have been conducted there or in collaboration with other European institutions. The mention of "international reference sera" suggests a diverse set of samples. The study appears to be retrospective, as it analyzed "results obtained for clinically defined sera."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not specify the "number of experts" or their "qualifications" involved in establishing the ground truth. It refers to "clinically defined sera" and "clinical definitions of samples," implying that the ground truth for CTD status (positive/negative) was established through clinical diagnosis, likely by physicians or rheumatologists, based on a comprehensive set of clinical criteria, medical history, and other diagnostic tests.
4. Adjudication Method for the Test Set
The adjudication method is not explicitly described. Given that the ground truth is derived from "clinical definitions," it likely represents a consensus clinical impression rather than a specific adjudication process between multiple readers of the assay results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not performed. This device is an in vitro diagnostic (IVD) kit for lab testing, not an AI-assisted diagnostic tool that helps human readers interpret images or complex data. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply to this submission.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was conducted. The reported "Agreement (%)" for both positive and negative samples (87.4% and 79.0%, respectively) represents the performance of the Varelisa ReCombi CTD Screen itself when tested against clinically defined samples, without human intervention in the result interpretation beyond standard lab protocols for reading ELISA plates (e.g., using a microplate reader). The ELISA kit itself is the "algorithm" in this context.
7. Type of Ground Truth Used
The ground truth used was clinical definitions/diagnosis of systemic rheumatic diseases. The text mentions "clinically defined sera" and "clinical definitions of samples," indicating that the diagnosis of CTD (or lack thereof for control samples) was established through medical evaluation of patients.
8. Sample Size for the Training Set
The document does not specify a training set size. This is common for traditional IVD kits as their development often involves iterative optimization and validation rather than a distinct "training set" in the machine learning sense. The "development" of the new device is mentioned in comparison to the predicate, implying an engineering and chemistry-focused development process rather than algorithmic training.
9. How the Ground Truth for the Training Set Was Established
Since a specific "training set" is not mentioned, the method for establishing ground truth for such a set is also not specified. If any internal validation or optimization was done during development, the ground truth would likely have been established similarly to the test set: through clinical definitions and classification of samples.
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).