(85 days)
To qualitatively aid in the identification by light microscopy of human cells of lymphoid origin, by recognizing kappa light chains in immunoglobulin secreting plasma cells and plasmacytoid B lymphocytes, in normal and pathologic paraffin embedded tissues precessed in neutral buffered formalin, B5, or Bouin's fixative. Positive results aid in the differential diagnosis, classification and immunophenotyping of lymphomas and must be interpreted by a pathologist within the context of clinical data, gross and microscopic morphological criteria and multiple chemical and immunohistochemical stains.
ChemMate™ Kappa is comprised of a rabbit polyclonal antibody to human kappa light chains. The antibody reacts with free kappa light chains as well as kappa chains in intact immunoglobulin molecules.
The provided text describes the ChemMate™ Kappa device, an antibody reagent used in immunohistochemistry. Instead of traditional "acceptance criteria" and a specific study proving the device meets them, the document focuses on demonstrating substantial equivalence to predicate devices and establishing the device's performance through immunoreactivity and reproducibility studies, supported by extensive literature review.
Here's an analysis based on the provided text, addressing your points where information is available:
1. Table of Acceptance Criteria and Reported Device Performance
The concept of "acceptance criteria" for this type of IVD (In Vitro Diagnostic) device in this 1997 submission is less about specific quantitative metrics like sensitivity/specificity thresholds and more about demonstrating consistent, expected performance aligned with its intended use and prior scientific understanding.
| Acceptance Criteria (Implied from the document) | Reported Device Performance |
|---|---|
| Reproducibility | Consistent staining results obtained across three runs conducted on different days. |
| Immunoreactivity (Qualitative) | Reacts with free kappa light chains and kappa chains in intact immunoglobulin molecules. |
| Expected staining patterns in normal tissues (Qualitative) | Kappa and lambda polytypic expression reported in non-malignant lymphoid hyperplasia, with positive cells including primary follicles, mantle zones, and dendritic reticulum cells. |
| Expected staining patterns in pathological tissues (Qualitative) | Kappa reactivity reported in B-cell lymphomas, typically as monotypic, and exceptionally as polytypic expression. Some plasmacytomas also reported as reactive for kappa. |
| Differentiation between neoplastic and reactive tissues (Qualitative) | Supports previous findings that reactive plasmacytosis/lymphoid hyperplasia are characterized by polyclonal proliferations (both kappa and lambda), while B-cell neoplasms typically express either kappa or lambda (monotypic). |
| Specificity (Implied, with caveats) | Generally specific for kappa light chains, but acknowledges product-specific limitations such as non-specific staining in poorly fixed tissues, rare T-cell lymphoma staining, Hodgkin's disease Reed-Sternberg cell staining, passive diffusion into neoplastic cells, and presence of kappa-positive B-cells in non-lymphoid tissues. |
| Compatibility with fixatives | Optimized for tissues processed in zinc formalin, neutral buffered formalin, Bouin's, or B5 fixative. |
| Compatibility with detection systems | Optimized for use with ChemMate™ SDK605 or SDK305 Secondary Detection - Peroxidase/DAB kit and Techmate™ automated stainer. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 281 tissue specimens (both normal and tumor specimens).
- Data Provenance: Not explicitly stated regarding country of origin. The study appears to be retrospective, as it uses "serial sections" of existing tissue specimens. No mention of prospective data collection for the reproducibility study itself. The references cited are from various journals, implying a broad, international scientific context, but the specific 281 specimens for the reproducibility study are from Ventana's internal testing.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. The reproducibility study focuses on consistent staining rather than a consensus on diagnostic interpretations by multiple experts. The document emphasizes that results must be interpreted by a pathologist within the clinical context, suggesting that human expert interpretation is crucial, but it doesn't detail how ground truth was established for the 281 specimens or for the referenced literature.
4. Adjudication Method for the Test Set
This information is not provided. Given the nature of a reproducibility study for an IHC stain, the primary assessment would likely be visual confirmation of consistent staining patterns rather than a formal adjudication process for discrete diagnoses.
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
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The submission predates widespread AI in medical imaging by several decades. This device is a reagent for manual or automated immunohistochemical staining, not an AI diagnostic tool.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
A standalone performance study was not done in the context of an algorithm. The device is a diagnostic reagent, and its performance is evaluated in terms of its chemical and biological reactivity (immunoreactivity and reproducibility), which directly enables human pathologists to make diagnoses. It is not an algorithm.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
For the reproducibility study, the ground truth for the 281 tissue specimens is implicitly based on established pathological diagnoses of "normal" or "tumor" for the tissue specimens themselves, against which consistent staining is evaluated. The literature cited extensively uses pathological diagnoses (e.g., non-malignant lymphoid hyperplasia, B-cell neoplasms, plasmacytomas, Hodgkin's disease, lymphomas) and immunophenotyping results as the "ground truth" to demonstrate the expected utility and reactivity of kappa light chain antibodies. Some references also mention Southern Blot analysis and clinical serum findings to confirm clonality, which serve as higher-level ground truth.
8. The Sample Size for the Training Set
There is no mention of a "training set" in the context of machine learning or AI. This device is a reagent, not an algorithm that requires training. The development and optimization of the antibody would have involved extensive R&D, but this is not characterized as a "training set" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
As there is no training set in the AI sense, this question is not applicable. The "ground truth" for the development and optimization of the antibody would be based on fundamental immunological principles, known cellular biology, and established pathological classifications of tissue types and disease states.
§ 866.5130
Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition,alpha -1-antitrypsin deficiency has been associated with pulmonary emphysema.(b)
Classification. Class II (performance standards).