(30 days)
GTI PF4 ENHANCED® is designed as a solid phase enzyme-linked immunosorbent assay (ELISA). The product is intended to be used as an in vitro diagnostics kit by hematology, (ELIG/Y). The produce is the pathology laboratories to assist in screening patient samples for the presence of heparin-associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis.
PF4 ENHANCED® Solid Phase ELISA microwells provide immobilized PF4:PVS complexes as a target for the detection of antibodies associated with Type II HIT which are found in some patients undergoing heparin therapy. The presence of these antibodies has been shown to be associated with heparin induced thrombocytopenia Type II (Type II HIT).
Patient serum is added to microwells coated with platelet factor 4 (PF4) complexed to polyvinyl sulfonate (PVS). If an antibody recognizing a site on PF4:PVS is present, binding will occur. Unbound antibodies are then washed away. An alkaline phosphatase labeled anti-human globulin reagent (Anti-IgG/A/M) is added to the wells and incubated. The unbound Anti-IgG/A/M is washed away and the substrate PNPP (p-nitrophenyl phosphate) is added. After a 30-minute incubation period, the reaction is stopped by addition of a sodium hydroxide solution. The optical density of the color that develops is measured in a spectrophotometer.
The document describes a 510(k) premarket notification for a device called "PF4 ENHANCED® Solid Phase ELISA" and its substantial equivalence to a predicate device, the "GTI-PF4 ELISA". The focus of the provided text is on demonstrating that the new device performs as well as the predicate device, especially considering changes to certain materials.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and the Reported Device Performance
The document does not explicitly state numerical "acceptance criteria" in a typical table format with specific thresholds (e.g., sensitivity > 90%). Instead, the acceptance criteria are implicitly defined by the goal of demonstrating substantial equivalence to the predicate device, the GTI-PF4 ELISA. The performance data was used to show that the PF4 ENHANCED® device performs "as well as" the predicate.
The reported device performance is a qualitative statement of equivalence rather than specific quantitative metrics against pre-defined thresholds.
| Acceptance Criteria (Implicit) | Reported Device Performance (Summary) |
|---|---|
| Equivalence in assay results after material change (wash buffer) | Data showed the effect of the material change on assay results using known patient samples, demonstrating equivalence to the predicate. (Details of specific results are not provided in the summary.) |
| Equivalence in kit stability (real-time) after material change (wash buffer) | Data showed the effect of the material change on kit stability (real-time stability), demonstrating equivalence. (Details not provided.) |
| Equivalence in component stability (accelerated and real-time) after stabilizer added | Data showed the effect of the material change on component stability (accelerated and real-time stability studies on the alkaline phosphatase conjugated anti-IgG/A/M), demonstrating equivalence. (Details not provided.) |
| Equivalence in kit stability (real-time) after stabilizer added | Data showed the effect of the material change on kit stability (real-time), demonstrating equivalence. (Details not provided.) |
| Equivalence in assay results after stabilizer added | Data showed the effect of the material change on assay results using known patient samples, demonstrating equivalence to the predicate. (Details not provided.) |
| Equivalence in assay reproducibility (within run, lot to lot, total) | Data showed the effect of the material change on assay reproducibility (within run precision, lot to lot reproducibility, and total reproducibility), demonstrating equivalence. (Details not provided.) |
| Equivalence in assay specificity (cross reactivity) | Data showed the effect of the material change on assay specificity (cross reactivity of other antibodies), demonstrating equivalence. (Details not provided.) |
| Overall Conclusion | The data show that PF4 Enhanced is equivalent to PF4 ELISA. |
| Based on comparison with the legally marketed PF4 ELISA, the data demonstrate that PF4 Enhanced ELISA performs as well as the predicate device and does not present new issues of safety and effectiveness. |
2. Sample size used for the test set and the data provenance
The document explicitly states that the studies used "known patient samples." However, it does not provide the specific sample size for the test set or the data provenance (e.g., country of origin, retrospective or prospective nature of the samples). The summary refers to "Section 8: Performance Data Section" for details, which is not included in the provided text.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not provide information on the number of experts used or their qualifications to establish ground truth for the test set. Given that it's an ELISA for detecting antibodies, the "ground truth" would likely be derived from a combination of clinical diagnosis of Type II HIT and potentially other laboratory tests, rather than expert interpretation of an image or signal that requires adjudication. The document states "known patient samples," implying the status of these samples (e.g., positive or negative for the target antibodies/HIT) was already established.
4. Adjudication method for the test set
The document does not specify an adjudication method. This type of assay (ELISA) typically produces quantitative results (Optical Density) that are then interpreted against cut-offs to yield a qualitative (Positive/Negative) result. Adjudication by multiple readers is less common for such objective assays unless there are borderline results or discrepancies in initial interpretations, which isn't mentioned here.
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 (IVD) ELISA kit, which is a laboratory assay. It does not involve human readers interpreting images or data directly to make a diagnosis in a way that would be "assisted by AI." Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable to this device.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
The device itself is a "standalone" assay in the sense that it produces an objective result (Optical Density) which leads to a qualitative determination (Positive/Negative). It is an "algorithm only" in the context of the assay's biochemical steps and optical density measurement leading to a result. However, this is not an "AI algorithm" in the common sense of the term. The performance data described are for the assay itself.
7. The type of ground truth used
The ground truth for the "known patient samples" would be based on clinical diagnosis of Type II HIT and potentially confirmatory laboratory tests, which establish whether the patient samples are truly positive or negative for the antibodies associated with Type II HIT. The document refers to "known patient samples," implying this established truth. It's not pathology (as in tissue biopsy) or purely outcomes data from a large cohort, but rather a pre-established clinical and laboratory status.
8. The sample size for the training set
The document does not mention a training set in the context of machine learning or AI. This is an ELISA kit validation, not an AI model development. The "known patient samples" mentioned would be considered the test set for validating the new device against the predicate.
9. How the ground truth for the training set was established
As there is no mention of a training set in the context of AI, there's no information on how its ground truth was established. The "known patient samples" for the performance studies would have their ground truth established as described in point 7.
§ 864.7695 Platelet factor 4 radioimmunoassay.
(a)
Identification. A platelet factor 4 radioimmunoassay is a device used to measure the level of platelet factor 4, a protein released during platelet activation by radioimmunoassay. This device measures platelet activiation, which may indicate a coagulation disorder, such as myocardial infarction or coronary artery disease.(b)
Classification. Class II (performance standards).