(366 days)
Phenytoin is intended for in vitro diagnostic use in the quantitative determination of the phenytoin concentration in human serum on T60 analyzer. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.
TDM Calibration set B is intended for in vitro diagnostic use as a calibrator in the quantitative measurement of the kit code 981647 Phenytoin assay on T60 Analyzer.
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The provided document describes a 510(k) submission for a Phenytoin test system and a TDM Calibration set B. The submission focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study against specific acceptance criteria. However, we can extract the reported performance of the new device and compare it to the predicate device, which can act as a proxy for acceptance criteria if the aim is to show similar performance.
Here's an analysis based on the provided text, addressing the requested information:
1. A table of acceptance criteria and the reported device performance
Since specific, pre-defined acceptance criteria are not explicitly stated as separate quantifiable thresholds in the document, I will use the predicate device's performance as the benchmark against which the new device's performance is implicitly evaluated for "substantial equivalence." The reported performance of the new device is compared directly to the predicate in "Table 1".
| Attribute | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (New Device) |
|---|---|---|
| Intended Use | For quantitation of phenytoin in human serum or plasma using automated clinical chemistry analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels to ensure proper therapy. | For in vitro diagnostic use in the quantitative determination of the phenytoin concentration in human serum on T60 analyzer. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy. |
| Indication for Use | Same as Intended Use (for predicate). | Phenytoin is intended for quantitative in-vitro diagnostic determination of the phenytoin concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy. |
| Assay Protocol | Uses recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. | Uses recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. |
| Traceability/ Standardization | Not explicitly stated (implied to be acceptable for a legally marketed device). | The calibration values are traceable to USP reference materials prepared gravimetrically to drug-free human serum. |
| Sample Type | Serum or plasma (Na or Li heparin, Na EDTA) | Serum |
| Reagent Storage | Store CEDIA® Phenytoin II reagents at 2-8 °C. Do not freeze. Refer to box/bottle labels for expiration date. | The unopened reagents are stable at 2...8 °C until the expiration date. DO NOT FREEZE the unopened or reconstituted reagents. |
| Expected Values | Therapeutic range: 10 - 20 µg/ml for adults, 6 - 14 µg/ml for children. | Therapeutic range for adults: 10 - 20 µg/ml or 40 - 79 µmol/l (1,2) |
| Instrument | Roche Hitachi 912 | T60 and DPC T60i, DPC T60i Kusti |
| Measuring Range | Between 0.6 µg/ml and ~40 µg/ml (158.4 µmol/l). | 0.8 - 38 µg/ml (3.2 – 150 µmol/l) |
| Precision (Within run - Level 6.3/8.6 µg/ml) | SD = 0.20, CV(%) = 3.2 | SD = 0.20, CV(%) = 2.4 |
| Precision (Within run - Level 14.8/20.0 µg/ml) | SD = 0.29, CV(%) = 2.0 | SD = 0.32, CV(%) = 1.6 |
| Precision (Within run - Level 26.8 µg/ml) | SD = 0.35, CV(%) = 1.3 | N/A (new device reports only two levels) |
| Precision (Total - Level 6.3/8.6 µg/ml) | SD = 0.32, CV(%) = 5.1 | SD = 0.39, CV(%) = 4.5 |
| Precision (Total - Level 14.8/20.0 µg/ml) | SD = 0.46, CV(%) = 3.1 | SD = 0.59, CV(%) = 3.0 |
| Precision (Total - Level 26.8 µg/ml) | SD = 0.60, CV(%) = 2.3 | N/A (new device reports only two levels) |
| Method Comparison (Correlation) | $Y=1.00x -0.19$, r = 0.998, Sy.x = 0.39 | $y = 1.00x - 0.8$, r = 0.995 |
| Method Comparison (Range/N) | Range 0.7 - 35.1 µg/ml, N = 114 | Range 1.3 - 38.3 µg/ml, N = 70 |
| Limitations (Bilirubin) | No significant interference up to I index of 60 (approx. 60 mg/dl). | No interference found up to 58 mg/dl (1000 µmol/l). |
| Limitations (Hemoglobin) | No significant interference up to H index of 1000 (approx. 1000 mg/dl). | No interference found up to 1000 mg/dl (10 g/l). |
| Limitations (Lipemia) | No significant interference up to L index of 1000 (approx. 2000 mg/dl Intralipid®). | No interference found up to 1000 mg/dl (10 g/l) of Intralipid®. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size for Method Comparison (Test Set): 70 samples (N = 70) were used for the new device's method comparison study.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given the submitter's country (Finland), it's possible the data originated there, but this is not confirmed.
3. 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)
This is a quantitative diagnostic test (immunoassay), not an imaging device requiring expert interpretation. The "ground truth" for such a device is typically established by comparing its results to a well-established reference method (often the predicate device itself, or a gold standard method like mass spectrometry, though not explicitly stated as distinct from the predicate here). Therefore, the concept of "experts" establishing ground truth in the way it applies to image interpretation in radiology is not directly applicable. The predicate device's measurements serve as the comparator.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Adjudication methods (like 2+1 or 3+1) are relevant for studies where human expert disagreement on interpretation is resolved. This is not applicable to a quantitative immunoassay where the comparison is numerical against a reference method. Therefore, the adjudication method is none.
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
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No, an MRMC comparative effectiveness study was not done. This type of study (MRMC, human-in-the-loop, AI assistance) is typically performed for image-based diagnostic aids or systems that augment human decision-making. The device described, a Phenytoin assay, is a standalone quantitative chemical analyzer component (reagent system) and does not involve human "readers" in the diagnostic interpretation cycle in the same way an imaging AI would.
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Therefore, there is no effect size for human reader improvement with/without AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, a standalone performance assessment was done. The performance metrics (Measuring Range, Precision, Method Comparison, Limitations) presented are characteristics of the device itself (the Phenytoin assay on the T60 analyzer) operating independently to produce a quantitative result. There is no human intervention in the result generation or interpretation to be removed.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the new device's performance was established by comparison to a legally marketed predicate device (CEDIA® Phenytoin II assay). For the method comparison study, the predicate device's results were used as the reference against which the new device's results were correlated. For other performance characteristics like precision, internal validation methods would have been used.
8. The sample size for the training set
The document describes a diagnostic assay, not a machine learning or AI algorithm in the conventional sense that would require a distinct "training set." Therefore, information regarding a "training set sample size" is not applicable to this type of device.
9. How the ground truth for the training set was established
As there is no "training set" in the context of an immunoassay, the concept of establishing ground truth for it is not applicable.
§ 862.3350 Diphenylhydantoin test system.
(a)
Identification. A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.(b)
Classification. Class II.