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The NeoBase Non-derivatized MSMS reagent kit is intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper. Quantitative analysis of these analytes (Table 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.

The measurement of amino acids, succinylacetone, free carnitine, and acylcarnitines with the NeoBase assay involves extraction of dried blood spots from newborns with a solution containing stable-isotope labeled internal standards and analysis using a tandem mass spectrometry (MSMS) system. The response of each analyte relative to their corresponding stable-isotope labeled internal standard is proportional to analyte concentration.

The provided 510(k) summary describes the NeoBase Non-derivatized MSMS Kit, intended for newborn screening of metabolic disorders by measuring amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from dried blood spots. The device's performance was compared to a legally marketed predicate device, the NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit (K031878).

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as numerical thresholds for precision, recovery, or correlation that the device must meet. Instead, it presents the device's performance characteristics and compares them to those reported for the predicate device to demonstrate substantial equivalence. The implication is that performance comparable to the predicate device is considered acceptable.

2. Sample Size Used for the Test Set and Data Provenance

• Non-clinical (Precision, Recovery, Measurable Ranges): The document doesn't specify a distinct "test set" for these parameters in terms of a separate sample size. The data for these characteristics is generated through laboratory experiments likely using controlled samples (e.g., spiked samples, internal controls) rather than clinical patient samples. The provenance is implied to be laboratory-generated.
• Method Correlation:
  • Sample Size: 158 samples.
  • Data Provenance: Not explicitly stated, but samples were "prepared in duplicates" and assayed using both devices. Implied to be laboratory-controlled or clinical samples processed for comparison, but specific origin (e.g., country) is not mentioned. Given the context of newborn screening, they would likely be dried blood spots.
• Clinical Correlation Studies:
  • Sample Size:
    • 9416 random neonatal samples
    • 104 samples with true positive diagnoses
    • 320 artificially enriched dried blood spots
  • Data Provenance: From two different US newborn screening laboratories. The studies evaluated the NeoBase kit "in parallel to the predicate device (identical specimens were analyzed as paired samples by both methods)." This suggests a retrospective collection of these samples, as they are referred to as "random neonatal samples" and "samples with true positive diagnoses."
  • True Positive Samples (Specific breakdown): 108 total true positive samples were analyzed (104 from screening sites + 4 Tyrosinemia Type I samples analyzed by PerkinElmer R&D). The two samples that weren't detected by either assay were CPT-2 and VLCAD cases which had degraded due to storage.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number of experts or their qualifications used to establish the ground truth for the clinical correlation studies or the true positive samples.

For the true positive samples, the text refers to them as "samples with true positive diagnoses" and later lists "Disorder Full name" for each, implying that the diagnoses were established clinically through standard diagnostic procedures. However, the exact method of ground truth confirmation or number of experts involved is not detailed.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set.

For the "Clinical Correlation Studies," it states that "Clinical correlation was established by assessing whether or not the methods were concordant in determining the paired samples to have analyte concentration values above or below their corresponding cutoffs." This implies a direct comparison of the readings from the NeoBase and predicate device against predetermined clinical cutoffs, rather than an expert adjudication process determining the ultimate "true" status of each sample for the purpose of the study.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.

This device is an in vitro diagnostic (IVD) kit for quantitative measurement of analytes using tandem mass spectrometry. Its performance evaluation focuses on analytical characteristics (precision, recovery, measurable range) and method correlation with a predicate device, as well as clinical correlation of quantitative measurements to established cutoffs. MRMC studies are typically used for imaging devices or other diagnostic tools where human readers interpret results, and the study would then compare human performance with and without AI assistance. This is not applicable here.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance evaluation was done.

The entire study described in the 510(k) refers to the performance of the device kit (NeoBase Non-derivatized MSMS Kit) itself. This is an assay system that produces quantitative values. The precision, recovery, measurable ranges, and direct comparisons of analyte concentrations to clinical cutoffs are all measures of the kit's standalone analytical performance. Human involvement is limited to operating the instrument and following the assay protocol, not to interpreting ambiguous results in a way that would alter the quantitative output.

7. The Type of Ground Truth Used

• Non-clinical (Precision, Recovery, Measurable Ranges): The ground truth for these studies would be based on known concentrations of analytes in controlled, laboratory-prepared samples (e.g., spiked samples, calibrators).
• Method Correlation: The "ground truth" here is the measurement from the predicate device. The study compares the new device's measurements against those from the established predicate device.
• Clinical Correlation Studies:
  • For the 9416 random neonatal samples, the ground truth was effectively the clinical cutoff values for each analyte. Samples were categorized as "above or below their corresponding cutoffs."
  • For the 104 (plus 4 Tyrosinemia Type I) "true positive samples," the ground truth was the established clinical diagnosis of specific metabolic disorders (e.g., 3-Methylcrotonyl-CoA Carboxylase Deficiency, Phenylketonuria, Tyrosinemia Type I). This implies outcomes data or a strong clinical consensus for the natural diagnosis itself.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the NeoBase Non-derivatized MSMS Kit. This is an in vitro diagnostic assay, not a machine learning algorithm that typically undergoes a distinct training phase on a large dataset. The development of such a kit involves analytical validation studies to optimize reagents and protocols, which is different from "training" an algorithm.

9. How the Ground Truth for the Training Set Was Established

As no training set is explicitly described in the context of an algorithm or machine learning, this question is not applicable based on the provided text. The "ground truth" in the development of an IVD kit is established through standard analytical chemistry principles, reference methods, and clinical validation.

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