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The Alkaline Phosphatase assay is used for the quantitation of alkaline phosphatase in human serum or plasma.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The Alkaline Phosphatase assay is an automated clinical chemistry assay.

Alkaline phosphatase in the sample catalyzes the hydrolysis of colorless p-nitrophenyl phosphate (p-NPP) to give p-nitrophenol and inorganic phosphate. At the pH of the assay (alkaline), the p-nitrophenol is in the yellow phenoxide form. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

The FDA document provided is a 510(k) premarket notification for an in vitro diagnostic device, the Alkaline Phosphatase assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving safety and effectiveness de novo. Therefore, the information provided relates to testing done to establish equivalence for a pre-existing device with modifications, not a new device.

The study proves that the modified device meets acceptance criteria, primarily by demonstrating that it performs equivalently to the predicate device and that incremental changes do not adversely affect its performance.

Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria, based on the provided text.

Acceptance Criteria and Reported Device Performance

The document provides a general statement that the device "met the pre-defined product requirements for all characteristics evaluated in the verification studies." It doesn't present a specific table of acceptance criteria vs. performance in the typical format of a clinical study, but rather a comparison of characteristics to a predicate device and a statement about the results of verification studies.

The key acceptance criterion discussed is substantial equivalence to the predicate device (K023807), particularly regarding:

• Intended Use and Indications for Use: The subject device is intended for the same use as the predicate: "quantitation of alkaline phosphatase in human serum or plasma," as an aid in diagnosis and treatment of various diseases.
• Methodology and Assay Principle: Both use para-nitrophenyl phosphate and a kinetic measurement method.
• Performance (specifically after IFCC calibration factor change): The 6.5% increase in reported results due to the optional IFCC calibration factor is deemed acceptable because it falls within the acceptable assay bias specifications (up to +/-10%) and the customer would be aware of this change.
• Risk Mitigation: The comprehensive risk-based assessment for all changes ensured that "the accumulated modifications did not impact the performance of the device."

Since this is an in vitro diagnostic device for measuring a specific analyte (Alkaline Phosphatase), the "performance" here refers to analytical performance characteristics rather than clinical diagnostic accuracy in the way a medical imaging AI would.

Here's a table summarizing the implicit acceptance criteria and the reported performance as derived from the document:

Study Details (based on the provided text, which is an FDA clearance letter for an IVD, not a detailed study report for AI/imaging device)

The document relates to modifications made to an existing in vitro diagnostic (IVD) device, not a new AI-powered diagnostic for imaging. Therefore, many of the typical questions for an AI/imaging device (e.g., sample size for test set, expert readers, MRMC study, ground truth for imaging) are not directly applicable or detailed in this type of FDA letter.

However, based on the information provided, we can infer some details relevant to an IVD device:

1. Sample Size used for the test set and the data provenance:

   • Sample Size: Not explicitly stated. The document refers to "verification studies" which typically involve testing samples across the measurement range, parallelism, interference, precision, etc. for an IVD. The exact number of samples (patients or analytical runs) isn't specified in this summary.
   • Data Provenance: Not specified regarding country of origin. The studies are described as "verification studies" and "comprehensive risk-based assessment." For IVDs, these are typically prospective laboratory studies conducted by the manufacturer to validate performance characteristics. It's safe to assume they were laboratory-controlled, likely prospective.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This question is not applicable in the context of this IVD device. "Ground truth" for an IVD like Alkaline Phosphatase is established by the analytical measurement itself, often compared to reference methods or known concentrations, or through internal validation against established performance claims. It does not involve human expert interpretation of an image or signal.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • This question is not applicable for this IVD. Adjudication methods like 2+1 or 3+1 are used in AI/imaging studies where multiple human readers interpret data that then needs to be reconciled to establish a "ground truth" for comparison with AI. For an IVD, there isn't subjective interpretation of this kind. The measurement process itself generates the result.

4. 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:

   • This type of study is not applicable to this IVD. MRMC studies are specific to AI-assisted imaging diagnostics, evaluating the impact of AI on human reader performance. This device provides a quantitative biochemical measurement, not an image for human interpretation.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • In a sense, yes, the fundamental performance of the IVD is "standalone" in that the automated analyzer (ARCHITECT c System) quantitatively measures alkaline phosphatase activity. The "algorithm" here is the chemical reaction and photometric measurement, and its output is a numerical value (U/L). The verification studies would assess this standalone analytical performance (e.g., precision, accuracy, linearity, detection limits) against pre-defined specifications. The IFCC factor is a mathematical change to this standalone output.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For an IVD like this, "ground truth" is typically established through:
     • Reference Methods: Comparison of results to established, highly accurate reference methods for alkaline phosphatase.
     • Known Concentrations: Testing samples with precisely known concentrations of alkaline phosphatase.
     • Clinical Correlation: Demonstrating that the assay measures the analyte in patient samples consistently and reliably across relevant patient populations, although the primary ground truth is analytical.
   • The document implies that the "pre-defined product requirements" and "acceptable assay bias specifications" served as the benchmarks for determining if the device performed acceptably. The 6.5% shift from the IFCC factor was evaluated against these analytical specifications.

7. The sample size for the training set:

   • This question is not directly applicable in the context of a traditional IVD chemical assay development, as there isn't an "AI model" that requires a training set in the typical sense. The "training" for such a system would be the chemical formulation and instrument calibration based on extensive R&D and optimization, not a data-driven machine learning process. The "validation" of the final product involves the verification studies mentioned.

8. How the ground truth for the training set was established:

   • As above, not directly applicable. The IVD operates on established biochemical principles. Its "ground truth" for development and optimization would be based on fundamental chemistry, enzyme kinetics, and metrological traceability to international standards (e.g., IFCC reference methods for calibrator values).

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The Alkaline Phosphatase2 assay is used for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The Alkaline Phosphatase2 assay is an automated clinical chemistry assay for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System. Alkaline Phosphatase in a sample catalyzes the hydrolysis of colorless para-nitrophenyl phosphate (p-NPP) to give para-nitrophenol (yellow phenoxide form at alkaline pH) and inorganic phosphate. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

The provided document is a 510(k) Premarket Notification for a clinical chemistry assay (Alkaline Phosphatase2) and does not describe an AI medical device. Therefore, the questions related to AI-specific acceptance criteria, ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and human-in-the-loop performance are not applicable.

The document focuses on the analytical performance of the Alkaline Phosphatase2 assay, demonstrating its substantial equivalence to a legally marketed predicate device. The information details various non-clinical performance studies to establish the device's reliability and accuracy for quantitating alkaline phosphatase in human serum or plasma.

Here's a breakdown of the relevant information from the document, tailored to the context of a diagnostic assay's performance evaluation, substituting the AI-specific questions with applicable details:

Acceptance Criteria and Device Performance for Alkaline Phosphatase2 Assay

This submission (K223317) is for a clinical chemistry assay, not an AI medical device. The acceptance criteria and performance studies are focused on the analytical performance of the assay to demonstrate its intended use for quantitative measurement of alkaline phosphatase.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" for regulatory review, but it details various performance studies with implicit acceptance ranges. The reported device performance metrics are presented instead.

Performance Metrics of Alkaline Phosphatase2 Assay (Representative Values)

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

The "test set" in this context refers to the samples used in the analytical performance studies.

• Precision Studies: 2 controls and 4 human serum panels were tested. Each sample type had n=80 replicates in the within-laboratory precision study. For system reproducibility, 5 levels of controls were tested with n=90 replicates.
• Accuracy: 2 materials standardized to the IFCC reference method were used across 3 reagent lots and 2 instruments. The specific number of replicates per material is not explicitly stated but implied by the bias calculation.
• Lower Limits of Measurement (LoB, LoD, LoQ): n ≥ 60 replicates of zero-analyte or low-analyte level samples were used.
• Linearity: The study used a dilution series across the analytical measuring interval. The exact number of points or samples is not specified but is typical for CLSI EP06.
• Interference: Each interfering substance was tested at 2 analyte levels. The number of replicates per level is not specified.
• Method Comparison: n=145 (Calibration method) and n=143 (Calibration Factor method) serum samples were used to compare with the predicate device.
• Tube Type: Samples were collected from a minimum of 40 donors.

Data Provenance: Not explicitly stated as "country of origin," but the studies were conducted by Abbott Ireland Diagnostics Division. The studies are non-clinical laboratory studies (analytical performance), using human serum/plasma samples. The studies are inherently prospective in their execution, as they involve performing tests on collected samples according to pre-defined protocols (e.g., CLSI guidelines) to establish performance characteristics.

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

For an in vitro diagnostic (IVD) assay like this, "ground truth" is established by reference methods, certified reference materials, and established analytical principles, rather than expert human interpretation of images or clinical cases.

• Ground Truth Establishment: Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP05-A3, EP09-A3, EP17-A2, EP06, EP07, EP34) were meticulously followed for study design and data analysis.
• Expert Oversight: While not explicitly stated how many individual experts (e.g., clinical chemists) were involved in establishing the "ground truth" per se for the test samples, the studies adhere to recognized international standards and practices in clinical chemistry. The assumption is that qualified laboratory scientists and statisticians designed and executed these studies, and the reference methods themselves (like the IFCC reference method for Alkaline Phosphatase) are the "ground truth" standard.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used for subjective assessments, such as image interpretation. For a quantitative diagnostic assay, the "adjudication" is achieved through:

• Statistical Analysis: Rigorous statistical methods (e.g., Passing-Bablok regression for method comparison, precision calculations) are employed to analyze the quantitative results.
• Reference Methods and Materials: The "truth" is determined by comparing the device's measurements to established reference methods (e.g., IFCC reference method) or certified reference materials, which are inherently objective.
• CLSI Guidelines: Adherence to CLSI guidelines ensures standardized and robust experimental design and data interpretation, minimizing subjective bias.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an analytical performance study for an in vitro diagnostic assay, not an AI-assisted diagnostic tool involving human readers interpreting cases. Therefore, there is no MRMC study, and no effect size for human reader improvement with AI assistance.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop)

This concept is less directly applicable but can be interpreted as the direct analytical performance of the instrument/reagent system. The presented non-clinical studies demonstrate the standalone performance of the Alkaline Phosphatase2 assay, meaning its performance characteristics (precision, accuracy, linearity, etc.) are evaluated intrinsically without direct human interpretation influencing the measurement itself. The human input is in setting up the test and interpreting the final quantitative result.

7. Type of Ground Truth Used

The ground truth for this diagnostic assay's performance evaluation largely relies on:

• Reference Methods: Specifically, the IFCC reference method for Alkaline Phosphatase is cited for accuracy studies.
• Certified Reference Materials: Standardized materials are used for calibration and accuracy verification.
• Statistical Definitions: For LoB, LoD, LoQ, and precision, the "ground truth" is established through statistical definitions based on replicate measurements of samples with known (or zero) analyte concentrations.
• Predicate Device Comparison: The predicate device's performance also serves as a comparative "ground truth" to demonstrate substantial equivalence, although the goal is to align with the IFCC standard.

8. Sample Size for the Training Set

Not applicable. This is a traditional IVD assay, not an AI model requiring a "training set" in the machine learning sense. The assay works based on established chemical principles, not on learned patterns from a large dataset. The reagent formulation and instrument algorithms are developed using R&D processes, not machine learning training.

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

Not applicable, as there is no "training set" in the context of an AI/ML model for this diagnostic device. The "truth" for developing such an assay would be based on fundamental chemical and biological understanding, robust experimental data from R&D, and adherence to analytical standards.

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For in vitro diagnostic use in the quantitative determination of alkaline phosphatase (orthophosphoric - monoester phospho-hydrolase, alkaline optimum, EC 3.1.3.1) activity in human serum or plasma on T60 instruments according to the IFCC method.

The Alkaline Phosphatase test system is intended for quantitative in-vitro diagnostic determination of the activity of the enzyme Alkaline Phosphatase in serum and plasma on T60 instrument according to the IFCC method. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver and bone diseases.

For in vitro diagnostic use on T60 instrument. eCal is used as a calibrator for enzyme tests using methods defined by Thermo Fisher Scientific Oy.

For in vitro diagnostic use for quantitative testing on T60 instrument. Nortrol is a control serum to monitor trueness and precision of the analytes listed in the separate Nortrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.

For in vitro diagnostic use for quantitative testing on T60 instrument. Abtrol is a control serum to monitor trueness and precision of the analytes listed in the separate Abtrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.

Alkaline Phosphatase (IFCC) plus, codes 981832 and 981833. Common name: Alkaline Phosphatase (IFCC). Classification: Clinical Chemistry, Class II, Product Code: CJE.
eCal, code 981830. Common Name: Calibrator, Multi-Analyte Mixture. Classification: Clinical Chemistry, Class II, Product Code: JIX.
Nortrol, code 981043. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.
Abtrol, code 981044. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.

The acceptance criteria and device performance for the Alkaline Phosphatase (IFCC) Plus test system are detailed below based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

Note: The table above primarily compares the new device's performance against the predicate device's stated performance, which is implicitly treated as the acceptance criteria for determining substantial equivalence.

2. Sample Size and Data Provenance for the Test Set

• Method Comparison (New device vs. Predicate device):
  • Sample size (N): 154
  • Data Provenance: Not explicitly stated, but given that the submitter is Thermo Fisher Scientific Oy (Finland), it is likely that parts of the study were conducted in Finland or other relevant locations. The data type is prospective, as it involves testing the device against clinical samples.
• Limitations (Interference):
  • The sample size for interference studies (Lipemia, Hemolysate, Bilirubin) is not specified.
  • Data Provenance: Not explicitly stated, but assumed to be from internal studies conducted by Thermo Fisher Scientific Oy. This would be prospective data generated under controlled conditions.

3. Number of Experts and Qualifications for Ground Truth

This document describes an In Vitro Diagnostic (IVD) assay for measuring alkaline phosphatase activity. For such assays, "ground truth" is typically established by:

• Reference Methods: The document states the new device is "traceable to the molar absorbance coefficient of p-nitrophenol" and the predicate device is "traceable to the IFCC reference method via patient sample correlation."
• Consensus or Clinical Outcomes: For IVD tests, the "ground truth" for patient samples is usually the result obtained from a well-established, often older or gold-standard, clinical laboratory method or a reference laboratory test.
• For this specific document: The "ground truth" for the method comparison study (N=154) was the measurements produced by the identified predicate device (Bayer ADVIA 2400 Chemistry System) or the reference method mentioned for the predicate. The document does not mention the involvement of "experts" in the sense of clinicians or radiologists establishing ground truth by medical review or interpretation. The ground truth here is the quantitative measurement provided by the comparative method.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative diagnostic assay, not an image-based diagnostic or clinical decision-support system requiring adjudication of interpretations by clinical experts. The comparison is based on numerical results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an IVD device measuring an enzymatic activity directly, not an AI system assisting human readers in interpreting clinical cases. Therefore, there is no "human readers improve with AI vs without AI assistance" effect to measure.

6. Standalone Performance (Algorithm Only without Human-in-the-loop Performance)

Yes, this study is inherently a standalone performance study. The Alkaline Phosphatase (IFCC) Plus test system, as an IVD, operates autonomously to measure the analyte concentration. Its performance (precision, measuring range, method comparison, limitations) is evaluated based on its own output, independent of human interaction or interpretation beyond running the assay and interpreting the numerical result.

7. Type of Ground Truth Used

The ground truth used for the method comparison study was quantitative measurements obtained from the predicate device (Bayer ADVIA 2400 Chemistry System) or a referenced IFCC method. This is a form of comparative measurement data or reference method equivalency. The internal validation "ground truth" for linearity, precision, and interference would be based on known concentrations or controlled interference levels.

8. Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. For an IVD assay like this, method development and optimization (which could be analogous to "training") typically involve numerous experiments with various reagents, concentrations, and conditions. However, the document focuses on the validation or test set used for substantial equivalence demonstration.

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

As no specific "training set" is mentioned in the context of machine learning, this question is not directly applicable. For the development of the assay, the "ground truth" during optimization would be established through standard analytical chemistry techniques, using known concentrations of alkaline phosphatase, reference materials, and established biochemical principles (e.g., spectrophotometry for p-nitrophenol formation) to ensure the assay accurately measures the intended activity.

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Intended for the In Vitro, quantitative determination of alkaline phosphatase in human serum on automated chemistry analyzers.

Alkaline phosphatase measurements are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Not Found

This document is a 510(k) premarket notification from the FDA, which confirms that a medical device (JAS Alkaline Phosphatase Liquid Reagent) is substantially equivalent to existing devices. It does not contain the detailed study information regarding acceptance criteria, device performance, sample sizes, expert qualifications, or ground truth establishment that you've requested.

Therefore, I cannot fulfill your request using the provided text. The document is essentially an approval letter, not a scientific study report.

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The Alkaline Phosphatase assay is intended to measure alkaline phosphatase in serum or plasma. Measurement of alkaline phosphatase is used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Alkaline Phosphatase is an in vitro diagnostic assay for the quantitative determination of alkaline phosphatase in human serum or plasma. Alkaline phosphatase in serum catalyzes the hydrolysis of colorless p-nitrophenyl phosphate (p-NPP) to give p-nitrophenol and inorganic phosphate. At the pH of the assay (alkaline), the p-nitrophenol is in the yellow phenoxide form. The rate of absorbance increase at 405 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

Here's an analysis of the provided text regarding the acceptance criteria and study for the AlkP (Alkaline Phosphatase) device:

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly state quantitative acceptance criteria in a dedicated section. However, based on the "Performance Characteristics" section, we can infer the criteria used for substantial equivalence. The primary criterion is strong correlation and similar clinical results to the predicate device.

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

The document does not explicitly state the sample size used for the "comparative performance studies" or "precision studies." It only refers to "two levels of control material" for precision.

The data provenance is not specified regarding country of origin. The studies appear to be retrospective in the sense that they are conducted on samples and controls to characterize the device's performance, rather than on new patient cohorts specifically for this submission.

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

This document describes an in vitro diagnostic assay, which measures a biochemical marker (alkaline phosphatase) in human serum or plasma. It does not involve human interpretation of images or other subjective data that would require a ground truth established by experts. The "ground truth" for this type of device is the actual concentration of the analyte, which is measured using a reference method or validated control materials.

4. Adjudication Method for the Test Set

Not applicable for this type of in vitro diagnostic device, as there is no subjective interpretation requiring adjudication among experts.

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

Not applicable. This is an in vitro diagnostic assay, not an AI-powered image analysis or diagnostic support tool for human readers.

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

Yes, the studies described are for the standalone performance of the AlkP assay (the device itself, which is a chemical assay run on an automated analyzer). The "algorithm" here is the chemical reaction and photometric measurement process. The "without human-in-the-loop" refers to the assay's direct measurement capability.

7. The Type of Ground Truth Used

For method comparison, the Roche Cobas Mira Plus Automated Chemistry System Alkaline Phosphatase assay served as the reference standard or "ground truth" for relative performance. For precision studies, control materials with known (or established) values were used. The document implies that these control materials represented different levels of alkaline phosphatase.

8. The Sample Size for the Training Set

Not explicitly stated. For an in vitro diagnostic assay, there isn't typically a "training set" in the machine learning sense. The assay's parameters (reagent concentrations, incubation times, measurement wavelengths) are developed and optimized through R&D without a distinct "training set" as understood in AI/ML. The provided data focuses on validation (test set performance).

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

Not applicable in the machine learning sense. The "ground truth" for developing and optimizing an in vitro diagnostic assay would be based on established biochemical principles, extensive laboratory testing, calibration against reference methods/materials, and analytical validation during the assay development process to ensure it accurately measures the analyte.

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For the quantitative determination of Alkaline Phosphatase in serum. For IN VITRO diagnostic use. Elevated alkaline phosphatase activity in serum is of interest in the diagnosis of several disease conditions including hepatobiliary disease and bone disease associated with increased osteoblastic activity. Alkaline phosphatase activity in serum may be elevated due to obstructive jaundice, occlusion of the common bile or hepatic duct, and cirrhosis.

Alkaline Phosphatase-SL Assay

The provided documents are a 510(k) clearance letter and an "Indications for Use" statement for the "Alkaline Phosphatase-SL Assay" device. These documents pertain to an in vitro diagnostic assay, not an AI/ML-powered device.

Therefore, the requested information (acceptance criteria, study details, sample sizes, expert qualifications, adjudication methods, MRMC studies, standalone performance, ground truth types, and training set information) regarding an AI/ML device is not applicable to this submission. The documents describe a laboratory assay for measuring alkaline phosphatase levels, which is a chemical test, not a software-based diagnostic tool.

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