Search Results

The Elecsys Vitamin D total II assay is intended for the quantitative determination of total 25-hydroxyvitamin D in human serum and plasma. This assay is to be used as an aid in the assessment of vitamin D sufficiency in adults. The electrochemiluminescence binding assay is intended for use on the cobas e 411 immunoassay analyzer.

CalSet Vitamin D total II is used for calibrating the quantitative Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.

PreciControl Vitamin D total II is used for quality control of the Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.

This CalCheck set is an assayed control for use in calibration verification of the assay range established by the Elecsys Vitamin D total II reagent on the cobas e 411 immunoassay analyzer.

Elecsys Vitamin D total II is a second generation assay by Roche Diagnostics for the in vitro quantitative determination of 25-hydroxyvitamin D in human serum and plasma. It is intended for use on the cobas e 411 immunoassay analyzer. The cobas e family of analyzers employs the electrochemiluminescence "ECLIA" technology. The assay is a 27 minute assay utilizing a competition principle and a pretreatment step to release the bound 25-hydroxyvitamin D from the vitamin D binding protein.

Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration against the master curve for that reagent lot.

The provided text describes the acceptance criteria and study proving the device meets those criteria for the Elecsys Vitamin D total II assay and its associated calibrators and controls.

Here's the breakdown of the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" in terms of specific thresholds for performance metrics. Instead, it describes various studies conducted to demonstrate performance and states that the data supports substantial equivalence. The "reported device performance" is woven throughout Section 4, "Non-Clinical Performance Evaluation," and Section 5, "External (Clinical) Testing."

However, we can infer some performance metrics and the studies that support them. The core of the device's acceptable performance is its substantial equivalence to a predicate device (Elecsys Vitamin D Assay K113546) and its traceability to a reference measurement procedure (ID-LC-MS/MS traceable to NIST SRM 2972).

Here's a table summarizing performance aspects:

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

The document describes various studies, each with its own sample size and provenance.

• Precision: 5 human serum samples (single donors, native and spiked).
• Analytical Sensitivity (LoB, LoD, LoQ):
  • LoB: 1 blank sample (Vitamin D depleted human serum pool), 60 determinations.
  • LoD: 5 low-level human serum sample pools (diluted), with replicates per run.
  • LoQ: At least 4 low-level samples of serum, Li-heparin, K2-EDTA, K3-EDTA plasma, 25 replicates/sample/reagent lot.
• Linearity/Assay Reportable Range: 1 high analyte serum and K3-EDTA plasma sample (single donors, spiked), diluted to at least 9 concentrations.
• High Dose Hook Effect: 1 human serum sample spiked to approx. 10,000 ng/mL, dilution series performed.
• Human Anti-Mouse Antibodies (HAMA): HAMA-serum (HAMA L2) and related basis serum (without interferent).
• Endogenous Interferences: For each interfering substance, three human serum samples (single donors, native as well as spiked) containing low, mid, and high concentrations of 25-OH Vitamin D.
• Exogenous Interferences (Drugs): Two human serum samples (single donors, native as well as spiked) with analyte concentrations approx. 30 and 70 ng/mL.
• Analytical Specificity/Cross-Reactivity: Native human sera with approximate 25-hydroxyvitamin D concentrations of 25, 40, and 60 ng/mL (spiked with cross-reactants).
• Sample Matrix Comparison: Minimum of 40 serum/plasma pairs per sample material (single donors - native, diluted, spiked).
• Method Comparison to Predicate: 105 serum samples (single donors, native).
• Method Comparison to Reference Method: 111 native single donor patient serum samples.
• Reagent Stability: 5 human serum (HS) samples and 2 controls for run qualification (for each stability study). Human serum samples were single donors (native as well as spiked).
• Calibrator Stability: "on-test" and "reference materials" (specific number of human serum samples not detailed for each study, but implied to be sufficient for analytical validation).
• PreciControl Vitamin D total II (Value Assignment): Native human serum sample panel (single donors).
• Calibration Stability: 5 human serum (HS) samples and 2 controls (PreciControl Vitamin D total II). Pools of human serum samples (native as well as spiked).
• CalCheck Vitamin D total II (Value Assignment): Not explicitly stated, but performed for each lot.
• External (Clinical) Testing (Reference Range): Approximately 600 study subjects. After exclusions, 421 subjects were used for the reference range calculation.

Data Provenance:

• Clinical Samples for Reference Range: Prospectively collected from three US sites (northern, midwest, southern) during summer and winter seasons.
• Method Comparison to Reference Method: Patient serum samples from the Vitamin D Standardization and Certification Program (VDSCP) with assigned values by the RMP (Reference Measurement Procedure) at CDC.
• Analytical Studies (Precision, Linearity, Interference, etc.): Predominantly used human serum and plasma samples, often from "single donors" (native as well as spiked). The document implies these were collected appropriately for laboratory studies, likely from a variety of sources but not specifically detailed by country of origin beyond the US sites for the reference range study. All analytical studies appear to be retrospective in the sense that samples were acquired for the purpose of the study rather than being prospectively collected specifically for patient outcomes.

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

The concept of "experts" as human readers establishing ground truth (common in imaging AI) is not directly applicable here. This device is an in vitro diagnostic (IVD) assay measuring a biomarker concentration.

• Ground Truth for Clinical Samples: For the Reference Range study (External/Clinical Testing), the "ground truth" is the measured Vitamin D total II concentration by the Elecsys Vitamin D total II assay itself, and the study then calculates the reference interval from this healthy population. The individuals themselves are not "experts" establishing a truth.
• Ground Truth for Analytical Studies:
  • Traceability and Standardization: The assay is traced to the ID-LC-MS/MS 25-hydroxyvitamin D Reference Measurement Procedure (RMP) at the University of Ghent, which is further traceable to the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 2972. This is the ultimate ground truth for Vitamin D concentration. These are established laboratory reference methods, not human expert consensus.
  • Value Assignment of Controls and Calibrators: Values are assigned for PreciControl Vitamin D total II and CalCheck Vitamin D total II based on measurements with the Elecsys Vitamin D total II assay, which is itself traceable to the RMP. The "ground truth" for these materials is their assigned concentration based on the reference standard.
  • Method Comparison: One comparison is against the ID-LC-MS/MS RMP at CDC, which serves as the independent reference standard (ground truth) for those 111 samples.
  • Sample Pools/Spiking: For many analytical studies (e.g., precision, linearity, interference), test samples were prepared by pooling or spiking human serum/plasma. The "true" concentration for these samples is derived from the known amounts of spiked analyte or the consensus value of the pool, assuming the measurement method for verification is accurate and traceable.

In summary, the "ground truth" is established through highly controlled, traceable analytical reference methods and materials, not by human expert interpretation.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in studies where multiple human readers interpret images or clinical data and discrepancies need to be resolved. This is not directly relevant to an IVD assay where the output is a quantitative concentration.

For the analytical studies, the "adjudication" is inherent in the rigorous statistical analysis and adherence to established CLSI guidelines (e.g., EP5-A3 for precision, EP17-A2 for LoB/LoD, EP6-A for linearity, EP07-A2 for interference). Any outlying data points would be addressed through statistical methods or re-testing according to study protocols, not through human adjudication of differing interpretations. The method comparison studies (against predicate and RMP) use statistical regression analyses (Deming, Passing Bablok) to assess agreement, rather than adjudication of individual results.

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

No, an MRMC comparative effectiveness study was not done. MRMC studies are specific to evaluating the impact of a medical device (often AI-powered) on the performance of human readers, commonly in imaging diagnostics. This device is an in vitro diagnostic (IVD) assay that directly measures a biomarker concentration. Its performance is evaluated analytically and against reference methods, not in how it assists human interpretation of complex cases.

Therefore, there is no effect size of how much human readers improve with AI vs. without AI assistance.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the primary evaluation of the Elecsys Vitamin D total II assay is its standalone analytical performance. The entire "Non-Clinical Performance Evaluation" (Section 4) is dedicated to demonstrating the performance of the device itself (the assay on the cobas e 411 analyzer) across various metrics like precision, sensitivity, linearity, interference, specificity, and stability. The "Method Comparison to Reference Method" (4.11) particularly assesses its direct agreement with the gold standard RMP.

The "human-in-the-loop" component in this context is the laboratory technician operating the analyzer and interpreting the quantitative results within a clinical context (e.g., in aid of assessing vitamin D sufficiency). The performance evaluated here is solely that of the analytical system.

7. The Type of Ground Truth Used

The ground truth used for the device's validation is primarily external reference measurement procedures (RMPs) and reference materials.

• Primary Ground Truth: The ID-LC-MS/MS 25-hydroxyvitamin D Reference Measurement Procedure (RMP), specifically from the University of Ghent and CDC, traceable to the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 2972. This is the metrological traceability chain that provides the "true" value for vitamin D concentration.
• Secondary Ground Truth/Comparators:
  • Predicate Device: The Elecsys Vitamin D Assay (K113546) served as a comparator for demonstrating substantial equivalence.
  • Healthy Adult Population (for reference range): For establishing the clinical reference range, the ground truth is simply the distribution of measured values from a carefully selected cohort of healthy individuals. This is a form of outcomes data in the sense of a normal physiological range.
  • Known Spiked Concentrations: For many analytical studies (e.g., linearity, interference, specificity), samples were spiked with known amounts of analyte or interfering substances. The "true" concentration or the expected impact of the interferent serves as the ground truth for evaluating recovery or cross-reactivity.

8. The Sample Size for the Training Set

The document is a 510(k) summary for an IVD device, not an AI/ML device. Therefore, the concept of a "training set" for an algorithm in the machine learning sense is not applicable. The Elecsys Vitamin D total II assay is a chemical immunoassay, not a learning algorithm that undergoes a training phase with a dataset.

The parameters of the assay (reagent formulation, calibration curves) are established through developmental optimization and analytical validation, not through an iterative learning process with a "training set."

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

As noted above, there is no "training set" in the machine learning sense. The assay's performance characteristics and calibration are established through the use of:

• Reference materials (calibrators): CalSet Vitamin D total II, which is traceable to the ID-LC-MS/MS RMP. These calibrators are used to establish the instrument-specific calibration curve for each reagent lot, ensuring the assay's accuracy against a known standard.
• Quality controls (controls): PreciControl Vitamin D total II, used to monitor the assay's performance and ensure it stays within predefined limits. Their assigned values are derived from measurements against the master calibration curve, which is ultimately traceable to the RMP.

Therefore, the "ground truth" during the development and routine use of the assay is established via the metrological traceability chain to international reference standards and reference measurement procedures.

Ask a specific question about this device