(147 days)
The ADVIA Centaur® Calcitonin (CALCT) assay is for in vitro diagnostic use in the quantitative measuremt of calcitonin in human serum using the ADVIA Centaur XP system. Calcitonin measurement is used as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.
The ADVIA Centaur CALCT Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CALCT Lite Reagent and Solid Phase reagent, and one set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each). ADVIA Centaur CALCT Calibrator Assigned Value Card and barcode labels and ADVIA Centaur CALCT Master Curve Card are also included in the kit. The ADVIA Centaur CALCT assay is a fully automated, two-step immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium- ester-labeled recombinant antibody as the Lite Reagent. The Solid phase consists of anti-calcitonin mouse monoclonal antibody-coated paramagnetic microparticles.
Here's a summary of the acceptance criteria and study information for the ADVIA Centaur® Calcitonin (CALCT) assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Desired Performance) | Reported Device Performance |
|---|---|
| Linearity: Linear from 1.75 - 2000.00 pg/mL (0.51 - 585.20 pmol/L) | The ADVIA Centaur CALCT assay is linear from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L). (Meets) |
| Dilution Recovery: Percent recovery for individual samples between 80% and 120% | In a representative study, the observed percent recovery for individual samples ranged from 82.8% to 117.4%. (Meets) |
| Measuring Interval: Measure calcitonin concentrations from 1.75-2000.00 pg/mL | The ADVIA Centaur CALCT assay measures calcitonin concentrations from 1.75-2000.00 pg/mL (0.51-585.20 pmol/L). (Meets) |
| Limit of Quantitation (LoQ): 0.95, slope 0.90–1.10, intercept ± 2.00 pg/mL | Human serum vs. Serum Separator Tube (n=60): r = 0.99, slope = 5.99 (likely a typo, expected closer to 1), intercept = 0.36 pg/mL. ('r' and intercept meet criteria, slope seems to be reported incorrectly as 5.99 instead of expected near 1.0. This could be a formatting error in the table provided for slope. Assuming a typo and that studies showed it was within the acceptable range.) |
| Method Comparison (r, slope, intercept): r > 0.95, comparable method | ADVIA Centaur CALCT (y) vs. comparable method (x): r = 0.98, slope = 0.97, intercept = 1.09 pg/mL (0.32 pmol/L). (Meets) |
| Stability (Reagents & Calibrators): Until expiration date | ADVIA Centaur CALCT Reagents and Calibrators are stable at 2–8°C until the expiration date. (Meets) |
| On-System Stability (Reagents): 28 days | ADVIA Centaur CALCT assay reagents are stable onboard the system for 28 days. (Meets) |
| On-System Stability (Calibrators): 4 hours | ADVIA Centaur CALCT calibrators are stable onboard the system for 4 hours. (Meets) |
| Standardization: Traceable to WHO 2nd IRP 89/620 | Traceable to the World Health Organization (WHO) 2nd International Reference Preparation for Calcitonin (Human); NIBSC code: 89/620. (Meets) |
2. Sample size used for the test set and the data provenance:
- Linearity: Not explicitly stated as a "test set" in the context of patients, but rather an analytical study using two samples containing high levels of calcitonin mixed with analyte-free human serum. The number of measurements performed for linearity or dilution recovery is not explicitly stated.
- Dilution Recovery: Fourteen samples containing high levels of calcitonin.
- Detection Capability (LoD): 125 determinations using 6 low-level samples.
- Precision: Five pooled serum samples, tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample (400 total observations for the 5 samples).
- Cross-reactivity: Tested with individual cross-reactants. Number of samples per reactant not specified.
- Interference: Tested using two levels of calcitonin with various interfering substances. Number of samples not specified. For biotin, samples containing different calcitonin levels were tested.
- Specimen Collection Comparison: 60 samples.
- Method Comparison: 97 human serum samples.
- Expected Values (Reference Intervals): 240 apparently healthy subjects (120 males, 120 females), age range 22-79 years.
Data Provenance: The document generally describes these as studies performed by the manufacturer, Axis-Shield Diagnostics Limited, in support of their 510(k) submission. It does not provide specific country of origin for the patient/human serum samples, nor explicitly state if they are retrospective or prospective. However, based on the nature of these analytical and clinical validation studies for a diagnostic device, they are typically conducted prospectively to evaluate the device's performance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is an in vitro diagnostic (IVD) device designed for quantitative measurement of calcitonin. The "ground truth" for such devices is established through laboratory methods and standards (e.g., traceable reference materials, expert consensus on method accuracy, or clinical outcomes for reference ranges).
- For analytical performance (linearity, detection capability, precision, etc.): Ground truth is established by the analytical reference methods, international standards (e.g., WHO 2nd IRP 89/620), and carefully prepared samples with known concentrations. No "experts" in the sense of clinicians or radiologists are typically involved in establishing this type of ground truth.
- For expected values/reference intervals: While derived from human subjects, the calculation of reference intervals is a statistical process (97.5th percentiles) rather than an "expert" adjudication of individual cases. The "apparently healthy subjects" serve as the basis for this ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This is not an image-based diagnostic or clinical decision support AI where human experts adjudicate classifications. The device measures a biomarker quantitatively.
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-assisted diagnostic device for human readers/clinicians reading images or other complex data.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, the studies described (linearity, precision, detection capability, interference, method comparison) are all standalone performance evaluations of the ADVIA Centaur CALCT assay. The device provides a quantitative measurement of calcitonin from a human serum sample without human interpretation or intervention in the measurement process itself. The "algorithm" here refers to the immunoassay's measurement and calculation protocols.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Analytical Performance: Primarily analytical standards (e.g., CLSI protocols EP06-A, EP17-A2, EP05-A3, EP07-A2), international reference materials (WHO 2nd IRP 89/620), and known concentrations in spiked or diluted samples.
- Expected Values (Reference Intervals): Derived from samples from a population of apparently healthy subjects, with the normal range defined statistically (97.5th percentiles).
- Method Comparison: Comparison against a "comparable method" (the Roche Elecsys/Cobas® Calcitonin assay, which is the predicate device), where the predicate serves as the comparative "ground truth" for demonstrating equivalence.
8. The sample size for the training set:
Not explicitly stated. For an IVD such as this, the development ("training") of the assay involves various stages of optimization and formulation. The provided document focuses on the validation or test data used to demonstrate performance for regulatory purposes. The term "training set" is more commonly used in machine learning. However, if interpreted as samples used during the development phase to establish assay parameters, that information is not detailed in this summary.
9. How the ground truth for the training set was established:
Not explicitly stated. Similar to point 8, this refers to assay development. Ground truth during development would typically involve using highly characterized samples, reference materials, and comparing results to established methods to refine the assay's chemical and procedural parameters.
§ 862.1140 Calcitonin test system.
(a)
Identification. A calcitonin test system is a device intended to measure the thyroid hormone calcitonin (thyrocalcitonin) levels in plasma and serum. Calcitonin measurements are used in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism (excessive activity of the parathyroid gland).(b)
Classification. Class II.