Search Results

For in-vitro diagnostic use only.

For the quantitative measurement of procalcitonin (PCT) in human serum and plasma (lithium heparin and EDTA) using the VITROS 3600 Immunodiagnostic System.

Used in conjunction with other laboratory findings and clinical assessments, the VITROS B R A PA - M S PCT test is intended for use as follows:

· to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock,

· to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, using a change in PCT level over time,

· to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department,

· to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

The VITROS B·R·A·H·M·S PCT test is performed using the VITROS B·R·A·H·M·S PCT Reagent Pack and the VITROS B·R·A·H·M·S PCT Calibrators on the VITROS Systems.

Reagent Pack Contents
1 reagent pack containing:

• 100 coated wells (rat monoclonal anti-procalcitonin antibody, 1.0 µg/mL) ●
• 10.20 mL assay reagent (buffer containing bovine gamma globulin, bovine serum ● albumin and antimicrobial agent)
• . 13.10 mL conjugate reagent (HRP-conjugated mouse monoclonal procalcitonin antibody. 1.65 ug/mL in buffer with bovine serum albumin and antimicrobial agent)

Calibrator Contents

• . 3 sets of VITROS B•R•A•H•M•S PCT Calibrators 1 and 2, 1.0 mL, procalcitonin in buffer with antimicrobial agent, nominal values 0.080 and 75.0 ng/mL (ug/L)
• . Lot calibration card
• Protocol card ●
  • 16 calibrator bar code labels (8 for each calibrator) ●

The provided text is a 510(k) Summary for the VITROS B·R·A·H·M·S PCT Reagent Pack and Calibrators, intended for quantitative measurement of procalcitonin (PCT). This document describes the device's performance characteristics and clinical studies to establish substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a 510(k) summary for an in vitro diagnostic device, the "acceptance criteria" are implied by the comparison to the predicate device and established analytical performance metrics. The key criterion is demonstrating substantial equivalence to the predicate device, B·R·A·H·M·S PCT sensitive KRYPTOR (K171338), especially at critical clinical decision points.

2. Sample Sizes and Data Provenance

• Test Set (Method Comparison with Predicate):

  • Sample Size: 266 patient samples were used for the regression analysis comparing the VITROS B·R·A·H·M·S PCT test to the B·R·A·H·M·S PCT sensitive KRYPTOR assay. 246 samples were within the measuring range.
  • Data Provenance: Not explicitly stated for analytical studies, but for the clinical performance study, samples were "retrospective samples from a study of 858 adult patients diagnosed with severe sepsis or septic shock recruited across 13 investigational sites in the United States." The original MOSES Study (DEN150009) collected samples from patients admitted to ICU from emergency departments, other wards, or directly from out of the hospital. EDTA samples were used.

• Test Set (Clinical Concordance):

  • Sample Size: 2168 samples (evaluating concordance at various PCT decision points).
  • Data Provenance: "serial sample sets obtained from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study collection, a well-characterized sample collection in 13 sites across the United States." This indicates a prospective collection used retrospectively for this specific device's evaluation.

• Test Set (28-Day Mortality Prediction):

  • Sample Size: 858 adult patients in the study, with an analysis population of 598 subjects.
  • Data Provenance: Retrospective samples from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study collection in 13 sites across the United States.

3. Number of Experts and Qualifications for Ground Truth

• For an in vitro diagnostic device measuring an analyte (procalcitonin), the "ground truth" for analytical studies is typically established by reference methods or gravimetric preparation with known concentrations. Experts are not typically involved in establishing ground truth for analytical performance like precision, linearity, LoD/LoQ, and interference.
• For clinical studies (concordance and mortality prediction), the primary "ground truth" for the device's performance against clinical decision points is the predicate device's measurement (B.R.A.H.M.S PCT sensitive KRYPTOR assay). Physician discretion and clinical assessments were used for patient diagnosis and mortality outcomes in the MOSES study, which provided the samples. While physicians made clinical diagnoses, they were not experts establishing a "ground truth score" for the device; rather, clinical outcomes (mortality, diagnosis of sepsis/septic shock) were endpoints. No individual "experts" were formally used to establish a ground truth for the test set, but rather the clinical outcomes and the predicate device's results served as the reference.

4. Adjudication Method

• Not applicable in the context of this 510(k) summary for an in vitro diagnostic device assessing an analyte level. Adjudication methods like 2+1 or 3+1 are typically used for subjective evaluations (e.g., imaging interpretation) where expert consensus is needed to determine the correct ground truth for a given case. Here, the ground truth for analytical performance is quantitative, and for clinical performance, it is the predicate device's measurement and observed clinical outcomes (e.g., 28-day mortality).

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

• No, an MRMC comparative effectiveness study was not performed. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply.

6. Standalone Performance Study

• Yes, the performance described is a standalone performance study of the VITROS B·R·A·H·M·S PCT Reagent Pack and Calibrators. The "algorithm only" in this context refers to the assay's ability to quantitatively measure PCT levels. All analytical performance studies (precision, linearity, detection limits, analytical specificity, matrix comparison, high-dose hook, sample auto-dilution, carry-over) were conducted to demonstrate the standalone performance of the VITROS B·R·A·H·M·S PCT test. The clinical concordance with the predicate device also serves as a standalone performance benchmark.

7. Type of Ground Truth Used

• Analytical Ground Truth: For analytical performance studies (precision, linearity, LoD/LoQ, interference, matrix equivalence, high dose hook, carry over), the ground truth was established by:
  • Reference calibrators: Traceable to in-house reference calibrators, which were value-assigned to correlate to B·R·A·H·M·S PCT sensitive KRYPTOR.
  • Known concentrations: Prepared by gravimetric spiking with recombinant PCT.
  • Validated analytical methods: Following CLSI guidelines (e.g., EP05-A3 for precision, EP17-A2 for detection limits, EP06-A for linearity, EP07-A3 for interference).
• Clinical Ground Truth:
  • Predicate device results: For clinical concordance, the measurements from the B·R·A·H·M·S PCT sensitive KRYPTOR assay were considered the reference for comparison.
  • Outcomes data: For the 28-day mortality prediction claim, the vital status (mortality) of patients at Day 28 was the ground truth. This outcome data was collected during the original MOSES study.

8. Sample Size for the Training Set

• This 510(k) document describes a traditional in vitro diagnostic device clearance, not an AI/ML software submission that often explicitly details "training sets."
• However, the device's calibration is "traceable to in-house reference calibrators, which have been value-assigned to correlate to B·R·A·H·M·S PCT sensitive KRYPTOR." The development of these in-house reference calibrators and the assay itself would have involved some form of "training" or optimization using an internal dataset, but its size and specific characteristics are not provided in this regulatory summary.
• The clinical study samples from the MOSES study were used for validation (evaluation) of the device's clinical performance, not as a training set for the assay's underlying methodology.

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

• As noted above, a formal "training set" in the AI/ML sense is not described. The ground truth for the development of the assay (e.g., for calibrator assignment) would have been established through a combination of:
  • Reference materials: Highly characterized procalcitonin standards.
  • Defined analytical methods: Using established laboratory practices and potentially comparing to existing, well-regarded PCT assays during the R&D phase to create the "in-house reference calibrators."
  • Value assignment: A process where the concentration of an analyte in a calibrator is accurately determined. This often involves multiple measurements using reference methods or by gravimetric preparation.

Ask a specific question about this device

The Atellica® IM BRAHMS Procalcitonin (PCT) assay is for in vitro diagnostic use in the quantitative determination of procalcitonin in human serum and plasma (EDTA, lithium heparin, and sodium heparin) using the Atellica® IM Analyzer.

The Atellica IM BRAHMS PCT assay is intended for use, in conjunction with other laboratory findings and clinical assessments, as an aid in:

· The risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.

• Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, using percent change in PCT level over time.

· Decision-making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department.

• · Decision-making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

The Atellica IM BRAHMS PCT assay is a 2-site sandwich immunoassay using direct chemiluminescent technology that uses 3 mouse monoclonal antibodies specific for PCT. The first antibody, in the Lite Reagent, is a mouse monoclonal anti-PCT antibody labeled with acridinium ester. The second and third antibodies, in the ancillary reagent, are mouse monoclonal anti-PCT antibodies labeled with fluorescein. The immunocomplex formed with PCT is captured with mouse monoclonal anti-fluorescein antibody coupled to paramagnetic particles in the Solid Phase.

A direct relationship exists between the amount of PCT present in the patient sample and the amount of relative light units (RLUs) detected by the system.

The provided text describes the Siemens Healthcare Diagnostics Atellica IM B.R.A.H.M.S Procalcitonin (PCT) assay, an in vitro diagnostic device. The study presented focuses on the analytical and clinical performance of this assay, comparing it to a predicate device and evaluating its utility in specific clinical scenarios related to sepsis and respiratory tract infections.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly derived from the performance goals demonstrated in the analytical and clinical studies. Since this is a 510(k) submission, the primary goal is to show substantial equivalence to a legally marketed predicate device (B.R.A.H.M.S PCT sensitive KRYPTOR). The performance characteristics are presented as meeting industry standards (CLSI guidelines) and showing comparable results to the predicate.

Here's a table summarizing the analytical performance with implicit acceptance criteria (typically, these would be defined before the study in a protocol, often as a deviation tolerance from the predicate or a specific measure):

Detailed Study Information:

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

   • Analytical Performance:
     • Precision: 5 contrived human serum samples, 80 replicates per sample.
     • Linearity: 9 samples (prepared from high and low human serum pools).
     • Dilution Recovery: 5 human serum samples.
     • Detection Limits (LoD): 360 determinations (160 blank, 200 low-level replicates).
     • Endogenous/Therapeutic Drug/Cross-Reactivity Interference: Not specified beyond "serum pools" and "serum and plasma."
     • Heterophile Interference: HAMA and RF positive patient samples + control samples.
     • Method Comparison: 623 native human serum samples with assigned values from the predicate device.
     • Matrix Comparison: 51 matched specimen sets in 4 tube types (Serum, EDTA plasma, Lithium Heparin Plasma, Sodium Heparin Plasma).
     • Expected Values/Reference Interval: 144 serum samples from normal subjects.
   • Clinical Studies:
     • 28-day Mortality: 858 adult patients (>18 years) diagnosed with severe sepsis or septic shock admitted to ICU. The analysis population comprised 598 subjects.
     • Antibiotic Therapy/Discontinuation Support: Systematic literature reviews and meta-analyses:
       • Study-level meta-analysis (Initiation/Discontinuation): 11 RCTs (4090 patients) published 2004-2016.
       • Patient-level meta-analysis (Initiation): 13 RCTs (3142 patients) published 2004-2011.
       • Patient-level meta-analysis (Discontinuation): 5 RCTs (598 patients) published 2008-2010.
   • Data Provenance:
     • Analytical Data: In-house or contracted lab studies (implied to be prospective given the detailed methodology descriptions).
     • Clinical Data: "Banked specimens that were collected from subjects... and included as part of the intention-to-diagnose population from the BRAHMS MOSES study (DEN150009)." This indicates retrospective use of previously collected clinical trial data. The original MOSES study subjects were recruited across 13 investigational sites in the US. The meta-analyses for antibiotic guidance consolidated data from previously published RCTs.

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

   • For the analytical test sets, ground truth is established by standard laboratory methods and reference materials (e.g., recombinant PCT, serum pools), not human experts.
   • For the clinical study, the ground truth for patient outcomes (e.g., severe sepsis/septic shock diagnosis, 28-day all-cause mortality, need for ICU care) was presumably established by the clinical assessments and medical records from the original BRAHMS MOSES study that provided the banked specimens. The document does not specify the number or qualifications of clinicians/experts who established these initial diagnoses and outcomes for the MOSES study, but it's implied to be standard clinical practice within a multi-site clinical trial.
   • For the meta-analyses, the "ground truth" for antibiotic management decisions and patient outcomes (mortality, LOS, etc.) derived from the various RCTs where those decisions and outcomes were prospectively recorded by the clinical teams involved in those trials.

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

   • For the analytical studies, the "ground truth" values are quantitative measurements or characteristics of samples, typically not subject to human adjudication in the same way as, for example, image interpretation. Internal laboratory quality control and statistical methods (e.g., regression analysis, CV calculations) serve as "adjudication."
   • For the clinical study, the data were obtained from previously collected "banked specimens" and "clinical assessments" from the BRAHMS MOSES study. The document does not describe a new adjudication process for this particular 510(k) submission's analysis of this retrospective data. The rigor of the original MOSES study's data collection and endpoint ascertainment would be relevant but is not detailed here.
   • The meta-analyses relied on data from published RCTs; any adjudication would have occurred within the original trials.

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:

   • No. This device is an in vitro diagnostic (IVD) assay that measures a biomarker (Procalcitonin) in human specimens. It is not an AI-assisted diagnostic imaging or pathology device that requires human "readers." Therefore, an MRMC study is not applicable and was not performed.

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

   • Yes, implicitly. The performance characteristics (precision, linearity, detection limits, interference, method comparison) are "standalone" results of the assay itself, demonstrating its analytical performance when run on the Atellica IM Analyzer. The clinical studies demonstrate the performance of the assay's results when used in conjunction with "other laboratory findings and clinical assessments," but the assay itself generates the PCT value independently of human interpretation of that specific run.

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

   • Analytical Studies: "Ground truth" for analytical studies is typically established by meticulously prepared reference materials, spike-in methods, and comparison to a well-validated predicate device using a large sample size of native patient samples.
   • Clinical Studies:
     • For the 28-day mortality prediction, the ground truth was outcomes data (survival status at 28 days) derived from a pre-existing clinical study (BRAHMS MOSES study).
     • For antibiotic guidance, the insights were derived from meta-analyses of published Randomized Controlled Trials (RCTs). The "ground truth" here is the aggregated, prospectively collected patient outcomes (antibiotic use, duration, mortality, complications, LOS) from these trials where patients were managed either by standard care or PCT-guided protocols.

7. The sample size for the training set:

   • This document describes a 510(k) premarket notification for an IVD assay, not an AI/ML device that typically requires a distinct "training set." The performance studies for an IVD device like this are primarily for validation and demonstrate clinical and analytical performance. There is no explicit "training set" in the context of machine learning.
   • However, if one were to consider the development of the assay's methodologies, the calibration and control materials (e.g., PCT MCM) would be used for standardization and quality control, which could be seen as analogous to internal "training" or optimization data during product development, but no specific sample size for this is detailed as "training set."

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

   • As noted above, the concept of a "training set" with ground truth establishment in the ML sense is not directly applicable to this type of IVD device submission. The assay is a chemical measurement system. Its "truth" is established via analytical validation showing its accuracy, precision, and comparability to reference methods/predicate devices.

Ask a specific question about this device