(273 days)
The Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application is the quantitative measurement of Monocyte Distribution Width (MDW). The Early Sepsis Indicator is intended for use with adult patients presenting to the emergency department, on whom a white cell differential test has been ordered.
MDW is measured from a (K2EDTA) whole-blood venous sample within 2 hours of collection. MDW values greater than 20.0 together with other laboratory findings and clinical information, aids in identifying patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission.
MDW values greater than 20.0 should be interpreted in association with other clinical information and diagnostic testing, as a proportion of patients without sepsis may have an elevated MDW value at baseline.
MDW values less than or equal to 20.0 cannot rule out sepsis or the development of sepsis within 12 hours of hospital admission. The Early Sepsis Indicator should not be used as the sole basis to determine the absence of sepsis.
The predictive value of the Early Sepsis Indicator for identifying sepsis in patients with hematological abnormalities has not been established.
The Early Sepsis Indicator (ESI) requires the use of the UniCel DxH 800 Coulter Cellular Analysis System (DxH 800) and its reagents, controls and calibrators last cleared under 510(k) K140911.
The UniCel DxH 800 Coulter Cellular Analysis System contains a quantitative, automated hematology analyzer (DxH 800) designed for in vitro diagnostic use in screening patient populations by clinical laboratories. The system provides a Complete Blood Count (CBC), Leukocyte 5 Part Differential (Diff), Reticulocyte (Retic), Nucleated Red Blood Cell (NRBC) on whole blood, as well as, Total Nucleated Count (TNC), and Red Cell Count (RBC) on Body Fluids (cerebrospinal, serous and synovial). This submission adds a new parameter, Monocyte Distribution Width (MDW) to those mentioned above. This parameter has been shown to aid in the early detection of Sepsis in emergency room patients.
The system consists of two primary components, the workstation and the DxH 800 analyzer as shown in Figure 1. DxH 800 System Configuration. The primary function of the DxH 800 analyzer is to process samples and provide results to the workstation. The primary functions of the workstation are: user interface, system control, results processing and storage and external communications. The analyzer runs embedded code and the workstation runs Microsoft Windows 7 Operating System (OS).
Here's the breakdown of the acceptance criteria and study detailed in the provided document:
Acceptance Criteria and Device Performance for UniCel DxH 800 Cellular Analysis System with Early Sepsis Indicator Application
The device is intended for the quantitative measurement of Monocyte Distribution Width (MDW) to aid in identifying adult patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission. The key acceptance criterion for clinical accuracy revolves around sensitivity and specificity at a specified MDW cut-off.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Study | Acceptance Criteria (Threshold) | Reported Device Performance (Result) |
|---|---|---|
| Clinical Accuracy (MDW Cut-off of 20.0) | - Sensitivity within predefined lower limit | - Validated the predefined cut-offs |
| - Specificity within predefined lower limit | - Demonstrated that the lower limit of sensitivity and specificity were within acceptance criteria for both cut-offs. |
Note: The document states that the study demonstrated that an MDW cut-off of 20.0 units provided an optimum diagnostic ability by balancing the ability to detect positive patients (sensitivity) and negative patients (specificity), and thus this cut-off was selected. Detailed numerical values for sensitivity and specificity at this cut-off are not explicitly provided in the table, but the text assures they met the acceptance criteria.
2. Sample Size and Data Provenance for Test Set
- Sample Size: Not explicitly stated for the "test set" in a distinct way, but the "Clinical Accuracy" study states it was a "multi-center prospective cohort study."
- Data Provenance:
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Primarily prospective. The clinical accuracy study was a "multi-center prospective cohort study."
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified.
Note: The document mentions "clinical information and diagnostic testing" and "other laboratory findings" were used in conjunction with MDW values, implying expert judgment in establishing the ground truth for sepsis diagnosis.
4. Adjudication Method
- Adjudication Method: Not specified.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study: No, an MRMC comparative effectiveness study was not done. This device measures a quantitative biomarker (MDW) from a blood sample, not something interpreted by human readers from images or complex data.
6. Standalone (Algorithm Only) Performance
- Standalone Performance: Yes, the fundamental performance assessed is the standalone diagnostic ability of the MDW parameter as an aid in identifying sepsis. The clinical accuracy study directly evaluated the MDW parameter's performance in detecting sepsis.
7. Type of Ground Truth Used
- Type of Ground Truth: The ground truth for sepsis diagnosis was established based on "other laboratory findings and clinical information" and "diagnostic testing." This suggests a comprehensive clinical diagnosis of sepsis, likely involving a combination of clinical assessment, laboratory parameters (beyond MDW), and potentially culture results or other confirmatory tests, as determined by clinicians.
8. Sample Size for Training Set
- Sample Size for Training Set: Not explicitly stated as a separate "training set" in the context of machine learning model development. The document focuses on the validation of the MDW parameter and its cut-off.
Note: The MDW parameter itself is a quantitative measurement derived from hematology analyzer data, not a machine learning model that would typically have a distinct training set in the conventional sense. The "training" or development of the algorithm to calculate MDW would have occurred prior to this validation study, but details are not provided here.
9. How Ground Truth for Training Set Was Established
- How Ground Truth for Training Set Was Established: Not specified, as a distinct training set for a machine learning model is not explicitly mentioned or implied for the MDW parameter's development in this document. The MDW value is a quantitative measurement from the analyzer, not a diagnosis itself.
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.