(355 days)
The RESOLVE® Systems Hemoglobin kit is designed to separate whole blood, cord blood or dried blood spot specimen for detection of normal and variant hemoglobins by isoelectric focusing. The kit is designed to be run on a flat-bed electrofocusing unit. This assay is intended for use as an aid in the diagnosis of neonatal and adult hemoglobinopathies.
The preparation and separation of hemoglobin is accomplished through the application of a hemoglobin sample onto a precast agarose gel containing RESOLVE Ampholytes pH 6-8. RESOLVE Ampholytes are composed of low molecular weight amphoteric molecules with varying isoelectric points. When an electrical current is applied to the gel, these molecules migrate through the gel to their isoelectric points (pl's) along the gel, forming a stable pH gradient. The hemoglobin variants also migrate through the gel until they reach the area where their individual pl's equal the corresponding pH on the gel. At this point, the charges on the variants are zero and migration ceases. The electric field counteracts diffusion and the hemoglobin variant forms a discrete thin band. Hemoglobin bands are visualized by using the JB-2 Staining System containing o-dianisidine. o-dianisidine, the active component of the Gel Stain Concentrate, is oxidized in the presence of hydrogen peroxide at the site of hemoglobin. This reaction produces an insoluble, colored precipitate proportional to the amount of hemoglobin.
Here's an analysis of the acceptance criteria and study detailed in the provided document for the RESOLVE® Hemoglobin kit:
Acceptance Criteria and Device Performance
The document describes a method comparison study to demonstrate substantial equivalence to predicate devices rather than pre-defined acceptance criteria with specific thresholds for sensitivity, specificity, or predictive values. The main performance metric used to establish equivalence is agreement percentage with the predicate devices. Precision is also evaluated.
| Acceptance Criteria Category | Specific Metric (as presented in the document) | Reported Device Performance (RESOLVE® Hb kit) |
|---|---|---|
| Method Comparison | Agreement with Predicate Device 1 (BioRad VARIANT Sickle Cell Short Program) | Study 1: 99.8% (95% lower CL: 99.2%) |
| Study 3: 99.1% (95% lower CL: 98.4%) | ||
| Agreement with Predicate Device 2 (BioRad VARIANT nbs Sickle Cell Program) | Study 2: 97.7% (95% lower CL: 96.7%) | |
| Precision | Within-gel precision (CV%) for Hb A1c vs. Hb C distance | 2.2% |
| Between-gel precision (CV%) for Hb A1c vs. Hb C distance | 1.8% | |
| Total precision within laboratory (CV%) for Hb A1c vs. Hb C | 2.8% | |
| Within-gel precision (CV%) for Hb A vs. Hb F distance | 3.3% | |
| Between-gel precision (CV%) for Hb A vs. Hb F distance | 2.9% | |
| Total precision within laboratory (CV%) for Hb A vs. Hb F | 4.4% |
Note: The document does not explicitly state pre-defined acceptance thresholds for these metrics, but rather presents the results as evidence of equivalence to the predicate devices, which are assumed to have acceptable performance. The FDA's 510(k) clearance confirms that these results were considered sufficient to demonstrate substantial equivalence.
Study Details
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Sample Sizes and Data Provenance:
- Test Set (Method Comparison):
- Study 1: 850 specimens
- Study 2: 837 specimens
- Study 3: 1031 specimens
- Total: 2718 specimens
- Data Provenance: The samples were a mix of "routine DBS samples or retrospective samples." The document does not specify the country of origin, but the submitting company is based in Finland, and the predicate device manufacturers are likely US-based, suggesting a possibility of data from different regions or a multi-site study. It's explicitly stated that the study was conducted at three sites.
- Test Set (Method Comparison):
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Number of Experts and Qualifications for Ground Truth of Test Set:
- The ground truth for the method comparison study was established by the predicate devices (BioRad's HPLC methods). The document does not mention the involvement of human experts to establish ground truth for the test set samples themselves, but rather the comparison is against the results generated by the established predicate devices. Therefore, the "experts" in this context are the predicate devices and their underlying methodologies.
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Adjudication Method for the Test Set:
- There is no mention of an adjudication method in the traditional sense of human review. The comparison is directly between the RESOLVE® Hb kit's results and the predicate device's results. Any discrepancies would likely be investigated through further testing or expert review, but this process is not detailed.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) kit for laboratory use, not typically a "reader" type AI device that assists human interpretation in a clinical setting where MRMC studies are common. The comparison is between the new kit and existing laboratory methods.
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Standalone Performance (Algorithm Only without Human-in-the-Loop Performance):
- Yes, the performance presented is standalone (algorithm/kit only without human-in-the-loop performance contribution). The RESOLVE® Hb kit is designed for laboratory separation of hemoglobins. While visual interpretation is part of the process (and an optional "Iso Scan imaging system" is mentioned), the "agreement" and "precision" metrics are based on the kit's ability to correctly categorize/separate hemoglobins compared to the predicate devices. The "interpretation" for the RESOLVE® Hb kit is described as "Visual interpretation of hemoglobin bands compared to position marker."
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Type of Ground Truth Used:
- The ground truth for the method comparison was established by the results from the predicate devices (BioRad's HPLC methods: VARIANT Sickle Cell Short Program and VARIANT nbs Sickle Cell Program). These methods are considered established and cleared for their intended use, making their results a de facto "ground truth" for comparison.
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Sample Size for the Training Set:
- The document does not provide information on a training set. This is expected because the RESOLVE® Hemoglobin kit operates on an isoelectric focusing principle, which is a biochemical separation technique, not an Artificial Intelligence (AI) or machine learning algorithm that typically requires a training set.
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How the Ground Truth for the Training Set Was Established:
- As there is no mention of a "training set" for an AI/ML algorithm within the description of this device, this question is not applicable.
§ 864.7415 Abnormal hemoglobin assay.
(a)
Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types.(b)
Classification. Class II (special controls). A control intended for use with an abnormal hemoglobin assay is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.