(27 days)
The Synovasure Alpha Defensin Lateral Flow Test Kit is a qualitative visually read immunochromatographic assay for the detection of human host response proteins, Alpha Defensins 1-3, in the synovial fluid of adults with a total joint replacement who are being evaluated for revision surgery. The Synovasure Alpha Defensin Lateral Flow Test Kit results are intended to be used in conjunction with other clinical and diagnostic findings as an aid in the diagnosis of periprosthetic joint infection (PJ). The Synovasure Alpha Defensin Lateral Flow Test Kit is not intended to identify the etiology or severity of a PJI.
The Synovasure Alpha Defensin Control Kit is used in the Synovasure Alpha Defensin Lateral Flow Test Kit as assayed quality control samples to monitor performance and reliability of the Synovasure Alpha Defensin Lateral Flow Test Kit.
The Synovasure Alpha Defensin (AD) Lateral Flow (LF) Test Kit is an immunoassay for the detection of alpha defensin levels in the synovial fluid of patients with a potential PJI. Antibodies specific to alpha defensin bind host alpha defensin in the synovial fluid, become immobilized on the lateral flow test strip, and are detected as a colored line due to the use of a colloidal gold reporter.
This document describes the Synovasure Alpha Defensin Lateral Flow Test Kit and its performance.
The device is a qualitative, visually-read immunochromatographic assay for detecting human host response proteins, Alpha Defensins 1-3, in synovial fluid of adults with total joint replacement being evaluated for revision surgery. It is intended to aid in the diagnosis of periprosthetic joint infection (PJI) when used with other clinical and diagnostic findings. It does not identify the etiology or severity of PJI.
Here's an analysis of the provided information regarding acceptance criteria and the study proving the device meets them:
1. A table of acceptance criteria and the reported device performance
The provided document does not explicitly state acceptance criteria in a quantitative table format for the device's performance. Instead, it references a "Method comparison study to demonstrate equivalent performance between proposed device with modified cassette geometry and existing version of the Alpha Defensin Lateral Flow Test Device was performed." This implies that the acceptance criterion was "equivalent performance" to the predicate device. However, specific metrics (e.g., sensitivity, specificity, accuracy) and their target values are not provided within this summary.
Therefore, a table cannot be fully constructed from the provided text. To illustrate, if specific targets were present:
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Not specified | Not specified | Not specified |
| Sensitivity | [e.g., >= 85%] | Not explicitly stated |
| Specificity | [e.g., >= 90%] | Not explicitly stated |
| Accuracy | [e.g., >= 88%] | Not explicitly stated |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document mentions a "Method comparison study," but it does not specify the sample size for this study. It also does not provide information on the data provenance (e.g., country of origin, retrospective or prospective nature of the data).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The document does not provide information on the number of experts used to establish ground truth or their qualifications. Given that the device detects "human host response proteins" and aids in "diagnosis of periprosthetic joint infection (PJI) ... in conjunction with other clinical and diagnostic findings," the ground truth likely involves clinical diagnosis of PJI, which would typically be established by medical professionals. However, specifics are missing.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not provide information on any adjudication method used for establishing the ground truth or evaluating the device's performance in the method comparison study.
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
This device is described as a "qualitative visually read immunochromatographic assay" (a lateral flow test kit) and not an AI-assisted diagnostic tool for image analysis. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study evaluating human readers' improvement with AI assistance would not be applicable to this type of device, and no such study is mentioned.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is a visually read test kit, implying a human-in-the-loop component for reading the test result. Therefore, a "standalone algorithm only" performance study would not be applicable in the same way it would be for an AI-driven image analysis algorithm. The "method comparison study" likely evaluates the performance of the device itself (including human interpretation) against a reference method or the predicate device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The document states the device results "are intended to be used in conjunction with other clinical and diagnostic findings as an aid in the diagnosis of periprosthetic joint infection (PJI)." This strongly suggests that the ground truth for PJI diagnosis was established based on clinical diagnosis, which typically involves an expert consensus of various clinical, laboratory, and imaging findings, and potentially surgical/pathological confirmation. However, the specific components of the ground truth (e.g., specific clinical criteria, culture results, pathology reports) are not detailed.
8. The sample size for the training set
The document describes a "method comparison study" between the proposed device and an existing version. It does not mention a separate "training set" as would be typical for machine learning models. This is likely because the device is a conventional in-vitro diagnostic test, not an AI/ML-based device.
9. How the ground truth for the training set was established
As there is no mention of a "training set" for an AI/ML model, this question is not applicable to the information provided. The "ground truth" for the performance evaluation set is implicitly clinical diagnosis of PJI, as discussed in point 7.
§ 866.3230 Device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections.
(a)
Identification. A device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections is identified as an in vitro diagnostic device intended for the detection and qualitative measurement, quantitative measurement, or both of one or more non-microbial analytes in human clinical specimens to aid in the assessment, identification, or both of a localized microbial infection 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) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) An intended use with a detailed description of what the device detects and measures, the type of results provided to the user, the sample type, whether the measure is qualitative and/or quantitative, the clinical indications for the test use, and the specific population(s) for which the device is intended.
(ii) A detailed description of the performance characteristics of the device for all intended specimen types from the analytical and clinical studies (as applicable) required under paragraphs (b)(3)(ii) and (iii) of this section.
(iii) A detailed explanation of the interpretation of results, including acceptance criteria for evaluating the validity of individual runs (
e.g., assessment of internal and/or external quality controls, as applicable).(iv) The following limiting statements:
(A) A statement that a negative test result does not preclude the possibility of infection;
(B) A statement that the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) A statement that consistent device performance is dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) A statement that details any limitations associated with the samples, as appropriate (
e.g., collected on the day of admission to the intensive care unit).(3) Design verification and validation must include the following:
(i) A detailed device description, including as appropriate, all device parts; control elements incorporated into the test procedure; instrument requirements; reagents required but not provided; and the principle of device operation and test methodology, including all preanalytical methods for the processing of specimens and the methodology from obtaining a sample to the result; design of primer/probe sequences; rationale for target analyte selection; and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies including analytical sensitivity (Limit of Detection, Limit of Quantitation, and Limit of Blank), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross-contamination, specimen stability, within-lab precision, reproducibility, and linearity, as applicable.
(iii) Detailed documentation and results either from a clinical study, that includes prospective (sequentially collected) samples for each intended specimen type that are representative of the intended use populations and, when determined to be acceptable by FDA, additional characterized clinical samples; or, when determined to be acceptable by FDA, an equivalent sample set. The clinical study must compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (
e.g., the predefined statistical analysis plan), clinical study report, testing results, and results of all statistical analyses.(iv) An evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and sex distribution) similar to the intended use population of the device.(v) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risks of false results, failure to operate the device correctly, and failure to interpret test results correctly.
(vi) An appropriate risk mitigation strategy to ensure that the device does not prevent any other device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(vii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.