(90 days)
AuraTek FDP is a rapid one-step gold dye particle lateral flow immunoassay indicated for the in vitro qualitative measurement of fibringen and fibrinogen degradation products (FDP) in human urine, to be used with standard cystoscopic examination to aid in the management of patients with a history of bladder cancer.
AuraTek FDP is a one-step gold dye particle immunoassay on a porous carrier. Mobile purple-red dye particles labeled with anti-FDP and fibrinogen antibody and immobile capture anti-FDP and fibringgen antibodies are coated as discrete zones on the porous carrier. In addition a test control zone with antimurine IgG (Reaction Control 2) is coated on the carrier. A sample placed on the device is absorbed by the porous carrier. The rehydrated colored sol particles move through the porous carrier to the capture anti-FDP and then to the anti-murine IgG. If the sample contains FDP and/or fibrinogen, the antibodylabeled sol particles will bind in a sandwich-type reaction to the capture anti-FDP and fibrinogen antibody producing a purple-red dot in the test result window. With a negative sample, the white test result window remains unchanged at the time of reading. AuraTek FDP has the unique feature that the test run validity is double-checked with the appearance and disappearance of color in the Reaction Control 1 window and development of a purple-red dot in the Reaction Control 2 window.
Here's a breakdown of the acceptance criteria and the study details for the AuraTek FDP device, based on the provided document:
Acceptance Criteria and Device Performance
The acceptance criteria are not explicitly stated as distinct thresholds in the document. Instead, the device's performance is presented in comparison to existing methods (cytology and hemoglobin dipstick) and against general clinical expectations for accuracy in bladder cancer monitoring. The key performance metrics are Sensitivity and Specificity.
Here's a table summarizing the reported device performance and implicitly, the targets it aims to meet or exceed:
| Metric | Acceptance Criteria (Implied/Compared to) | Reported Device Performance (AuraTek FDP) |
|---|---|---|
| Sensitivity | Better than cytology (35%) | 68% (All Stages), 100% (Invasive T2, T3, T4) |
| Specificity | 80% (Comparable to Bard BTA) | 96% (Healthy Subjects), 80% (Cystoscopy negative patients with history of bladder cancer) |
| Limit of Detection | - | 30 ng Fibrinogen Equivalents (FE) / ml |
| Reproducibility | Qualitative agreement | Total qualitative agreement at each control level |
| High Dose Hook Effect | No hook effect up to 2000 ng FE/ml | No hook effects seen at concentrations up to 2000 ng FE/ml |
| Interfering Substances | No interference at specified concentrations | Many substances tested without interference. Whole blood and plasma may cause positive interference at levels > 0.0156% vol/vol. |
Study Details
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Clinical Sensitivity Study: 192 patients with a history of bladder cancer undergoing cystoscopic examination.
- 79 patients with confirmed bladder tumors (positive cystoscopy with confirmatory biopsy).
- 113 patients with negative cystoscopy results (used for specificity analysis).
- Specificity Study (Healthy Subjects): 73 healthy subjects.
- Specificity Study (Non-Bladder Cancer Urological Disease): 232 subjects with various non-bladder cancer urological diseases.
- Clinical Sensitivity Study: 192 patients with a history of bladder cancer undergoing cystoscopic examination.
- Data Provenance: The study was a "multi-center study" involving "a general urology practice." While specific countries are not mentioned, the context of a 510(k) submission to the FDA suggests the data would be primarily from the United States. The study is prospective as it involved patients "undergoing cystoscopic examination," implying data collection at the time of follow-up.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not explicitly stated.
- Qualifications of Experts: The ground truth for bladder cancer confirmation was established by positive cystoscopy results with confirmatory biopsy. This implies a pathologist would be involved in interpreting the biopsy and a urologist in performing the cystoscopy. Specific years of experience are not mentioned, but these are standard clinical practices performed by qualified medical professionals.
4. Adjudication Method
- The document implies that the ground truth for cancer diagnosis was established by confirmatory biopsy following cystoscopy. This is a definitive diagnostic method, not typically requiring additional adjudication among experts in the same way imaging interpretations might. The mention of "positive cystoscopy results with confirmatory biopsy" suggests a definitive, pathological diagnosis. Therefore, a specific adjudication method (like 2+1 or 3+1) among multiple readers of the same data type isn't detailed, as the biopsy serves as the ultimate diagnostic confirmation.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a MRMC comparative effectiveness study was not done in the context of human readers improving with AI vs. without AI assistance.
- The study compares the performance of the AuraTek FDP device to standard clinical methods (cytology and hemoglobin dipstick) directly, not as an AI-assisted tool for human readers. It's a standalone device performance study.
6. Standalone Performance Study
- Yes, a standalone (algorithm only without human-in-the-loop performance) study was done. The entire "Summary of Studies" section (1.7) details the performance of the AuraTek FDP device in isolation, evaluating its sensitivity, specificity, reproducibility, high dose hook effect, and interference from various substances. The reported sensitivity and specificity values are for the device itself.
7. Type of Ground Truth Used
- The primary ground truth for the presence of bladder cancer in the clinical sensitivity study was Pathology (confirmatory biopsy following positive cystoscopy).
- For the specificity analyses, ground truth was derived from "healthy subjects," "cystoscopy negative patients with a history of bladder cancer," and patients diagnosed with "non-bladder cancer urological disease" (presumably confirmed by standard clinical diagnostic procedures relevant to their conditions).
8. Sample Size for the Training Set
- Not applicable / Not explicitly stated. This device is a rapid immunoassay (lateral flow immunoassay), not an AI/machine learning device that typically requires a large 'training set' in the conventional sense. The "training" of such a device involves optimization of its chemical and physical components (e.g., antibody concentrations, membrane properties) during its development, rather than a data-driven algorithmic training process. The document describes analytical validation and clinical performance studies, not an AI model's training phase.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As explained in point 8, this is not an AI/machine learning device. Therefore, there isn't a "training set" with ground truth in the context of an algorithm learning from data. The device's performance is driven by its biological and chemical design (monoclonal antibodies, gold dye particles, etc.).
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.