(59 days)
Portrait Toxigenic C. difficile Assay, a prescription device under 21 CFR Part 801.109 that is indicated for the detection of toxigenic Clostridium difficile in human fecal samples collected from patients suspected of having Clostridium difficile infection (CDI). The test utilizes automated blocked primer enabled helicase-dependent amplification (bpHDA) to detect toxin gene sequences associated with toxin producing C. difficile. The Portrait Toxigenic C. difficile Assay is intended as an aid in the diagnosis of CDI.
The Portrait Toxigenic C. difficile Assay as run on the Portrait Analyzer is a bench top fully automated in vitro diagnostics system that includes the Portrait Analyzer, control Laptop PC and single-use Portrait Toxigenic C. difficile Test Cartridges and sample preparation apparatus. The Portrait Analyzer is designed to perform automated sample extraction; blocked primer mediated thermophilic helicasedependent amplification (bpHDA); and chip-based detection with integrated data analysis in approximately 85 minutes.
The sample to be tested is inserted into the sample preparation that has been preloaded with buffer and briefly vortexed. The vortexed mixture is then loaded into the assay cartridge. The cartridge is loaded into the Portrait Analyzer which performs extraction (cell lysing), amplification, hybridization and signal formation on the detection chip. The resulting signal(s) are detected and interpreted by the automated Portrait Analyzer.
In addition to the necessary probes and primers to detect the presence of tcdB (toxin B gene) performance of the Portrait Toxigenic C. difficile Assay includes an integrated SPC to insure the adequate processing of the sample during preparation and subsequent extraction and amplification steps.
Here's an analysis of the Portrait Toxigenic C. difficile Assay's acceptance criteria and the study proving it meets them, based on the provided text:
Acceptance Criteria and Device Performance for Portrait Toxigenic C. difficile Assay
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in a table format for sensitivity, specificity, PPV, and NPV. However, the reported clinical performance implicitly serves as the criteria the device met for de novo classification. The reproducibility and precision studies also have implicit agreement rate criteria that were "within the expected percent." For this table, I will present the reported clinical performance statistics.
| Metric | Reported Device Performance (%) | Implied Acceptance Criteria (Achieved) |
|---|---|---|
| Sensitivity | 98.0% (92.4-99.6% CI95) | ≥ 92.4% |
| Specificity | 90.9% (87.7-93.3% CI95) | ≥ 87.7% |
| PPV | 71.4% (63.1-78.6% CI95) | ≥ 63.1% |
| NPV | 99.5% (98.0-99.9% CI95) | ≥ 98.0% |
Reproducibility Study Results (Agreement)
| Sample Type | All Sites (%) | Implied Acceptance Criteria (Achieved) |
|---|---|---|
| Moderate Positive | 97.8% | "within the expected percent" |
| Low Positive | 96.7% | "within the expected percent" |
| High Negative | 95.6% | "within the expected percent" |
Precision Study Results (Agreement)
| Sample Type | In-house (%) | Implied Acceptance Criteria (Achieved) |
|---|---|---|
| Moderate Positive | 100% | "within the expected percent" |
| Low Positive | 98.3% | "within the expected percent" |
| High Negative | 93.1% | "within the expected percent" |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size (Clinical Evaluation): 540 eligible specimens.
- Data Provenance: The clinical evaluation was a "multi-site clinical evaluation at 4 US institutions." This indicates prospective data collection for the clinical study directly comparing the device to the reference method.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the number or qualifications of experts involved in establishing the ground truth for the clinical test set. The ground truth method, "reference culture/cell cytotoxicity (TBC/CCNA) testing," implies laboratory testing rather than expert consensus on interpretation.
For the Reproducibility Study:
- Site 1 (external): Dr. Gerald Denys, PI (Principal Investigator)
- Site 4 (external): Dr. Nate Ledeboer, PI (Principal Investigator)
- The document implies that these PIs oversaw the testing at their respective sites, but it doesn't state they were involved in establishing the ground truth for a test set. Rather, they likely ensured proper execution of the reproducibility protocol.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method for establishing the ground truth for the clinical test set. The ground truth was based on "reference culture/cell cytotoxicity (TBC/CCNA) testing."
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. The study compares the device's performance against a reference laboratory method (TBC/CCNA), not against human readers or with AI assistance to human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the primary clinical study is a standalone (algorithm only) performance evaluation. The "Portrait toxigenic C. difficile Assay" (the device/algorithm) was directly compared to the "reference culture/cell cytotoxicity (TBC/CCNA) testing." The results (sensitivity, specificity, PPV, NPV) are for the device acting on its own.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for the clinical test set was reference laboratory testing, specifically "reference culture/cell cytotoxicity (TBC/CCNA) testing." This is a gold standard diagnostic method for C. difficile infection.
8. The Sample Size for the Training Set
The document does not provide information regarding a specific training set or its sample size. This is typical for in vitro diagnostic (IVD) devices where the device development often involves internal optimization and verification using various strains and analytical samples (as described in the nonclinical studies), rather than a distinct "training set" in the machine learning sense. The non-clinical studies detail testing with 44 additional toxigenic C. difficile strains and other microorganisms for analytical performance.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is described in the provided text in the context of machine learning, there is no information on how its ground truth was established. The analytical performance studies (LoD, cross-reactivity) used known strains and concentrations, where the "ground truth" was inherently defined by the composition of the tested samples.
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.