(83 days)
The Solana® C. difficile Assay is an in vitro diagnostic test for the direct, qualitative detection of the Clostridium difficile Toxin A gene (tcdA) in unformed stool specients of patients suspected of having Clostridium difficile-infection (CDI). The Solana C. difficile Assay is intended for use as an aid in diagnosis of CDI. The assay utilizes helicase-dependent amplification (HDA) for the amplification of a highly conserved fragment of the Toxin A gene sequence. The Solana C. difficile Assay is intended for use only with the Solana® instrument.
The Solana C. difficile Assay combines simple sample processing and Helicase-Dependent Amplification (HDA) performed in Solana for the detection of toxigenic Clostridium difficile directly from CDI-suspected diarrheal specimens.
A small amount of specimen is transferred to a Lysis Tube using a swab. The Lysis Tube is then subjected to heat-treatment at 95°C for 5 minutes. The heat-treated sample is added to a Dilution Tube, and then transferred to a Reaction Tube. The Reaction Tube contains lyophilized HDA reagents, dNTPs, primers and probes. Once rehydrated with the diluted sample, the Reaction Tube is placed in Solana for amplification and detection of target sequence. In Solana, the target sequence is amplified by specific primers and detected by a specific fluorescence probe included in the Reaction Tube. A competitive process control (PRC) is included in the Lysis Tube to monitor sample processing, inhibitory substances in clinical samples, reagent failure or device failure. The PRC is amplified by the target-specific primers and detected by a PRC specific fluorescence probe.
The target and PRC probes are labeled with a quencher on one end and a fluorophore on the other end. Upon annealing to target or PRC amplicons, the fluorescence signal increases due to physical separation of fluorophore from quencher. Solana measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana then report the test results to the user on its display screen, and it can print out the results via a printer.
Here's a breakdown of the acceptance criteria and study details for the Solana C. difficile Assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate section with predefined thresholds. However, the "Performance in Comparison to Enhanced toxigenic bacterial culture" section for sensitivity and specificity can be considered as the primary clinical performance evaluation against a recognized gold standard. The "Performance in Comparison to FDA-cleared molecular device" provides comparative performance.
Given this, I will present the clinical performance metrics as the reported device performance against what would typically be considered implicit acceptance targets for diagnostic devices of this type.
Table 1: Reported Device Performance Against Ground Truth (Enhanced Toxigenic Culture)
| Performance Metric | Reported Performance (95% CI) |
|---|---|
| Sensitivity | 93.0% (86.9% - 96.4%) |
| Specificity | 99.2% (98.2% - 99.6%) |
Table 2: Reported Device Performance Compared to an FDA-Cleared Molecular Device
| Performance Metric | Reported Performance (95% CI) |
|---|---|
| Positive Percent Agreement | 97.0% (91.59% - 99.0%) |
| Negative Percent Agreement | 97.9% (96.6% - 98.7%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 854 raw specimens were collected. After removing 2 invalid specimens, 852 specimens were used for analysis.
- Data Provenance:
- Country of Origin: United States. The study was conducted at "three distinct geographical sites across the United States."
- Retrospective or Prospective: Prospective. The study documents state, "Performance characteristics of the Solana C. difficile Assay were established during a prospective study conducted November 2016 to February 2017."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not specify the number of experts or their qualifications for establishing the ground truth (enhanced toxigenic culture). It describes the methodology for the enhanced toxigenic culture, which is a laboratory-based process, rather than an expert human interpretation.
4. Adjudication Method for the Test Set
The document does not explicitly detail an adjudication method beyond the methodology for the enhanced toxigenic culture. It mentions, "Three (3) of the six (6) specimens were positive for C. difficile toxin gene DNA by an alternate FDA cleared molecular device, three (3) were negative." and "Six (6) of eight (8) specimens were found positive for C. difficile toxin gene DNA by an alternate FDA cleared molecular device., and two (2) were negative", which suggests some level of discordant analysis against a second method, but no formal expert adjudication process is described for the ground truth establishment itself.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic test that provides a qualitative result (positive/negative) directly from the instrument. It is not designed to be interpreted by human readers, nor does it assist human readers in making a diagnosis. Therefore, the concept of human readers improving with or without AI assistance does not apply here.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire clinical performance evaluation described compares the "Solana C. difficile Assay" (the algorithm/device) directly against the enhanced toxigenic culture (ground truth) and an FDA-cleared molecular device. The results reported are for the device's performance without human intervention in the interpretation of the C. difficile Toxin A gene (tcdA) detection.
7. Type of Ground Truth Used
The primary ground truth used for evaluating the Solana C. difficile Assay was enhanced toxigenic bacterial culture.
An "alternate FDA cleared molecular device" was also used for comparison in cases of discordance, but the initial sensitivity and specificity calculations used the enhanced toxigenic culture as the reference.
8. Sample Size for the Training Set
The document does not provide information regarding a specific training set size or methodology for the Solana C. difficile Assay. The information provided focuses on the analytical and clinical validation of the final product. For an IVD like this, the "training" may happen during internal development and optimization phases, which are not typically detailed in 510(k) summaries.
9. How the Ground Truth for the Training Set Was Established
As no specific training set or its sample size is mentioned, the method for establishing ground truth for a training set (if one existed separately from analytical validation) is not described in the provided document. The ground truth for the clinical test set was established by enhanced toxigenic bacterial culture.
§ 866.3130 Clostridium difficile toxin gene amplification assay.
(a)
Identification. AClostridium difficile toxin gene amplification assay is a device that consists of reagents for the amplification and detection of target sequences inClostridium difficile toxin genes in fecal specimens from patients suspected of havingClostridium difficile infection (CDI). The detection of clostridial toxin genes, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of CDI caused byClostridium difficile. (b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection ofClostridium difficile; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.