(158 days)
The BioStar® CdTOX A OlA assay is an Optical ImmunoAssay test for the rapid qualitative detection of Clostridium difficile Toxin A in human fecal samples from patients suspected of having Clostridium difficile associated disease (CDAD). This test is intended for in vitro diagnostic use as an aid in the diagnosis of CDAD.
The CdTOX A OIA test involves the qualitative detection of the enterctoxin (Toxin A) produced by Clostridium difficile. The Optical Immuno Assay technology enables the direction of a physical change in the optical thickness of molecular this change is a result of antigen-antibody binding on an optical surface (silicon wafer). When a sample containing Toxin A (antigen) from Clostridium difficile is placed directly on the optical surface, the immobilized specific antibody captures the antigen. After washing, the substrate is added, increasing the thickness (Mass Enhancement) of the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color changes in optical thickness produce a distinct, visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the surface retains the original gold color indicating a negative result.
The provided text describes the acceptance criteria and the study that proves the device meets those criteria for the BioStar® CdTOX A OIA® assay.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a separate list with specific numerical targets for all metrics. However, it presents analytical and clinical performance data in comparison to a predicate device and a reference method (cytotoxicity assay), implying these are the metrics against which the device's performance is judged. The primary comparison is often to demonstrate substantial equivalence to the predicate device and acceptable performance against a gold standard (cytotoxicity assay).
| Metric / Criterion | Reported Device Performance (CdTOX A OIA) | Comparative Performance (Predicate Device - Premier EIA) | Reference Method Performance (Cytotoxicity Assay - CTA) |
|---|---|---|---|
| Analytical Sensitivity (Limit of Detection) | |||
| Buffer Control | 3 ng/g | Not specified | Not specified |
| Liquid Stool | 3-8 ng/g | Not specified | Not specified |
| Semi-Solid Stool | 4-8 ng/g | Not specified | Not specified |
| Formed Stool | 3-5 ng/g | Not specified | Not specified |
| Analytical Specificity (Cross Reactivity) | |||
| Microorganisms tested | No reactivity or interference observed. | Not specified | Not specified |
| Cryptosporidium parvum and Giardia lamblia | No reactivity or interference observed. | Not specified | Not specified |
| Interfering Substances | |||
| Whole blood, RBC, WBC, mucous, barium sulfate | Did not interfere. | Not specified | Not specified |
| Toxin Stability | Sufficiently stable. | Not specified | Not specified |
| Reproducibility (Hospital Labs) | 94.4% (85/90) overall | Not specified | Not specified |
| Reproducibility (Artificial Stool Matrix Study - Hospitals) | 97.5% (117/120) | Not specified | Not specified |
| Reproducibility (Artificial Stool Matrix Study - POLs) | 97.8% (88/90) | Not specified | Not specified |
| Reproducibility (Overall Artificial Stool Matrix Study) | 97.6% (205/210) | Not specified | Not specified |
| Clinical Sensitivity (vs. CTA) | 77.3% | 81.8% | 100% (as the reference) |
| Clinical Specificity (vs. CTA) | 93.8% | 92.0% | 100% (as the reference) |
| Clinical Concordance (vs. CTA) | 91.0% | 90.3% | 100% (as the reference) |
| Concordance (vs. Premier EIA) | 95.0% (98+/+, 684 -/-) | 100% (as the reference) | Not applicable |
| Discordance (vs. Premier EIA) | 5.0% (19 +/-, 22 -/+) | 0% (as the reference) | Not applicable |
2. Sample size used for the test set and the data provenance:
- Analytical Sensitivity: No specific sample size is given for the "test set" in the traditional sense. It involved adding known concentrations of Toxin A to five specimens each of liquid, semi-solid, and solid stools, tested in duplicate.
- Analytical Specificity (Cross Reactivity) & Interfering Substances: Microorganisms grown to ~1.0 X 10 cfu/mL or greater; Cryptosporidium parvum and Giardia lamblia rested at 1.25 X 10^6 cysts for cross-reactivity. For interfering substances, whole blood, RBC, WBC, mucous (25mg/g), and barium sulfate (58% w/w suspension) were tested. The number of specimens tested with interfering substances is not explicitly stated.
- Reproducibility:
- Three hospital laboratories study: 10 blinded samples tested at each site at three separate times. Total: 10 samples * 3 sites * 3 times = 90 tests.
- Artificial stool matrix study (four hospital labs and three physician office labs): Comparable samples prepared and tested. Total: 210 tests.
- Clinical Sensitivity and Specificity (vs. CTA): A study performed at a central hospital lab. Number of samples used for this specific comparison is not explicitly stated.
- Clinical Performance Evaluation (versus Premier EIA): 874 specimens.
- Data Provenance:
- Clinical Sensitivity and Specificity (vs. CTA): "a central hospital lab."
- Clinical Performance Evaluation (versus Premier EIA): "four clinical trial sites (central hospital labs) located in the Southwest, Mid-Atlantic and East Coast regions of the United States."
- Reproducibility: "three hospital laboratories" and "four hospital laboratories and three physician office laboratories (POLs)".
- All clinical samples were "from patients suspected of having or with a history of CDAD." The clinical studies appear to be retrospective as samples were "submitted for C. difficile testing on the basis of clinical history of the patient."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not explicitly mention the number or qualifications of experts used to establish the ground truth.
4. Adjudication method for the test set:
The document does not describe an adjudication method for the test set.
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 is not applicable as the device is a diagnostic assay (in vitro diagnostic device) for detecting a toxin, not an AI-assisted imaging or interpretation device that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device (CdTOX A OIA) itself is a standalone assay. It's a chemical test ("Optical ImmunoAssay technology") that provides a visual result ("A positive result appears as a purple spot on the predominant gold background"). There is no "algorithm" or human-in-the-loop interpretation beyond visual inspection of the color change, which is inherent to the test's design. The clinical studies evaluated the performance of this standalone assay.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the clinical sensitivity and specificity evaluation, the cytotoxicity assay (CTA) was used as the ground truth.
- For the comparison with the predicate device, the Premier EIA (another commercial immunoassay) was used as a comparative method, not strictly a ground truth, although concordance was evaluated against it.
8. The sample size for the training set:
The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. The development and analytical testing of an in vitro diagnostic device typically involve iterative design and optimization, but not in the same way as training a machine learning model.
9. How the ground truth for the training set was established:
As no explicit "training set" in a machine learning context is mentioned, this question is not applicable. The device's development likely relied on established biochemical principles and extensive internal analytical validation using spiked samples and characterization, rather than a separate training set with ground truth labels.
§ 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.