(49 days)
The PREMIER Platinum HpSA PLUS enzyme immunoassay (EIA) is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection and to monitor response during and post-therapy in patients. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least four weeks following completion of therapy.
The PREMIER Platinum HpSA® PLUS test is a microwell-based enzyme immunoassay that detects H. pylori antigens present in human stool. The test utilizes a plurality (mixture) of monoclonal antibodies adsorbed to microwells. Diluted patient samples and an enzyme conjugate reagent are added to the microwells and incubated for one hour at room temperature. A wash is performed to remove unbound material. Substrate is added and incubated for 10 minutes at room temperature. Color develops in the presence of bound enzyme. Stop solution is added and the results are interpreted visually or spectrophotometrically. No calculations are required and the visual color change makes the interpretation of results objective and simple.
In addition, the HpSA test permits assessment of established or novel anti-H. pylori treatment during and posttherapy to monitor for treatment effectiveness, relapse or eradication.
PREMIER Platinum HpSA PLUS (K053335), as the predicate device for this submission, was a modification of PREMIER Platinum HpSA (K983255, K980076) that provided increased signal strengths with positive test results and better discrimination between low positive and negative tests. This submission is for modifications to the antibodies used in the microwells and conjugate reagent.
The PREMIER Platinum HpSA PLUS assay is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool, intended to aid in the diagnosis of H. pylori infection and to monitor response during and post-therapy.
Here's the breakdown of the acceptance criteria and study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The modification being assessed is to the antibodies used in the microwells and conjugate reagent of the PREMIER Platinum HpSA® PLUS. The relevant performance characteristics for comparison are based on the predicate device.
| Performance Metric | Acceptance Criteria (Predicate Device) | Reported Device Performance (Modified Device) |
|---|---|---|
| Analytical Sensitivity (LoD) | ≥ 4.67 ng H. pylori protein/mL of stool | 4.66 ng H. pylori protein/mL of stool (meets) |
| Clinical Sensitivity (PPA) | 100% | 100% |
| Clinical Specificity (NPA) | 94.8% | 100% |
| Reproducibility | Not explicitly stated as a minimum, but implied to be high based on predicate acceptance | 100% (300/300) of results as expected |
| Cross-Reactivity | None of the listed organisms affected positive or negative test results | None of the listed organisms affected positive or negative test results |
| Interfering Substances | None of the listed substances interfered with positive or negative test results | None of the listed substances interfered with positive or negative test results |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Study: 159 archived, unpreserved stool samples.
- Data Provenance: The samples were from symptomatic patients but no country of origin is specified. The samples were "archived," indicating a retrospective study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The documentation does not provide details on the number or qualifications of experts used to establish the ground truth for this specific clinical study comparing the modified device to the predicate. The "ground truth" for this comparison was the result obtained from the predicate device itself.
4. Adjudication Method for the Test Set
Not applicable. The study involved a direct comparison of the modified device's results against the predicate device's results. There was no independent adjudication of individual cases against an external ground truth in the traditional sense, as the predicate served as the reference.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in-vitro diagnostic (EIA) test for detecting antigens, not an imaging or diagnostic aid that involves human readers interpreting results in a variable manner. The interpretation of results is visual or spectrophotometric, implying a more objective, less reader-dependent outcome.
6. Standalone Performance Study
Yes, a standalone performance of the modified device was effectively demonstrated by comparing its results against the predicate device on the same set of samples. The performance metrics (sensitivity, specificity, reproducibility, analytical sensitivity, cross-reactivity, interfering substances) are all measures of the algorithm's (or device's) standalone performance under specified conditions.
7. Type of Ground Truth Used
For the clinical study, the ground truth was established by the predicate device (PREMIER Platinum HpSA® PLUS K053335). The study aimed to demonstrate substantial equivalence by showing agreement between the modified device and the predicate. For analytical studies, the ground truth was based on controlled experimental conditions (e.g., known concentrations of H. pylori protein for LoD, known presence/absence of microorganisms for cross-reactivity, known interfering substances).
8. Sample Size for the Training Set
The document does not specify a separate "training set" sample size. The PREMIER Platinum HpSA PLUS is an enzyme immunoassay, implying a deterministic chemical reaction, not a machine learning algorithm that requires a separate training phase. The development of the device would involve optimization and internal testing, which might be analogous to model training, but these details are not provided in terms of sample size or methodology.
9. How the Ground Truth for the Training Set Was Established
As noted above, there's no mention of a traditional "training set" in the context of an EIA device. The "ground truth" during initial development and optimization would have been established through controlled experiments using known concentrations of H. pylori antigens and various other substances (cross-reactants, interferents) to characterize the assay's performance and specificity. This would involve laboratory standards and analytical methods to confirm the composition of samples.
§ 866.3110
Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).