Search Results

The Pylori-Chek Test System is intended for use with the LARA Laser Assisted Ratio Analyzer for the qualitative detection of urease associated with Helicobacter pylori infection in the human stomach and as an aid in the diagnosis of H. pylori infection in symptomatic adult patients. The Pylori-Chek Test system consists of a Pylori-Chek test kit for the collection of breath samples and a LARA Laser Assisted Ratio Analyzer for the measurement of the ratio of 13CO2 to 12CO2 in the breath sample.

For use by healthcare professionals. To be administered under a physician's supervision.

The Alimenterics LARA Breath Test System is comprised of two components:
(1) the Pylori-Chek Breath Test Kit; and
(2) the LARATM (Laser Assisted Ratio Analyzer) System

The Alimenterics LARA Breath Test System is based on the ability of the H.pylori organism to produce large amounts of the enzyme urease, which hydrolyses urea to NHL and CO3, the latter being exhaled. Using 30-labeled urea, an increase in the ratio of 130, to "CO, over time is an indication for the presence of H. pylori. This change can be detected by the LARA System based on a comparison of pre- and post-ingestion measurements of the patient's breath.

The Alimenterics breath test procedure involves a pre-ingestion analysis of a sample of the patient's breath to determine the baseline ratios of '30, to '200, Following ingestion of a test meal and 100 mg 13C-labeled urea, breath samples are collected at thirty and sixty minutes thereafter. The samples are then introduced into the LARA analyzer which, based on the laser optogalvanic effect, measures the ratio of 13CO2 to 12CO2 The results of the three readings, with respect to a calibration standard, are determined concurrently by the analyzer. A specified change in the ratio of 13CO2 to 12CO2 in the 30 or 60 minute samples as compared to the baseline sample constitutes a positive test. Test values are generated and a report is printed for each patient.

The Alimenterics LARA Breath Test System aims to detect Helicobacter pylori (H.pylori) infection. The regulatory submission includes details for two clinical studies: a Pivotal Study and a Supplemental ("Cold Trap") Study.

Here's an analysis of the provided information, focusing on acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity, specificity, PPV, and NPV thresholds that the device had to meet for approval. Instead, it presents the achieved performance metrics and concludes that these results are "comparable to other diagnostic methods" and "could be replicated and even improved."

However, we can infer the desired performance from the reported ranges, especially for the modified device which is intended for the clinical product.

2. Sample Size Used for the Test Set and Data Provenance

• Pivotal Study:

  • Test Set Sample Size: 875 subjects were included in the analysis out of 1048 enrolled.
  • Data Provenance: Not explicitly stated, but the mention of "10 clinical sites" suggests a multi-center study, likely within the US, given the FDA submission. It is a prospective study as patients were enrolled and underwent the breath test.

• Supplemental ("Cold Trap") Study:

  • Test Set Sample Size: 397 patients were included in the analyses out of 432 enrolled (431 attempted the test).
  • Data Provenance: Not explicitly stated, but this was a follow-up study to the Pivotal Study, suggesting similar provenance (likely multi-center, US, prospective).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

The document mentions "five different reference standards" used to establish ground truth:

• the IDE protocol standard
• the CDER standard
• the CDRH standard
• the CLOtest
• central histopathology

The document does not explicitly state the number of experts or their qualifications involved in establishing each of these reference standards. For "central histopathology," it implies that pathologists would be involved, but specific numbers and experience levels are not provided. The CLOtest itself is a diagnostic device, not a human expert. The other "standards" likely refer to regulatory or internal protocols, not direct expert consensus on individual cases.

4. Adjudication Method for the Test Set

The document does not describe a specific adjudication method (e.g., 2+1, 3+1) for resolving discrepancies between multiple expert readings to establish ground truth. It refers to five different reference standards, and the results are presented against each of these. This suggests that the reference standards themselves were considered the "ground truth" without a further adjudication step for the breath test results against these standards.

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

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted or described. This device is a standalone diagnostic test (a breath analyzer) and does not involve human readers interpreting images or data with or without AI assistance. Its performance is compared to established diagnostic reference standards.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-loop Performance) Was Done

Yes, the studies performed evaluate the standalone performance of the Alimenterics LARA Breath Test System. The system itself measures the ratio of 13CO2 to 12CO2 and applies a diagnostic cutoff to determine a positive or negative result for H. pylori. There is no human interpretation of the LARA system's output that is then "assisted" by the algorithm. The results (sensitivity, specificity, etc.) are for the algorithm's output directly against the reference standards.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth for the test set was established using multiple methods, referred to as "five different reference standards":

• Histopathology: Explicitly mentioned as "central histopathology." This involves examining biopsy tissue under a microscope, typically by a pathologist.
• CLOtest: A rapid urease test performed on biopsy tissue.
• Other Standards (IDE protocol, CDER, CDRH): These likely refer to specific diagnostic criteria or protocols defined by relevant Ideal-Device-Exemplar (IDE) or regulatory bodies (Center for Drug Evaluation and Research - CDER, Center for Devices and Radiological Health - CDRH) for H. pylori infection, which often combine results from various diagnostic tests (e.g., biopsy, culture). The exact composition of these standards is not detailed beyond their names.

8. The Sample Size for the Training Set

The document does not explicitly state a separate training set sample size. The diagnostic cutoff values (7.88 in the Pivotal Study and later 6.18 in the Supplemental Study) were calculated from the results of the respective studies.

• For the Pivotal Study, the cutoff of 7.88 was "calculated with an indeterminate zone between 7.018 and 8.600" based on the "results in this study" (875 subjects).
• For the Supplemental Study, an ROC analysis was performed on the data from that study (397 subjects) to yield a new cutoff of 6.18.

This suggests that the entire study populations were used for both performance evaluation and the determination/optimization of the diagnostic cutoff. There isn't a clear distinction between a separate training and test set in the traditional machine learning sense, where a model is trained on one dataset and then evaluated on a completely unseen, independent test set. The Supplemental Study served as an "independent test (challenge) of the sensitivity and specificity calculated using the diagnostic cutoff and indeterminate zone determined in the Pivotal Study," but it also then re-optimized the cutoff for the modified device using its own data.

9. How the Ground Truth for the Training Set Was Established

As noted above, a distinct "training set" is not explicitly defined. If we consider the data used to calculate the diagnostic cutoffs as a form of "training," then the ground truth for this process would be established using the same "five different reference standards" (IDE protocol, CDER, CDRH, CLOtest, and central histopathology) as described for the test set. The cutoffs were determined by optimizing against these reference standards within the respective study populations.

Ask a specific question about this device