The MERETEK UBT® Breath Test Collection Kit is intended for use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients. The test may be used for monitoring treatment if used at least four weeks following completion of therapy. For these purposes, the system utilizes a Gas Isotope Ratio Mass Spectrometer ("GIRMS") for the measurement of the ratio of 13CO2 to 12CO2 in breath samples.

For administration by health care professionals. To be administered under a physician's supervision.

Device Description

The device is a combination kit diagnostic drug/device composed of the following principle components: Test Meal (of approximately 220 calories), Pranactin Diagnostic Drug Dosage, Sterile Water, Breath Bag, Evacuated Breath Specimen Collection Tubes. In the MERETEK UBT® Breath Test for H. pylori, 125 mg of reconstituted 13C-urea is ingested by the patient. In the presence of urease associated with gastric H. pylori, 13Curea is decomposed to 13CO2 and NH4+. The 13CO2 is absorbed in the blood, then exhaled in the breath. This results in an increase in the ratio of 13CO2 to 12CO2 in a TEST breath sample compared to a BASELINE sample taken before the Pranactin® solution was consumed. Analysis of the breath samples is performed by Gas Isotope Ratio Mass Spectrometry ("GIRMS").

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the MERETEK UBT® Breath Test for H.pylori, based on the provided text:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific performance thresholds (e.g., "Sensitivity must be >= X%"). Instead, it presents the device's performance characteristics as "results" in comparison with established diagnostic methods. The implicit acceptance is based on the reported sensitivities and specificities, which are deemed sufficient by the FDA for the device's intended use.

Here's a table summarizing the reported device performance compared to various ground truth methods:

Criteria/Comparison	Reported Device Performance (Sensitivity)	Reported Device Performance (Specificity)
Initial Diagnosis - Comparison with CLOtest®	92.8% (95% CI: 89.9, 95.0)	94.1% (95% CI: 71.3, 99.9)
Initial Diagnosis - Comparison with Histology	95.2% (95% CI: 92.6, 97.0)	90.0% (95% CI: 73.5, 97.9)
Initial Diagnosis - Comparison with Combined Endoscopic Methods	95.2% (95% CI: 92.6, 97.0)	89.7% (95% CI: 72.6, 97.8)
Post-Treatment Monitoring (1-6 Months Combined)	95.5% (95% CI: 93.0, 97.2)	96.0% (95% CI: 93.0, 98.0)
Negative Predictive Value (NPV) for Post-Treatment Monitoring (90% treatment efficacy)	>99%	N/A
Negative Predictive Value (NPV) for Post-Treatment Monitoring (50% treatment efficacy)	>95%	N/A

Study Details

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

Sample Size (Initial Diagnosis): The tables show different totals depending on the comparison method:
- Comparison with CLOtest®: 445 patients
- Comparison with Histology: 444 patients
- Comparison with Combined Endoscopic Methods: 444 patients
Sample Size (Post-Treatment Monitoring):
- 1 Month EOT: 295 patients
- 3 Months EOT: 222 patients
- 6 Months EOT: 178 patients
- 1-6 Months Combined: 495 patients (sum of positive and negative cases; the total number of unique patients is not explicitly stated as the sum of EOT, but it's derived from the combined table entries.)
Data Provenance: The studies included "499 adult patients with duodenal ulcer disease at 75 clinical sites in the United States." The data is prospective as patients were followed through various post-treatment intervals. It is described as "two (2) independent double blind clinical field trials."

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

The document does not explicitly state the specific "number of experts" or their detailed "qualifications" (e.g., "radiologist with 10 years of experience") for establishing the ground truth. However, it indicates that the ground truth methods used were:

CLOtest®: A rapid urease test, typically read by laboratory personnel or clinicians.
Histopathology: Involves microscopic examination of tissue samples, performed by pathologists.
Microbiological culture: Growing bacteria from samples, performed by microbiologists.

These methods inherently require expertise in their respective fields (pathology, microbiology, and clinical interpretation of rapid tests).

3. Adjudication Method for the Test Set

The document describes the ground truth for initial diagnosis as being established by comparing the MERETEK UBT® Breath Test results with:

CLOtest®
Histology
Combined endoscopic method results (CLOtest®, histology, and culture) per DAIDP guidelines.

For post-treatment monitoring, the ground truth was established by comparing the MERETEK UBT® Breath Test results with:

Combined endoscopic methods (histology and culture) per DAIDP guidelines.

The specific "adjudication method" beyond using these combined references (e.g., a "2+1" rule for discordant results between the ground truth components) is not explicitly stated. It implies that the combined methods served as the reference standard.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a MRMC comparative effectiveness study was not done. The study's focus was on the stand-alone performance of the MERETEK UBT® Breath Test against established diagnostic methods, not on how human readers improve with or without AI assistance. The device is a diagnostic test kit, not a software AI assistant for human interpretation.

5. If a Standalone Study Was Done

Yes, a standalone study was done. The entire clinical testing section describes the performance of the MERETEK UBT® Breath Test itself (the "algorithm only") in detecting H. pylori by measuring 13CO2/12CO2 ratios. The results (sensitivity, specificity) presented in the tables are precisely the standalone performance characteristics of the diagnostic test.

6. The Type of Ground Truth Used

The ground truth used was a combination of established clinical and laboratory diagnostic methods:

For Initial Diagnosis: CLOtest®, Histopathology, and Microbiological Culture. The "combined endoscopic methods" standard for initial diagnosis included CLOtest®, histology, and culture.
For Post-Treatment Monitoring: Histopathology and Microbiological Culture. The "combined endoscopic methods" standard for post-treatment monitoring included histology and culture.

These methods represent a form of expert consensus if multiple methods were combined to form a reference standard, or a pathology-like reference (histology and culture are pathology methods). It is not directly called "outcomes data," though the goal is to ultimately inform patient outcomes.

7. The Sample Size for the Training Set

The document does not specify a training set sample size. This implies that the device in question (MERETEK UBT® Breath Test) is a diagnostic kit with a fixed methodology (measuring 13CO2/12CO2 ratio) and does not involve AI or machine learning models that typically require a separate training set. The study described is for validation and performance assessment, not for training a model.

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

Since there is no mention of a "training set" for an AI/ML model, the establishment of ground truth for a training set is not applicable to this document. The ground truth as described for the test set was established by concurrent clinical and laboratory diagnostic methods (CLOtest, histology, culture).

Summary

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Image /page/0/Picture/1 description: The image shows a sequence of alphanumeric characters, seemingly handwritten. The sequence reads 'K9723552'. The characters are rendered in a bold, somewhat irregular style, giving them a distinct, hand-drawn appearance. The contrast between the characters and the background is high, making them easily readable.

510(k) SUMMARY

The MERETEK UBT® Breath Test for Detection of H.pylori

Applicant's Name, Address, Contact Person, and Date of Preparation A.

MERETEKdiagnostics, inc. 618 Grassmere Park Drive Suite 20 Nashville, Tennessee 37211

Please direct any requests for information to:

Mr. Kerry C. Bush Vice President and Chief Operating Officer MERETEKdiagnostics, inc. 618 Grassmere Park Drive Suite 20 Nashville, Tennessee 37211

(615) 333-6336 Phone: (615) 333-6202 Fax:

This 510(k) summary was prepared October, 1997.

Device Name and Classification B.

Trade Name of the Device: The MERETEK UBT® Breath Test for H.pylori

Common Name of the Device:

Breath Test for Helicobacter pylori; UBT

Classification:

Campylobacter pylori (presence) Name: Campylobacter pylori was officially renamed Helicobacter pylori in 1989. Note: Class: I

C. The Predicate Device

Since this Premarket Notification is for labeling modification to a cleared device (K952220), the predicate device is the device itself: The MERETEK UBT® Breath Test for Detection of H. pylori.

Description of the Device D.

The device is a combination kit diagnostic drug/device composed of the following principle components:

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Test Meal (of approximately 220 calories) Pranactin Diagnostic Drug Dosage Sterile Water Breath Bag Evacuated Breath Specimen Collection Tubes

Principle of the Test

In the MERETEK UBT® Breath Test for H. pylori, 125 mg of reconstituted 13C-urea is ingested by the patient. In the presence of urease associated with gastric H. pylori, 13Curea is decomposed to 13CO2 and NH4+ according to the following equation:

(NH2)213CO + H2O + 2H+ - 40Urease > 13CO2 + 2NH4+ 13C-urea

The 13CO2 is absorbed in the blood, then exhaled in the breath. This results in an increase in the ratio of 13CO2 to 12CO2 in a TEST breath sample compared to a BASELINE sample taken before the Pranactin® solution was consumed. Analysis of the breath samples is performed by Gas Isotope Ratio Mass Spectrometry ("GIRMS") at Meretek's clinical laboratories or at other qualified laboratories licensed by MERETEKdiagnostics, inc.

E. Intended Use

For administration by health care professionals. To be administered under a physician's supervision.

Technological Characteristics of the Device and the Predicate Device F.

The technological characteristics of the subject device are the same as the predicate device.

G. Clinical Testing

Experimental Design

The method comparison data presented here were collected from two (2) independent double blind clinical field trials which involved treatment of H.pylori infection. The studies included 499 adult patients with duodenal ulcer disease at 75 clinical sites in the United States. Patients were tested for H.pylori infection initially (using histopathology, microbiological culture, CLOtest®, and the MERETEK UBT®), and at various posttreatment intervals throughout the study (using histopathology, microbiological culture, and the MERETEK UBT®). In these clinical trials patients were treated with various

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combinations of clarithromycin, omeprazole and placebo. Note, however, that there is no evidence that differing treatment regimens affect the performance of the MERETEK UBT®.

Results

Method comparison results are presented in two-way contingency tables. In tables 1, 2 and 3, the MERETEK UBT® Breath Test results are compared with the CLOtest®, histology and with the combined endoscopic method results for the initial patient visit. In table 4, the MERETEK UBT® Breath Test results are compared with the combined endoscopic method results (histology and culture) for the post-treatment visits which occurred four weeks or more after end of treatment. The exact binomial distribution was used to calculate the lower and upper limits of the 95% confidence intervals of the performance statistics. The confidence intervals are entered in parentheses following the point estimate of the statistic.

Performance Characteristics for Initial Diagnosis

Table 1. Comparison with CLOtest® for Initial Visit

Meretek UBT® Breath Test results
CLOtest®	positive	negative	Total
positive	397	31	428
negative	1	16	17
Total	398	47	445

Relative sensitivity: 92.8 % [95% CI: (89.9,95.0)] Relative specificity: 94.1 % [95% CI: (71.3,99.9)]

Table 2. Comparison with histology for Initial Visit
------------------------------------------------------	--	--	--	--	--

Meretek UBT® Breath Test results
Histology	positive	negative	Total
positive	394	20	414
negative	3	27	30
Total	397	47	444

Relative sensitivity: 95.2 % [95% CI: (92.6,97.0)] Relative specificity: 90.0 % [95% CI: (73.5,97.9)]

Table 3. Comparison with combined endoscopic methods for Initial Visit (Combined endoscopic methods used were CLOtest®, histology and culture per DAIDP guidelines for pre-treatment diagnosis.)

Meretek UBT® Breath Test results
Endoscopy	positive	negative	Total
positive	395	20	415
negative	3	26	29
Total	398	46	444

Sensitivity: 95.2 % [95% CI: (92.6,97.0)] Specificity: 89.7 % [95% CI: (72.6,97.8)}

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Performance Characteristics for Post-Treatment Monitoring

	1 MonthEOT		3 MonthsEOT		6 MonthsEOT		1-6 MonthsCombined
Endoscopy	pos	neg	pos	neg	pos	neg	pos	neg
positive	187	6	123	8	91	5	401	19
negative	5	97	4	87	2	80	11	264
Sensitivity	96.9		93.9		94.8		95.5
(95% CI)	(93.4,98.8)		(88.3,97.3)		(88.3,98.3)		(93.0,97.2)
Specificity	95.1		95.6		97.6		96.0
(95% CI)	(88.9,98.4)		(89.1,98.8)		(91.5,99.7)		(93.0,98.0)

Table 4. Comparison with combined endoscopic methods * for Post-Treatment Visits (four weeks or more after End of Treatment (EOT))

* Combined endoscopic methods used were histology and culture per DAIDP guidelines for post-treatment monitoring)

Please note that the post-treatment performance characteristics at 1, 3 and 6 months after therapy are not statistically different. Therefore, the single best estimates of sensitivity and specificity are presented in the 1-6 Months Combined column.

Negative Predictive Value (NPV) for Post-Treatment Monitoring

Given the post-treatment sensitivity (95.5%) and specificity (96.0%) observed in these studies, and assuming a treatment efficacy of 90% (10% prevalence of residual H.pylori infection), the NPV of the MERETEK UBT® is greater than 99%. When efficacy of treatment drops to 50%, the NPV is still greater than 95%.

H. Adverse Events

There were no adverse events related to the use of the MERETEK UBT® reported during the clinical trials.

I. Conclusion

The MERETEK UBT® is safe and effective for its intended use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of a human figure, with three overlapping profiles suggesting a sense of community or interconnectedness. The figure is positioned within a circular border, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the upper half of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 2 9 1997

Claudia T. Hitchcock President & Chief Executive Officer Meretek Diagnostics, Inc. 618 Grassmere Park Drive Suite 20 Nashville, TN 37211

Re: K972352

Trade Name: The Meretek UBT™ Breath Test for Helicobacter pylori Regulatory Class: II Product Code: MSQ Dated: September 2, 1997 Received: September 3, 1997

Dear Mr. Bush:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. -Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely vours.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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X. STATEMENT OF INDICATIONS FOR USE

Device Name:

MERETEK UBT™ Breath Test For H.pylori

Indications for Use:

The MERETEK UBT™ Breath Test Collection Kit is intended for use in the qualitative detection of urease associated with Helicobacter pylori in the human stomach and as an aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori infection in adult patients. For this purpose, the system utilizes a Gas Isotope Ratio Mass Spectrometer ("GIRMS") for the measurement of the ratio of 13CO, to 12CO2 in breath samples. ----------------------------------------

For administration by health care professionals. To be administered under a physician's supervision.

Prescription Use: Yes

Alan Cooper

on Sign-Off Division of Clinical Laboratory Devices 510(k) Number

Prescription Use (Per 21 CFR 801.109)

Over-The Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 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).