The BTA stat test is an in vitro diagnostic immunoassay indicated for the qualitative detection of bladder turnor associated antigen in urine of persons diagnosed with bladder cancer. This test is indicated for use as an aid in the management of bladder cancer patients in conjunction with cystoscopy.

The BTA stat test is a qualitative test indicated for use as an aid in the management of bladder cancer patients in conjunction with cystoscopy.

Device Description

The BTA stat test for bladder tumor associated antigen is an immunochromatographic assay utilizing monoclonal antibodies to specifically detect the presence of bladder tumor associated antigen in urine. Patient urine is added to the sample well and allowed to react with a colloidal gold-conjugated antibody. If the antigen is present in the sample, an antigen conjugate complex is formed and a line in the patient (P) test zone appears.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Bard BTA stat™ Test, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The 510(k) summary for the Bard BTA stat™ Test does not explicitly state pre-defined acceptance criteria (e.g., "device must achieve X sensitivity and Y specificity"). Instead, it presents the device's performance metrics and implicitly asks the FDA to accept these results as substantially equivalent to the predicate device. The performance is primarily evaluated through clinical sensitivity and clinical specificity.

Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Sensitivity (Overall)	Adequate for its intended use as an aid in managing bladder cancer patients, comparable to or better than the predicate device.	For 220 patients with histological confirmation of bladder cancer: 66%
Clinical Sensitivity (by Stage)	Adequate per stage, especially for more advanced or aggressive disease.	Ta: 51%, T1: 90%, ≥T2: 88%, Tis: 61%
Clinical Sensitivity (by Grade)	Adequate per grade, especially for higher grades.	Grade 1: 42%, Grade 2: 66%, Grade 3: 83%
Monitoring Sensitivity (for patients with history of bladder cancer)	Adequate for recurrence monitoring.	67% (95% CI: 60-73)
Clinical Specificity (Overall for subjects with no history of bladder cancer)	Adequate to minimize false positives in individuals without bladder cancer.	For 555 individuals: Overall 80% (calculated from Table VI: (1670.95 + 1050.93 + 1520.72 + 770.73 + 540.33) / 555) - Note: The document states 80% specifically for healthy individuals from Table VI, but the overall specificity for the 555 individuals needs careful calculation from the table.* The document also states "The realite indicated that heathy inclivity in the was 20%, respective)", which implies a 80% healthy specificity.
Monitoring Specificity (for patients with history of bladder cancer, no evidence of disease)	Adequate for monitoring, comparable to or better than predicate device.	70% (95% CI: 61-79)
Interference	No significant interference from common urine constituents, microbial contaminants, or therapeutic agents at physiologically relevant concentrations.	Many substances showed no interference at high levels. Bilirubin (unconjugated), Caffeine, Nicotine, Sodium chloride, Candida albicans, Acetaminophen, Acetyl Salicylic Acid, Phenazopyridine-HCl, Ioversol, Uriced showed interference at very high levels or exhibited negative interference.
High Dose Hook Effect (Prozone Effect)	No prozone effect.	No prozone effect up to 12,400 U/ml.
Reproducibility	Consistent results across different lots, readers, and days.	Nearly total agreement, with expected variability near the limit of detection.

Study Details

Here's the breakdown of the study components:

Sample sizes used for the test set and the data provenance:
- Clinical Sensitivity:
  - Initial cohort: 220 patients with histologically confirmed bladder cancer.
  - Subset for comparison with Bard BTA test: 181 patients from the sensitivity cohort.
  - Subset for comparison with Voided Urine Cytology (VUC): 131 patients (with histologically confirmed bladder cancer).
  - Data Provenance: Samples were "collected from 5 different may and the no have you intelles. United States." (This phrasing is a bit ambiguous, but suggests multiple sites within the US, prospectively collected for the study). Samples were stored frozen (-80°C) until tested.
- Clinical Specificity:
  - No history of bladder cancer cohort: 555 individuals.
  - History of bladder cancer - No Evidence of Disease cohort: 107 patients. This cohort's no evidence of disease was confirmed by cystoscopy and/or biopsy.
  - Data Provenance: Samples were "collected from 5 different may and the no have you intelles. United States." (as above). Stored frozen (-80°C).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The primary ground truth for clinical sensitivity was histological confirmation of bladder cancer. This implies that pathology reports from pathologists were used. The number of pathologists involved is not specified, but it's standard practice in clinical studies for a pathologist to confirm diagnosis.
- For the "History of Bladder Cancer - No Evidence of Disease" specificity cohort, ground truth was established by cystoscopy and/or biopsy. The experts performing these procedures (e.g., urologists) and interpreting the results (e.g., pathologists for biopsies) are not explicitly quantified or qualified in this summary.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- The summary does not explicitly mention an adjudication method for the final diagnosis (ground truth). The reliance on "histological confirmation" and "cystoscopy and/or biopsy" suggests that these established diagnostic methods served as the definitive ground truth, implying standard clinical practice for diagnosis rather than a specific multi-reader adjudication process for the test device interpretation. The device itself is a qualitative assay with a direct positive/negative result.
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 mentioned. This device is an in-vitro diagnostic (IVD) assay designed for direct interpretation (presence/absence of a line), not an AI-powered image analysis tool requiring human reader interpretation in comparison.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this entire study is a standalone performance evaluation of the Bard BTA stat™ Test as an algorithm/device only without a human-in-the-loop component for interpretation. The device provides a direct qualitative result (positive or negative based on line appearance).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Pathology: "Histological confirmation" was the primary ground truth for bladder cancer diagnosis (clinical sensitivity).
- Clinical Outcomes/Procedures: "Cystoscopy and/or biopsy" confirmed "no evidence of disease" for defining part of the specificity cohort.
The sample size for the training set:
- The document describes performance studies, which are equivalent to test set evaluations. It does not specify a separate training set for the development of the Bard BTA stat Test itself. This is typical for IVD devices where the analytic and clinical performance are assessed once the device's formulation and design are finalized. The device operates based on a fixed immunological reaction rather than a machine learning algorithm that requires a separate training phase.
How the ground truth for the training set was established:
- As there's no mention of a separate "training set" for the device's development in the context of machine learning, this question isn't directly applicable. The device's "training" or development involved optimizing the immunochromatographic assay components, which would have been done using known positive and negative samples, but these are not described as a "training set" in the sense of a machine learning model.

Summary

{0}------------------------------------------------

K92461

APR 16 1997

510(k) SUMMARY INFORMATION

This 510(k) summary information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitter's Information: A.

Submitter's Name: Address: Contact Person: Contact Person's Phone: Contact Person's Fax: Date of Preparation:

Device Name: B.

Trade Name: Common / Usual Name: Classification Name:

Bard Diagnostic Sciences, Inc. 12277 134th Ct., NE Glen Paul Freiberg (206) 814-1520 (206) 814-1521 September 11, 1996

Bard® BTA stat™ Test BTA stat™Test Tumor Associated Antigen Immunological Test System

C. Predicate Device Name:

Trade Name:

Bard® BTA® Test P940018 - Reclassified to Class II

Bard Diagnostic Sciences, Inc., claims substantial equivalence to the above mentioned test.

{1}------------------------------------------------

510(k) SUMMARY INFORMATION Bard BTA stat Test Page 2

The BTA stat test for bladder tumor associated antigen is D. Device Description: an immunochromatographic assay utilizing monoclonal antibodies to specifically detect the presence of bladder tumor associated antigen in urine. Patient urine is added to the sample well and allowed to react with a colloidal gold-conjugated antibody. If the antigen is present in the sample, an antigen conjugate complex is formed and a line in the patient (P) test zone appears.

E. Intended Use:

F. Indications for Use:

The BTA stat test is a qualitative test indicated for use as an aid in the management of bladder cancer patients in conjunction with cystoscopy.

G. Substantial Equivalence & Technological Characteristics Summary:

The Bard BTA stat Test and the Bard BTA Test are both rapid format qualitative assays. The Bard BTA stat test is a lateral flow assay which detects antigen though antigen-specific antibodies. The Bard BTA Test is a test strip assay which detects "bladder tumor associated analytes" through an agglutination interaction with IgG coated latex particles. Both assays are intended for management of bladder cancer patients, but they detect different substances.

{2}------------------------------------------------

EXPECTED RESULTS

: : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : :

: 24, 21

CLINICAL SENSITIVITY

BTA stat test sensibily (Table ) was cleters and senter were collection and and and and and and and one of the man and and and and and and and and Incl. Teelig of semple for this study we performed at 07% canode Societ assemble
Inc. Themge of senties for this study we performed at 7% canada Stations of Addesse, presented below by stage and by grade of the turnor.

	Table I. BTA stat TEST SENSITIVITY BY STARE AND GRADE-	1.2

STAGE	N	SENSITIVITY (%)
Ta	111	51
T1	38	90
≥T2	50	88
Tis	18	61
GRADE	N	SENSITIVITY (%)
1	57	42
2	58	66
3	95	83

*3 patients without stage and 12 without grade determinations.

A subset of the patients studied (181) also had the Bard BTA test performed on the same sample as the BTA stat test. In this study the Berd BTA test had a sensitivity of 50% while the STA stat toot had a sensitivity of 66% (p=0.233).

					Table II, COMPARISON OF BTA stat TEST TO BARD BTA TEST

		1:10 TTA
				And acc
A Churchil Child the Chical	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------1	MANAGE CONSULTIONAL CONSULTIONAL CONTRACTOR COLLEGIONAL CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACTOR COLLECTION CONTRACT		.
		------	Chicago
	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	---------	1Microsoft and the charges of the dramating in the close of

Tible II presents the ventily in 220 patents with historges

Table III. BTA stat TIEST REBULTS FROM PATIENTS With a History of Bladder Cancer

17.
	1000011V	And Antiques of
	-----
A Charles Children Children	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------A	0------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Active a career	--------	3	BUCK CARDED

Monitoring sensitivity = 67% (60 - 73, 96% confidence interval)
Monitoring specificity = 70% (61 - 79, 96% confidence interval)

Using the data in Table III and a 10%, 20%, and 30% hypothetical prevalonce of bladder oomg to aller in the a rela a 1970 2014 and see with proclicity the blesse of the cystoscopy, the true specificity in these psitents and the positive and negative preciletive values are likely to be higher.

Table IV, HYPOTHETICAL POSITIVE PREDICTIVE VALUES (PPV) AND NEGATIVE PREDICTIVE VALUES (4PV) OF THE ISTA stat TEST

BLADDER CANCERRECURRENCEPREVALENCE	PPV	NPV
10%	19.8	95.0
20%	35.8	89.4
30%	48.8	83.1

. '· : · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

{3}------------------------------------------------

A subset of the patients with histologically confirmed blacider cancer (131) also had voided urine cytology (VUC) performed on the same semple as the BTA stat test (Table V). The BTA stat tast was shown to be more sensible than VUC in all categories except ior Tis (tumor in situ).

STAGE	N	SENSITIVITYBTA stat (%)	SENSITIVITYVUC (%)	SENSITIVITYBTA stat + VUC (%)
Ta	73	45	7	49
T1	27	85	41	85
≥T2	16	75	38	81
Tis	15	53	60	80

Table V. BTA stat TEST AND VUC SENSITIVITIES

in a subset of patients (96) with a history of blackler cancer and no evidence of disease the specificity of the BTAstattest was 68% compared to VUC with a specificity of 97%.

CLINICAL SPECIFICITY

. Printer States and Parties

... で

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

...

. . '

. …

. .

国际网站 - 国际

ﻳﺮﺍ ﻓﻲ ﺍﻟﻤﻘﺎﻭﻣﺔ ﺍﻟﻤﺘﻮﻗﻊ ﺍ

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ಿ ಸಾಮಾನ್ಯ ಸಾಮಿಕಾ :

:: :
. :

... .. :

112 11

BTA stat test specificity (Table VI) was cistermined using urine samples from 555 individuals with no history of bladder cancer. Samples were collected from 5 different may and the no have you intelles. United States and stored fremen (-80°C) until instact. Testing of samples for this study was periormed at Bard Diagnostic Sciences, Inc. The average age was 55 years, 52% were fornalse, 80% were caucasion, 8% African American, 4% Asian, Hispanic or other, and 3% of unionown ethnicky. The normal healthy cancers (71% of samples provided by formated) included cliabetee, arthrille, lupus our (of 1 % of campos province by charactive dasvesse, as well as louismin
erythemas, breast, lang and gastroinselles The non-blection (nonalded (pensi il as leulosmia, s) consisted of prostate, renal coll cancers category (60% of samples provided by make comes. The GU disease category renal TCC, endometrial, ovarian and other GU on (52% of samples provided by fornalse) occasions with beness, urinery tracter infections (UT), incontinence, sexually transmilled diseases (STD) and other disorders.

The realite indicated that heathy inclivity in the was 20%, respective). Posted on the many and and patients with renal cancer including upper tract TCC. Expected results may vary depending on the patient population tested.

PATIENT TYPE	NUMBER OFSUBJECTS	TESTNEGATIVE (%)
Healthy Subjects	167	95
Non-smokers	100	93
Smokers	67	97
Non-Genitourinary Benign Diseasesand Cancers	105	93
Non-Genitourinary Benign Diseases	52	96
Non-Genitourinary Cancers	53	89
Genitourinary Diseases	152	72
BPH	26	88
Benign Renal Disease	32	50
Misc. GU Disease	94	76
UTI/cystitis	30	60
STD	24	79
Other	40	85
Genitourinary Cancers	77	73
Prostate Cancers	45	78
Renal Cancers	7	29
Renal TCC	1	0
Renal Cell Carcinoma	6	33
Other Cancers	25	76
Genitourinary Trauma	54	33
TOTAL	555	NA
History of Bladder Cancer -No Evidence of Disease	107	70

Table VI. BTA stat TEST SPECIFICITY REBULTS

total of subjects with no history of blacider canosr

No evidence of disease confirmed by cystoscopy and/or biopsy; 78% of patients in this category were males.

{4}------------------------------------------------

PERFORMANCE CHARACTERISTICS

HIGH DOSE HOOK EFFECT

Hich does hook (prozone) effect tests were conducted to determine if the BTA stat isset is free from interference from high concentration por ent sumples. Results showed . that there was no prozone offect up to 12,400 Umi. blad ler turnor associated antigen in a patient's urine semple, which was the highest concentration available for testing.

REPRODUCIBILITY

Three lots of BTA stat devices were used for the reproducibility studies to determine day to-day, reader to-reader and lot-to-lot variability. These studies were consisted by sory reproduct readers for each ict of devices. Betw . Were son k 2007 of 4 b conducted at these laboratories by testing 10 rep as on one lot of BTA stat devices. All reproductibility studies showed nearly total ag mant with the exception of samples near the limit of detection, which is to be expected for qua tests.

INTERFERING SUBSTANCES

Normal and TCC positive urine pools containing the substances listed below were tected in the BTAstat test.

SUBSTANCE	HIGHEST LEVELTESTED WITH NOINTERFERENCE	LEVEL AT WHICHSUBSTANCEINTERFERED
Possible Urine Constituents
Hemoglobin	100 mg/dL	No interference at MLT*
White Blood Cells	$10^6$ cells/mL	No interference at MLT
Red Blood Cells	$10^6$ cells/mL	No interference at MLT
Albumin	1 g/dL	No interference at MLT
Bilirubin (unconjugated)	0.4 mg/dL	0.8 mg/dL^
IgG	10 mg/dL	No interference at MLT
Uric Acid	250 mg/dL	No interference at MLT
Ascorbic Acid	5 g/dL	No interference at MLT
Caffeine	58.3 mg/dL	117 mg/dL^
Nicotine	14 mg/dL	28 mg/dL^
Sodium chloride	365 mg/dL	730 mg/dL^
Ethanol	1% (v/v)	No interference at MLT
Possible Microbial Contaminants
Candida albicans	1.25 x $10^6$ CFU/mL	2.5 x $10^6$ CFU/mL
Escherichia coli	2.5 x $10^6$ CFU/mL	No interference at MLT º
Pseudomonas aerugenosa	2.5 x $10^6$ CFU/mL	No interference at MLT º
Therapeutic Agents
Ampicillin	600 mg/dL	No interference at MLT
Acetaminophen	520 mg/dL	5.2 g/dL^
Acetyl Salicylic Acid	520 mg/dL	5.2 g/dL^
Doxorubicin-HCl	10 mg/dL	No interference at MLT
Mitomycin C	10 mg/dL	No interference at MLT
Nitrofurantoin	50 mg/dL	No interference at MLT
Phenazopyridine-HCl	80 mg/dL	100 mg/dL^
Thiotepa	10 mg/dL	No interference at MLT
Trimethoprim	50 mg/dL	No interference at MLT
Bacillus Calmette Guerin	20 mg/dL	No interference at MLT
Finasteride	2.5 mg/dL	No interference at MLT
Flutamide	100 mg/dL	No interference at MLT
Ioversol, 74% (imagingcontrast agent)	1%	5%^
Uriced	17.5 mg/dL	35 mg/dL°

Table VII. INTERFERING SUBSTANCES

MLT - maximum lawai tastad

Negative Interfarence: substance decreased the intensity of a TCC positive urine test result

Subjecting samples to one freeze/thaw cycle resulted in no interference at 1.25 x 10" CFU/mL,

the MIJ.

Results of Interior noe studies unchanged by subjecting samples to one freeze/thew cycle

Substance's coloration caused results for both normal and TCC positive urine to be difficuit to Reports

In conclusion, the Bard BTA stat Test is substantially equivalent to the predicate device referenced in this submission.

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.