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The ASI Automated RPR (rapid plasma reagin) Test for Syphilis, for use on the ASI Evolution Automated Analyzer, is a qualitative and semiquantitative flocculation test for the detection of nontreponemal antibodies in human serum and plasma to aid in the diagnosis of syphilis. All reactive RPR test samples should be further tested with a treponemal test to determine serological evidence of syphilis infection. The test is intended to be used for in vitro diagnostic testing.

The ASI Evolution is an integrated digital particle analyzer designed to objectively interpret certain slide agglutination tests manufactured by Arlington Scientific. Inc. (ASI). The ASI Evolution fully automates the sample and reagent handling steps of the test procedure. Qualitative and semiquantitative tests are performed by laboratory professionals who use the ASI Evolution to provide standardized test interpretation using criteria that define reactive and nonreactive agglutination reactions.
The ASI Evolution employs a camera that uses light reflectance to create a highly sensitive and high-resolution image of the agglutination immunoassay. This image is then analyzed by the proprietary software algorithm to interpret the agglutination pattern.

The ASI Evolution further provides tools that enable the creation, storage, retrieval and transmittal of the test results.

The ASI Automated RPR Test for Syphilis reagents include the following:

CARBON ANTIGEN - 0.003% cardiolipin, 0.020-0.022% lecithin, 0.09% cholesterol, charcoal (activated) as visual enhancer, phosphate buffer, 0.1% sodium azide as preservative and stabilizers.

CONTROLS (REACTIVE, WEAK REACTIVE, NONREACTIVE) - Human serum or defibrinated plasma (liquid), with 0.1% sodium azide as preservative.

Reagents have two-year expiration dating from date of manufacture. The specific expiration date is located on the label on the vial.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary:

This submission is for a new algorithm for an existing device, the ASI Evolution Automated Syphilis Analyzer, used with the ASI Automated RPR Test for Syphilis. The study aims to demonstrate substantial equivalence of the new algorithm to the original algorithm. Therefore, the acceptance criteria and study design are geared towards showing comparable performance rather than de novo validation against a clinical gold standard.

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the goal of demonstrating substantial equivalence to the original algorithm. This means the new algorithm's performance (positive agreement and negative agreement) should be comparable to or better than the original algorithm's. While explicit numerical thresholds for acceptance are not stated for agreement, the 95% Confidence Intervals are provided, which typically are evaluated against a pre-defined acceptance range (e.g., lower bound of 90% for positive agreement). The reproducibility section demonstrates 100% agreement, which is a strong indicator of meeting a high standard for reproducibility.

Table of Acceptance Criteria (Implicit) and Reported Device Performance (Calculated from provided data)

Details of the Study Proving Device Meets Acceptance Criteria

1. Sample Sizes Used for the Test Set and Data Provenance:

• Retrospective Study Comparing Algorithms:
  • Serum Samples: 872 individual retrospective samples.
  • Plasma Samples: 890 individual retrospective samples.
  • Pregnant Women Testing: 280 samples (30 reactive, 250 nonreactive).
  • Total Samples for Algorithm Comparison: 872 (serum) + 890 (plasma) + 280 (pregnant women) = 2042 samples.
• Reproducibility Study:
  • 7 samples (2 nonreactive, 2 reactive 1:2, 1 reactive 1:4, 1 reactive 1:8, 1 reactive 1:16).
  • Each sample tested in duplicate within the panel, for 5 non-consecutive days, producing 60 data points per sample (60/60 reported). Total 7 samples x 60 data points = 420 data points.
• End-point Titer Testing:
  • 9 samples (2 nonreactive, 7 reactive with varying titers).
  • Each sample tested in 8 replicates on 10 different days, resulting in 80 data points for each sample. Total 9 samples x 80 data points = 720 data points.
• Data Provenance: Retrospective samples, with identifiers removed, collected from different Departments of Public Health Labs and Blood Banks. No specific country of origin is mentioned, but "U.S. Food & Drug Administration" implies U.S. data.

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

• For Algorithm Equivalence Study: The "ground truth" for the algorithm comparison study was the results interpreted by the original ASI Evolution algorithm (K173376 and K182391). This device was already cleared by the FDA, implying its outputs were considered reliable. No human experts were explicitly stated to establish ground truth for this direct comparison between two algorithms. However, for discordant results:
  • The 6 discordant serum results (new algorithm nonreactive, original algorithm reactive) were investigated and tested with a treponemal test and found to be reactive. This implies confirmation by an independent, more specific test, which is a common form of "ground truth" for syphilis diagnosis.
  • The 6 discordant plasma results (1 new reactive/original nonreactive, 5 new nonreactive/original reactive) were investigated. The new reactive/original nonreactive sample was tested with a treponemal test and found to be nonreactive. The 5 new nonreactive/original reactive samples were attributed to bubbles or artifacts in the test well. This also points to investigation and confirmation using a more definitive test or root cause analysis, serving as a form of expert adjudication or outcome-based truth.
• For Reproducibility and End-point Titer Testing: The "Expected Result" for these tests was established either by the manual interpretation method prior to testing (for end-point titer samples) or by the known characteristics of the control samples used. This implies laboratory or subject matter expert consensus or established reference values.

3. Adjudication Method for the Test Set:

• For the algorithm comparison (serum and plasma), discordant results between the new and original algorithms were investigated using a treponemal test (for biological confirmation) or attributed to technical issues (e.g., bubbles/artifacts). This serves as an adjudication method based on a more definitive test or root cause analysis.
• For the pregnant women testing, the comparison was made against the "ASI RPR Card Test for Syphilis on the ASiManager-AT Result," which acts as the reference.
• No explicit "2+1" or "3+1" human expert adjudication method was described as the primary ground truth establishment for the algorithm comparison, as the goal was algorithm-to-algorithm equivalence rather than algorithm-to-human.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

• No, an MRMC comparative effectiveness study was not performed as the primary validation for this submission. The study focused on demonstrating substantial equivalence between two automated algorithms (new vs. original ASI Evolution algorithm), not on comparing human readers with and without AI assistance.
• Effect size of human readers improving with AI vs. without AI assistance: Not applicable to this study design.

5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

• Yes, the core of the submission is a standalone performance study comparing the new algorithm's interpretation capabilities against the existing, cleared original algorithm on the same instrument. The "Performance Data" section explicitly states, "A comparison of the digital interpretation of the results from the ASI Evolution using the original interpretation algorithm... to establish substantial equivalence to the interpretation made by the ASI Evolution using the new interpretation algorithm was conducted."

6. The Type of Ground Truth Used:

• Algorithm vs. Algorithm (Predicate Device as Reference): The primary "ground truth" for the main algorithm comparison study was the output of the predicate device's algorithm (original ASI Evolution algorithm).
• Confirmatory Treponemal Test: For discrepant results in the algorithm comparison studies, a treponemal test was used as a more definitive clinical ground truth to resolve ambiguities.
• Manual Interpretation Methods / Known Reactivity: For reproducibility and end-point titer testing, the "expected result" was based on prior manual interpretation methods or known characteristics of control samples.
• No pathology or direct outcomes data was cited as the primary ground truth for the device clearance.

7. The Sample Size for the Training Set:

• Not specified in the provided document. The document describes a study comparing the new algorithm's performance against the old one (test set). It does not provide details about if or how the new algorithm itself was "trained" using specific data. Given the context of medical device clearance, it's presumed that the algorithm development (training, if any) would have occurred prior to this validation study.

8. How the Ground Truth for the Training Set was Established:

• Not specified in the provided document. As the training set details are not provided, neither is the method for establishing its ground truth.

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The ASI Automated RPR (rapid plasma reagin) Test for Syphilis, for use on the ASI Evolution Automated Syphilis Analyzer, is a qualitative and semi-quantitative nontreponemal flocculation test for the detection of reagin antibodies in human serum and plasma as a screening test for serological evidence of syphilis. All reactive RPR test samples should be further tested with a treponemal test. The ASI Automated RPR Test for Syphilis is for professional use only. The test is intended to be used for in vitro diagnostic testing and blood donor screening.

The ASI Evolution is intended to be used as a fully automated analyzer to objectively interpret the results of the ASI Automated RPR Test for Syphilis. The ASI Evolution is designed to provide standardized test interpretation and to provide for storage, retrieval, and transmittal of the test results. It is intended to be acquired, possessed and used only by health care professionals. The ASI Evolution analyzer, in conjunction with the ASI Automated RPR Test for Syphilis is intended to be used for in vitro diagnostic testing and blood donor screening.

The Automated RPR Test for Syphilis performed on the ASI Evolution is an automated nontreponemal flocculation test for the detection of reqain antibodies in human serum and plasma.

The ASI Evolution is an integrated digital particle analyzer designed to objectively interpret certain slide agglutination tests manufactured by Arlington Scientific, Inc. (ASI). The ASI Evolution fully automates the sample and reagent handling steps of the test procedure. Qualitative and semiquantitative tests are performed by laboratory professionals who use the ASI Evolution to provide standardized test interpretation using criteria that define reactive and nonreactive agglutination reactions.

The ASI Evolution employs a camera that uses light reflectance to create a highly sensitive and high-resolution image of the agglutination immunoassay. This image is then analyzed by the proprietary software algorithm to interpret the agglutination pattern.

The ASI Evolution further provides tools that enable the creation, storage, retrieval and transmittal of the test results.

The ASI Automated RPR Test for Syphilis reagents include the following:

CARBON ANTIGEN - 0.003% cardiolipin, 0.020-0.022% lecithin, 0.09% cholesterol, charcoal (activated) as visual enhancer, phosphate buffer, 0.1% sodium azide as preservative and stabilizers.

CONTROLS (REACTIVE, WEAK REACTIVE, NONREACTIVE) - Human serum or defibrinated plasma (liguid), with 0.1% sodium azide as preservative.

Reagents have two-year expiration dating from date of manufacture. The specific expiration date is located on the label on the vial.

The provided text describes the acceptance criteria and the study that proves the device meets those criteria for the ASI Automated RPR Test for Syphilis on the ASI Evolution, specifically focusing on the semi-quantitative claim for endpoint titer determination.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Test Set Description: A randomized and blinded panel of 10 human serum samples with known reagin antibody endpoint titers.
• Sample Size: Each of the 10 samples was tested a minimum of 80 times, for a total of 800 tests (10 samples * 80 tests/sample).
  • 2 of the 10 samples were non-reactive (total 160 non-reactive tests).
  • 8 of the 10 samples were reactive (total 640 reactive tests).
• Data Provenance: The tests were performed in-house on at least five different days by one operator using a single ASI Evolution instrument. The origin of the human serum samples themselves (e.g., country of origin) is not explicitly stated, but they are described as having "known reagin antibody endpoint titers." The study can be considered prospective as it involved testing pre-selected samples with the device to determine its performance against established ground truth.

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

• The ground truth for the 10 human serum samples (known reagin antibody endpoint titers) was "determined by the ASI RPR Card Test for Syphilis on the ASiManager-AT."
• The document does not explicitly state the number or qualifications of experts used to establish the ground truth via the ASI RPR Card Test on the ASiManager-AT. It implies that this was an established method of determining titers, rather than an expert consensus process for this specific study.

4. Adjudication Method for the Test Set

• None specified. The study setup describes the device's output being compared directly against the "known reagin antibody endpoint titers" established by the ASiManager-AT, implying a direct comparison rather than an adjudication process between human readers or the device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No. The provided text describes an analytical study evaluating the semi-quantitative performance (endpoint titer validation) of the automated system. It does not include an MRMC study comparing human reader performance with and without AI assistance for this specific indication.
• The document mentions "Clinical performance of the ASI Automated RPR Test for Syphilis on the ASI Evolution was evaluated under K173376," but focuses on overall qualitative detection rather than human reader AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes. The described study is a standalone performance evaluation of the ASI Evolution device itself, as it automates the interpretation of the RPR test. The device's proprietary software algorithm analyzes the image and interprets the agglutination pattern to report results (Reactive, Nonreactive, endpoint titers).

7. Type of Ground Truth Used

• The ground truth used was "known reagin antibody endpoint titers," which were "determined by the ASI RPR Card Test for Syphilis on the ASiManager-AT." This can be classified as a reference standard method (another established diagnostic test) rather than direct pathology or outcomes data from patients.

8. Sample Size for the Training Set

• The sample size for the training set is not specified in the provided text. The document describes pre-market validation for the analytical performance and refers to previous clinical performance evaluations (K173376) for qualitative detection. It does not provide details on the data used to train the proprietary software algorithm itself.

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

• As the training set size is not specified, how its ground truth was established is also not detailed in this document. It is implicitly understood that for an automated system, the training data would also require established ground truth to enable the algorithm to learn to interpret agglutination patterns, but the specifics are not provided here.

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The ASI Automated RPR (rapid plasma reagin) Test for Syphilis, for use on the ASI Evolution Automated Syphilis Analyzer, is a qualitative nontreponemal flocculation test for the detection of reagin antibodies in human serum and plasma as a screening test for serological evidence of syphilis. All reactive RPR test samples should be further tested with a treponemal test. The ASI Automated RPR Test for Syphilis for use on the ASI Evolution produces only a reactive or non-reactive result and does not report RPR titers for reactive samples. The ASI Automated RPR Test for Syphilis is for professional use only. The test is intended to be used for in vitro diagnostic testing. The ASI Evolution is intended to be used as a fully automated analyzer to objectively interpret the results of the ASI automated RPR test for syphilis. The ASI Evolution is designed to provide standardized test interpretation and to provide for storage, retrieval, and transmittal of the test results. It is intended to be acquired, possessed and used only by health care professionals. The ASI Evolution analyzer, in conjunction with the ASI Automated RPR Test is intended to be used for in vitro diagnostic testing. The ASI Automated RPR Test for Syphilis for use on the ASI Evolution produces only a reactive or non-reactive result and does not report RPR titers for reactive samples.

The ASI Evolution is an integrated digital particle analyzer designed to objectively interpret certain slide agglutination tests manufactured by Arlington Scientific, Inc. (ASI). The ASI Evolution fully automates the sample and reagent handling steps of the test procedure. Qualitative tests are performed by laboratory professionals who use the ASI Evolution to provide standardized test interpretation using criteria that define reactive and nonreactive aqqlutination reactions. The ASI Evolution employs a camera that uses light reflectance to create a highly sensitive and high-resolution image of the agglutination immunoassay. This image is then analyzed by the proprietary software algorithm to interpret the agglutination pattern. The ASI Evolution further provides tools that enable the creation, storage, retrieval and transmittal of the test results. The ASI Automated RPR Test for Syphilis reagents include the following: CARBON ANTIGEN - 0.003% cardiolipin, 0.020-0.022% lecithin, 0.09% cholesterol, charcoal (activated) as visual enhancer, phosphate buffer, 0.1% sodium azide as preservative and stabilizers. CONTROLS (REACTIVE, WEAK REACTIVE, NONREACTIVE) - Human serum or defibrinated plasma (liquid), with 0.1% sodium azide as preservative. Reagents have two-year expiration dating from date of manufacture. The specific expiration date is located on the label on the vial.

This document describes the regulatory approval for the ASI Automated RPR Test for Syphilis ASI Evolution. The product is a qualitative nontreponemal flocculation test for the detection of reagin antibodies in human serum and plasma for syphilis screening. It is designed to be used with the ASI Evolution Automated Syphilis Analyzer, which objectively interprets test results as reactive or non-reactive.

Here is a summary of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the ASI Automated RPR Test for Syphilis ASI Evolution are based on demonstrating substantial equivalence to its predicate device, the ASI RPR Card Test for Syphilis on the ASiManager-AT. The key performance metrics are positive and negative agreement rates.

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

• Prospective Samples: 1,068 individual samples. Collected at two different Departments of Public Health Labs. Data provenance is prospective.
• Retrospective Serum Samples (Agreement Study): 10 individual samples. Collected from various reference labs and serum and plasma vendors from across the United States. Data provenance is retrospective.
• Retrospective Plasma Samples (Agreement Study): 1,003 individual samples. Collected from various reference labs and serum and plasma vendors from across the United States. Data provenance is retrospective.
• ASI Evolution Characterized Specimen Testing (Clinical Diagnosis): Total of 1,068 + 1,013 = 2,081 samples (Total samples from prospective and retrospective studies)
  • Prospective Random Samples:
    • Site a: 567 Serum samples (country not specified, likely US based on other descriptions)
    • Site b: 501 Serum samples (country not specified, likely US based on other descriptions)
  • Retrospective Samples:
    • Site c: 17 Known infected samples (serum & plasma, from across the United States)
    • Site c: 996 Known uninfected samples (serum & plasma, from across the United States)
    • Total Retrospective samples: 1013
• Performance with Samples from Pregnant Women: 250 non-reactive and 30 reactive samples from pregnant women. Serum samples. Country not specified, likely US.
• Precision Testing: 10 samples (3 nonreactive, 7 reactive at various titers), each tested 192 times (total 1920 tests).
• Reproducibility Testing (7 samples): 7 samples (2 nonreactive, 5 reactive at various titers), tested at 3 sites, each sample tested 180 times across various conditions (total 1260 tests).
• Reproducibility Testing (448 samples): 448 retrospective serum samples (48 nonreactive, 400 reactive), tested at 3 sites (total 1344 tests). Samples collected from various reference labs and serum and plasma vendors from across the United States.
• Cross Reactivity/Interfering Substances: 368 samples across various categories (e.g., ANA (+), HIV (+), pregnant women, etc.).
• Carry-Over: 48 aliquots per run (24 reactive, 24 nonreactive). Run over 5 days.
• On-board Stability Testing: 4 samples (1 nonreactive, 3 reactive at various titers), each run in triplicate morning and afternoon for 5 days by 2 operators (total 120 tests).
• Frozen vs. Refrigerated Testing: Total of 55 samples (20 non-reactive, 35 reactive at various titers) tested as both frozen and refrigerated.

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

The document does not explicitly state the "number of experts" or their "qualifications" for establishing the ground truth for the test set in the comparative studies.

• For the comparative studies against the ASiManager-AT, the predicate device's results (interpreted by "trained laboratory professionals") served as the reference. These professionals are implicitly qualified by their training to interpret RPR tests.
• For the "ASI Evolution Characterized Specimen Testing," the "Expected results are based on known clinical diagnosis." This implies that clinical experts (e.g., physicians, specialists) established the diagnosis, which then served as a proxy for ground truth.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method like 2+1 or 3+1. For the comparative studies, the results of the ASiManager-AT, interpreted by trained laboratory professionals, were considered the comparator. In cases of discrepancies or challenges, no specific adjudication process is detailed for these studies. For the Characterized Specimen Testing, the "known clinical diagnosis" itself serves as the ground truth, implying no further adjudication on the test results against the diagnosis.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a traditional MRMC comparative effectiveness study, where multiple human readers interpret cases with and without AI assistance to measure improvement in human performance, was not performed. The study focused on the standalone performance of the ASI Evolution device compared to the predicate device (ASiManager-AT) and known clinical diagnoses. When human operators were involved (e.g., for ASiManager-AT interpretation), they were trained professionals, but the study did not measure their improvement with AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies primarily assessed the standalone performance of the ASI Evolution. The device is described as a "fully automated analyzer to objectively interpret the results" of the RPR test. The comparison against the ASiManager-AT (which involves human interpretation of results) and known clinical diagnoses evaluates the ASI Evolution's direct output.

7. The Type of Ground Truth Used

The ground truth used varied:

• Comparative Studies: The results obtained from the predicate device, the ASI RPR Card Test for Syphilis on the ASiManager-AT, interpreted by trained laboratory professionals, served as the comparator/reference.
• Characterized Specimen Testing: "Known clinical diagnosis" was used as the ground truth. This implies diagnoses established by medical professionals through various clinical and laboratory indicators.
• Precision, Reproducibility, Cross-Reactivity, Carry-Over, On-board Stability, Frozen vs. Refrigerated Testing: Expected results for controls and characterized samples (e.g., "RPR nonreactive," "RPR reactive 1:1 titered samples") were used as the ground truth. These expected results are typically established during the characterization and manufacturing of the control materials themselves.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set of the ASI Evolution's algorithm. It mentions that the "same proprietary interpretive algorithm used in the predicate device (ASiManager-AT) is used in the ASI Evolution." This suggests that the algorithm was developed and potentially trained using data prior to this submission, possibly with data collected for the ASiManager-AT validation. However, details of that training are not provided here.

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

As the document does not specify a training set for the ASI Evolution's algorithm, it also does not detail how the ground truth for such a set was established. Given the claim that the algorithm is the "same proprietary interpretive algorithm" as in the predicate device, it is likely that the ground truth for any initial algorithm development would have been established through expert human interpretation of RPR flocculation patterns over a large set of samples, potentially correlated with confirmatory treponemal tests or clinical diagnoses.

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The BioPlex Syphilis Total & RPR kit is a multiplex flow immunoassay intended for the qualitative detection of total (IgG/IgM) antibodies to Treponema pallidum and the qualitative detection and/or titer determination of non-treponemal reagin antibodies in human serum or plasma. The Syphilis Total or RPR assays may be used to supplement a previously determined reactive treponemal or non-treponemal test. The test system should be used in conjunction with other laboratory tests and clinical findings to aid in the diagnosis of syphilis infection.

The BioPlex 2200 Syphilis Total & RPR kit is not intended for use in screening blood or plasma donors

The BioPlex 2200 Syphilis Total & RPR kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex 2200 Syphilis Total & RPR Control Set is intended for use as an assayed quality control to monitor the performance of the BioPlex 2200 Instrument and BioPlex 2200 Syphilis Total & RPR assay in the clinical laboratory. The performance of the BioPlex 2200 Syphilis Total & RPR Control Set has not been established with any other Syphilis Total & RPR assays.

The BioPlex 2200 Syphilis Total & RPR Calibrator Set is intended for the BioPlex 2200 Syphilis Total & RPR Reagent Pack.

BioPlex 2200 Syphilis Total & RPR kit includes the following components:

• One (1) 10 mL vial, containing dyed beads coated with recombinant Syphilis ● rTP47/rTP17 fusion protein, a cardiolipin antigen, an Internal Standard Bead (ISB) and a Serum Verification Bead (SVB) in MOPS (3-[N-Morpholino] propanesulfonic acid) buffer containing bovine proteins with protein stabilizers. ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (

Here's an analysis of the provided text, extracting the acceptance criteria and study details as requested:

BIO-RAD BioPlex 2200 Syphilis Total & RPR Kit Evaluation

1. Table of Acceptance Criteria and Reported Device Performance

The document describes internal precision and reproducibility acceptance criteria implicitly through the reported values for %CV within CLSI guidelines. For clinical performance, acceptance criteria are not explicitly stated as numerical thresholds (e.g., minimum sensitivity/specificity), but agreement percentages are reported. The provided tables are direct results from the studies and serve as the reported performance against assumed internal/regulatory acceptance ranges.

For Syphilis Total Assay (Treponemal Test):

For RPR Assay (Non-Treponemal Test):

2. Sample Size and Data Provenance for Test Set

• Total Samples for Clinical Studies: 2008 samples.
• Test Set Breakdown:
  • Prospective Samples: 1001 samples.
    • Country of Origin: Approximately 91% US (23.6% Northeast, 18.7% Southwest, 28.4% Southeast, 9.2% Midwest, 10.8% Unknown), 9% outside US (3.5% Argentina, 3.2% France/Europe, 1.4% China, 1.2% Others).
  • Retrospective Samples: 661 samples.
    • Country of Origin: Not explicitly broken down for retrospective samples, but generally stated to be from "multiple commercial suppliers" with the 91% US / 9% outside US split likely encompassing both.
  • Clinically Diagnosed Individuals: 160 individuals (separate cohort from prospective/retrospective samples with specific diagnoses).
• Data Provenance: Both prospective and retrospective samples were used. Prospectively collected samples were from apparently healthy subjects, syphilis/RPR test ordered patients, pregnant women, and HIV positive individuals. Retrospective samples were from known RPR/VDRL positive, clinically diagnosed syphilis, pregnant syphilis positive, and HIV/Syphilis dual positive individuals.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number or qualifications of "experts" used for establishing the ground truth directly. Instead, it relies on a "Final Comparator Algorithm Result" for the Syphilis Total assay, which is derived from multiple commercially available syphilis assays (predicate devices). For the RPR assay, the ground truth is primarily based on a commercially available RPR Card Test (Predicate).

• No specific number of human experts is mentioned for adjudicating individual cases or establishing the final ground truth. The "ground truth" seems to be established algorithmically or through established predicate diagnostic tests.

4. Adjudication Method

• For BioPlex 2200 Syphilis Total assay: The ground truth was established using a "2 out of 3" rule from three commercially available syphilis assays:
  1. Treponemal chemiluminescent immunoassay (primary predicate)
  2. RPR Card Test (non-treponemal assay)
  3. Treponema Pallidum Particle Agglutination (TP-PA) (second treponemal assay)
     If at least two of these predicate assays agreed, that was considered the final comparator result. If there was no agreement (e.g., 1 positive, 1 negative, 1 inconclusive), the result was deemed "indeterminate" and excluded from analysis.
• For BioPlex 2200 RPR assay: The ground truth was established by comparing directly to a commercially available RPR Card Test (Predicate). No explicit "adjudication" among multiple assays is described here.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC or human-in-the-loop study is described in this document. The device is an automated immunoassay system, and its performance is compared to other diagnostic assays (predicate devices), not to human readers. Therefore, there is no effect size reported for human readers improving with or without AI assistance.

6. Standalone Performance Study

• Yes, a standalone performance study was done. The entire document describes the standalone performance of the BioPlex 2200 Syphilis Total & RPR kit. The device is an algorithm only (automated immunoassay) without a human-in-the-loop component in the diagnostic process itself. The clinical performance tables explicitly show the agreement of the BioPlex 2200 with the "Final Comparator Algorithm Result" (for Syphilis Total) or the "Predicate RPR Result" (for RPR).

7. Type of Ground Truth Used

• For Syphilis Total assay: A composite comparator algorithm based on the results of three commercially available diagnostic assays (predicate Treponemal CIA, RPR Card Test, TP-PA). This could be categorized as a form of expert consensus using established diagnostic tests rather than pathology or direct outcomes data for every individual case.
• For RPR assay: A single predicate diagnostic assay (RPR Card Test).

8. Sample Size for Training Set

• The document does not explicitly state the sample size used for the training set. It mentions the "feasibility phase of BioPlex 2200 Syphilis Total & RPR assay development" where cutoff values were established using "native human samples from apparently healthy subjects, patients sent to the laboratory for syphilis testing and patients diagnosed with syphilis infection." However, specific numbers for this development/training phase are not provided.

9. How Ground Truth for Training Set Was Established

• The cutoff values for the Syphilis Total and RPR assays were established "in the feasibility phase" using Native human samples from:
  • Apparently healthy subjects
  • Patients sent to the laboratory for syphilis testing
  • Patients diagnosed with syphilis infection
• The establishment involved Receiver Operating Characteristics (ROC) analysis using "predicate results as standard". This indicates that the ground truth for establishing the cutoffs was derived from existing, legally marketed assays (predicates). Calibrator values were then adjusted based on this analysis to align with the 1.0 AI cutoff. Further confirmation of cutoff values involved comparing BioPlex results from patient samples to commercially available assays, and ultimately, clinical studies validated the cutoff.

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The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a non-treponemal flocculation test that can qualitatively determine the presence of reagin antibodies in human serum. It may be used to aid in the diagnosis of syphilis when used in conjunction with supplemental treponemal laboratory tests and other clinical information. This test may also be used to detect non-treponemal antibodies in samples serially diluted to establish titer information. This test is not intended for screening blood or tissue donors.

The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System in a non-treponemal test for the qualitative determination of reagin antibodies in human serum to aid in the diagnosis of syphilis. This test is also used to detect non-treponemal antibodies in samples serially diluted to establish titer information. The system consists of the Gold Standard Diagnostics RPR test reagents and the Gold Standard Diagnostics AIX1000 Agglutination Analyzer. The AIX1000 Analyzer delivers serum from collection tubes into test wells. After antigen suspension is added, the test wells are then incubated while being shaken. An onboard camera creates a high resolution image. The image is then analyzed by the proprietary software algorithm to produce a result.

Here's an analysis of the acceptance criteria and the studies that prove the device meets these criteria, based on the provided text:

Device Name: Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System
K Number: K150358

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a bulleted or numbered list with predefined thresholds for all studies. However, performance expectations are implied by the nature of the tests conducted and the reported agreement percentages. I will interpret the reported performance metrics as demonstrating the device meets an implied acceptance for its intended use, particularly through comparison to a predicate device.

• Low RPR Reactivity (1:4): 100% agreement (93.6% - 100% C.I.)
• Moderately Reactive (1:16): 100% agreement (93.6% - 100% C.I.)
• Reactive (1:64): 97.8% agreement (88.2% - 99.9% C.I.)
• Highly Reactive (1:128): 100% agreement (93.6% - 100% C.I.)
• Reactive control: 100% agreement (54.9% - 100% C.I.)
• Non-reactive control: 100% agreement (54.9% - 100% C.I.) |
  | Reproducibility | High agreement (e.g., >90%) within ± 1 titer across operators, instruments, days, and runs. | - Non-Reactive Serum: 100% (Between-Runs, Between-Days, Between-Operators, Between-Instruments)
• Low RPR Reactivity (1:4): 100% (all categories)
• Moderately Reactive (1:16): 100% (all categories)
• Reactive (1:64): 100% (Between-Runs, Between-Operators, Between-Instruments), 97.8% (Between-Days)
• Highly Reactive (1:128): 100% (Between-Runs, Between-Days, Between-Instruments), 98.1% (Between-Operators)
• Reactive control: 100% (90.5% - 100% C.I.)
• Non-reactive control: 100% (90.5% - 100% C.I.) |
  | Carry-over | No evidence of carry-over (no false positives in negative samples due to highly reactive samples). | All 480 replicates of the negative samples were reported as non-reactive when highly reactive samples were alternated with non-reactive samples. |
  | Clinical Agreement (Prospective Samples vs. Predicate) | High Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with predicate. | PPA: 95.5% (C.I. 77.2% - 99.9%)
  NPA: 99.9% (C.I. 99.3% - 100%) |
  | Clinical Agreement (Retrospective Samples vs. Predicate) | High PPA and NPA with predicate. | PPA: 97.2% (C.I. 95.5% - 98.4%)
  NPA: 99.1% (C.I. 98.5% - 99.5%) |
  | Special Populations (Pregnant Women vs. Predicate) | High PPA and NPA with predicate. | PPA: 100% (C.I. 90.5% - 100%)
  NPA: 100% (C.I. 98.8% - 100%) |
  | Special Populations (HIV Positive Individuals vs. Predicate) | High PPA and NPA with predicate. | PPA: 100% (C.I. 90.5% - 100%)
  NPA: 100% (C.I. 98.8% - 100%) |
  | Healthy Individuals | Low and expected reactivity in a healthy, no-risk population. | All 100 samples from apparently healthy individuals (not at risk, no syphilis test ordered) were non-reactive. |
  | Clinical Stages Correlation | High agreement with clinically diagnosed syphilis cases across various stages. | Primary Treated (13/13 reactive), Primary Untreated (12/12 reactive), Secondary Treated (25/25 reactive), Secondary Untreated (25/25 reactive), Latent Treated (25/25 reactive), Latent Untreated (25/25 reactive). All showed 100% agreement with corresponding 95% C.I. ranges of 77.9%-100% to 88.7%-100%. |

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

The document describes several test sets:

• Cross Reactivity: Panels of 10-16 individual patient samples per condition (totaling 17 conditions for viral, bacterial, and autoimmune).
• Interfering Substances: 5 samples (1 non-reactive, 4 reactive) per interfering substance.
• Precision: 5 samples (Non-reactive, Low RPR (1:4), Moderately Reactive (1:16), Reactive (1:64), Highly Reactive (1:128)). Each tested in 9 replicates.
• Reproducibility: The same 5 sample panels as precision, tested across 6 operators, 3 instruments, 2 runs over 5 days.
• Carry-over: 1 reactive (1:64), 1 highly reactive (1:128), and 2 non-reactive samples. Highly reactive samples alternated with non-reactive samples 96 times per run over 5 runs.
• Clinical Studies - Prospectively Collected Samples:
  • Sample Size: 765 serum samples.
  • Data Provenance: Collected prospectively from patient samples with a physician's order for syphilis testing. Collected at two geographically distinct reference laboratories (Southeastern and Western United States).
• Clinical Studies - Retrospectively Collected Samples:
  • Sample Size: 2,246 samples.
  • Data Provenance: Collected retrospectively from patients referred for syphilis testing. Obtained from sample brokers who collect from multiple sites across the United States. Collection dates: January 2005 - July 2014.
• Clinical Studies - Pregnant Women (Retrospective):
  • Sample Size: 250 non-reactive, 30 reactive (spiked) samples. Total 280.
  • Data Provenance: Retrospectively collected from pregnant women at one site (Southeastern United States). Collection dates: July 2012 - August 2013.
• Clinical Studies - HIV Positive Individuals (Retrospective):
  • Sample Size: 250 non-reactive, 30 reactive samples. Total 280.
  • Data Provenance: Retrospectively collected from HIV positive individuals at four sites (one Southeastern, one Mid-Western States). Collection dates: February 2012 - June 2015.
• Apparently Healthy Individuals (Prospective):
  • Sample Size: 100 serum samples.
  • Data Provenance: Prospectively collected from healthy individuals not at risk for syphilis and for whom a syphilis test had not been ordered (submitted for routine chemistry testing).
• Correlation with Clinically Diagnosed Syphilis Sera - Various Stages (Purchased Panel):
  • Sample Size: Primary Treated (13), Primary Untreated (12), Secondary Treated (25), Secondary Untreated (25), Latent Treated (25), Latent Untreated (25).
  • Data Provenance: Purchased from serum brokers, characterized by clinical diagnosis.

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

The document does not mention the use of human experts to establish ground truth for the test sets in the context of adjudication or interpretation of the RPR results. Instead, it relies on:

• Reference laboratory results (for prospective samples).
• Predicate device results (for comparison in clinical studies).
• FDA-cleared treponemal (TP) assays (for further investigation of discrepant non-treponemal results).
• Clinical diagnosis (for the purchased syphilis stage panel).
• Serum broker confirmation of disease markers (for cross-reactivity samples).

Therefore, there is no direct information on the number or qualifications of experts involved in establishing ground truth through manual interpretation of RPR images or similar tasks for the "AIX1000" aspect. The 'AI' component is described as proprietary software interpreting images (standalone).

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used when multiple human readers interpret the same image/case and disagreements need to be resolved. This device is an automated test system for a flocculation assay where the "AIX1000 Agglutination Analyzer" uses a proprietary software algorithm to produce a result.

For the discrepancies in the clinical studies where the GSD AIX1000 RPR Test System disagreed with the comparator device:

• Prospective Samples: The two discrepant samples were tested on a "third FDA cleared RPR assay."
• Retrospective Samples: The 31 discrepant samples were tested on a "third FDA cleared RPR assay."

This suggests a form of tie-breaking or external reference testing for discrepant results, rather than a human expert adjudication of visual interpretations by the device itself.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not conducted. The device is an automated test system that interprets RPR assay results without direct human intervention in the interpretation process described. The comparisons were between the automated device and a predicate automated device or clinical outcomes, not between human readers with and without AI assistance.

6. If a Standalone Performance (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, the studies reported represent standalone performance of the Gold Standard Diagnostics AIX1000 RPR Automated Test System. The device's proprietary software algorithm directly produces the results from images captured by its onboard camera. The clinical studies (prospective, retrospective, special populations) directly compare the device's output to a predicate device's output or clinical diagnosis, without human modification or override of the AIX1000's initial determination. The interpretation of the flocculation assay itself is automated.

7. The Type of Ground Truth Used

The ground truth or reference methods varied depending on the study:

• Clinical Studies (Prospective and Retrospective): The primary ground truth for comparison was the legally marketed predicate device (Arlington Scientific Inc. (ASI) RPR Card Test for syphilis on the ASiManager-AT Analyzer). For discrepant samples, a third FDA cleared RPR assay was used as a tie-breaker. Further investigation for NT+ samples used an FDA cleared treponemal (TP) assay.
• Correlation with Clinically Diagnosed Syphilis Sera: Clinical Diagnosis (Primary, Secondary, Latent stages as characterized by documented symptoms, dark field microscopy, and reactive treponemal/non-treponemal tests).
• Cross-Reactivity Study: Confirmation of disease markers by serum brokers.
• Special Populations (Pregnant Women, HIV Positive): Predicate device results, and also confirmed pregnancy status via HCG test and HIV positive status.
• Apparently Healthy Individuals: Lack of risk factors and no physician's order for syphilis testing defined this as "healthy."

8. The Sample Size for the Training Set

The document does not provide information on the sample size used for the training set for the proprietary software algorithm. This information is typically proprietary to the manufacturer and not usually detailed in 510(k) summaries unless specifically requested or deemed critical for substantial equivalence. The focus of the 510(k) is often on comparing the new device's performance to a predicate, rather than the internal development of its algorithm.

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

Similar to the training set size, the document does not provide information on how the ground truth for the training set was established. Since the device uses a "proprietary software algorithm" to analyze images for flocculation, it can be inferred that this algorithm was developed and trained using a collection of RPR test results with established reactivity and titer values. However, the specifics of this ground truth (e.g., expert consensus on visual flocculation, correlation with other assays) are not detailed in this submission.

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