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The Xpert® Xpress GBS test, performed on the GeneXpert® Instrument Systems, is an automated, real-time PCR test for the qualitative detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens collected from pregnant patients for intrapartum testing at term (e.g., >37 weeks) who have unknown or unavailable antepartum GBS screening test results and no additional risk factors that would warrant empiric antibiotic prophylaxis. The Xpert Xpress GBS test performed during intrapartum is intended to aid in the detection of GBS colonization in patients presenting in labor who may be candidates for antibiotic prophylaxis.

The Xpert Xpress GBS test does not provide antimicrobial susceptibility test results. Culture is necessary to obtain isolates to perform susceptibility testing as recommended for penicillin-allergic patients.

This test is conducted using direct specimen without enrichment is recommended to enhance detection of GBS colonization). In contrast to a positive test result, which can indicate colonization, a presumptive negative result cannot exclude the possibility of GBS colonization. A false negative test result at intrapartum carries a potential harm to the infant if it is used in making decisions regarding empiric antibiotic prophylaxis. Providers must use caution and default to known patient risk factors and clinical guidance regarding a role for intrapartum prophylaxis.

The Xpert® Xpress GBS test is an automated in vitro diagnostic test for the qualitative detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens collected from pregnant patients at intrapartum.

The Xpert Xpress GBS test is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx. GeneXpert Infinity-48s and GeneXpert Infinity-80 systems), which consist of an instrument, computer and preloaded software for running tests and viewing the results. The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and real-time detection. Depending on the instrument, the GeneXpert Instrument Systems can have from 1 and up to 80 randomly accessible modules, each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR as well as detection. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self- contained, cross-contamination between cartridges during the testing process is minimized.

The Xpert Xpress GBS test includes reagents for the simultaneous detection of target GBS DNA from vaginal/rectal swab specimens. The primers and probes in the Xpert Xpress GBS test are designed to amplify and detect unique sequence in two conserved chromosomal targets in S. agalactiae: a) a member of the glycosysl transferase gene family, and b) a LysR transcriptional regulator. A Sample Adequacy Control (SAC), Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SAC is a non-target sequence naturally present in the specimen. which is amplified along with the assay target. In the Xpert Xpress GBS test, the SAC detects the presence of the human hydroxymethylbilane synthase (HMBS) gene to ensure that the sample is properly collected and contains adequate human cells from the vaginal/rectal flora. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The PCC verifies reagent rehydration. PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress GBS test is designed for use with vaginal/rectal swab specimens collected from pregnant patients at intrapartum and placed into a collection device. The ancillary specimen collection kit validated for use with the Xpert Xpress GBS test is the Cepheid Collection Device (Catalog 900-0370). The sample collection device allows dual vaginal/rectal swab specimens from patients to be collected and transported to laboratory prior to analysis with the Xpert Xpress GBS test.

Here's a breakdown of the acceptance criteria and study details for the Xpert® Xpress GBS device, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific numeric thresholds for sensitivity, specificity, PPV, and NPV. However, it presents the clinical performance results as compared to enriched bacterial culture + MALDI-TOF MS. The implied acceptance is that the device's performance is deemed "acceptable for its intended use" and "substantially equivalent to the predicate device."

Here are the reported performance metrics from the clinical study:

2. Sample Size and Data Provenance for the Test Set

• Sample Size for Test Set: A total of 899 intrapartum vaginal/rectal specimens were included in the performance analysis. Initially, 912 specimens were enrolled, but 13 were excluded due to non-determinate Xpert Xpress results upon retest or no culture results.
• Data Provenance: The study was conducted at twelve (12) clinical sites from geographically diverse regions within the United States. This indicates the data is prospective and multi-site (US).

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number or qualifications of experts used to establish the ground truth. The ground truth was established by "enriched bacterial culture with species identification via MALDI-TOF MS." This method is considered a laboratory-based gold standard for GBS detection. The interpretation of these results would typically be done by trained laboratory personnel.

4. Adjudication Method

The document mentions that discordant results between the Xpert Xpress GBS test and the comparator method (enriched culture + MALDI-TOF MS) were investigated using an FDA-cleared nucleic acid amplification test (NAAT). However, the exact adjudication method (e.g., 2+1, 3+1, etc.) for resolving these discrepancies to establish a final ground truth is not explicitly described. The text states that the results of the FDA-cleared NAAT are "footnoted in Table 5-8, for informational purposes only," suggesting that the primary "ground truth" remained the enriched culture, and the NAAT was used for further investigation of discrepancies rather than as a tie-breaker in a formal adjudication process.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. This device is an automated, standalone diagnostic test and does not involve human readers for interpretation in the same way an imaging AI algorithm would.

6. Standalone Performance Study

Yes, a standalone performance study (i.e., algorithm only without human-in-the-loop performance) was performed. The clinical performance characteristics were evaluated by directly comparing the Xpert® Xpress GBS test results to an enriched bacterial culture with species identification via MALDI-TOF MS.

7. Type of Ground Truth Used

The primary ground truth used for the clinical performance study was enriched bacterial culture with species identification via MALDI-TOF MS.

8. Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. The study detailed in the document focuses on the clinical performance evaluation of the finished device.

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

Since no information on the training set is provided, the method for establishing its ground truth is also not detailed in this document. Typically, for PCR-based tests like this, development and training would involve a combination of characterized GBS strains and cultured clinical samples verified by traditional microbiology methods.

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The Xpert GBS LB XC test, performed on the GeneXpert® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens, using real- time polymerase chain reaction (PCR).

Xpert GBS LB XC testing is indicated as an aid in determining the GBS colonization status of antepartum women.

· The Xpert GBS LB XC test is intended for antepartum testing on enriched Lim broth cultures of vaginal/rectal swabs after 18-24 hours of incubation

· The Xpert GBS LB XC test does not provide antimicrobial susceptibility test results. Culture is necessary to obtain isolates to perform susceptibility testing as recommended for penicillin-allergic women

The Xpert GBS LB XC test is an automated in vitro diagnostic test for qualitative detection of DNA from Group B Streptococcus (GBS) from vaginal-rectal swab specimens obtained from pregnant women that are transported to the laboratory following enrichment in Lim broth.

The primers and probes in the Xpert GBS LB XC test are designed to simultaneously amplify and detect two unique GBS chromosomal targets: the first is a target within a coding region for a glycosyl transferase family protein and the second is within a coding region for a LysR family transcriptional regulator of Streptococcus agalactiae DNA.

The Xpert GBS LB XC test includes reagents for the detection of DNA from GBS in Lim broth-enriched vaginal/rectal swabs. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate extraction and processing of the target sequences and to monitor for the presence of inhibitors in the PCR reaction. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dve stability.

The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of GBS genomic DNA in as little as 27 minutes with high titer specimens; GBS negative specimens generate results in approximated 43 minutes. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.

The Xpert GBS LB XC test is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection. The GeneXpert systems consist of an instrument, computer, and preloaded software for running tests and viewing the results.

The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert GBS LB XC cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document describes the performance of the Xpert GBS LB XC test, a qualitative in vitro diagnostic test for the detection of Group B Streptococcus (GBS) DNA. The acceptance criteria are implicitly derived from the reported performance characteristics.

Study Details

1. Sample size used for the test set and the data provenance:

   • Test Set Sample Size: 621 specimens were included in the Xpert GBS LB XC versus Composite Comparator analysis.
   • Data Provenance: The study was a multi-site clinical study conducted in the United States. It used vaginal/rectal swab specimens collected from pregnant females as part of routine care. The nature of the specimen collection ("as a part of routine care") suggests it was likely a prospective collection for this study, though it might have utilized leftover samples. The text specifies "aliquots of leftover Lim broth samples were obtained for testing."

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth was established using a "composite comparator method" which involved enriched bacterial culture and an FDA cleared NAAT. For the culture component, species identification was performed via Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectroscopy (MALDI-TOF MS). While MALDI-TOF MS requires skilled lab personnel, the term "expert" in the sense of a medical professional making a diagnostic determination is not used for this ground truth establishment.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • The adjudication method for the test set was: "a specimen was considered positive if either enriched bacterial culture or the FDA cleared NAAT was positive and negative when both enriched bacterial culture and the FDA cleared NAAT were negative." This is a rule-based composite comparator rather than an expert adjudication method like 2+1.

4. 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, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human readers improving with AI assistance was not done. This device is an automated in vitro diagnostic test (NAAT) for detecting GBS DNA. It does not involve human "readers" in the diagnostic process beyond laboratory technicians operating the equipment and interpreting the automated qualitative results.

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

   • Yes, the clinical "Performance of Xpert GBS LB XC v Composite Comparator" (Table 9) is a standalone performance assessment. The Xpert GBS LB XC test is an automated qualitative test where the instrument system performs sample preparation, amplification, and real-time detection, with the software running tests and viewing results. This is inherently an "algorithm only" performance, as the final output is a qualitative (Positive/Negative) result generated by the device itself.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

   • A composite comparator method was used as the ground truth. This method combined:
     • Enriched bacterial culture with species identification via Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectroscopy (MALDI-TOF MS).
     • An FDA cleared Nucleic Acid Amplification Test (NAAT).

7. The sample size for the training set:

   • The document describes a clinical validation study for regulatory submission. It does not provide information about the sample size used for the training set of the algorithm or device. Regulatory submissions typically focus on validation performance rather than development/training data.

8. How the ground truth for the training set was established:

   • Since information on the training set (including its sample size) is not provided, the method for establishing its ground truth is also not detailed in this document.

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The Strep A Rapid Test Strip (Throat Swab) is a rapid chromatographic immunoassy for the qualitative detection of Streptococcus pyogenes (Group A B-hemolytic Streptococcus, Strep A) antigen from throat swab specimens of symptomatic patients to aid in the diagnosis of Group A Streptococcus bacterial infection.

All negative test results should be confirmed by bacterial culture because negative results do not prection with Group A Streptococcus and should not be used as the sole basis for treatment.

Healgen Strep A Rapid Test Strip (Throat Swab) is a qualitative, lateral flow immunoassay for the detection of Strep A antigen directly from a throat swab sample.

In this test, antibody specific to Strep A carbohydrate antigen is coated on the test line region of the test. During testing, the extracted throat swab specimen reacts with an antibody to Strep A that is coated onto particles. The mixture migrates up the membrane to react with the antibody to Strep A on the membrane and generate a color line in the test line region. The presence of this color line in the test line region indicates a positive result, while its absence indicates a negative result. To serve as a procedural control, a colored line will always appear in the control line region, indicating that proper volume of specimen has been added and membrane wicking has occurred.

Here's a breakdown of the acceptance criteria and study details for the Healgen Strep A Rapid Test Strip (Throat Swab):

1. Table of Acceptance Criteria and Reported Device Performance

• True negative sample: 0% (0/180)
• Moderate positive sample (1.8x10^4 CFU/mL): 100% (180/180)
• LoD sample (7.2x10^3 CFU/mL): 95.6% (172/180)
• Low negative sample (3.6x10^3 CFU/mL): 44.4% (80/180)
  (Concluded: No significant differences between users, sites, lots, and days; results are reproducible with good precision.) |
  | Limit of Detection (LoD) | The LoD should be clearly established for both clinical matrix and saline solution. | LoD in clinical matrix: 7.2x10^3 CFU/mL (equivalent to 360 bacteria on the swab) based on 95.2% detection (20/21) at 7.2x10^4 CFU/mL.
  LoD in saline solution: 7.2x10^3 CFU/mL (equivalent to 360 bacteria on the swab) based on 95.2% detection (20/21) at 7.2x10^3 CFU/mL. |
  | Interference | No false positive or false negative results with common interfering substances (blood, mucus, saliva, medications). | No false positive or false negative results observed with various interfering substances (blood, mucin, OTC mouthwashes, lozenges, throat sprays, cough syrups, active ingredients such as acetaminophen, ibuprofen, etc.) at tested concentrations (e.g., 20% vol/vol for liquids, 5mg/mL for solids). |
  | Analytical Specificity | No cross-reactivity with other common respiratory tract organisms (bacteria and viruses). | No cross-reactivity found for a comprehensive list of organisms (e.g., Arcanobacterium haemolyticum, Bordetella pertussis, Candida albicans, Enterococcus faecalis, Escherichia coli, various Streptococcus species, Adenovirus, Cytomegalovirus, HSV, etc.) at tested concentrations. |
  | Clinical Performance | | |
  | Clinical Sensitivity | Performance comparable to the legally marketed predicate device (Predicate: 95% CI (88-98%)). | Overall Clinical Sensitivity: 97.1% (200/206) with 95% CI (93.7-98.8%)
• Age 0-5: 97.4% (74/76)
• Age 5-21: 96.7% (119/123)
• Age 21+: 100% (7/7)
  (No statistical differences between age groups.) |
  | Clinical Specificity | Performance comparable to the legally marketed predicate device (Predicate: 98% CI (96-99%)). | Overall Clinical Specificity: 99.4% (161/162) with 95% CI (96.2-100.0%)
• Age 0-5: 98.1% (52/53)
• Age 5-21: 100% (88/88)
• Age 21+: 100% (21/21)
  (No statistical differences between age groups.) |
  | Consistency | Performance across different age groups should be consistent. | No statistical differences in performance between age groups. |

2. Sample size used for the test set and the data provenance

• Test Set Sample Size:
  • Clinical Study: 368 subjects (206 culture-positive, 162 culture-negative).
  • Analytical Precision: 180 determinations per sample type (60 determinations per site across 3 sites).
  • Analytical LoD: 21 results per dilution (7 operators x 3 lots).
  • Analytical Interference: Multiple tests across 3 lots for each interfering substance, for both positive and negative specimens.
  • Analytical Specificity (Cross-reactivity): Multiple tests across 3 lots for each organism by 3 professional users.
• Data Provenance:
  • The document does not explicitly state the country of origin for the clinical data.
  • The clinical study appears to be prospective/concurrent as it describes testing "subjects...exhibiting symptoms of pharyngitis by both the Healgen Strep A Rapid Test Strip (Throat Swab) and the culture studies." This implies collection of samples and testing using both methods at the time of study.
  • The analytical studies (precision, LoD, interference, specificity) were laboratory-based, performed internally or by designated personnel.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Clinical Study Ground Truth: The ground truth for the clinical study was established by bacterial culture. The document implies that the culture results were considered the reference standard. It does not explicitly state the number of experts or their qualifications involved in performing or interpreting these cultures. However, bacterial culture is a standard clinical laboratory method typically performed by trained medical technologists or microbiologists.
• Analytical Studies:
  • Precision/Reproducibility: 6 professional operators (2 at each of 3 sites) participated. Their specific qualifications are not detailed beyond "professional operators."
  • LoD: 7 operators performed the testing. Their specific qualifications are not detailed beyond "operators."
  • Interference: 3 laboratory assistants with relevant experience performed the test.
  • Analytical Specificity: 3 professional users performed the test.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

• The document does not describe an adjudication method (like 2+1 or 3+1) for establishing the ground truth in the clinical study. The reference standard (bacterial culture) appears to have been used directly.

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 Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done in the context of AI assistance. This device is a manual rapid diagnostic test strip, not an AI-assisted diagnostic tool. Therefore, the concept of human readers improving with AI assistance is not applicable here. The "operators" or "users" in the analytical studies are performing the manual test according to instructions.

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

• This question is not applicable as the device is a manual rapid test strip, not an algorithm or AI-driven system. It does not operate without human interaction.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

• The ground truth for the clinical study was bacterial culture, which is considered the gold standard for diagnosing Group A Streptococcus bacterial infection.
• For the analytical studies (LoD, interference, specificity), the ground truth was based on known concentrations of target analytes (S. pyogenes) or known presence/absence of interfering/cross-reacting organisms.

8. The sample size for the training set

• The document does not mention a training set in the context of machine learning or AI. This is a traditional rapid diagnostic test, not a learning algorithm. The "training" of the device refers to its manufacturing and validation process, not data-driven machine learning.

9. How the ground truth for the training set was established

• This question is not applicable as there is no mention or indication of a "training set" for an AI or machine learning model in this submission.

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The ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test is an in vitro, rapid, lateral flow test, also known as a lateral flow immunochromatographic assay, intended for the qualitative detection of Streptococus pneumoniae and Legionella pneumophila antigens in urine specimens with symptoms of pneumonia. The assay is intended to aid in diagnosis of S. pneumoniae and L. pneumophila serogroup 1 infections. The assay is further intended to aid in the diagnosis of S. pneumoniae infection of S. pneumoniae antigen in cerebrospinal fluid (CSF). Results from the ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test should be interpreted in conjunction with the patient's clinical evaluation and other diagnostic methods.

ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test is a rapid lateral flow test for qualitative detection of S. pneumoniae in human urine and CSF samples and L. pneumophila (primarily serogroup 1) antigens in human urine samples. The test is effective in presumptive diagnosis of pneumococcal pneumonia caused by S. pneumoniae or Legionella pneumonia (Legionnaires' disease) caused by L. pneumophila, in conjunction with culture and other methods. Correct and early treatment is vital for the prognosis of both diseases and therefore quick methods to confirm both diseases in the initial phase are very important in order to initiate the proper antibiotic treatment as soon as possible.

This document describes the validation of the ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test, an in vitro lateral flow immunochromatographic assay.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device are implicitly demonstrated by the reported sensitivities and specificities, and positive/negative percent agreements achieving certain levels across various studies (retrospective, prospective, analytical). While explicit numerical acceptance criteria are not stated in a dedicated table, the consistently high performance metrics across both S. pneumoniae and L. pneumophila detection in urine and CSF demonstrate the device's acceptable performance.

Here's a summary of the reported device performance, which serves as evidence of meeting implicit acceptance criteria:

Table 1: Summary of ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test Performance

2. Sample Sizes and Data Provenance

• Retrospective Study (Urine Samples):

  • S. pneumoniae: 100 culture-positive urine samples (48 from Sweden, 52 from Denmark, all from blood culture positive patients). 221 known negative urine samples.
  • L. pneumophila: 98 culture-confirmed urine samples (55 from Europe, 43 from the United States (US), these 43 were previously determined positive in a urinary antigen test). 240 known negative urine samples.
  • Data Provenance: Retrospective, samples from Europe (Sweden, Denmark) and the United States.

• Prospective Study (Urine Samples):

  • Total Samples: 306 freshly collected urine samples (with 92 having to be frozen before testing due to practicalities).
  • Data Provenance: Prospective, collected from two sites in Spain and Denmark. These were from "all comers" at risk of community-acquired pneumonia.

• Clinical Study (CSF Samples):

  • S. pneumoniae: 14 culture-positive CSF specimens (9 from US labs, 5 from European labs). 169 known negative CSF samples (113 from US labs, 56 from European labs).
  • Data Provenance: Retrospective/Clinical, samples from US and Europe.

• Spiked CSF Testing:

  • S. pneumoniae: 50 human CSF samples spiked at the LOD. 10 additional unspiked negative CSF samples.

• Analytical Studies (Cross-Reactivity, LOD, Interfering Substances, Strain Reactivity): Sample sizes vary by test and are described in the relevant sections (e.g., 143 samples for cross-reactivity with spiked bacteria/viruses in urine, 47 interfering agents tested).

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth. However, the ground truth for clinical studies (both retrospective and prospective) is defined as culture-confirmed results for S. pneumoniae and L. pneumophila infections, and "known negative" samples based on culture.

For the CSF study, patients were "suspected of meningitis," and the ground truth was also culture-confirmed S. pneumoniae.

Given that these are in vitro diagnostic tests, the "experts" in establishing ground truth would primarily be laboratory personnel performing culture confirmation, which is the gold standard for defining infection status.

4. Adjudication Method

The document does not describe any specific adjudication method (e.g., 2+1, 3+1 concensus) for establishing the ground truth for the test sets. The ground truth appears to be based on culture results, which typically do not require adjudication by multiple human interpreters in the same way imaging studies might.

For the reproducibility study, the reading and interpretation of the panels were performed visually by operators. Errors in reading (e.g., operator interpreted S. pneumoniae Band result as negative even though band was present) are mentioned, indicating potential for individual variability, but a formal adjudication process for disagreements is not explicitly stated beyond what happens when "invalid" results occur.

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

No multi-reader, multi-case (MRMC) comparative effectiveness study was performed or described. This device is an in vitro diagnostic (IVD) lateral flow assay, which is primarily a standalone test designed to provide a direct result, not an AI-assisted diagnostic tool for human readers. Therefore, there is no discussion of how human readers' performance might improve with AI assistance.

6. Standalone Performance

Yes, extensive standalone performance testing was done. The entire study described focuses on the "algorithm only" (i.e., the ImmuView test's intrinsic performance) without human-in-the-loop assistance for interpretation. The results in the tables for sensitivity, specificity, and agreement are all measures of the device's standalone performance against established ground truth (culture or comparator tests).

7. Type of Ground Truth Used

The primary type of ground truth used was culture confirmation for S. pneumoniae and L. pneumophila from urine and CSF samples.

• Urine Retrospective Study: Culture-positive urine samples (blood culture positive for S. pneumoniae, culture confirmed for L. pneumophila) and known negative (culture confirmed negative) urine samples.
• CSF Clinical Study: Culture-positive CSF specimens.
• Prospective Study: Comparison with other lateral flow urine antigen tests (Comparator) was used, implying the Comparator's results served as an indirect ground truth or reference in this specific study, although the retrospective studies relied on culture.
• Analytical Studies: Ground truth was based on known concentrations of purified antigens (pg/mL, ng/mL) or specific colony-forming units (CFU/mL) for LOD and strain reactivity, and known substances/organisms for cross-reactivity and interfering substances.

8. Sample Size for Training Set

The document does not explicitly mention a "training set" in the context of an algorithm or AI development. This product is a lateral flow immunoassay, a biochemical test, not a machine learning algorithm that undergoes a training phase. Therefore, the concept of a "training set" as it pertains to AI/ML models is not applicable here. The samples described were used for validation and performance evaluation.

9. How Ground Truth for Training Set Was Established

As explained under point 8, the product is a lateral flow immunoassay, not an AI/ML model. Therefore, there is no "training set" in the computational sense, and thus no ground truth establishment specific to a training set for an algorithm. All samples were used for validation and performance assessment, with ground truth established primarily by culture confirmation as described in point 7.

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The DiaSorin Molecular Simplexa™ GBS Direct assay is a real-time polymerase chain reaction (PCR) assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of Group B Streptococcus (GBS) nucleic acid from 18 to 24 hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Assay results can be used as an aid in determining the colonization status of antepartum women, but are not intended to diagnose or monitor treatment of a GBS infection.

The Simplexa™ GBS Direct assay does not provide susceptibility results. Culture isolates are needed to perform susceptibility testing as recommended for penicillin-allergic women.

Simplexa™ GBS Positive Control Pack

The Simplexa™ GBS Positive Control Pack is intended to be used as a control with the Simplexa™ GBS Direct kit. This control is not intended for use with other assays or systems.

The Simplexa™ GBS Direct assay system is a real-time PCR system that enables the direct amplification and qualitative detection of Group B Strep bacterial DNA from vaginal swabs enriched in Lim Broth for eighteen to twenty-four (18 to 24) hours that have not undergone a nucleic acid extraction. The system consists of the Simplexa™ GBS Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.

In the Simplexa™ GBS Direct assay, primers and fluorescent probes are used together to amplify Group B Streptococcus bacterial DNA and the Internal Control (DNA IC). The assay targets a conserved region of the cfb gene to identify Group B Streptococus in the specimen. The DNA IC is used to detect PCR failure and/or inhibition.

The provided document is a 510(k) Summary for a medical device called Simplexa™ GBS Direct. This document primarily focuses on the device's analytical and clinical performance for the qualitative detection of Group B Streptococcus (GBS) nucleic acid in Lim broth enrichments. It is not an AI/ML medical device in the typical sense that would involve human interpretation of images or other data assisted by an AI, but rather a PCR-based diagnostic assay.

Therefore, many of the requested items related to AI/ML device studies (e.g., number of experts, adjudication methods, MRMC studies, human reader improvement) are not applicable to this type of device. The study described focuses on the device's accuracy against a culture reference method and its analytical performance characteristics.

Here’s a breakdown of the information that can be extracted and which requested items are not applicable:

Acceptance Criteria and Study for Simplexa™ GBS Direct

The "acceptance criteria" for this device are implicitly tied to a demonstration of substantial equivalence to a predicate device, which includes showing acceptable clinical and analytical performance. The study described is the clinical performance evaluation.

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state pre-defined "acceptance criteria" in terms of specific sensitivity and specificity thresholds that were set before the study. Instead, it presents the clinical performance results. The implicit acceptance is based on these results being deemed sufficient for substantial equivalence.

2. Sample size used for the test set and the data provenance

• Test Set Sample Size: 432 clinical samples were used for the prospective clinical performance study.
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the applicant (DiaSorin Molecular LLC) is based in Cypress, California, USA, suggesting the data is likely from the United States.
  • Retrospective or Prospective: The clinical study was prospective. Samples were collected from pregnant women at 35-37 weeks of gestation, and Lim broth enrichments were made and tested fresh.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is not applicable as this is not an AI/ML device involving human interpretation of data where expert consensus is required for ground truth. The ground truth for the clinical performance study was established by a "GBS culture reference method." This refers to standard microbiological laboratory procedures for culturing and identifying GBS, not to human expert interpretation of an AI's output.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This is not applicable for the same reason as above. Discrepancies between the device and the culture reference method (ground truth) were investigated by testing with an "alternate FDA cleared NAAT" (Nucleic Acid Amplification Test). For example:

• 3/3 samples where Simplexa™ GBS Direct was negative and Culture was positive, were found negative by alternate NAAT.
• 11/13 samples where Simplexa™ GBS Direct was positive and Culture was negative, were found positive by alternate NAAT.
  This indicates a form of discrepant analysis, not human reader adjudication.

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

This is not applicable as this is not an AI/ML device where human readers interact with or are assisted by AI. The device is a standalone diagnostic assay.

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

Yes, the primary clinical performance study (Table 1) represents the standalone performance of the Simplexa™ GBS Direct assay against a culture reference method. The results provided (Sensitivity and Specificity) represent the algorithm's diagnostic accuracy.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical performance study was established by a "GBS culture reference method." This is a laboratory-based microbiological culture and identification process, considered the gold standard for GBS detection in this context.

8. The sample size for the training set

The document describes a 510(k) submission for a diagnostic assay, not an AI/ML model that undergoes a "training" phase with a large dataset. Therefore, the concept of a "training set" for an AI model is not directly applicable here. The device's PCR primers and probes are designed based on biological knowledge (targeting the cfb gene) rather than being learned from data. Extensive analytical studies (LoD, reactivity, cross-reactivity, interference, inhibition) are done during development and validation, but this isn't analogous to training an AI model.

9. How the ground truth for the training set was established

As the concept of a "training set" in the context of AI/ML is not applicable to this diagnostic assay, this question is also not applicable. The underlying assays are developed based on known biological targets and validated through a series of analytical and clinical studies.

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The Panther Fusion GBS assay is an automated qualitative in vitro diagnostic test utilizing real-time PCR for detection of Group B Streptococcus DNA from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18-24 hours incubation.

This test is performed on the Hologic Panther Fusion system and is intended to aid in determining the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The Panther Fusion GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

The Panther Fusion GBS assay involves the following steps: Sample lysis, nucleic acid capture and elution, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.

Sample Collection and Enrichment: After collecting and transporting a swab sample to the laboratory, the swab is placed in Lim Broth or Carrot Broth for 18 to 24 hours of enrichment. Prior to testing on the Panther Fusion system, enriched specimens are then transferred to a tube containing specimen transport media (STM) that lyses the cells, releases target nucleic acid and protects them from degradation during storage.

Nucleic Acid Capture and Elution: Specimens are then first incubated in an alkaline reagent (FER-X) to enable cell lysis. The Internal Control (IC-X) is added to each test specimen and controls via the working Panther Fusion capture Reagent-X (wFCR-X). The IC-X monitors specimen processing, amplification and detection. Magnetic particles with covalently bound oligonucleotides, contained in Panther Fusion capture Reagent-X (FCR-X), mediate the nucleic acid capture by hybridizing to total nucleic acid in the test specimen. The capture nucleic acids are then separated from residual specimen matrix in a magnetic field by a series of wash steps with a mild detergent. The captured nucleic acid is then eluted from the magnetic particles with a reagent of low ionic strength (Panther Fusion Elution Buffer).

Elution transfer and PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion Reaction tube already containing oil and reconstituted mastermix. PCRbased target amplification subsequently occurs with target-specific forward and reverse primers, generating a fluorescence signal. The Panther Fusion GBS Software computes a cycle threshold result (Ct) to qualitatively determine the presence of the analyte targets and corresponding fluorescent channels used in the Panther Fusion GBS Assay are summarized in the Table 1 below.

The document describes the Panther Fusion GBS Assay, an automated qualitative in vitro diagnostic test for the detection of Group B Streptococcus DNA. The acceptance criteria and the study proving the device meets these criteria are outlined in sections G, H, and I of the 510(k) summary.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance metrics aimed for during the studies. While explicit "acceptance criteria" are not listed in a dedicated table, the studies aim to demonstrate high sensitivity and specificity as is standard for such diagnostic tests.

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

• Test Set Sample Size: A total of 947 clinical leftover samples.
• Data Provenance: The study was conducted from January 2018 to March 2018 at three geographically distinct sites in the United States. The data was obtained from prospective collection of leftover enriched culture samples (Lim broth and Carrot broth) from vaginal/rectal specimens from antepartum women during routine GBS screening. This is considered prospective for the purpose of the study as the samples were collected and then tested by the investigational device and reference method.

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth. However, the ground truth was established by the reference culture method following CDC recommendations. This implies that the laboratory personnel performing and interpreting these cultures are qualified, but specific details are not provided in this summary.

4. Adjudication Method for the Test Set

The document states that results obtained using the Panther Fusion GBS Assay were compared to those obtained with the reference method. It doesn't describe a specific adjudication method (e.g., 2+1, 3+1) if there were discrepancies between the investigational device and the reference method. For the 16 false positives in Lim Broth, it notes that 14 (87.5%) were positive on the Becton Dickinson BD MAX GBS Assay, suggesting some form of secondary verification for discordant results, but not a formal adjudication process involving multiple human readers as might be found in an imaging study.

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging devices where human interpretation is a key component, comparing human reader performance with and without AI assistance. The Panther Fusion GBS Assay is an in vitro diagnostic (IVD) device, where the result is determined by the instrument/assay, not by human interpretation of complex images.

6. Standalone (Algorithm Only) Performance

Yes, this study essentially represents standalone performance of the Panther Fusion GBS Assay. The device is an automated qualitative in vitro diagnostic test. Its performance (sensitivity, specificity) is measured directly against the reference standard without human 'in-the-loop' assistance from the device output for diagnosis. The output (positive/negative) is the direct result of the algorithm.

7. Type of Ground Truth Used

The ground truth used was the reference culture method following CDC recommendations. This is a laboratory-based, established gold standard for GBS colonization status.

8. Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This 510(k) summary focuses on the validation of the finished device (the "test set" in the context of typical AI/ML development), not the development or training process of the assay components. For molecular diagnostic assays, while there's an underlying 'algorithm' (primer design, probe chemistry, cutoff values), it's not typically an AI/ML algorithm that learns from a dataset in the way a deep learning model would. Therefore, a distinct "training set" in the AI/ML sense is not described.

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

Since information about a dedicated "training set" in the AI/ML sense is not provided, the method for establishing its ground truth is also not described. For an IVD assay like this, the "training" involved designing and optimizing the molecular components (primers, probes) and establishing the cut-off values for detection based on analytical studies and perhaps smaller internal development studies. The ground truth for such optimization would similarly rely on controlled lab experiments and reference methods, but is not detailed here.

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The NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from 18-24 hour Lim broth enrichments of vaginal/rectal swabs from pregnant women. The test incorporates automated DNA extraction to isolate the target nucleic acid from the specimen and real-time polymerase chain reaction (PCR) to detect an 88 bp region of the pcsB gene sequence in the Streptococcus agalactiae chromosome. Results from the NeuMoDx™ GBS Assay can be used as an aid in determining colonization status in antepartum women.

The NeuMoDx™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

The NeuMoDx™ GBS Assay (Subject Device) as implemented on the NeuMoDx™ 288 Molecular System is an automated, qualitative, in vitro diagnostic test for the detection of group B Streptococcus (GBS), also known as Streptococcus agalactiae from vaginal/rectal swabs collected from pregnant women at 35 - 37 weeks of gestation and enriched in a commercially available Lim broth medium. An aliquot of an overnight Lim broth culture added to the NeuMoDx™ GBS Assay is used for the testing. All further specimen handling is automated.

The GBS Assay test strip, in combination with required NeuMoDx buffers, extraction reagents, wash and release solutions, as well as the microfluidic cartridge (non-active,) and the fully automated NeuMoDx™ 288 Molecular System (a real time nucleic acid amplification system), utilizes real-time polymerase chain reaction (PCR) for the amplification of GBS DNA and fluorogenic target-specific TaqMan® probes for the detection of the amplified GBS DNA. General use components and the System are packaged and provided separately by NeuMoDx.

After the test is processed, a determination of the presence/absence of GBS DNA in the specimen is automatically made based on the amplification status of GBS and the Sample Process Control using preestablished decision criteria. The test results will be reported as Negative, Positive, Indeterminate or Unresolved based on the amplification status of the target and sample processing control. Results are reported based on the decision algorithm noted in Table 1.

The provided text describes the NeuMoDx™ GBS Assay, an in vitro diagnostic test for Group B Streptococcus (GBS), and its performance data to establish substantial equivalence to a predicate device. This is a molecular diagnostic test, not an AI/imaging device, so many of the requested elements pertaining to AI and imaging studies (e.g., number of experts, adjudication methods, MRMC studies, effect size of human readers improving with AI) are not applicable. However, I will detail the available information relevant to acceptance criteria and performance as presented in the document.

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

Acceptance Criteria and Reported Device Performance

Note: For molecular diagnostic devices, acceptance criteria are typically defined by performance characteristics such as sensitivity, specificity, Limit of Detection (LoD), inclusivity, and exclusivity. The document doesn't explicitly state "acceptance criteria" for clinical performance in a table, but it presents the results of a comparative study against a reference method, which implicitly serves as the standard for acceptance. For analytical performance, criteria are demonstrated through detailed studies (e.g., 100% detection rate at LoD).

Clinical Performance:

Analytical Performance:

Study Details:

1. A table of acceptance criteria and the reported device performance: Done in the table above.

2. Sample size used for the test set and the data provenance:

   • Clinical Performance Test Set: 1193 specimens with complete, valid, and compliant results were included in the study.
   • Data Provenance: The study was a "prospective clinical method comparison study" conducted at "three (3) geographically diverse laboratory locations." The data were collected from pregnant women in the US (implied by FDA submission to US authority). Specimens were collected for "routine standard of care screening purposes."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This is a molecular diagnostic test. The "ground truth" for clinical performance was established by "conventional culture methods recommended by the Center for Disease Control (CDC) to identify GBS from subcultures of enriched Lim broth." This involves laboratory procedures and standard microbiological protocols rather than expert human interpretation of images. Therefore, the concept of "experts" as in radiologists for imaging is not directly applicable here.
   • The document implies that "qualified laboratory personnel" were involved in processing samples and establishing the ground truth via culture.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • Not applicable as this is a molecular diagnostic test where the ground truth is established by a predefined laboratory culture method, not human adjudication of ambiguous cases. Discordant results between the device and the reference culture method would be analyzed, but not "adjudicated" in the sense of multiple human readers coming to a consensus.

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:

   • Not applicable. This is a standalone diagnostic device (an automated in vitro diagnostic test) and not an AI-assisted imaging device. There are no "human readers" in the context of interpreting the primary test output or "AI assistance" provided to human readers.

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

   • Yes, the performance characteristics (sensitivity, specificity, LoD, inclusivity, exclusivity, etc.) described for the NeuMoDx™ GBS Assay are "standalone" performance, meaning they relate directly to the output of the automated system. The device automatically determines "Positive, Negative, Indeterminate or Unresolved" results based on pre-established decision criteria (Table 1).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Clinical Performance Ground Truth: "Conventional culture methods recommended by the Center for Disease Control (CDC) to identify GBS from subcultures of enriched Lim broth" (specifically the 2010 CDC guidelines). This is a laboratory-based reference method, considered the "gold standard" for GBS colonization status.
   • Analytical Performance Ground Truth: Established through prepared spiked samples with known concentrations (CFU/mL) of GBS and other organisms.

8. The sample size for the training set:

   • The document describes a 510(k) submission for substantial equivalence, not a de novo premarket submission that typically details a separate training set for a machine learning algorithm.
   • For a molecular diagnostic test like this, "training" often refers to the internal development and optimization of the assay parameters using characterized samples, rather than a distinct "training set" in the machine learning sense. The document does not specify a formal "training set" size.

9. How the ground truth for the training set was established:

   • As noted above, a formal machine learning "training set" is not explicitly defined. Assay development and optimization would have relied on internally validated methods and known concentrations of GBS and non-GBS organisms to establish parameters such as Ct thresholds and call criteria (Table 1). This process implicitly establishes the "ground truth" for the test's internal logic.

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The Solana® GBS assay is a qualitative in vitro diagnostic test for detection of Group B Streptococcus in either LIM or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation. The Solana® GBS Assay utilizes helicase-dependent amplification (HDA) of the Thiolase (atoB) gene sequence. The Solana® GBS Assay is intended for use only with the Solana® Instrument.

The Solana® GBS Assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

The Solana GBS Assay amplifies and detects GBS DNA isolated from enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation.

The assay consists of two (2) major steps: 1) specimen preparation, and 2) amplification and detection of target sequence specific to GBS using isothermal Helicase-Dependent Amplification (HDA) in the presence of target-specific fluorescence probe.

Patient specimen is transferred to a Process Buffer tube, subjected to heat treatment at 95 ± 2°C for 5 minutes and mixed. The processed sample is transferred to a Reaction Tube and mixed. The Reaction Tube contains lyophilized HDA reagents, dNTPs, primers and probes. Once rehydrated with the processed sample, the Reaction Tube is placed in Solana for amplification and detection of specific target sequences. In Solana, the GBS target sequence is amplified by GBS specific primers and detected by a GBS specific fluorescence probe included in the Reaction Tube. A competitive process control (PRC) is included in the Process Tube to monitor sample processing, for the presence of inhibitory substances in clinical samples, reagent or device failure. The PRC target is amplified by specific primers and detected by a PRC specific fluorescence probe.

The target and PRC probes are labeled with a quencher on one end and a fluorophore (FAM or ROX, respectively) on the other end. In addition, the target and PRC probes carry a ribonucleic acid. Upon annealing to GBS or PRC amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. Solana measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana will then report the test results to the user on its display screen, and it can print out the results using the attached printer.

Here's a breakdown of the acceptance criteria and study details for the Solana GBS Assay, based on the provided text:

Acceptance Criteria and Device Performance

The provided document defines the analytical and clinical performance characteristics of the Solana GBS Assay. While explicit "acceptance criteria" are not presented as a direct table of pass/fail thresholds before the study, the "Comparison with predicate" section (Table 4) and the "Clinical studies" section (Table 13) present the performance of the predicate device and the new device, respectively. The implication is that the new device's performance needs to be comparable or superior to the predicate for substantial equivalence.

Here's a table summarizing the reported device performance, with the predicate performance included for comparison where available:

Table: Acceptance Criteria (Implied) and Reported Device Performance

Study Details

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

   • Test Set Sample Size: 753 specimens were collected for the clinical study. One specimen was invalid, resulting in 752 specimens analyzed.
     • 403 specimens used LIM broth.
     • 350 specimens used Carrot broth.
   • Data Provenance: Prospective study. Specimens were collected from four distinct geographical sites across the United States.

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

   • The document states that specimens were tested by "bacterial culture" to establish ground truth.
   • The specific number of experts and their qualifications (e.g., radiologist with 10 years of experience) are not specified in the provided text. The ground truth for this in vitro diagnostic device is standard laboratory bacterial culture, which is typically considered the gold standard for GBS detection. Expert adjudication as would be seen in an imaging study is not applicable here.

3. Adjudication Method for the Test Set:

   • Not applicable in the context of this in vitro diagnostic bacterial culture-based study. The ground truth was established by bacterial culture. For samples where the Solana GBS Assay was positive but bacterial culture was negative (False Positives), these were further tested by "an additional FDA-cleared molecular test" (19 of 23 instances were confirmed positive by this molecular test). This serves as a form of adjudication or further investigation for discordant results.

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

   • No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for AI-assisted diagnostic tools that involve human interpretation (e.g., radiologists reading images with AI-aid). The Solana GBS Assay is an automated in vitro diagnostic device, not an AI assistance tool for human readers.

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

   • Yes, the primary performance evaluation (clinical study) is a standalone performance assessment of the Solana GBS Assay compared to bacterial culture. The device "measures and interprets the fluorescent signal, using on-board method-specific algorithms" and "then reports the test results to the user on its display screen." There is no human interpretation component in the device's determination of positive/negative results.

6. The Type of Ground Truth Used:

   • Bacterial Culture was used as the primary ground truth for clinical sensitivity and specificity.
   • For discordant results (Solana Positive/Culture Negative), an additional FDA-cleared molecular test was used to further confirm positive status.

7. The Sample Size for the Training Set:

   • The document does not explicitly state the sample size used for the training set. The performance characteristics listed (LOD, reproducibility, analytical specificity, clinical performance) are derived from the validation studies of the device. For in vitro diagnostic molecular assays like this, the "training" (development) of the assay's parameters (e.g., primer design, probe chemistry, HDA conditions, detection algorithms) is an internal process, but the specific datasets used for that initial development are not typically disclosed in a 510(k) summary for these types of devices. The clinical and analytical studies described serve as the test set for regulatory submission.

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

   • As the training set size is not explicitly mentioned, the method for establishing its ground truth is also not described in the document. However, for developing such assays, ground truth for training would typically involve well-characterized bacterial cultures (known positive and negative strains at various concentrations) and potentially clinical samples with established culture results, similar to how the ground truth for the validation test set was established.

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The Sofia Strep A+ FIA detects Group A Streptococcal antigens from patients with signs and symptoms of pharyngitis, such as sore throat. All negative test results should be confirmed by either bacterial culture or an FDA-cleared molecular assay because negative results do not prection and should not be used as the sole basis for treatment. The test is intended for professional and laboratory use as an aid in the diagnosis of Group A Streptococcal infection.

The Sofia Strep A+ FIA may be used with Sofia or Sofia 2.

The Sofia Strep A+ FIA involves the extraction of the antigenic components of the Group A Streptococcus (GAS) bacteria. The patient's Swab sample is placed in the Reagent Tube containing the Reagent Solution, during which time the bacterial antigens are extracted, making them more accessible to the specific antibodies. An aliquot of the extracted sample is dispensed into the Test Cassette sample well. From the sample well, the sample migrates through a test strip containing various unique chemical environments. If Group A Streptococcal antigens are present, they will be bound by antibodies coupled to fluorescent microparticles that migrate through the test strip. The fluorescent microparticles containing bound antigen will be captured by antibodies at a defined location on the test strip where they are detected by Sofia or Sofia 2. If antigens are not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia or Sofia 2.

Depending upon the user's choice, the Test Cassette is either placed inside of Sofia or Sofia 2 for automatically timed development (WALK AWAY Mode) or placed on the counter or bench top for a manually timed development and then placed into Sofia 2 to be scanned (READ NOW Mode).

Sofia or Sofia 2 will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. Test results will be displayed (Positive, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected.

Sofia 2 is a microprocessor-controlled device about the size of a desk top telephone and weighs less than 3 pounds. Sofia 2 uses a fluorescent tag that is illuminated by an Ultraviolet (UV) light source to generate specific results.

The Sofiea Strep A+ FIA is a device intended to detect Group A Streptococcal antigens from throat swabs of patients with signs and symptoms of pharyngitis. All negative test results must be confirmed by either bacterial culture or an FDA-cleared molecular assay.

As this is a 510(k) submission, the device does not have explicit acceptance criteria mentioned, but rather demonstrates substantial equivalence to a predicate device. The performance data section of the document describes several studies undertaken to document the performance characteristics of the Sofia 2 and the Sofia Strep A+ assay, as well as to compare performance between Sofia and Sofia 2.

Here's the information about the studies presented:

1. Table of Acceptance Criteria and Reported Device Performance:

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

The document does not explicitly state the sample sizes used for each test set in these studies, nor does it specify the country of origin of the data or whether the studies were retrospective or prospective. It refers to "a panel of clinical samples" for the Method Comparison study and "a panel of test samples" for the Reproducibility study.

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

This information is not provided in the document. The nature of the device (antigen detection) likely implies a microbiological gold standard (e.g., bacterial culture), rather than expert consensus on interpretation.

4. Adjudication Method for the Test Set:

This information is not provided in the document.

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

A MRMC comparative effectiveness study involving human readers and AI assistance is not mentioned. The studies focus on the performance of the device itself and its equivalence to a predicate device.

6. Standalone Performance Study:

Yes, standalone performance studies were done. All the studies listed in the "Performance Data" section (LoD, Precision, Assay development time, Method Comparison, Reproducibility) assess the performance of the Sofia Strep A+ FIA on Sofia 2 (and its comparison to Sofia) as a standalone algorithm/device without explicit human-in-the-loop performance measurement.

7. Type of Ground Truth Used:

The document mentions that negative test results "should be confirmed by either bacterial culture or an FDA-cleared molecular assay." This implies that bacterial culture or an FDA-cleared molecular assay would serve as the ground truth for determining the presence or absence of Group A Streptococcal infection in the clinical sample studies.

8. Sample Size for the Training Set:

The document does not provide information about a specific training set or its sample size. This is common for this type of in vitro diagnostic device, where performance is evaluated against known concentrations or clinical samples with confirmed status, rather than training a machine learning model in the conventional sense.

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

As there is no mention of a traditional training set for a machine learning model, the method for establishing ground truth for a training set is not applicable or described in this document. The "ground truth" for the performance evaluation studies would be established using validated methods like bacterial culture or FDA-cleared molecular assays, as mentioned in the indications for use.

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The GenePOC™ GBS LB assay performed on the revogene™ instrument is a qualitative in vitro diagnostic test designed to detect Group B Streptococus (GBS) DNA from 18-24 hour LIM broth enrichments of vaginal/rectal specimen swabs obtained from pregnant women. The GenePOC GBS LB assay utilizes automated sample processing and real-time polymerase chain reaction (PCR) to detect a cfb gene sequence specific to the Streptococcus agalactiae genome.

The GenePOC GBS LB assay is indicated for the identification of antepartum GBS colonization and does not provide susceptibility results. It is not intended to diagnose or monitor treatment of GBS infection. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

The GenePOC GBS LB assay is a single-use test for the qualitative detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens using realtime Polymerase Chain Reaction (PCR) technology with fluorogenic detection of the amplified DNA. The GenePOC GBS LB assay utilizes the GBS LB microfluidic cartridge for the simultaneous detection of the target GBS DNA and the internal process control (PrC) DNA (to monitor processing, amplification, and the absence of reaction inhibitors). The GenePOC GBS LB assay is an automated assay performed on the revogene™ including sample processing.

The GenePOC Group B Strep (GBS) LB is composed of a GBS specific disposable microfluidic cartridges, Sample Buffer Tube (SBT) and Disposable Transfer Tool (DTT). These components are used to lyse and dilute the sample, amplify, and detect GBS nucleic acid from vaginal/rectal swabs following LIM broth enrichment. User intervention is required for sample preparation, discharging the LIM broth enriched sample into the SBT, transferring the sample into the cartridge and loading/unloading the cartridge into the revogene instrument. Once the sample is added into the cartridge, the process is then fully automated.

Each GenePOC GBS LB Test kit contains 24 individual pouches, and each pouch has components for 1 test including 1 cartridge, 1 SBT, and 1 DTT. The GBS LB Test is run on the revogene instrument which can process from one up to a maximum of 8 samples simultaneously in the same run. On completion of a run, the results are interpolated by the revogene™ from measured fluorescent signals and embedded calculation algorithms. For the GBS application, two spectral signals are processed: GBS target and Internal Process Control. The output results include positive, negative, indeterminate, and unresolved. On completion of a run, the user removes the used cartridges and disposes of them in normal biological waste. Results may be viewed, printed, transferred, and/or stored by the user.

The provided document describes the GenePOC GBS LB assay, a qualitative in vitro diagnostic test for detecting Group B Streptococcus (GBS) DNA. Here's a breakdown of the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" in a separate table. However, it presents performance metrics that serve as the basis for FDA's substantial equivalence determination. We can infer the "acceptance criteria" from the reported performance results, particularly from the overall clinical performance.

2. Sample size used for the test set and the data provenance:

• Clinical Test Set Sample Size: A total of 771 compliant specimen results were used to determine the clinical performance.
  • 170 GBS positive samples
  • 601 GBS negative samples
• Data Provenance: The data was obtained from a prospective multicenter trial conducted at 4 geographically diverse clinical trial sites, consisting of two Canadian and two US clinical sites.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

The document describes the ground truth for the clinical study as a "composite reference method consisting of LIM Broth enrichment of the vaginal/rectal swab followed by a subculture on blood agar plate and biochemical identification of GBS." This method is a laboratory-based standard and does not involve a subjective assessment by a human expert (like a radiologist reviewing an image). Therefore, the concept of "number of experts used to establish ground truth" with specific qualifications is not applicable in this context.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Since the ground truth is established by a laboratory-based composite reference method (culture and biochemical identification), no human expert adjudication method (like 2+1 or 3+1 for imaging studies) was performed or needed for the ground truth establishment. The results are based on objective laboratory testing.

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 MRMC comparative effectiveness study was done. This device is a standalone in vitro diagnostic (IVD) assay designed for direct detection of GBS DNA, not an AI-assisted imaging analysis tool. Therefore, the concept of human readers improving with AI assistance is not applicable.

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

Yes, a standalone performance evaluation was done. The entire performance characterization (analytical and clinical) presented in the document assesses the GenePOC GBS LB assay as a standalone device without human-in-the-loop performance modification. The revogene™ instrument processes the sample and provides the result based on its embedded calculation algorithms. User intervention is limited to sample preparation and loading/unloading.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth used for the clinical study was a laboratory-based composite reference method, specifically:

• LIM Broth enrichment of the vaginal/rectal swab
• Followed by subculture on blood agar plate
• And biochemical identification of GBS

8. The sample size for the training set:

The document does not specify a separate training set size. As this is an in vitro diagnostic device for molecular detection, the "training" aspect is typically related to the development and optimization of the assay itself (e.g., primer design, probe chemistry, algorithmic thresholds) rather than training a machine learning model on a distinct dataset with labeled ground truth in the same way an AI imaging algorithm would be trained. The performance data presented refers to the testing of the developed and finalized assay.

9. How the ground truth for the training set was established:

Since a distinct "training set" with ground truth (in the AI/ML sense) is not described, the question of how its ground truth was established is not directly applicable. However, the development of the assay itself would have relied on well-characterized GBS strains and clinical samples with known GBS status, likely determined through standard microbiological culture and identification methods (similar to the clinical ground truth). This iterative development-and-testing process leads to the final assay's performance characteristics.

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