Search Results

The Simplexa C. auris Direct is a real-time polymerase chain reaction (RT-PCR) assay intended for use on the LIAISON MDX instrument for the direct in vitro qualitative detection of Candida auris DNA from a composite swab of bilateral axilla/groin from patients suspected of C. auris colonization.

The test is intended to aid in the prevention and control of C. auris infection in healthcare settings by detecting C. auris from colonized patients.

Positive results indicate that the patient is colonized with C. auris. A positive result cannot rule out co-colonization with other pathogens. A negative result does not preclude C. auris colonization or infection and should not be used as the sole basis for treatment or other patient management decisions. Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory information available to the clinician evaluating the patient. The test is not intended to diagnose or monitor treatment for C. auris infection. Concomitant cultures are necessary to recover organisms for epidemiological typing or for antimicrobial susceptibility testing.

The Simplexa C. auris RT-PCR system is intended for the amplification and qualitative detection of nucleic acid from Candida auris in composite bilateral axilla/groin swab specimens and consists of the following:

1. The Simplexa C. auris Direct is the RT-PCR assay kit that contains all the reagents for the amplification reaction, including the primers and fluorescent probes for the detection of nucleic acid from Candida auris. The primers and fluorescent probes amplifies the C. auris DNA and Internal Control DNA. In addition, the kit comes with a barcode card, which contains assay specific parameters and lot information.
2. The Simplexa C. auris Positive Control Pack is the separately packaged external positive quality control kit for use with the Simplexa C. auris Direct assay.
3. The Simplexa C. auris Sample Prep Kit is the enzymatic buffer solution to receive the sample solution (bilateral axilla/groin swab in Amies transport media) from the patient.

The Simplexa C. auris RT-PCR system is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software), the RT-PCR thermocycler that amplifies the nucleic acid from biological specimens and uses real-time fluorescence detection to identify targets, and the Direct Amplification Disc (DAD), which is the accessory containing the input sample wells for use on the LIAISON MDX. The instrument and accessory were previously cleared under K102314 and K120413. The instrument is controlled by an external laptop running the software. The DAD consumable is compartmentalized into eight (8) separate wedges and can process up to eight (8) separate specimens or controls on each disc. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow as well as a reaction/detection chamber.

The provided document describes the analytical and clinical performance of the Simplexa C. auris Direct RT-PCR system. However, it does not explicitly state pre-defined acceptance criteria in a table format that the device needed to meet. Instead, it presents the results of various studies (precision, analytical specificity, limit of detection, inclusivity, clinical performance) and then often concludes whether these results are "acceptable."

For example, for precision, it states: "For the multisite study, the test device showed ≥ 98.9% agreement of the qualitative result and ≤ 8.2% CV for each of the variance components, which is acceptable." This implies that ≥ 98.9% agreement and ≤ 8.2% CV were the internal acceptance criteria for precision.

Similarly, for the clinical performance, the reported Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values are presented as the device's performance, but explicit pre-defined minimum thresholds for PPA and NPA as acceptance criteria are not given. They are implied by the fact that the De Novo request was granted.

Given this, I will infer the acceptance criteria from the reported "acceptable" results where possible and present the device performance based on the clinical study results.

Here's the information requested based on the provided text:

1. Table of Acceptance Criteria (Inferred) and Reported Device Performance

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

Test Set (Clinical Study):

• Total Evaluable Clinical Specimens (Combined Cohort): 2,020 specimens.
  • Prospective Cohort: 1,930 evaluable specimens.
  • Retrospective/Enriched Cohort: 90 evaluable specimens (11 retrospective pre-selected C. auris positive + 202 enriched specimens, of which 90 were evaluable).
• Data Provenance:
  • Geographic Locations: Six study sites across four geographically diverse locations within the United States and one in Italy.
  • Type of Data:
    • Prospective: Prospectively collected specimens (axilla/groin swabs) from patients suspected of C. auris colonization. Tested either fresh or frozen. Collected from April to July 2023.
    • Retrospective/Enriched: Leftover, de-identified composite bilateral axilla/groin swabs. Included 11 pre-selected C. auris positive retrospective specimens and 202 enriched specimens (identified as positive by a laboratory-verified RT-PCR test, then blinded and tested).

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

The document states that the ground truth for the clinical study was established by a reference method consisting of "standard of care (SOC) culture followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for identification." These are laboratory methods, not human expert interpretation of images or other subjective data.

For discordant analysis, "Bi-directional sequencing (BDS) assays were performed when the candidate assay results differed from the comparator method." Again, this is a laboratory method.

The document does not specify human experts or their qualifications for establishing the ground truth for the test set.

4. Adjudication Method for the Test Set

The primary ground truth was established by the reference method (SOC culture + MALDI-TOF MS). For discordant results between the candidate assay and the reference method, Bi-directional Sequencing (BDS) was performed. However, "The results from discordant analysis were not used to alter the original performance but are provided in footnotes to the performance tables."

Therefore, there wasn't a human-based adjudication method in the traditional sense (e.g., 2+1 or 3+1 radiologists making a consensus decision). The reference method and supplemental BDS purely relied on objective laboratory techniques.

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

No, this document describes a diagnostic device (RT-PCR assay) for detecting nucleic acids of Candida auris. It is not an AI-assisted diagnostic imaging device for which an MRMC study comparing human readers with and without AI assistance would be relevant. The study focuses solely on the direct performance of the molecular diagnostic test against a laboratory reference method.

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

Yes, the entire clinical evaluation (Sections VI.C) and analytical performance studies (Sections VI.A) describe the standalone performance of the Simplexa C. auris Direct RT-PCR system. This device is an automated molecular diagnostic test and does not involve human interpretation in a loop, except for the user performing the test steps according to the instructions. The results (Ct values, positive/negative calls) are generated directly by the instrument platform (LIAISON MDX).

7. The Type of Ground Truth Used

The primary ground truth used for the clinical study was Standard of Care (SOC) culture followed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) for identification. For discordant results, Bi-directional Sequencing (BDS) was used as a supplemental ground truth, though these results did not alter the original performance metrics. This is a form of laboratory reference standard.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm that would undergo a distinct training phase. This document describes a molecular diagnostic assay, not a machine learning model. The development of such assays involves establishing parameters (like fluorescence and Ct thresholds) using initial data, which could be considered an internal "calibration" or "development" process rather than a "training set" in the AI sense.

It states: "The fluorescence and Ct thresholds for C. auris and Internal Control were established using 717 sample runs of No Template Control (NTC), Limit of Detection (LoD), Microbial Inhibition, Interference and Limiting Dilution samples. The established thresholds were then confirmed using an independent data set comprising 2,924 sample runs..." These 717 runs could be considered the data used for establishing (or "training") the assay's interpretive parameters.

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

Given that this is a molecular diagnostic assay and not an AI/ML system, the concept of "ground truth for a training set" as it pertains to labeled examples for model learning is not directly applicable.

Instead, the "establishment" of the assay's operating parameters (like Ct thresholds) was based on experimental data where the expected outcome (presence/absence of C. auris, inhibition, etc.) was known by design:

• No Template Control (NTC): Expected negative.
• Limit of Detection (LoD): Contrived samples with known concentrations of C. auris.
• Microbial Inhibition/Interference: Samples with C. auris at known concentrations (e.g., 3x LoD) spiked with other substances/organisms.
• Limiting Dilution: Samples serially diluted to determine the lowest detectable concentration.

These experiments provide the "ground truth" for setting the assay's interpretive parameters and analytical performance characteristics. The known concentrations, presence/absence of target nucleic acids, and presence/absence of interfering substances served as the factual basis for defining how the device should interpret its signals (e.g., Ct value thresholds for positivity).

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ COVID-19 & Flu A/B Direct is a real-time RT-PCR assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection and differentiation of nucleic acid from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B virus in nasopharyngeal swabs (NPS) from individuals with signs and symptoms of respiratory tract infection.

The Simplexa™ COVID-19 & Flu A/B Direct assay is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A and influenza B infection.

Negative results do not preclude SARS-CoV-2, influenza B infection and should not be used as the sole basis for patient management decisions. Positive results do not rule out coinfection with other organisms. Results should be combined with clinical observations, patient history, and epidemiological information.

The Simplexa™ COVID-19 & Flu A/B Direct assay is intended for use by qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures.

The Simplexa™ COVID-19 & Flu A/B Direct assay system is a real-time RT-PCR system that enables the direct amplification, detection and differentiation of SARS-CoV-2 RNA, human influenza A (Flu A) virus RNA and human influenza B (Flu B) virus RNA from unprocessed nasopharyngeal swabs (NPS) that have not undergone nucleic acid extraction. The system consists of the Simplexa™ COVID-19 & Flu A/B Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc and associated accessories.

In the Simplexa™ COVID-19 & Flu A/B Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify SARS-CoV-2, Flu A, Flu B and internal control RNA targets. For COVID-19 detection, the assay targets two different regions specific to the SARS-CoV-2 genome; the S gene which encodes the spike glycoprotein and the ORF1ab region which encodes wellconserved non-structural proteins and therefore is less susceptible to recombination. For Flu detection the assay targets conserved regions of influenza A viruses (matrix gene) and influenza B viruses (matrix gene). The assay provides three results; COVID-19 (ORF1ab and/or S gene detection), influenza A viruses (matrix gene detection) and influenza B viruses (matrix gene detection). An RNA internal control is used to detect RT-PCR failure and/or inhibition.

This document describes the analytical and clinical performance studies for the DiaSorin Molecular Simplexa™ COVID-19 & Flu A/B Direct assay.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the clinical performance are generally indicated by the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with their corresponding 95% Confidence Intervals (CI).

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

• Prospective Samples: Over 1400 total specimens (nasopharyngeal swabs (NPS)) were collected between August 2021 and March 2022 from six geographically diverse clinical sites within the United States. The exact number of prospective samples used for each target in the agreement analysis can be inferred from the TP/(TP+FN) and TN/(TN+FP) values in Table 2:
  • Influenza A: 1168 (62 positive, 1106 negative, plus 5 and 2 discrepant)
  • Influenza B: 1165 (all negative)
  • SARS-CoV-2: 496 (68 positive, 428 negative, plus 1 and 11 discrepant)
• Retrospective Samples: 82 positive influenza B specimens and 62 negative specimens were used. These were blinded and randomized for the study. The exact number of retrospective samples used for each target in the agreement analysis can be inferred from the TP/(TP+FN) and TN/(TN+FP) values in Table 3:
  • Influenza A: 258 (82 positive, 176 negative)
  • Influenza B: 258 (114 positive, 144 negative)
  • SARS-CoV-2: 252 (all negative)

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

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 for the test set.

4. Adjudication Method for the Test Set

• SARS-CoV-2: For SARS-CoV-2, a composite reference method (CRM) was used. This involved three COVID-19 Emergency Use Authorized (EUA) NAAT assays. The adjudication method was:
  • "Detected" CRM if two out of three EUA assays were positive.
  • "Not Detected" CRM if two out of three EUA assays were negative.
• Influenza A and B: For influenza A and B, the comparator was an FDA-cleared NAAT. There is no mention of a multi-assay composite reference method, suggesting a single FDA-cleared NAAT was used as the ground truth. Discrepancy analysis involved additional FDA cleared NAATs and PCR followed by BDS.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on the standalone performance of the diagnostic assay rather than human reader performance with or without AI assistance.

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

Yes, a standalone performance study was done. The entire clinical performance section evaluates the Simplexa™ COVID-19 & Flu A/B Direct assay's ability to detect and differentiate nucleic acids directly, without human interpretation in the results reporting, other than laboratory personnel operating the instrument. The results are presented as the assay's agreement with reference methods.

7. The Type of Ground Truth Used

• SARS-CoV-2: Composite reference method (CRM) based on the consensus of three COVID-19 Emergency Use Authorized (EUA) NAAT assays.
• Influenza A and B: An FDA-cleared NAAT was used as the primary comparator. In cases of discrepancy, additional FDA-cleared NAATs and PCR followed by Bidirectional Sequencing (BDS) were used for confirmation.

8. The Sample Size for the Training Set

The document describes the clinical performance (test set) and analytical studies. It does not explicitly mention a "training set" in the context of machine learning. The assay is a real-time RT-PCR assay, which typically relies on pre-defined primer and probe sequences rather than a machine learning model that requires a distinct training set in the conventional sense. The development and optimization of the primer/probe sets (e.g., analytical reactivity, inclusivity) can be considered analogous to a "training" or development phase, but no specific dataset labeled as such is provided.

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

As noted in point 8, a traditional "training set" with ground truth establishment in the context of machine learning is not applicable to this RT-PCR assay. The analytical studies (Limit of Detection, Analytical Reactivity/Inclusivity, Cross-Reactivity, Interfering Substances, Competitive Interference, Microbial Interference) use quantitated viral stocks, cultured isolates, purified nucleic acids, or in silico analysis against public strain databases (e.g., GISAID) to demonstrate the assay's analytical performance across a wide range of relevant targets and conditions. This ensures the assay's biochemical design (primers, probes) is sound and effective.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ Congenital CMV Direct is a real-time PCR assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of cytomegalovirus (CMV) from saliva swabs and urine from infants less than 21 days of age. Positive results from saliva are presumptive and should be confirmed with urine. The results of the Simplexa™ Congenital CMV Direct assay should be used in conjunction with the results of other clinical findings as an aid in the diagnosis of congenital CMV infection.

This test has not been cleared for screening of blood products for the presence of CMV or for use with samples other than urine and saliva swabs.

DiaSorin Molecular's Simplexa™ Congenital CMV Positive Control Pack is intended to be used as a control with the Simplexa Congenital CMV Direct kit for use on the LIAISON MDX instrument. This control is not intended for use with other assays or systems.

The Simplexa™ Congenital CMV Direct assay is a real-time PCR system that enables the direct amplification and detection of CMV DNA from either saliva swab or urine specimens without nucleic acid extraction. The system consists of the Simplexa™ Congenital CMV Direct Reaction Mix, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.

In the Simplexa™ Congenital CMV Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify CMV DNA. A well-conserved region of the CMV UL83 gene is targeted to identify CMV DNA. An internal control is used to detect PCR failure and/or inhibition.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state quantitative acceptance criteria in a dedicated table format. However, the reported performance metrics imply the criteria for acceptance. For the purpose of this response, I'll infer the implicit acceptance criteria based on the demonstrated performance, generally implying "high agreement" for positive and negative cases.

2. Sample Size and Data Provenance

• Retrospective Study:

  • Saliva Swab: 173 total specimens (3 removed due to indeterminate CRM result, 170 analyzed)
  • Urine: 173 total specimens
  • Provenance: "collected during the clinical study", "stored at a central site", then distributed to three (3) laboratories. The document doesn't explicitly state the country of origin for these retrospective samples, though the testing sites were in the USA. These were pre-selected positive and negative samples based on routine laboratory results.

• Prospective Study:

  • Saliva Swab: 1,859 initially collected, 6 deemed ineligible, resulting in 1,853 analyzed specimens.
  • Urine: 1,656 initially collected, 32 deemed ineligible, resulting in 1,624 analyzed specimens.
  • Provenance: Prospectively collected (frozen and/or fresh) from ten (10) collection sites across the USA and two (2) collection sites outside the USA. Testing was performed at six (6) testing sites located in the USA.

3. Number of Experts and Qualifications

The document states that a "Composite Reference Method (CRM)" was used, which involved "two (2) validated PCR followed by bi-directional sequencing assays." One (1) central laboratory performed these comparator assays.

• The document does not specify the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with 10 years of experience). It relies on the validation of the PCR and bi-directional sequencing assays as the basis for ground truth, implying that these are established and reliable laboratory methods.

4. Adjudication Method

The ground truth for the clinical agreement studies (both retrospective and prospective) was established via a "Composite Reference Method (CRM)".
This CRM "utilized two (2) validated PCR followed by bi-directional sequencing assays. A sample had a final sequencing result of 'Detected' if one or both sequencing results were 'Detected'. Conversely a sample had a final sequencing result of 'Not Detected' if both results were 'Not Detected'." This implies a form of 2+0 or 1+1 adjudication model where if either reference method detects CMV, the sample is considered positive, and both must be negative for the sample to be considered negative.

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

No, an MRMC comparative effectiveness study was not done. This study focuses on the diagnostic performance of the device itself against a laboratory-based reference method, not on how human readers/clinicians improve with AI assistance.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance evaluation was done. The Simplexa™ Congenital CMV Direct assay is a real-time PCR assay and its performance was evaluated directly against the Composite Reference Method (CRM) without human-in-the-loop assistance. The reported PPA and NPA values represent the algorithm's standalone performance.

7. Type of Ground Truth Used

The ground truth used was expert consensus on laboratory results, specifically based on a "Composite Reference Method (CRM) utilized two (2) validated PCR followed by bi-directional sequencing assays." This is a highly robust and objective form of ground truth for nucleic acid detection devices, often considered a gold standard in molecular diagnostics.

8. Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. This is typical for submissions of this nature, where the focus is on the validation of the final device/algorithm using a separate, independent test set, rather than details of the developmental (training) phase.

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

The document does not provide information on how the ground truth for the training set was established, as details about the training phase are not included in this summary.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ COVID-19 Direct is real-time RT-PCR assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of nucleic acid from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs (NPS) and nasal swabs (NS) from symptomatic individuals suspected of COVID 19 by their healthcare provider. The Simplexa™ COVID-19 Direct assay is an aid in the diagnosis of SARS-CoV-2 infection.

Positive results are indicative of the presence of SARS-CoV-2 RNA. Clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out co-infection with other pathogens. Negative results do not preclude SARS-CoV-2 infection and should not be used as tor patient management decisions.

Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the relevant public health authorities.

The Simplexa COVID-19 Direct is a real-time RT-PCR (rRT-PCR) system that enables the direct amplification and detection of SARS-CoV-2 (COVID-19) RNA from nasopharyngeal swab or nasal swab that has not undergone nucleic acid extraction. The system consists of the Simplexa COVID-19 Direct reaction mix, the LIAISON MDX (with LIAISON MDX Studio Software), the Direct Amplification Disc and associated accessories. The assay uses forward and reverse primers and associated fluorescent probe(s) included in the reaction mix to amplify SARS-CoV-2 cDNA reverse transcribed from RNA. The primers and probe sets are designed to detect SARS-CoV-2 ORF 1ab and S gene from the viral RNA in nasopharyngeal swab or nasal swab. An RNA internal control, with associated primers and a fluorescent probe, is included in the reaction mix to detect RT-PCR failure and/or inhibition.

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

Device: Simplexa™ COVID-19 Direct

1. Table of Acceptance Criteria and Reported Device Performance

For the Simplexa™ COVID-19 Direct assay, the primary acceptance criteria revolve around its accuracy in detecting SARS-CoV-2 (COVID-19) RNA in patient samples, as well as its reproducibility, analytical sensitivity (Limit of Detection), analytical reactivity (ability to detect various strains), and specificity (cross-reactivity and interference).

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

• Clinical Agreement Test Set:

  • Total Samples: 1,150 prospective (fresh and/or frozen) samples collected.
  • Samples analyzed: 1,011 samples (114 excluded due to insufficient evidence for media types, 24 invalid results, 1 indeterminate CRM result).
  • Breakdown: 299 Nasopharyngeal Swabs (NPS) and 712 Nasal Swabs (NS).
  • Provenance: Collected from four (4) geographically diverse collection sites, one of which was outside the United States (OUS). Samples were prospective (fresh and/or frozen).
  • Timeframe: October 2020 to April 2021.

• Reproducibility Test Set:

  • Total replicates: 90 replicates per panel member (4 panel members), totaling 360 individual tests.
  • Panel members: 2 contrived low positive (LP), 2 contrived moderate positive (MP), 1 positive control, 1 negative (UTM).
  • Provenance: Tested at two (2) external clinical sites and one (1) internal site.
  • Study Design: Each panel member tested in triplicate per run, for 2 runs per day, for 5 non-consecutive testing days. Each site had two operators.

• Analytical Sensitivity (LoD) Test Set:

  • NPS: 40 replicates for confirmation.
  • NS: 20 replicates for confirmation.
  • WHO International Standard: 40 replicates for confirmation.

• Analytical Reactivity (Wet testing) Test Set:

  • 3 replicates per strain for 5 SARS-CoV-2 strains.

• Cross-Reactivity Test Set:

  • 3 replicates per organism for 47 different viruses, bacteria, and fungi (some 6 replicates for Leptospira interrogans).

• Potential Interfering Substances Test Set:

  • 3 replicates per substance (some 6 replicates for saliva and Zanamivir).

• Interference by Other Microorganisms Test Set:

  • 3 replicates per organism (some 6 replicates for Lactobacillus plantarum 17-5).

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

The ground truth for the clinical agreement test set was established using a "Composite Reference Method (CRM)" based on three (3) COVID-19 EUA approved NAAT assays. The rule for CRM agreement was: "Two out of three positive results determined 'Detected' CRM and two out of three negative results determined 'Not Detected' CRM."

The document does not specify the number or qualifications of experts (e.g., medical technologists, clinical lab scientists, or physicians) who performed these NAAT assays or interpreted their results for the CRM. It's implied that these were standard laboratory personnel qualified to run EUA-approved molecular diagnostic tests.

For analytical studies (LoD, reproducibility, reactivity, cross-reactivity, interference), the ground truth was based on the known composition and concentration of the samples (e.g., spiked RNA, cultured organisms, negative matrix). No external experts beyond the study design team would have been needed for this type of ground truth establishment.

4. Adjudication Method for the Test Set

For the clinical agreement test set, the adjudication method for the ground truth (CRM) was clearly defined: "Two out of three positive results determined 'Detected' CRM and two out of three negative results determined 'Not Detected' CRM." This is a form of consensus-based adjudication, specifically a majority rule.

For other analytical studies, adjudication was not described as it involved pre-defined positive/negative samples rather than interpretive human judgment.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on the in vitro diagnostic performance of a molecular assay (RT-PCR) in a laboratory setting, not on the interpretative performance of human readers (e.g., radiologists) with or without AI assistance. Therefore, there is no discussion of human readers or an effect size of AI assistance.

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

Yes, the primary clinical performance and analytical studies are standalone (algorithm only) performance. The Simplexa™ COVID-19 Direct is an RT-PCR assay. Its "performance" refers to its ability to detect SARS-CoV-2 RNA based on its set algorithms for signal detection (Ct values for S gene and ORF1ab targets) and interpretation. The results (detected/not detected) are determined directly by the instrument and its software, not by a human interpreting images or complex patterns. The human involvement is in sample preparation and loading, and reviewing the qualitative output from the instrument.

7. The Type of Ground Truth Used

• Clinical Agreement Test Set: Composite Reference Method (CRM) using results from three (3) COVID-19 EUA approved NAAT assays, with a "two out of three" majority rule for determining "Detected" or "Not Detected." This is a form of expert consensus based on other validated diagnostic tests.
• Analytical Studies (Reproducibility, LoD, Reactivity, Cross-Reactivity, Interference): Known analytical truth established by spiking known concentrations of inactivated viral particles or other organisms into negative matrices. This is a laboratory-controlled ground truth.

8. The Sample Size for the Training Set

The provided document describes a premarket notification (510(k)) for an in vitro diagnostic device. For such devices, particularly RT-PCR assays, the "training set" typically refers to internal development and optimization data, rather than a distinct, formally defined "training set" for machine learning algorithms that would be tested on a separate "test set."

The document does not specify a numerical sample size for a training set. The assay's design (primers, probes, conditions) would have been developed and optimized internally by DiaSorin Molecular using various samples and experiments, but these are not enumerated as a specific "training set" in this regulatory submission. The "in silico inclusivity analysis" section points to the use of GISAID databases (millions of sequences) which could be considered a form of "training data" for validating the generalizability of the primer/probe design, but not as a conventional, labeled "training set" in a machine learning context.

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

Since a formal "training set" with established ground truth is not explicitly detailed in the way a machine learning model's training data would be, we can infer the following:

• Assay Development & Optimization: The ground truth for the development phase would have been based on known positive and negative samples, viral loads, and various SARS-CoV-2 strains or synthetic genetic material. This involves standard molecular biology techniques where the presence or absence of the target nucleic acid, and its concentration, are experimentally determined and controlled.
• In Silico Inclusivity: For the evaluation of primer/probe design against genetic variants, the "ground truth" is the published, annotated SARS-CoV-2 genome sequences available in the GISAID database. This involves bioinformatic analysis to determine sequence homology and potential binding efficacy.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ Flu A/B & RSV Direct Gen II assay is intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection and differentiation of influenza B virus, and respiratory syncytial virus (RSV) RNA in nasopharyngeal swabs (NPS) from human patients with signs and symptoms of respiratory tract infection in conjunction with clinical and epidemiological risk factors. This test is intended for use as an aid in the differential diagnosis of influenza A. influenza B. and RSV viral infections in humans.

Negative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions.

Performance characteristics for influenza A were established with clinical specimens collected during the 2010/2011 influenza season when 2009 H1N1 influenza and H3N2 were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to the state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

The DiaSorin Molecular Simplexa™ Flu A/B & RSV Positive Control Pack is intended to be used as a control with the Simplexa™ Flu A/B & RSV Direct kit and the Simplexa™ Flu A/B & RSV Direct Gen II kit for use on the LIAISON® MDX instrument. This control is not intended for use with other assays or systems.

Not Found

The provided document is a 510(k) clearance letter from the FDA for the DiaSorin Molecular Simplexa™ Flu A/B & RSV Direct Gen II assay. It primarily focuses on the device's regulatory clearance and indications for use, not on the detailed study results and acceptance criteria for performance evaluation.

Therefore, I cannot extract the detailed information requested in your prompt regarding acceptance criteria and performance study specifics from this document. The document states that the device is "substantially equivalent" to a legally marketed predicate device, implying that its performance was assessed, but the actual data and criteria are not included here.

To provide the answers you're looking for, I would need a different type of document, such as a summary of safety and effectiveness data (SSED) or the actual clinical study report that was submitted to the FDA for review.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ VZV Swab Direct assay is intended for use on the LIAJSON® MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA present in cutaneous and mucocutaneous lesion swabs from patients with signs and symptoms of VZV infection. This test is intended as an aid in the diagnosis of VZV infection. Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions.

The Simplexa™ VZV Positive Control Pack is intended to be used as a control with the Simplexa™ VZV Direct kit and the Simplexa™ VZV Swab Direct kit on the LIAISON® MDX Instrument. It is not intended for use with other assays or systems.

The Simplexa™ VZV Swab Direct assay is a real-time PCR system that enables the direct amplification and detection of VZV DNA from unprocessed cutaneous and mucocutaneous lesion swab specimens without nucleic acid extraction. The system consists of the Simplexa™ VZV Swab Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.

In the Simplexa™ VZV Swab Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition.

This document describes the validation of the DiaSorin Molecular Simplexa™ VZV Swab Direct assay. The assay is intended for the qualitative detection of varicella-zoster virus (VZV) DNA directly from cutaneous and mucocutaneous lesion swabs.

1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly defines acceptance criteria through the results of the clinical and analytical studies, which consistently demonstrate high agreement and sensitivity/specificity.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ VZV Direct assay is intended for use on the LIAISON® MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS).

Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions.

The assay is not intended for use as a donor screening test. The assay is for professional use only.

The Simplexa™ VZV Positive Control Pack is intended to be used as a control with the Simplexa™ VZV Direct kit.

This control is not intended for use with other assays or systems.

The Simplexa™ VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa™ VZV Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc and associated accessories. In the Simplexa™ VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition.

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

Acceptance Criteria and Device Performance for Simplexa™ VZV Direct Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly list "acceptance criteria" as a set of predefined thresholds. Instead, it presents performance metrics from various studies. Based on the provided clinical agreement study, the implicit acceptance criteria for clinical performance would likely be a high Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). For analytical performance, the LoD is a key metric.

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

• Sample Size (Clinical):
  • Prospective Samples: 637 clinical samples.
  • Contrived Samples: 240 contrived VZV positive samples.
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the submission is to the U.S. FDA by a company in Cypress, California, USA, and the testing was performed at "testing sites" and "DiaSorin Molecular, Cypress, CA", suggesting U.S.-based data.
  • Retrospective or Prospective: The study included both:
    • Prospective and prospectively banked collections from eight (8) collection sites (February 2018 to November 2018).
    • Contrived samples were used to supplement low prevalence true positive clinical samples.

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

Not applicable. This device is an in vitro diagnostic (IVD) based on molecular detection. Ground truth for diagnostic assays like this is typically established by comparative methods rather than expert human interpretation of images or other subjective data. No human "experts" were used to establish the ground truth in the sense of clinical decision-making from images.

4. Adjudication Method for the Test Set

Not applicable in the sense of expert human review (e.g., 2+1, 3+1). The ground truth for the clinical samples was established using a composite reference method:

• Two (2) validated real-time PCR assays.
• Followed by confirmation of positive PCR amplification products with bi-directional sequencing.
• Decision Rule: Samples were characterized as positive if one (1) or both PCR assays were positive AND confirmed by bi-directional sequencing. Samples were characterized as negative if both PCR assays were negative.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) designed for laboratory use to detect VZV DNA. Its performance is evaluated against reference methods, not against human readers (e.g., radiologists, pathologists). Therefore, improvement for human readers with AI assistance is not applicable in this context.

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

Yes, the primary performance studies presented focus on the standalone performance of the Simplexa™ VZV Direct assay. The "Clinical Agreement" section directly compares the Simplexa™ VZV Direct results to the composite reference method without explicit human intervention in the interpretation of the Simplexa™ VZV Direct results. The assay is an automated real-time PCR system.

7. Type of Ground Truth Used

The ground truth for the clinical agreement study was established using a composite reference method. This method involved:

• Two (2) validated real-time PCR assays.
• Confirmation of positive PCR amplification products with bi-directional sequencing.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is an in vitro diagnostic (IVD) based on real-time PCR technology, which relies on molecular biology principles (primers and probes) rather than machine learning models that require distinct training and test sets. The assay design and optimization would involve internal development and validation, but not typically a "training set" in the AI sense.

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

Not applicable, as a "training set" for an AI model is not described or relevant for this type of molecular diagnostic device. The analytical characteristics and design of the PCR assay (e.g., primer and probe specificity) are established through various analytical studies (e.g., analytical sensitivity, specificity, cross-reactivity) rather than a ground-truthed training set for machine learning.

Ask a specific question about this device

The DiaSorin Molecular Simplexa™ Bordetella Direct assay is an in vitro diagnostic test intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids from nasopharyngeal swab (NPS) specimens from patients with signs and symptoms of Bordetella infection of the respiratory tract.

The Simplexa™ Bordetella Direct assay is performed on the LIAISON® MDX instrument and utilizes real-time PCR amplification to detect B. pertussis by targeting the IS481 insertional element of the B. pertussis genome and to detect B. parapertussis by targeting the IS1001 insertional element of the B. parapertussis genome. The IS481 insertional element can also be present in B. holmesii and B. bronchiseptica. Specimens collected from patients with respiratory infection caused by B. pertussis, B. holmesii or B. bronchiseptica may yield positive test results in IS481 assays. B. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.

Negative results for the Simplexa™ Bordetella Direct assay do not preclude Bordetella infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the Simplexa™ Bordetella Direct assay should be used with other clinical findings and epidemiological information as an aid in diagnosis of Bordetella infection. Test results should not be used as the sole basis for treatment or other patient management decisions.

Simplexa™ Bordetella Positive Control Pack

The Simplexa™ Bordetella Positive Control Pack is intended to be used as a control with the Simplexa™ Bordetella Direct kit.

This control is not intended for use with other assays or systems.

The Simplexa™ Bordetella Direct assay system is a real-time PCR assay that enables the direct amplification, detection and differentiation of Bordetella pertussis and Bordetella parapertussis DNA from unprocessed nasopharyngeal swabs (NPS) without nucleic acid extraction. The system consists of the Simplexa™ Bordetella Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc and associated accessories.

In the Simplexa™ Bordetella Direct assay, primers and fluorescent probes are used together to amplify and detect Bordetella pertussis, Bordetella parapertussis and internal control targets. Insertion sequences IS481 and IS1001 are targeted to identify Bordetella pertussis and Bordetella parapertussis DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.

The provided text details the 510(k) summary for the Simplexa™ Bordetella Direct and Simplexa™ Bordetella Positive Control Pack, specifically focusing on the update to include fresh nasopharyngeal swab (NPS) samples. While the document mentions "acceptance criteria" and "design inputs" for the validation, it does not explicitly state the quantitative acceptance criteria for device performance (e.g., specific thresholds for PPA and NPA) in the provided sections. Instead, it presents the results of the clinical studies.

However, based on the provided data, we can infer that 100% PPA and a high NPA (above 95%) were considered acceptable, given the reported results.

Here's a breakdown of the available information:

1. Table of Acceptance Criteria and Reported Device Performance

As stated, the document does not explicitly list the acceptance criteria as specific numerical targets for PPA and NPA (e.g., "PPA must be ≥ 95%"). However, the reported performance is provided. We can infer that the observed performance was deemed acceptable by the FDA for the device's clearance.

Note: The confidence intervals are provided in the source document but are not included in this table for brevity.

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

Bordetella pertussis (Fresh Samples):

• Sample Size: 369 evaluable fresh samples.
• Data Provenance: Prospectively collected from five (5) geographically diverse sites in the US (inferred, as it's an FDA submission for a US company) from May 2018 to October 2018, from patients with signs and symptoms of Bordetella infection.

Bordetella parapertussis (Fresh Samples):

• Sample Size: 176 evaluable fresh samples (out of 178 collected).
• Data Provenance: Prospectively collected from six (6) geographically diverse sites in the US (inferred) between July 2017 and August 2017, from patients with signs and symptoms of Bordetella infections.

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

The document does not specify the number of experts or their qualifications used to establish the ground truth.

4. Adjudication Method for the Test Set

• For B. pertussis (Table 3): The reference method was an "FDA Cleared NAAT" (Nucleic Acid Amplification Test). The document does not describe the adjudication method if results between different reference tests varied or whether a composite ground truth derived from multiple tests was used, other than referencing a single FDA cleared NAAT.
• For B. parapertussis (Table 4): The reference method was a "composite reference method" consisting of "two well-characterized real-time PCR assays followed by confirmation of positive PCR amplification products with bidirectional sequencing, per target." Samples were characterized as positive if one or both composite reference methods were positive and confirmed by bi-directional sequencing. Samples were characterized as negative if both composite reference methods were negative. This describes an adjudication method that combines results from multiple tests.

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

No, a MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test for qualitative detection of nucleic acids, not an imaging device requiring human reader interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.

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

Yes, the performance presented is standalone algorithm performance. The Simplexa™ Bordetella Direct assay is an automated real-time PCR assay performed on the LIAISON® MDX instrument, which provides automated test interpretation and report generation. There is no human-in-the-loop performance described for the diagnostic decision-making process based on the assay's output.

7. The Type of Ground Truth Used

• For B. pertussis (Table 3): The ground truth was established by an "FDA Cleared reference method testing."
• For B. parapertussis (Table 4): The ground truth was established by a "composite reference method" combining two well-characterized real-time PCR assays and bidirectional sequencing confirmation. This is a form of expert-defined molecular diagnostic ground truth.

8. The Sample Size for the Training Set

The document does not provide information on a specific training set size. The studies described are for "Method Comparison" using prospectively collected samples, which typically serve as validation or test sets for device performance rather than training sets. For molecular diagnostic assays like this, the "training" usually involves optimizing primer/probe design and assay conditions, which isn't described in terms of a "training set" with ground truth in the same way an AI/ML model would be.

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

As no training set is described in the provided document, the method for establishing its ground truth is also not applicable/not provided.

Ask a specific question about this device

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.

Ask a specific question about this device

Simplexa™ Bordetella Direct MOL2750
The DiaSorin Molecular Simplexa™ Bordetella Direct MOL2750 assay is an in vitro diagnostic test intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids from frozen nasopharyngeal (NPS) specimens from patients with signs and symptoms of Bordetella infection of the respiratory tract.
The Simplexa™ Bordetella Direct assay is performed on the LIAISON® MDX instrument and utilizes realtime PCR amplification to detect B. pertussis by targeting the IS481 insertional element of the B. pertussis genome and to detect B. parapertussis by targeting the IS1001 insertional element of the B. parapertussis genome. The IS481 insertional element can also be present in B. holmesii and B. bronchiseptica. Specimens collected from patients with respiratory infection caused by B. pertussis, B. holmesii or B. bronchiseptica may yield positive test results in IS481 assays. B. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the Simplexa™ Bordetella Direct assay do not preclude Bordetella infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the Simplexa™ Bordetella Direct assay should be used with other clinical findings and epidemiological information as an aid in diagnosis of Bordetella infection. Test results should not be used as the sole basis for treatment or other patient management decisions.
Simplexa™ Bordetella Positive Control Pack MOL 2760
The Simplexa™ Bordetella Positive Control Pack MOL2760 is intended to be used as a control with the Simplexa™ Bordetella Direct kit. This control is not intended for use with other assays or systems.

The Simplexa™ Bordetella Direct assay system is a real-time PCR assay that enables the direct amplification, detection and differentiation of Bordetella pertussis and Bordetella parapertussis DNA from unprocessed nasopharyngeal swabs (NPS) without nucleic acid extraction. The system consists of the Simplexa™ Bordetella Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc and associated accessories.
In the Simplexa™ Bordetella Direct assay, primers and fluorescent probes are used together to amplify and detect Bordetella pertussis, Bordetella parapertussis and internal control targets. Insertion sequences IS481 and IS1001 are targeted to identify Bordetella pertussis and Bordetella parapertussis DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.
The DiaSorin Molecular Simplexa™ Bordetella Direct kit contains sufficient reagents for 24 reactions. Upon receipt, store at -10 to -30ºC (do not use a frost-free freezer). Each vial contains sufficient material for a single reaction. Use within 30 minutes of thawing.

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

Acceptance Criteria and Reported Device Performance

Study Details from the Provided Text:

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

• Test Set Sample Size (Clinical Performance/Method Comparison):
  • 1113 evaluable prospectively collected frozen nasopharyngeal swab (NPS) samples.
  • An additional 112 samples: 56 contrived Bordetella parapertussis samples (at 2-50 X LoD) and 56 negative samples, randomized together.
• Data Provenance:
  • Country of Origin: Not explicitly stated, but samples were "prospectively collected and frozen from five (5) geographically diverse sites" (Page 7). This often implies within the USA for FDA submissions, but not definitively confirmed.
  • Retrospective or Prospective: Primarily prospective.
    • "One thousand one hundred and forty-two (1142) samples were prospectively collected and frozen..." (Page 7).
    • "The Bordetella pertussis prospectively banked frozen sample results are shown in Table 1." (Page 7).
    • "The Bordetella parapertussis prospectively banked frozen sample results are shown in Table 2 and the Bordetella parapertussis contrived sample results are shown in Table 3." (Page 7).

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

• The text does not specify the number or qualifications of experts directly establishing ground truth. Instead, it describes a "composite reference method."

4. Adjudication method for the test set:

• The ground truth was established using a "composite reference method [which] consisted of two well-characterized real-time PCR assays followed by confirmation of positive PCR amplification products with bi-directional sequencing, per target."
• "Samples were characterized as positive if one or both composite reference methods were positive and confirmed by bi-directional sequencing. Samples were characterized as negative if both composite reference methods were negative." (Page 7).
• This suggests a form of consensus/confirmation, but not a 2+1 or 3+1 expert adjudication in the typical human-in-the-loop sense for imaging. It's an algorithmic/laboratory "adjudication" against established molecular methods.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) PCR assay, not an AI-assisted imaging device. Its performance is evaluated directly against a reference method, not in comparison to human readers.

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

• Yes, the primary clinical performance ("Method Comparison") and all analytical studies (Reproducibility, LoD, Reactivity, Specificity, Interference, etc.) represent the standalone performance of the Simplexa™ Bordetella Direct assay. It's an automated molecular diagnostic assay, designed to operate without human interpretation of the primary signal for diagnosis.

7. The type of ground truth used:

• The ground truth was established using a composite reference method consisting of:
  • Two "well-characterized real-time PCR assays."
  • "Confirmation of positive PCR amplification products with bi-directional sequencing, per target." (Page 7).

8. The sample size for the training set:

• The document describes performance studies for a finalized device. It does not provide information about a separate "training set" in the context of machine learning, because this is a PCR assay with defined primers and probes, not a machine learning model that requires training data in that sense. The analytical and clinical studies serve to validate the assay's performance.

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

• Not applicable, as this is not a machine learning device with a distinct "training set" ground truth. The development of the assay (designing primers, probes, optimizing conditions) is an engineering process, not a data-driven model training process.

Ask a specific question about this device