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The Chagas Detect™ Plus (CDP) Rapid Test is a rapid immunochromatographic strip assay for the qualitative detection of human IgG antibodies to Trypanosoma cruzi (T. cruzi) in human serum and whole blood matrices (venous and capillary (finger prick) whole blood). CDP is a non-invasive diagnostic test for use in a primary care setting by personnel trained to obtain whole blood or serum samples. Reactive test results will be presumptive evidence of infection with T. cruzi. The CDP when used in conjunction with other serological and clinical information is useful for the diagnosis of individuals with Chagas disease. Definitive diagnosis of an acute phase infection (including acute congenital infection) must be made by alternative methods, e.g., hemoculture, blood smear. This test is not intended for use on cord blood or for screening blood or plasma donors.

The Chagas Detect™ Plus (CDP) Rapid Test is a rapid immunochromatographic strip assay for the qualitative detection of human IgG antibodies to Trypanosoma cruzi (T. cruzi) in human serum and whole blood matrices (venous and capillary (finger prick) whole blood).

The provided text is a 510(k) premarket notification letter from the FDA regarding the Chagas Detect™ Plus Rapid Test. It confirms the device's substantial equivalence to legally marketed predicate devices.

However, the document does not contain any information about a study that proves the device meets specific acceptance criteria in the context of an AI/ML medical device submission. It is for a rapid immunochromatographic strip assay, which is a laboratory diagnostic test, not an AI/ML device. Therefore, the requested information about acceptance criteria, study details, expert involvement, and ground truth for an AI/ML model's performance evaluation cannot be extracted from this document.

The document discusses:

• The device name: Chagas Detect™ Plus Rapid Test
• Its intended use: Qualitative detection of human IgG antibodies to Trypanosoma cruzi (T. cruzi) in human serum and whole blood.
• Regulatory information: Regulation Number, Name, Class, and Product Code.
• The FDA's determination of substantial equivalence.
• General controls provisions and other regulatory requirements for the device.

To fulfill the request, a document describing an AI/ML medical device's performance study would be necessary.

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ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of antibodies (Immunoglobulin G) to Trypanosoma cruzi (T. cruzi) in human adult serum (glass, plastic, or serum separator tubes) and plasma (EDTA, lithium heparin or citrate) using whole-cell lysate antigens. Reactive assay results are presumptive evidence of past infection, and in conjunction with other serological and clinical information, may be used for the laboratory diagnosis of individuals with Chagas' disease.

Definitive diagnosis of an acute phase of infection (including acute congenital infection) must be made by alternate methods, e.g., hemoculture, blood smear.

This test is not intended for use on samples of cord blood or screening blood or plasma donors.

The ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay (ELISA). ELISA technology utilizes the principle that antibodies bound to the solid phase can be detected by complementary antibodies or antigens labeled with an enzyme capable of acting on a chromogenic substrate. When substrate is applied, the presence of antigens or antibodies can be detected by development of a colored end product. The optical densities are read spectrophotometrically.

This ELISA was developed to detect human antibodies to T. cruzi in serum and plasma. The assay utilizes microwells coated with a whole-cell lysate containing T. cruzi antigens as the solid phase. The assay procedure is a three-stage test carried out in a microwell coated with lysate (antigens) prepared from T. cruzi. In the first stage, test specimen, Negative Control, and Positive Calibrator are diluted directly in the test well containing Specimen Diluent, and incubated for a specified length of time. If antibodies to T. cruzi are present, antigen-antibody complexes will form on the microwell surface. If antibodies to T. cruzi are absent, complexes will not form. Unbound antibodies in the sample will be removed during the subsequent wash step.

In the second stage, murine monoclonal antibody conjugated with Horseradish Peroxidase (Conjugate) is added to the test well. The Conjugate binds specifically to the antibody portion of the antigen-antibody complex. If complexes are not present, the unbound Conjugate is removed by the subsequent wash step.

In the third stage, an enzyme detection system composed of o-phenylenediamine (OPD) and hydrogen peroxide is added to the test well. If bound Conjugate is present, the OPD with be oxidized, resulting in a colored end product. Sulfuric acid is then added to stop the reaction. The color intensity depends on the amount of bound Conjugate and, therefore, is a function of the concentration of antibodies to T. cruzi present in the specimen. The intensity of color in the substrate solution is then determined with a microwell reader (spectrophotometer) designed to measure light absorbance in a microwell.

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

Device: ORTHO® T. cruzi ELISA Test System

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical thresholds for performance metrics. However, the performance study data implicitly demonstrates the device's acceptable performance by showing strong agreement with established methods and probable T. cruzi antibody status. The key performance metrics are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).

Given the context of a 510(k) submission, the implicit acceptance criteria would be for the device to perform comparably to, or demonstrate a high level of agreement with, the established comparator methods and the "most probable T. cruzi antibody status."

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

• Sample Size for Test Set:
  • High and Low Risk Subjects Study: N = 1074 subjects
  • Serological Presumed Positive Population Study: N = 810 specimens
• Data Provenance:
  • Country of Origin: The "Serological Presumed Positive Population" study explicitly states specimens were obtained from endemic countries: Bolivia (17.8%), Brazil (24.7%), Chile (10.6%), Guatemala (2.2%), Mexico (32.5%), and Nicaragua (12.2%). The provenance for the "High and Low Risk" subjects is not explicitly stated, but given T. cruzi is endemic to Latin America, it's highly likely they came from similar regions or populations with risk factors associated with these regions.
  • Retrospective or Prospective: Not explicitly stated, but the description of "specimens from 1074 subjects" and "specimens obtained from" suggests these were pre-collected samples, which typically implies a retrospective study design.

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

• The document does not specify the number of experts used to establish the ground truth.
• It refers to "a pre-specified testing algorithm" involving the ORTHO T. cruzi ELISA Test System, a comparator T. cruzi IFA (indirect immunofluorescence assay), and supplemental T. cruzi RIPA (radioimmunoprecipitation assay) testing to determine the "most probable T. cruzi antibody status." This implies a laboratory-based algorithm rather than subjective expert interpretation for each individual case ground truth.
• Qualifications of Experts: Not specified. However, the reliance on established serological methods (IFA, RIPA) suggests that interpretation would be done by qualified laboratory personnel following established protocols, though individual "experts" for ground truth adjudication are not mentioned.

4. Adjudication Method for the Test Set

The adjudication method used to establish the "most probable T. cruzi antibody status" for the test sets was a pre-specified testing algorithm rather than an expert consensus method like 2+1 or 3+1.

• For High and Low Risk Subjects:
  • Specimens negative with both the ORTHO T. cruzi ELISA and the T. cruzi IFA were assigned a "most probable T. cruzi antibody status of negative" (if not tested with RIPA).
  • Specimens tested with RIPA were assigned a most probable status of positive, negative, or indeterminate based on RIPA results.
• For Serological Presumed Positive Population:
  • Specimens that were ORTHO T. cruzi ELISA repeatedly reactive AND positive with the T. cruzi IFA were assigned a "most probable T. cruzi antibody status of positive" without further RIPA testing.
  • All specimens negative with both assays OR with discordant results between the two assays were tested with the T. cruzi RIPA, and their status was assigned "based upon the RIPA results."

This method essentially uses a hierarchical testing algorithm with RIPA as a confirmatory test for ambiguous cases, which acts as the adjudicator.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and 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 ELISA diagnostic kit, which is an in vitro diagnostic (IVD) assay to detect antibodies in serum/plasma. It is not an AI-assisted diagnostic device that would involve human readers interpreting images or data with or without AI assistance. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply here.

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

• Yes, the performance presented in the report is for the device operating in a standalone capacity (algorithm only).
• The ORTHO T. cruzi ELISA Test System is an automated/semi-automated in vitro diagnostic assay. The results (optical densities) are read spectrophotometrically, and the interpretation (reactive/nonreactive) is based on a pre-defined cutoff. While human operators are involved in running the assay (pipetting, washing, loading), the diagnostic decision itself from the optical density reading is based on the device's internal algorithm/parameters, not human interpretation of a raw signal. The performance metrics (PPA, NPA) directly reflect this standalone assay performance against the established ground truth.

7. The Type of Ground Truth Used

The ground truth used was a "most probable T. cruzi antibody status" established by a pre-specified testing and interpretation algorithm involving:

• The ORTHO T. cruzi ELISA Test System itself
• A comparator T. cruzi IFA
• Supplemental T. cruzi RIPA testing (Radioimmunoprecipitation Assay) as a confirmatory assay.

This approach combines multiple serological methods, with RIPA acting as the highest tier for ambiguous results, to arrive at a "most probable" truth, which is a form of composite reference standard or multi-test algorithm ground truth.

8. The Sample Size for the Training Set

• The document does not specify any sample size for a training set.
• This is common for in vitro diagnostic (IVD) devices like ELISA kits, which are often developed and optimized using a variety of samples during their analytical validation phase, but the rigorous performance evaluation for regulatory submission typically focuses on a distinct clinical validation (test) set. The concepts of "training set" and "test set" are more explicitly separated for machine learning/AI models.

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

• Since a "training set" is not explicitly mentioned or detailed in the provided document, there is no information on how its ground truth was established. If one were used in development, it would likely follow similar principles of using established serological methods and clinical information for sample characterization.

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The Wiener Laboratory enzyme-linked Immunosorbent assay (ELISA) recombinante V. 3.0 test system is a manual and automated instrument assay for the qualitative detection of total antibodies (IgG and IgM) to Trypanosoma cruzi in human serum and plasma (EDTA, heparin, or Citrate) using recombinant antigens of T. cruzi. Reactive results are presumptive evidence of present or past infection with Trypanosoma cruzi.

In this qualitative technique for the detection of antibodies anti-T. Cruzi, the sample is diluted in the wells in which recombinant antigens starting from specific proteins from the epimastigote and trypomastigote stages of the T. cruzi corresponding to highly conserved zones are immobilized. These antigens are proteins with aminoacid sequences repeated in tandem. SAPA (shed acute phase antigen) antigens detect antibodies in 93% of the patients' sera during the acute phase of the infection. It comes from the trypomastigote-bloodstream form of the parasite; #1, #2 and #30 antigens detect antibodies in chronic patients; #13 and #36 specially detect antibodies in sera both from acute and chronic patients.
If the sample contains Chagas' antibodies, they bind to the antigens bound to the support. The unbound antigens and antibodies are removed by washing, after which anti-human immunoglobulin antibodies conjugated to peroxidase are added. If a reaction was produced in the first step of the process, the conjugate is bound. After a new washing step and the addition of a chromogenic substrate and stopping reagent, specimens containing antibodies to T. cruzi produce a color reaction which can be read with a standard ELISA plate reader.

Here's an analysis of the provided text to extract information about acceptance criteria and the study that proves the device meets them:

Device Name: Chagatest ELISA recombinante v.3.0 (also referred to as Wiener lab Chagatest ELISA rec. v.3.0)

Intended Use: Qualitative detection of antibodies to Trypanosoma cruzi (causative agent of Chagas' disease) in human serum and plasma. Useful in establishing prior exposure to T. cruzi and as an aid in diagnosis.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in a dedicated section. However, it presents "Performance Characteristics" including "Relative Sensitivity," "Relative Specificity," and "Relative Agreement," with specified confidence intervals. It also highlights an overall relative sensitivity of 97.9% and relative specificity of 97.8% (after resolution of discordant samples) or 97.9% and 97.8% (before resolution of discordant samples) from a combined analysis of multiple sites.

Given the context of a 510(k) summary seeking substantial equivalence, implicit acceptance criteria would likely involve demonstrating high relative sensitivity and specificity that are comparable to or better than predicate devices and meet general diagnostic accuracy expectations for such assays. While not explicitly stated as "acceptance criteria," the reported performance values are what would be used by the FDA to determine substantial equivalence.

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

The test set consisted of multiple studies performed at different sites. The total sample size and data provenance are:

Total combined sample size for comparative effectiveness/performance studies appears to be over 5000 specimens across various studies. All data appears to be retrospective based on the nature of the studies (testing existing specimens, panels, or comparing against established methods). The countries of origin include Argentina, Mexico, Chile, and Brazil, with some studies also including low-risk individuals from the U.S.

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 or specific qualifications of individual experts. However, it describes that ground truth was established using:

• Comparison methods: Predicate devices (MERIDIAN Premier™ Chagas' IgG ELISA, ABBOTT Chagas Antibody EIA) were used as primary comparators.
• Confirmatory/Reference tests: Radio Immuno Precipitation Assay (RIPA), Indirect Hemagglutination Assay (IHA), Immunofluorescence Assay (IFA), and xenodiagnosis were used as reference methods, particularly for resolving discordant results or establishing the status of selected panels.
• Clinical context: Specimens were often from "patients with confirmed Chagas' disease by xenodiagnosis, IHA and IFA," "blood donors," or "patients from an endemic area."
• The reference tests (IHA, IFA, RIPA, xenodiagnosis) are typically performed and interpreted by experienced laboratory personnel or medical professionals.

4. Adjudication Method for the Test Set

Adjudication methods are described for discordant results:

• Discordant results between the Wiener lab ELISA and predicate devices were often adjudicated using reference methods like RIPA, IHA, and/or IFA.
  • For example: "Out of 5 specimens with discordant results, all 5 were reactive by Wiener lab ELISA and a RIPA, but non-reactive by Meridian." (Section 1.2)
  • "Of the 12 specimens with discordant results... 6 specimens were reactive by Wiener lab Chagatest ELISA rec.v.3.0 and non-reactive by Abbott Chagas Antibody EIA. Out of those 6 specimens, 3 were reactive by IFA." (Section 1.3)
  • "7 specimens were reactive by Wiener lab ELISA, reactive by IHA / IFA / RIPA and/or Meridian ELISA and non-reactive by Abbott ELISA." (Section 1.5a)

The specific process for how these reference results were used to adjudicate a final ground truth (e.g., majority vote, hierarchy of tests) is not explicitly detailed but implied that the consensus or superior reference test determined the final status.

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

No, an MRMC comparative effectiveness study was not explicitly described. This is an in vitro diagnostic device for laboratory use, and its performance is typically assessed by comparing its numerical output (e.g., signal/cut-off ratio) to a threshold and then to gold standard/reference methods, rather than human readers interpreting images or data for diagnosis. The studies focused on comparing the device's diagnostic accuracy (sensitivity, specificity, agreement) to other assays and established reference methods.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies reported are standalone performance evaluations of the Wiener lab Chagatest ELISA recombinante v.3.0. The "algorithm" here refers to the ELISA assay itself, which generates quantitative results (absorbance, s/c ratio) that are then interpreted against a predefined cutoff. The performance metrics (relative sensitivity, specificity, agreement) measure the device's accuracy in identifying positive or negative samples independently, without direct human intervention in the interpretation of each test result beyond comparing it to the cutoff. The studies compare the device's output to other test systems.

7. The Type of Ground Truth Used

The ground truth for the test sets was established using a combination of:

• Expert Consensus/Reference Methods: Primarily through established serological tests like Indirect Hemagglutination Assay (IHA), Immunofluorescence Assay (IFA), Radio Immuno Precipitation Assay (RIPA), and in some cases, previous ELISA results from other reference systems.
• Pathology/Outcomes Data (Indirectly): Xenodiagnosis, a biological method for detecting T. cruzi infection, was used for some "confirmed Chagas' disease" cases (e.g., Section 2.3, 2.11, 5). This can be considered a strong indicator of true infection.
• Clinical context: Patients from endemic areas and those with confirmed Chagas' disease were used to ensure the presence of antibodies, while low-risk individuals were used for specificity studies.

Therefore, the ground truth is a composite ground truth, derived from multiple established diagnostic methods and clinical confirmation strategies.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" or "validation set" in the context of machine learning model development. This is an ELISA kit, which is a biochemical assay, not a machine learning algorithm that requires a training phase. The "studies" described are performance evaluations against established predicate devices and reference methods using various clinical samples. The "training" data for such a kit would implicitly be the data used during its development and optimization, which is not detailed here. The studies provided demonstrate the device's performance on various patient populations, which serves as a clinical validation.

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

As noted above, this is an ELISA assay, not a machine learning model, so the concept of a "training set" ground truth in the AI context does not directly apply. The establishment of ground truth for the samples used in the performance evaluations (analogous to a test set in ML) is described in point 7 (composite ground truth from various reference methods and clinical confirmation).

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