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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support.

Here's a breakdown of the acceptance criteria and study information for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay, based on the provided text:

Acceptance Criteria and Device Performance

The study evaluates the analytical performance and clinical performance of the device.

Analytical Performance Acceptance Criteria:

The key acceptance criteria for analytical performance are related to precision, linearity, and specificity. While explicit quantitative criteria were provided for precision, linearity had implied criteria based on excellent regression statistics, and specificity was demonstrated by successful inhibition.

Clinical Performance Acceptance Criteria:

The acceptance criteria for clinical performance are based on the agreement of the device's results with clinical diagnosis, measured by sensitivity, specificity, and overall agreement.

Study Details

2. Sample sizes used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

• Analytical Test Set Sample Size:
  • Precision: For each allergen lot and each positive sample level, N=80 measurements were performed (2 aliquots per run, 2 runs per day, 20 days). For combined lot precision, N=240 (80 measurements x 3 lots) where applicable. Negative controls were also tested.
  • Linearity: 11 or 12 data points (depending on the allergen) from 2-fold serial dilutions, including undiluted (neat) samples.
  • Specificity (Inhibition): Not explicitly stated how many unique serum samples were used "a single serum sample or pool of sera". For cross-reactivity, one positive sample was tested with three unrelated allergen extracts.
• Clinical Test Set Sample Size:
  • Total Patients: 693 individuals were tested (193 clinically positive, 500 clinically normal).
• Data Provenance: Not explicitly stated for either analytical or clinical studies. However, the manufacturer (Siemens Healthcare Diagnostics Inc. and Siemens Healthcare Diagnostics Products, LTD) has locations in Tarrytown, NY, and Llanberis, Gwynedd, UK. It is likely that the data originates from studies conducted or coordinated by these facilities, potentially involving samples from different geographic locations. The document does not specify whether the data was retrospective or prospective.

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)

• Analytical Studies: No external experts were used; ground truth was established by the experimental design (e.g., known concentrations for linearity, known positive/negative samples for precision and specificity).
• Clinical Studies: The ground truth for clinical performance was "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." The number and qualifications of experts (e.g., allergists, physicians) involved in making these clinical diagnoses are not specified in the provided text.

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

• Clinical Studies: The document does not describe any specific adjudication method for establishing the "clinical diagnosis." It refers to "clinical findings and other laboratory tests," implying a standard clinical diagnostic process rather than a formalized adjudication among multiple experts for the purpose of the study.
• Analytical Studies: Adjudication is not applicable as ground truth is based on known analytical properties.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic assay for quantitative measurement of allergen-specific IgE in human serum. It is an automated laboratory test, not an imaging device or AI-assisted diagnostic tool that would involve human readers or AI assistance in interpretation. The study evaluates the performance of the analytical device itself.

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

• This is a standalone diagnostic assay. The IMMULITE® 2000 3gAllergy™ Specific IgE Assay, when run on the IMMULITE® 2000 Analyzer, operates as an automated system. The performance data presented (precision, linearity, specificity, and clinical agreement) reflects the "algorithm only" or "device only" performance, without human interpretive input for the final result beyond operating the analyzer and reviewing the quantitative output. The results are quantitative IgE levels, not qualitative interpretations requiring human judgment (e.g., image reading).

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

• Analytical Studies: The ground truth was based on known properties of the samples and experimental design:
  • Precision: Replicates of the same sample, the true value of which is the mean of the replicates.
  • Linearity: Gravimetrically prepared dilutions with known expected concentrations.
  • Specificity: Known inhibitor extracts and known unrelated allergens.
• Clinical Studies: The ground truth for clinical performance was "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This can be classified as a form of clinical diagnosis and outcomes data, likely based on patient history, physical examination, symptom evaluation, and other relevant diagnostic tests, rather than a single definitive pathology result.

8. The sample size for the training set

• Not applicable / Not explicitly stated. This document describes a 510(k) submission for new allergens to an existing IMMULITE® 2000 3gAllergy™ Specific IgE assay. It details the validation and performance studies for these additional allergens. The IMMULITE® 2000 system and the 3gAllergy™ assay are commercially available, validated technologies. The concept of a "training set" as understood in machine learning (where algorithms are "trained" on data) is not directly applicable here. The assay itself uses established immunochemical principles; it's not a machine learning algorithm that undergoes a training phase with a distinct dataset.

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

• Not applicable. As explained above, this device does not involve an "AI algorithm" or "machine learning" in the traditional sense that would require a separate training set and ground truth establishment for that training phase. The analytical and clinical performance studies are for validation of the assay for the specific new allergens.

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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer/co-polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

The provided document describes the Siemens Healthcare Diagnostics Inc. IMMULITE® 2000 3gAllergy™ Specific IgE Assay, which is an in vitro diagnostic device for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The document focuses on demonstrating the substantial equivalence of nine additional specific allergens for use with this existing assay.

Here's an analysis of the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for each performance characteristic (e.g., "Total CV must be < 10%"). Instead, it presents the results of the studies and concludes that the analytical performance is "acceptable" and the assay "compares well with clinical documentation." However, we can infer some criteria based on industry standards for similar assays and the presented data.

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

• Precision and Linearity: The document does not explicitly state the total number of individual patient samples used for precision and linearity.
  • Precision: For each allergen, "three positive samples and one negative sample" were tested. Positives 1-3 were assayed in two aliquots, two runs/day over 20 days. Positive 4 was assayed in two aliquots, two runs/day over 10 days.
  • Linearity: For each allergen, "two samples were diluted in 2-fold serial dilutions to 5 levels." N refers to the number of data points for regression, which ranges from 8 to 12.
• Specificity (Inhibition): A "single serum sample or pool of sera" was used for competitive inhibition. A "negative sample" was used for background. For cross-reactivity, "one positive sample with three unrelated allergen extracts" was used.
• Clinical Performance:
  • Test Set Size: 828 total samples (228 clinically positive, 600 clinically normal/negative).
  • Data Provenance: Not explicitly stated regarding country of origin. The study appears to be retrospective, as results were compared to "accompanying clinical information" and "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity," implying existing patient data.

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 or qualifications of experts who established the "clinical data" or "clinical documentation" used as ground truth for the clinical performance study. It refers generally to "clinical findings and other laboratory tests" and "signs, symptoms and other diagnostic evidence of allergen sensitivity."

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for establishing the clinical ground truth. It simply refers to "clinical data" and "clinical documentation."

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 an in vitro diagnostic assay, not an imaging device or AI-powered diagnostic that involves human readers interpreting results in a "multi-reader multi-case" scenario. Therefore, an MRMC comparative effectiveness study involving human readers with/without AI assistance is not applicable and was not performed.

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

This is a standalone diagnostic assay (IMMULITE® 2000 3gAllergy™ Specific IgE Assay) which provides quantitative measurements of IgE. Its performance is presented as the "algorithm only" or "device-only" performance, as it reports a numerical result. The assay is intended to be used "in conjunction with clinical findings and other laboratory tests," indicating that a human (clinician) interprets the result within the broader clinical context, but the assay itself is not a human-in-the-loop system in the sense of AI-assisted image interpretation.

7. The Type of Ground Truth Used

• Analytical Studies (Precision, Linearity, Specificity): The ground truth for these studies is based on established analytical methods and reference materials (e.g., known concentrations for linearity, relevant inhibitor extracts for specificity).
• Clinical Performance Study: The ground truth used was clinical documentation and findings, including "case histories of suspected clinical reactions to the specific allergen or allergy" for allergic patients, and classification as "non-atopic individuals" for controls. This falls under outcomes data or expert clinical consensus based on patient history, symptoms, and other diagnostic evidence, rather than a single definitive pathology report for each case.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning or AI development. This is a traditional immunoassay, not an AI/ML algorithm that requires a separate training set. The data presented demonstrates the analytical and clinical performance of the manufactured assay.

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

As this is not an AI/ML device, there is no "training set" in that sense, and therefore no ground truth was established for a training set. The assay's design and parameters would have been developed through R&D processes, likely involving internal validation with characterized samples.

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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

The Siemens Healthcare Diagnostics Inc. IMMULITE® 2000 3gAllergy™ Specific IgE Assay is intended for the quantitative measurement of allergen-specific IgE in human serum, to aid in the clinical diagnosis of IgE-mediated allergic disorders.

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria for precision, linearity, or clinical performance in numerical terms for the new allergens to be cleared. However, the study results are presented to demonstrate acceptable analytical performance and comparability to clinical data.

Precision:
Precision was evaluated by calculating the intra-assay (Within-Run) and inter-assay (Total) percent coefficients of variation (%CV) for positive samples. The reported CVs are generally low, with within-run CVs mostly below 5% (with some exceptions like Positive #4 for Lime at 9.15%) and total CVs mostly below 6% (with some exceptions like Positive #4 for Lime at 11.47%). The document states that "acceptable analytical performance including precision" was demonstrated, implying these values met internal or regulatory expectations.

Linearity:
Linearity was assessed by comparing observed to expected data from 2-fold serial dilutions. The regression equations show slopes very close to 1 and intercepts close to 0, with 95% confidence intervals for both slope and intercept generally containing 1 and 0 respectively. This indicates good linearity across the tested range. The document states "acceptable analytical performance including linearity" was demonstrated.

Specificity (Inhibition Studies):
Specificity was confirmed through competitive inhibition testing. The acceptance criterion was explicitly stated as achieving a target % inhibition of 50% for the highest inhibitor concentration tested. The reported performance is that this target was met for all tested allergens.
Additional inhibition studies for cross-reactivity used a criterion of results being below 9.9% for specific allergens when tested with unrelated allergen extracts. The reported performance states that results were below 9.9% for Asparagus, Blueberry, Cauliflower, and Perch when tested with unrelated extracts, and for Apricot, Chili Pepper, Chub Mackerel, Ginger, Lime, and Whey.

Clinical Performance:
The document presents an agreement rate with clinical data. The acceptance criteria for clinical performance are implicitly defined by the reported lower and upper confidence intervals, which fall within generally accepted ranges for such diagnostic assays.

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

• Precision Test Set: The number of samples varied. For each allergen, "two aliquots of each test sample in two runs per day on 20 different days" were used for Positive 1-3. For Positive #4, "two aliquots of each test sample in two runs per day on 10 different days" were used. Three allergen lots were tested using three positive and one negative sample. The allergen specificity results involved a single serum sample or pool of sera for inhibition studies.
• Linearity Test Set: For each allergen, two samples were diluted in 2-fold serial dilutions to 5 levels, plus the undiluted sample. The "N" in the regression table (e.g., 11 or 12) likely refers to the number of data points used for regression analysis, representing these diluted samples.
• Specificity (Inhibition) Test Set: A single serum sample or pool of sera was used for each specific allergen, tested with various concentrations of inhibitor extract. For cross-reactivity, one positive sample with three unrelated allergen extracts was used.
• Clinical Performance Test Set: A total of 1,398 serum samples were tested: 396 from clinically diagnosed atopic individuals and 1,002 from non-atopic individuals.
• Data Provenance: The document does not explicitly state the country of origin for the clinical or analytical samples. The study appears to be retrospective, as it refers to "serum samples from clinically diagnosed atopic and non-atopic individuals" and "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity."

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

N/A. For this IVD device, ground truth for clinical performance was established by "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." It does not involve human readers/experts evaluating images or other subjective data, but rather diagnoses and other medical records.

4. Adjudication Method for the Test Set

N/A. Ground truth for clinical performance was based on "clinical documentation." There is no mention of an adjudication method among multiple experts for establishing this ground truth, as it's based on existing clinical diagnoses and evidence.

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

No, an MRMC comparative effectiveness study was not done. This is not applicable to a standalone immunoassay device like the IMMULITE® 2000 3gAllergy™ Specific IgE Assay, which performs an automated quantitative measurement and does not involve human readers interpreting results in the same way as, for example, diagnostic imaging studies.

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

Yes, the studies described are essentially "standalone" performance studies for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay. The device performs the quantitative measurement of allergen-specific IgE without human intervention in the analytical process. The results are then compared to "clinical documentation," but the device's measurement itself is autonomous.

7. The Type of Ground Truth Used

• Analytical Performance (Precision, Linearity): Ground truth is based on the inherent properties of the quality control materials (e.g., known concentrations for linearity, statistical properties for precision).
• Specificity (Inhibition): Ground truth for inhibition is the expected biochemical reaction demonstrating specific binding. Ground truth for cross-reactivity is established by using known unrelated allergens and expecting a low response.
• Clinical Performance: The ground truth for the clinical performance study was based on clinical diagnoses and "other diagnostic evidence of allergen sensitivity" from medically documented cases (e.g., atopic or non-atopic individuals). This is considered outcomes data or existing clinical records.

8. The Sample Size for the Training Set

N/A. This document describes the validation of a laboratory diagnostic assay, not an AI/machine learning algorithm that typically requires a distinct training set. The assay's "design" is based on established immunochemistry principles rather than training on a dataset.

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

N/A. As this is not an AI/ML algorithm, there is no "training set" in that context.

Ask a specific question about this device

Ask a specific question about this device

For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

The Siemens Healthcare Diagnostics Inc. IMMULITE® 2000 3gAllergy™ Specific IgE Assay is an in vitro diagnostic device intended for the quantitative measurement of allergen-specific IgE in human serum, to aid in the clinical diagnosis of IgE-mediated allergic disorders. The provided document focuses on the clearance of 27 additional specific allergens for use with this existing assay.

Here's an analysis of the acceptance criteria and study data provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for precision, linearity, or specificity (inhibition). Instead, it presents the study results and concludes that they demonstrate "acceptable analytical performance." For clinical performance, it discusses general agreement with clinical data.

Therefore, the table below will summarize the reported performance metrics, implying that these results were deemed acceptable by the manufacturer and the FDA for substantial equivalence.

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

• Precision: Three positive samples and one negative sample were tested for each allergen. Each sample was assayed in two aliquots, two runs per day, on 20 different days, for three allergen lots. This setup aims to assess within-run and total precision across different batches and extended testing periods.
• Linearity: For each allergen, two samples were diluted in 2-fold serial dilutions to 5 levels. Each diluted and undiluted sample was tested.
• Specificity (Inhibition): A "single serum sample or pool of sera" was used for competitive inhibition testing for each allergen. A negative sample was used as a background control. Inhibition experiments involved 70uL of undiluted and minimally 4-5 levels of serially diluted inhibitor extract (5, 1, 0.2, 0.04, 0.008 mg/mL, and sometimes more dilute levels). Each sample mixture with inhibitor extract and controls was assayed with 1 lot of each allergen.
• Clinical Performance: 4,118 samples were tested: 1,238 from clinically positive individuals and 2,880 from clinically normal (non-atopic) individuals.
• Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective for any of these studies. It can be inferred that these are prospective studies conducted by the manufacturer, Siemens Healthcare Diagnostics Inc., for regulatory submission.

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

• Precision, Linearity, Specificity: For these analytical performance studies, the "ground truth" is based on the inherent properties of the measurements and controls, rather than expert interpretation of a diagnostic outcome. The accuracy of the assay itself is being evaluated.
• Clinical Performance: For the clinical performance study, the "ground truth" (clinical data for IgE-mediated allergic disorders) was established based on "clinically diagnosed atopic and non-atopic individuals." The document does not specify the number or qualifications of the experts (e.g., allergists, physicians) who performed these clinical diagnoses.

4. Adjudication Method for the Test Set

• Precision, Linearity, Specificity: Not applicable. These are analytical studies where results are quantitative measurements against known standards or controls.
• Clinical Performance: The document states that the ground truth for clinical performance was based on "clinical data" to define individuals as "clinically diagnosed atopic and non-atopic individuals." There is no mention of an adjudication method (like 2+1, 3+1 consensus) explicitly detailed for the clinical diagnoses themselves. It implies that these were established clinical classifications prior to testing with the IMMULITE® 2000.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an imaging device or AI algorithm intended to assist human readers in interpretation. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply here.

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

Yes, the studies evaluating the IMMULITE® 2000 3gAllergy™ Specific IgE Assay are fundamentally standalone. The device performs quantitative measurements of IgE levels in serum, and its performance (precision, linearity, specificity, and comparison to clinical diagnoses) is assessed based on these measurements. There is no "human-in-the-loop" component in the analytical operation of the assay or the interpretation of its quantitative output for the purpose of these performance studies. Clinicians then use these quantitative results, alongside other clinical information, for diagnosis.

7. Type of Ground Truth Used

• Precision, Linearity: Ground truth is based on known concentrations or expected values derived from serial dilutions.
• Specificity (Inhibition): Ground truth is based on the known presence and concentration of the inhibitor extract and the expected inhibition of the specific allergen reaction.
• Clinical Performance: The ground truth was "clinical data," referring to the diagnosis of "clinically diagnosed atopic and non-atopic individuals." This would typically involve a combination of patient history, physical examination, and potentially other diagnostic tests (e.g., skin prick tests, other lab results, patient symptoms, and outcomes). It is not solely pathology or "outcomes data" in a broader sense but relies on a clinical determination of allergy status.

8. Sample Size for the Training Set

The document describes performance studies for the device itself, not the development of an algorithm that would require a distinct "training set" in the context of machine learning or AI. Therefore, the concept of a training set for an AI algorithm is not applicable to this submission. The studies detailed are for validation of the assay performance.

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

As explained in point 8, the concept of a "training set" for an AI algorithm is not applicable to these studies for this in vitro diagnostic device.

Ask a specific question about this device

For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support.

The provided text details the analytical and clinical performance of the IMMULITE® 2000 3gAllergy™ Specific IgE Assay for several new allergens.

Here's an analysis based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for precision, linearity, or specificity. Instead, it presents the results of these studies and concludes that the performance is "acceptable" or "compares well" to clinical documentation.

However, based on the conclusions drawn and the type of data presented, implicit acceptance criteria can be inferred from the reported performance. The clinical performance section, in particular, provides quantifiable results that the device is deemed to meet.

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

• Test Set Sample Size:

  • Precision: For each allergen, three positive samples and one negative sample were tested (with a fourth positive sample for Poplar and Careless Weed). Each sample was assayed in two aliquots per run, over 20 different days, across three allergen lots. This indicates a substantial number of individual measurements (e.g., 4 samples/allergen * 2 aliquots * 2 runs/day * 20 days = 320 measurements per allergen per lot for general precision, plus additional for Poplar/Careless Weed)
  • Linearity: For each allergen, two samples were diluted in 2-fold serial dilutions to 5 levels (total 6 concentrations including neat). "N" values in the table are 8 or 12, likely representing the number of data points used in the regression analysis for each allergen.
  • Specificity (Inhibition): A single serum sample or pool of sera was used, tested at 5 or 6 different inhibitor concentrations.
  • Clinical Performance: A total of 928 samples were tested (289 from atopic patients, 639 from non-atopic individuals).

• Data Provenance: The document does not explicitly state the country of origin for the clinical data. The study describes "atopic patients with case histories of suspected clinical reactions" and "non-atopic individuals," suggesting real-world patient samples. It's a prospective collection of data for the purpose of the study, as it describes "demonstrated by testing samples..." and comparing results to "accompanying clinical information."

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

• Number of Experts: The document does not specify the exact number of experts.
• Qualifications of Experts: The ground truth for the clinical performance study was established by "clinical data" including "case histories of suspected clinical reactions to the specific allergen or allergy group" and "documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This implies evaluation by clinical allergists or immunologists, though their specific titles or years of experience are not provided.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (e.g., 2+1, 3+1). The "ground truth" for the clinical study was established by "accompanying clinical information" and "documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This suggests that a medical diagnosis, likely by a single expert or a standard clinical practice, served as the ground truth rather than a multi-reader adjudication process for the specific study.

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

No. The provided text does not describe a multi-reader multi-case (MRMC) comparative effectiveness study. This study focuses on the analytical and clinical performance of the automated assay itself, not on how human readers interact with or are augmented by AI. Therefore, there is no effect size reported for human readers improving with or without AI assistance.

6. Standalone Performance Study

Yes. The entire performance evaluation presented for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay is a standalone (algorithm only) performance study. The device is an automated in vitro diagnostic immunoassay, meaning it directly measures allergen-specific IgE levels in human serum using a machine, without a human-in-the-loop for interpretation of the assay's direct output. The results are quantitative measurements (kU/L) produced solely by the instrument.

7. Type of Ground Truth Used

• Analytical Studies (Precision, Linearity, Specificity): Ground truth was established through known concentrations, dilutions, or inhibition properties of the samples used, verified through established laboratory methods and controls.
• Clinical Performance Study: The ground truth was based on clinical data, specifically "documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity" and "case histories of suspected clinical reactions to the specific allergen or allergy group." This is a form of clinical diagnosis or outcomes data related to a patient's allergic status.

8. Sample Size for the Training Set

The document does not specify a separate training set or its sample size. This type of in vitro diagnostic assay, particularly one based on immunoassay technology for detecting specific biomarkers, typically doesn't involve a machine learning "training set" in the way an AI image analysis algorithm would. The development of the assay reagents and protocols is based on scientific principles of immunology and chemistry, rather than iterative learning from a large dataset of patient samples to "train" an algorithm.

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

As no explicit training set for a machine learning algorithm is mentioned or implied, the concept of establishing ground truth for a training set in this context does not apply. The development of this type of diagnostic assay relies on validating the chemical and biological reactions against known standards and clinically defined conditions over years of research and development inherent in immunoassay technology.

Ask a specific question about this device

For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support.

Here's a breakdown of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on analytical and clinical performance without explicitly stating numerical acceptance criteria prior to presenting the results. However, we can infer implied acceptance criteria from the reported performance, especially for linearity and specificity (inhibition). For clinical sensitivity and specificity, the provided confidence intervals suggest a critical range.

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

• Precision: For each of the seven allergens, three positive samples and one negative sample were tested. Each sample was assayed in two aliquots per day for 20 different days, totaling 40 measurements per sample.
• Linearity: For each allergen, two samples were diluted into 5 levels (undiluted + 4 dilutions). The table shows N=12 for each allergen, implying 2 samples * 5 dilutions + 2 undiluted samples.
• Specificity (Inhibition): A single serum sample or pool of sera was used for each allergen.
• Clinical Performance:
  • Total Patients: 1,157 individuals.
  • Clinical Data: 261 positive, 896 normal.
  • Data Provenance: The document does not explicitly state the country of origin. It samples were described as "samples from non-atopic individuals and samples from atopic patients with case histories of suspected clinical reactions." This indicates that the data is retrospective clinical data for the "clinical data" ground truth, likely collected from patients presenting with symptoms.

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.
• For clinical performance, the ground truth is referred to as "clinical data" which includes "case histories of suspected clinical reactions to the specific allergen or allergy group" and "documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This suggests that the clinical diagnosis was established by medical professionals, but not explicitly stated as a panel of "experts" for the study itself.

4. Adjudication Method for the Test Set

• The document does not describe a formal adjudication method (e.g., 2+1, 3+1). The "clinical data" appears to be the established reference.

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

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This study evaluates an in vitro diagnostic (IVD) assay (IMMULITE® 2000 3gAllergy™ Specific IgE Assay), which is a laboratory test, not an AI system that assists human readers. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply.

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

• Yes, the performance presented for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay is standalone (algorithm only). This device is an automated in vitro diagnostic test that quantitatively measures allergen-specific IgE. Its performance is evaluated independently of human interpretation of the assay results, though human clinicians will interpret a patient's overall clinical picture, including the assay results.

7. The Type of Ground Truth Used

• Precision and Linearity: Internal quality control materials or spiked samples with known concentrations.
• Specificity (Inhibition): Known relevant inhibitor extracts and negative control samples.
• Clinical Performance: "Clinical data" described as "case histories of suspected clinical reactions to the specific allergen or allergy group" and "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." For the egg allergen, comparison studies were done against previously cleared individual egg constituents (egg white and egg yolk allergens). This is best characterized as clinical documentation/diagnosis.

8. The Sample Size for the Training Set

• The document does not mention a training set. This is not applicable as the device is a chemiluminescent immunoassay, not a machine learning algorithm that requires a training set. The "assay" itself is the device, and its development involves chemical and biological optimization, not algorithm training.

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

• Not applicable, as there is no training set for this type of device.

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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid.phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer/co-polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support.

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

Description of Device: The IMMULITE® 2000 3gAllergy™ Specific IgE Assay is a solid-phase, two-step, chemiluminescent immunoassay for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. This submission focuses on clearance for eleven additional specific allergens.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for precision, linearity, or inhibition (specificity). Instead, the studies demonstrate the performance and imply that the results obtained are considered acceptable for a device of this type. The table below summarizes the reported performance for each study.

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

• Precision Test Set:

  • For each of the 11 allergens, three positive samples and one negative sample were used. These were assayed in two aliquots per run, across two runs per day, for 20 different days.
  • Provenance: Not specified, but generally, such studies are conducted in-house by the manufacturer.
  • Retrospective/Prospective: Prospective, as it involved controlled experimental conditions.

• Linearity Test Set:

  • For each allergen, two samples were diluted into 5 levels (undiluted + 4 serial dilutions).
  • Provenance: Not specified, likely internal.
  • Retrospective/Prospective: Prospective.

• Specificity (Inhibition) Test Set:

  • A single serum sample or a pool of sera was used for each allergen against a relevant inhibitor extract. A negative sample was also used to measure background response.
  • Provenance: Not specified, likely internal.
  • Retrospective/Prospective: Prospective.

• Clinical Studies Test Set:

  • Total N: 1,957 samples
  • Composition: Samples from "non-atopic individuals" and "atopic patients with case histories of suspected clinical reactions to the specific allergen or allergy group."
  • Provenance: Not specified (e.g., country of origin). The mention of "clinical data" suggests real-world patient samples.
  • Retrospective/Prospective: Not explicitly stated, but the comparison to "case histories" and clinical documentation suggests a retrospective analysis of collected samples with known clinical status.

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

• Precision, Linearity, Specificity: These are analytical performance studies and do not rely on expert ground truth in the same way clinical studies do. The ground truth for these is established by the known concentrations (linearity), or the inherent characteristics of the samples and inhibitors (specificity, precision) as determined by laboratory methods. No external experts are mentioned for establishing ground truth for these analytical tests.

• Clinical Studies:

  • The ground truth for the clinical study was "clinical data," meaning "accompanying clinical information" and "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity."
  • The document does not specify the number of experts, nor their qualifications (e.g., allergists, physicians with specific experience) who established this clinical ground truth.

4. Adjudication Method for the Test Set

• Precision, Linearity, Specificity: Not applicable, as these are quantitative analytical measurements.
• Clinical Studies: The document does not describe an adjudication method for the "clinical data" to establish ground truth. It simply refers to "accompanying clinical information" or "clinical documentation."

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

• No, an MRMC comparative effectiveness study was not done. The device is an in vitro diagnostic assay, not an imaging or interpretation aid for human readers. It provides a quantitative measurement.

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

• Yes, the conducted studies are standalone evaluations of the assay's performance. The IMMULITE® 2000 3gAllergy™ Specific IgE Assay itself is the "algorithm/device" in this context, providing a quantitative value. The clinical study compares its output against clinical information, not against human reader interpretations of results.

7. The Type of Ground Truth Used

• Precision, Linearity, Specificity: Ground truth is established by laboratory standards, known concentrations, and controlled experimental conditions for biochemical reactions.
• Clinical Studies: The ground truth used was "clinical data," which includes "case histories of suspected clinical reactions" and "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This falls under outcomes data / clinical diagnosis as determined by medical professionals.

8. The Sample Size for the Training Set

• The document does not describe a separate "training set" for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay. This device is an in vitro diagnostic assay, typically developed and validated using a different paradigm than AI/machine learning algorithms that require distinct training, validation, and test sets. The studies described are performance evaluations of the assay itself.

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

• As there is no mention of a "training set" in the context of this immunoassay's development as an AI/ML device, this question is not applicable. The development of such assays involves optimizing reagents and conditions rather than training an algorithm on a data set with established ground truths.

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For in vitro diagnostic use with the IMMULITE® 2000 Analyzer - for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders.

IMMULITE® 2000 3gAllergy™ Specific IgE is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support, such as a paper disk. The allergens are covalently bound to a soluble polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. Incubation Cycles: 2 × 30 minutes.

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes several performance criteria for the IMMULITE® 2000 3gAllergy™ Specific IgE Assay, including precision, linearity, and specificity. Clinical performance is also assessed.

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

• Precision Studies: Three positive samples and one negative sample were tested for each allergen lot. The testing involved two aliquots of each test sample in two runs per day on 20 different days, following CLSI document EP5-A2. The exact number of individual measurements can be calculated from these parameters (3 positive samples * 2 aliquots/sample * 2 runs/day * 20 days = 240 measurements for positive samples per lot, plus negative control measurements).
• Linearity Studies: For each allergen, two samples were diluted into 5 levels. These 12 samples (2 original + 10 diluted) were tested.
• Specificity (Inhibition) Studies: A single serum sample or pool of sera was used for each allergen. For each inhibition experiment, 70uL of undiluted and 4 levels of 5-fold serially diluted inhibitor extract were mixed with 250uL of sample or pool.
• Clinical Studies: A total of 1,100 samples were used. This included 288 samples from atopic patients with case histories of suspected clinical reactions to the specific allergen or allergy group, and 812 samples from non-atopic individuals.
• Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the clinical studies describe "samples from non-atopic individuals" and "samples from atopic patients with case histories of suspected clinical reactions to the specific allergen or allergy group," which implies a prospective or at least carefully selected retrospective collection for diagnostic relevance.

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

The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense of image interpretation or complex diagnostic decision-making.

• For the Precision, Linearity, and Specificity (Inhibition) studies, the "ground truth" is based on the inherent biochemical properties of the assay and the measured values, not expert interpretation.
• For the Clinical Studies, "clinical data" was used as the reference. This "clinical data" is described as "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity" and "case histories of suspected clinical reactions." This implies that the ground truth was established by medical professionals (e.g., allergists, physicians) based on patient history, symptoms, and other diagnostic findings; however, the specific number and qualifications of these experts are not provided in this document.

4. Adjudication method for the test set:

Not applicable. The types of studies described (analytical performance and comparison to clinical documentation) do not involve adjudication methods like those used for expert consensus in medical image analysis.

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 versus without AI assistance:

Not applicable. This document describes an in vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers.

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

Yes, the studies presented are all standalone performance evaluations of the IMMULITE® 2000 3gAllergy™ Specific IgE Assay itself (the "device" being the assay system), without human-in-the-loop interaction for interpretation beyond standard laboratory procedures. The device provides a quantitative measurement of allergen-specific IgE.

7. The type of ground truth used:

• Precision, Linearity, Specificity: Ground truth is based on physical and chemical measurement principles and established scientific methods for evaluating assay performance (e.g., known concentrations for linearity, defined inhibition protocols for specificity).
• Clinical Studies: The ground truth used was "clinical data," consisting of "clinical documentation of presence or absence of signs, symptoms and other diagnostic evidence of allergen sensitivity" and "case histories of suspected clinical reactions" to specific allergens. This can be categorized as outcomes data and expert clinical assessment.

8. The sample size for the training set:

The document describes performance evaluation studies and does not refer to a "training set" in the context of machine learning or AI development. The studies are for validating the assay's performance against established clinical and analytical benchmarks.

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

Not applicable, as there is no mention of a "training set" in the provided document. The studies focus on analytical validation and clinical concordance of the assay itself.

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