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For the in vitro quantitative determination of degradation products of type I collagen in human serum and plasma, for assessing individual bone resorption. The test may be used as an aid in monitoring anti-resorptive therapies (e.g. bisphosphonates, hormone replacement therapy - HRT) in postmenopausal women and individuals diagnosed with osteopenia. The elecrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche ELECSYS 1010 and 2010 immunoassay analyzers.

The ELECSYS® β-CrossLaps/serum Test is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code card.

This document describes a 510(k) submission for the ELECSYS® β-CrossLaps/serum Immunoassay, seeking substantial equivalence to a predicate device. It does not contain a study proving the device meets specific acceptance criteria in the traditional sense of a clinical trial with pre-defined performance thresholds for accuracy, sensitivity, or specificity against a ground truth.

Instead, the submission focuses on demonstrating "substantial equivalence" to a legally marketed predicate device (Osteometer Serum CrossLaps™ One Step ELISA) by comparing various performance characteristics. The acceptance criteria are implicitly defined by the comparable performance of the predicate device.

Here's an analysis of the provided information:

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

Since this is a substantial equivalence claim, the "acceptance criteria" are the performance characteristics of the predicate device, and "reported device performance" is the performance of the ELECSYS® β-CrossLaps/serum Immunoassay.

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

The document does not explicitly state the total sample size used for the performance characteristic studies (e.g., precision, analytical sensitivity, interference).

• Precision: "Human sera" and "Controls" are mentioned, implying multiple samples were tested at different concentrations. Specific numbers are not provided.
• Interference: Various substances were tested for interference, but the number of samples or specific experimental setup for these tests is not detailed.

The data provenance (country of origin, retrospective/prospective) is not mentioned. Given it's a submission to the FDA, it's likely the studies were conducted under good laboratory practices, but the location is not specified.

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

This type of immunoassay does not typically involve human experts establishing a "ground truth" in the same way an imaging device might. The "ground truth" for an immunoassay is typically established by:

• Reference materials/standards: The analytical sensitivity and calibration are based on purified peptides and internal reference standards.
• Clinical correlation: While the intended use includes monitoring therapies, the document primarily focuses on analytical performance. Clinical correlation studies (e.g., comparing results to patient outcomes) are not detailed here as the primary "ground truth" for the device's technical performance.

Therefore, this question is not directly applicable to the type of device and study described.

4. Adjudication Method for the Test Set

Not applicable. This is an immunoassay, and measurements are quantitative. There's no human interpretation or subjective assessment of results that would require an adjudication method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve With AI vs Without AI Assistance

Not applicable. This is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic imaging device for human readers.

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

Yes, the performance characteristics (precision, analytical sensitivity, interference) provided are for the device (ELECSYS® β-CrossLaps/serum Immunoassay) operating in a standalone mode on the ELECSYS 1010 and 2010 immunoassay analyzers, without human-in-the-loop performance influencing the measurement itself. Humans operate the machines and interpret the results, but the analytical performance data are intrinsic to the device.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The "ground truth" for an immunoassay's analytical performance (as presented here) relies on:

• Reference standards/Calibrators: Purified peptide standards are used for calibration and traceability. These are the fundamental "ground truth" for achieving accurate quantitative measurements.
• Validated measurement methods: The performance characteristics are measured against established laboratory practices and often using validated control materials.

For the intended use of "assessing individual bone resorption" and "monitoring anti-resorptive therapies," the ultimate ground truth would involve clinical factors like bone mineral density (BMD) changes, fracture rates, or other clinical outcomes. However, this submission focuses on the analytical equivalence of the assay itself, not a full clinical outcome study.

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense of developing a model. The "training" for such a device involves establishing calibration curves and optimizing manufacturing processes, which utilizes internal quality control and validation data rather than a distinct "training set" for an algorithm.

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

Not applicable, as there is no "training set" for an algorithm in this context. The "ground truth" for the device's operational parameters (e.g., calibration curve) is established using validated controls and reference materials with known concentrations of the analyte (degradation products of type I collagen).

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Osteomark NTx Point of Care (POC) is a urinary assay for the quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) normalized to urinary creatinine (nM Bone Collagen Equivalents/mM creatinine). The test is used to monitor bone resorption changes following initiation of antiresorptive therapy (e.g., hormone replacement therapy).

Osteomark NTx Point of Care (POC) is a urinary assay for the quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) normalized to urinary creatinine (nM Bone Collagen Equivalents/mM creatinine).

This document is a 510(k) clearance letter from the FDA for a device called "OSTEOMARK® NTx Point of Care (POC)". It is not a study report, and therefore, it does not contain the detailed information necessary to answer the questions about acceptance criteria and study design.

Specifically, the document does not provide:

• A table of acceptance criteria and reported device performance.
• Sample sizes for test sets, data provenance, or details on training sets.
• Information on ground truth establishment (number of experts, qualifications, adjudication method, type of ground truth).
• Details on multi-reader multi-case (MRMC) comparative effectiveness studies or standalone performance.

The letter simply states that the FDA has reviewed the 510(k) notification and determined the device is substantially equivalent to legally marketed predicate devices, allowing it to be marketed. It refers to the "Indications For Use" which describes what the device does (measures N-telopeptides of type I collagen to monitor bone resorption changes following antiresorptive therapy).

To answer these questions, you would need to refer to the actual 510(k) submission document (K992997) or other study reports related to the OSTEOMARK® NTx Point of Care (POC) device, which are not included in this provided text.

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The Serum CrossLaps™ One Step ELISA assay is intended for in vitro diagnostic use as an indication of human bone resorption and may be used as an aid in : Monitoring bone resorption changes of A. 1.) Anti-resorptive therapies in postmenopausal women: a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies 2. ) Anti-resorptive therapies in individuals diagnosed with osteopenia; a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies B. Predicting skeletal Response (Bone Mineral Density) in postmenopausal woman under going anti-resorptive therapies a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs b) Bisphosphonate therapies

The Serum CrossLaps™ One Step ELISA kit was developed for the quantitative measurement of Type I Collagen C-Telopeptide (CrossLaps™) in human plasma and serum. The EIA format is a non-competitive binding protein assay. The Serum CrossLaps 114 One Step ELISA is based on two highly specific monoclonal antibodies against the amino acid sequence of EK AHD-B-GGR, where the aspartic acid residue (D) is ß-isomerized. In order to obtain a specific signal in the Serum CrossLaps 114 One Step ELISA, two chains of EK AHD-S-GGR must be cross-linked Standards, control, or unknown serum samples are pipetted into the appropriate microtitre wells coated with streptavidin, followed by application of a mixture of a biotinylated antibody and a peroxidase-conjugated antibody. Then, a complex between CrossLaps 110 antigens, biotinylated antibody and peroxidase-conjugated antibody is generated, and this complex binds to the streptavidin surface via the biotinylated antibody. Following the one-step incubation at room temperature, the wells are emptied and washed. A chromogenic substrate is added and the colour reaction is stopped with sulfuric acid. Finally, the absorbance is measured at 450 nm.

The provided text describes the Serum CrossLaps™ One Step ELISA device and its pre-market notification (K990843) for FDA clearance. However, the document does not contain a detailed study proving the device meets specific acceptance criteria with reported device performance metrics. Instead, it focuses on demonstrating substantial equivalence to a previously cleared predicate device (CrossLaps™ ELISA, K972788).

Therefore, I cannot fully complete all sections of your request based solely on the provided text. I will fill in the information that is available and indicate where data is missing.

Acceptance Criteria and Study Proving Device Meets Acceptance Criteria

The primary study detailed in this pre-market notification is a demonstration of substantial equivalence to a legally marketed predicate device (CrossLaps™ ELISA, K972788). This type of submission relies on showing that the new device is as safe and effective as the predicate device, not necessarily by meeting pre-defined numerical acceptance criteria for novel performance.

Please note: The document explicitly states the "pre-market notification includes clinical data demonstrating that" without elaborating on the specifics of this data or presenting numerical acceptance criteria or performance metrics directly from that data. The focus is on the intent for use and equivalence.

1. Table of acceptance criteria and the reported device performance

• Monitoring bone resorption changes in:
  a) Postmenopausal women undergoing anti-resorptive therapies (HRT, Bisphosphonate).
  b) Individuals with osteopenia undergoing anti-resorptive therapies (HRT, Bisphosphonate).
• Predicting skeletal response (Bone Mineral Density) in postmenopausal women undergoing anti-resorptive therapies (HRT, Bisphosphonate). |
  | Performance equivalent to predicate device (K972788) for the stated indications for use. | Clinical data demonstrates substantial equivalence to predicate device K972788 (details of this data or specific performance metrics are not provided in the summary). |

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

• Sample size for test set: Not explicitly stated in the provided text. The document mentions "clinical data demonstrating that" without specifying the number of samples or subjects used in this clinical data.
• Data provenance: Not explicitly stated in the provided text (e.g., country of origin). The data is described as "clinical data," implying human subjects, but specifics are missing. It is implied to be retrospective or prospective as part of a pre-market notification, but this is not explicitly stated.

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

• This information is not provided in the given text. The device measures a biochemical marker (Type I Collagen C-Telopeptide). Ground truth for such a device would typically involve comparing its measurements to established reference methods or clinical outcomes, rather than expert consensus on images.

4. Adjudication method for the test set

• This information is not provided in the given text, as the context is a biochemical assay, not an imaging device requiring expert adjudication of results.

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 question is not applicable to the described device. The Serum CrossLaps™ One Step ELISA is an in vitro diagnostic (IVD) assay for measuring a biochemical marker, not an AI-assisted diagnostic imaging device that involves human readers.

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

• This question is not applicable in the AI sense. The device is a standalone diagnostic assay (an ELISA kit) that provides quantitative results without human interpretation of complex patterns, thus already "algorithm only" in its biochemical analysis. It's not an AI algorithm but a laboratory test.

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

• The ground truth would most likely be established by comparison to existing, validated methods for measuring Type I Collagen C-telopeptides or correlation with clinical outcomes data relevant to bone resorption (e.g., Bone Mineral Density changes, fracture rates). However, the specific type of ground truth used in the substantial equivalency demonstration is not detailed in the provided text. The submission relies on "clinical data demonstrating" equivalence to a predicate device, which implies the predicate device's established performance serves as a benchmark rather than a new 'ground truth' being established from scratch.

8. The sample size for the training set

• This information is not provided in the given text. For an ELISA kit, "training set" doesn't apply in the same way it would for an AI algorithm. Development and validation would involve studies to establish assay linearity, precision, accuracy, etc., potentially using various sample types and concentrations, but these are not explicitly referred to as a "training set" with a specified size.

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

• This information is not provided and is not applicable in the AI sense for this type of device. The "ground truth" for developing an ELISA method is typically based on the known concentrations of target analytes in reference materials or samples, or by comparison to established gold standard methods for the biochemical measurement.

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Osteomark® NTx Serum EIA provides a quantitative measure of cross-linked Ntelopeptides of type I collagen (NTx) in serum as an indicator of human bone resorption. Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Prior to initiating antiresorptive therapy, serum NTx level is used to determine the probability for a decrease in bone mineral density after one year in postmenopausal women treated with hormonal antiresorptive therapy relative to those treated with calcium supplement.

The Osteomark NTx Serum EIA is a competitive-inhibition enzyme-linked immunosorbent assay (ELISA/EIA) for quantitative determination of NTx present in human serum. NTx is adsorbed to a 96-well microplate: Diluted samples are added to the microplate wells, followed by a horseradish peroxidase labeled monoclonal antibody. NTx in the specimen competes with the NTx epitope on the microtiter plate for antibody binding sites. Following a wash step, the amount of labeled antibody bound is measured by colorimetric generation of a peroxide substrate. NTx concentration is determined spectrophotometrically and calculated using a standard calibration curve. Assay values are reported in nanomoles Bone Collagen Equivalents per liter (nM BCE).

The Osteomark NTx Serum EIA is a competitive-inhibition enzyme-linked immunosorbent assay (ELISA/EIA) designed for the quantitative determination of NTx in human serum. This assay is used to predict skeletal response to antiresorptive therapy and to monitor changes in bone resorption after therapy initiation. It also helps determine the probability of bone mineral density decrease in postmenopausal women on hormonal antiresorptive therapy versus those on calcium supplements.

1. Table of Acceptance Criteria and Reported Device Performance

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

The document describes several studies:

• Reference Range Studies:
  • Premenopausal Women: N = 257 (multi-center, cross-sectional study at five regional sites). The country of origin is not specified but implied to be the US given the FDA submission. This was a prospective study to determine reference ranges.
  • Men: N = 176 (multi-center, cross-sectional study at three regional sites). The country of origin is not specified but implied to be the US. This was a prospective study to determine reference ranges.
• Intra-subject Variability Studies:
  • Postmenopausal Women: n=271 (short-term), n=261 (long-term). Provenance not specified. Retrospective/Prospective not specified for this specific study, but the overall context suggests prospective data collection in clinical settings.
  • Men: n=32 (short-term), n=27 (long-term). Provenance not specified. Retrospective/Prospective not specified for this specific study.
• Assay Reproducibility and Precision Studies:
  • Intra-assay variability: Four human serum specimens. Provenance not specified. Not directly tied to a clinical population, but rather assay samples.
  • Inter-assay variability: Eight human serum specimens. Provenance not specified. Not directly tied to a clinical population, but rather assay samples.
  • Total assay precision: Level I Serum Control and Level II Serum Control tested at four clinical laboratories. Provenance not specified. These are control materials, not patient samples.
• Antigen Recovery: Nine serum specimens. Provenance not specified. These are assay samples.
• Dilutional Linearity: Five serum specimens. Provenance not specified. These are assay samples.
• Clinical Studies (HRT):
  • Postmenopausal Women treated with HRT: The study enrolled a cohort of postmenopausal women. The baseline NTx mean was 15.9 nM BCE. Post-treatment mean was 12.2 nM BCE. While a specific N for the HRT group is not provided in this summary, the context suggests a clinical trial. The study results (Reference 4) indicate the source is likely from U.S. clinical trials. This was a prospective clinical trial.
• Clinical Studies (Bisphosphonate):
  • Postmenopausal Women treated with Bisphosphonate: The study was conducted at a regional specialty hospital in the northeast United States. The study was randomized and double-blind. N is not explicitly stated in the summary, but it involved women randomized to either placebo or alendronate. This was a prospective clinical trial.

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

The document does not describe the use of human "experts" to establish ground truth for the device performance studies in the traditional sense of a diagnostic interpretation.

For the clinical efficacy studies (HRT and Bisphosphonate), the "ground truth" was clinical outcomes:

• Bone Mineral Density (BMD) changes: Measured by objective methods (e.g., DEXA scans) over time. This is an objective clinical measurement, not expert consensus on an image or test result.
• Response to therapy: Defined by changes in NTx levels and subsequent changes in BMD.

4. Adjudication Method for the Test Set

Not applicable. The reported studies evaluate the analytical performance of the assay and its correlation with clinical outcomes (BMD changes), not the interpretation of results by human readers requiring adjudication.

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

No. The Osteomark NTx Serum EIA is an in-vitro diagnostic assay for quantitative measurement. It does not involve human readers interpreting images or data where AI assistance would be relevant for a MRMC study.

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

Yes, implicitly. The performance characteristics (variability, recovery, linearity) and the clinical utility of the assay itself (e.g., "Osteomark NTx Serum EIA mean baseline values... fell significantly after 3 months of therapy") are reported as standalone performance of the diagnostic kit. There is no human-in-the-loop component for the assay's execution or the interpretation of the numerical NTx values for these studies. The physician uses the derived NTx value in clinical management.

7. Type of Ground Truth Used

• Analytical Performance: The ground truth for analytical performance (variability, recovery, linearity) is based on established laboratory analytical methods and expected theoretical values for spiked samples or diluted controls.
• Clinical Studies: The ground truth for the clinical studies (HRT and Bisphosphonate) is outcomes data and objective clinical measurements:
  • Bone Mineral Density (BMD) assessed after one year.
  • Changes in NTx levels post-therapy. This is an outcome of the intervention, not an externally established ground truth for the device itself.

8. Sample Size for the Training Set

The document describes the device performance validation and clinical studies. There is no description of a "training set" in the context of machine learning (AI) for this diagnostic assay. The terms "training set" and "test set" are not applicable in the typical AI sense to this type of in-vitro diagnostic device. Instead, the studies cited relate to establishing reference ranges and validating analytical and clinical performance.

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

Not applicable, as no "training set" in the AI sense is described. The analytical and clinical performance data were established through direct laboratory measurements and clinical trial outcomes, respectively, as outlined above.

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Vitros NTx Reagent Pack - For in-vitro quantitative measurement of cross linked N-telopeptides of type I collagen (NTx) in human urine as an indicator of human bone resorption. A single NTx value cannot provide the rate of bone resorption as reported results do not contain a measure of time. Use of this test has not been established in primary hyperparathyroidism or hyperthyroidism.
Vitros NTx Calibrators - For in-vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of NTx in human urine.
Vitros NTx Controls - For in-vitro use in the monitoring of the performance of the VITROS Immunodiagnostic System when used for the quantitative measurement of NTx in human urine.

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma and urine. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products NTx Reagent Pack, VITROS Immunodiagnostic Products NTx Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS NTx assay). 2. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. 3. Common reagents used by the VITROS System in each assay.

The provided text describes a 510(k) summary for the VITROS Immunodiagnostic Products NTx assay, asserting its substantial equivalence to a predicate device, the Osteomark NTx Test. The study primarily focuses on demonstrating this equivalence by comparing the performance of the new device against the predicate.

Here's an analysis of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The text does not explicitly state formal "acceptance criteria" with quantitative targets for accuracy, precision, sensitivity, or specificity in the way one might see for a completely novel device. Instead, the primary acceptance criterion is substantial equivalence to the predicate device, K980518.

The device performance is reported in the context of this equivalence:

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

• Test Set Sample Size: The text states, "Comparisons of the VITROS NTx assay and the predicate device were performed with samples from a variety of clinical categories." It also mentions "patient specimens covering a variety of clinical categories." However, no specific number or range for the sample size of the test set is provided.
• Data Provenance: The text does not explicitly state the country of origin. It indicates that "currently commercially available reagents along with patient specimens" were used, implying the data
  • Retrospective/Prospective: Not specified.

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

This type of information is not applicable to this study. The study focuses on the analytical performance and correlation of a diagnostic assay (measuring NTx levels in urine) against a legally marketed predicate device. The "ground truth" for each sample is assumed to be the measurement obtained by the predicate device and/or the actual NTx concentration in the urine sample, rather than an expert's interpretation of an image or clinical condition. Therefore, no experts were used to establish a ground truth in the context of interpretation or diagnosis.

4. Adjudication Method for the Test Set

Not applicable. As the study involves quantitative laboratory measurements and comparison to a predicate device, adjudication by a panel of human experts is not relevant. The comparison is based on numerical results and statistical correlation methods like Deming's Regression.

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

No, a MRMC comparative effectiveness study was not done. This type of study is typically associated with imaging diagnostics or clinical assessments requiring human interpretation. This submission is for an in-vitro diagnostic (IVD) assay where performance is objectively measured by the instrument.

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

Yes, this is essentially a standalone performance study. The VITROS Immunodiagnostic System, which performs the NTx assay, operates as an automated system without direct human-in-the-loop performance affecting the measurement itself. The results are quantitative measurements generated by the instrument. The comparison to the predicate device is also a standalone comparison between two analytical methods.

7. The Type of Ground Truth Used

The ground truth used for this study is primarily the measurements obtained from the predicate device (Osteomark NTx Test) for the purpose of demonstrating substantial equivalence. Additionally, typical "ground truth" for analytical studies of IVDs would involve:

• Reference materials/standards with known concentrations: Used for analytical sensitivity, specificity, and calibration.
• Split samples analyzed by both devices: Demonstrating correlation between the new device and the predicate.

Pathology or outcomes data are not mentioned as direct ground truth for this specific 510(k) submission, whose primary goal is substantial equivalence for an analytical test.

8. The Sample Size for the Training Set

The text does not explicitly mention a "training set" or its size. For an IVD assay like this, the development process would involve extensive analytical characterization and optimization, which could be considered an internal "training." However, the document focuses on the validation against the predicate, not the internal development data.

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

Since no explicit "training set" is described, the method for establishing its ground truth is not provided. In the context of IVD development, ground truth during internal development (analogous to training) would typically involve:

• Using international reference materials.
• Comparing results to established laboratory methods.
• Verifying against carefully characterized samples to ensure accuracy across the assay's dynamic range.

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The CrossLaps™ ELISA assay is intended for in vitro diagnostic use as an indication of human bone resorption and may be used as an aid in :
A. Monitoring bone resorption changes of

1. ) Anti-resorptive therapies in postmenopausal women:
   a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
   b) Bisphosphonate therapies
2. ) Anti-resorptive therapies in individuals diagnosed with osteopenia;
   a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
   b) Bisphosphonate therapies
3. } Anti-resorptive therapies in individuals diagnosed with Paget's disease of bone
   B. Predicting skeletal Response (Bone Mineral Density) in postmenopausal woman under going anti-resorptive therapies
   a) Hormone Replacement Therapies (HRT) with hormones and hormone like drugs
   b) Bisphosphonate therapies

The CrossLaps™ ELISA kit was developed for the quantitative measurement of Type I Collagen C-Telopeptide (CrossLaps™) in human urine. The EIA format is a competitive binding protein assay. CrossLaps™ in the urine competes with the antigen coated to the microtitration wells for the enzyme labeled antibody displacing it from binding to the antigen coated wells. Separation of free form the bound CrossLaps™ is achieved by washing the well. The resultant is analyzed in a spectrophotometer for absorbance The amount of enzyme labeled CrossLaps™ present in the sample.

The provided text describes the CrossLaps™ ELISA kit, an in vitro diagnostic device for measuring Type I Collagen C-Telopeptide in human urine, and its expanded indications for use. However, the document (K972788) is a 510(k) pre-market notification that demonstrates substantial equivalence to a previously cleared device (K960171), rather than a detailed study report proving the device meets specific acceptance criteria based on performance studies.

Therefore, many of the requested details about acceptance criteria, study design, sample sizes, expert involvement, and ground truth establishment are not explicitly present in the provided text. The document focuses on the unchanged nature of the device's technical and clinical performance despite a minor component change (one-component TMB instead of two-component TMB) from its predicate device. It also outlines the expanded indications for use that were supported by "clinical data" but does not detail that data.

Based on the information available:

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

This information is not provided in the document. The document states:

"The technical and clinical performance of the device is not influenced by this substitution and no issues of safety and effectiveness are raised by this change."
This implies that the previous performance (of the predicate device K960171) was considered acceptable, and the minor change to the TMB substrate did not alter that performance. However, specific performance metrics or acceptance criteria are not quantified.

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

This information is not provided. The document mentions "clinical data demonstrating that The CrossLaps™ ELISA assay is intended for in vitro diagnostic use..." but does not elaborate on the sample size, design, or provenance of this clinical data.

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 information is not provided. As the document is a 510(k) for substantial equivalence and expanded indications rather than a detailed performance study, it does not include specifics about expert adjudication or ground truth establishment.

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

This information is not provided.

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 information is not applicable/provided. The CrossLaps™ ELISA is an in vitro diagnostic assay, not an imaging device or AI-assisted diagnostic tool that would involve multi-reader studies or human-in-the-loop performance measurement.

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

This information is not applicable/provided. As an ELISA kit, this device performs a biochemical measurement and doesn't involve an "algorithm" in the sense of AI or image interpretation. Its performance is inherent to the assay's chemical and biological interactions.

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

This information is not provided. For an in vitro diagnostic measuring a biomarker, the "ground truth" would typically involve correlation with clinical status, disease progression, or response to therapy, often established through clinical endpoints or reference methods. The document states the assay is "an indication of human bone resorption" and "an aid in monitoring bone resorption changes" and "Predicting skeletal Response (Bone Mineral Density)". This implies its performance is validated against these clinical outcomes or established markers. However, the specifics of how this ground truth was derived for any supporting clinical data are not detailed.

8. The sample size for the training set:

This information is not provided. ELISA kits do not typically have a "training set" in the same way machine learning models do. The development and validation of such assays involve different types of studies (e.g., analytical validation for sensitivity, specificity, accuracy, precision, linearity, and clinical validation for correlation with disease/outcomes). The document refers to "clinical data" but doesn't elaborate on its nature or sample size.

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

This information is not provided and is largely not applicable in the context of an ELISA assay's development.

In summary, the provided document is a regulatory submission focused on demonstrating substantial equivalence for an expanded indication for use, not a detailed scientific study report. It states that the device's performance is unchanged from its predicate despite a minor component alteration, but it does not detail the specific performance metrics, acceptance criteria, or the studies that would formally establish these for the current or predicate device.

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Measurement of Dpd is intended for use as an aid in monitoring bone resorption changes in postmenopausal women receiving hormonal or bisphosphonate antiresorptive therapies and in individuals diagnosed with osteoporosis.

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The provided document is an FDA 510(k) clearance letter for the Pyrilinks®-D Assay Kit. It confirms that the device is substantially equivalent to legally marketed predicate devices. However, this document does not contain any information regarding acceptance criteria, device performance studies, sample sizes, ground truth establishment, or expert involvement as requested in the prompt.

Therefore, I cannot provide the requested information from this document. The letter is administrative in nature, confirming regulatory clearance, but it does not delve into the technical details of the performance study that would have been submitted to the FDA.

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IMMULITE® Pyrilinks-D is a solid-phase, chemiluminescent enzyme immunoassay for use with the IMMULITE Automated Analyzer and is designed for the quartitative measurement of deoxypyridinoline (DPD) in urine. It is intended strictly for in vitro diagnostic use in monitoring type 1 collagen resorption changes, especially in bone in post menopausal women diagnosed with osteoporosis and receiving antiresorptive therapy (amino-bisphosphonate).

IMMULITE® Pyrilinks* - D is a clinical device for use with the IMMULITE® Automated Immunoassay Analyzer. IMMULITE® Pvrilinks"-D is a solid-phase, chemiluminescent immunoassay for use with the IMMULITE Automated Immunoassay Analyzer. The solid-phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for DPD, The patient sample and alkaline phosphatase-conjugated DPD are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, DPD in the sample competes with enzyme-labeled DPD for a limited number of antibody-binding sites on the bead. Unbound material is then removed by a centrifygal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes. The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex-and thus also the photon output, as measured by the luminometer- is inversely proportional to the concentration of DPD in the sample.

Here's an analysis of the provided text regarding acceptance criteria and the study that proves the device meets those criteria:

It's important to note that this document describes a 510(k) premarket notification for an in vitro diagnostic (IVD) device (IMMULITE® Pyrilinks®-D). For IVDs, the "acceptance criteria" and "study" typically revolve around demonstrating substantial equivalence to a predicate device, focusing on analytical performance rather than clinical effectiveness in the same way a therapeutic device might. The "performance equivalence" section addresses this.

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

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

• Sample Size for Test Set: Seventy-five (75) patient urine samples.
• Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, it's typically understood to be retrospective for method comparison studies like this, using archived samples or freshly collected samples specifically for the comparison. The fact that it's "patient urine samples" suggests it's human biological samples.

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

This type of information is generally not applicable for an IVD method comparison study. The "ground truth" here is the measurement obtained by the predicate device (Metra Biosystems® Pyrilinks®-D), not an expert panel's interpretation. The goal is to show the new device performs similarly to an already cleared device, not to independently establish a diagnosis based on expert consensus.

4. Adjudication method for the test set

This is not applicable for this type of IVD method comparison study. Adjudication methods (like 2+1, 3+1) are used to resolve disagreements among multiple human readers or experts who are establishing a ground truth for diagnostic imaging or clinical assessment. Here, the "truth" is the quantitative value from the predicate device.

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. This document describes an in vitro diagnostic device, not an AI-assisted diagnostic system where human readers interact with AI. The device directly measures a biomarker in urine.

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

This is implicitly a standalone study, in the sense that the IMMULITE® Pyrilinks®-D assay (the algorithm/methodology) was directly compared to the predicate device, without a specific human-in-the-loop component being evaluated for performance improvement in this section. The "human" element comes in the form of a lab technician operating the analyzer, but their interpretive skill is not being assessed here.

7. The type of ground truth used

The "ground truth" (or reference standard) for this method comparison was the results obtained from the legally marketed predicate device: Metra Biosystems® Pyrilinks®-D. The study aimed to demonstrate that the new device's measurements correlated well with those from the predicate.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" for the method comparison study itself. For an IVD, the "training" of the assay involves developing the reagents, optimizing the assay parameters, and establishing calibration curves during the device's development phase. This information is typically proprietary and not detailed in a 510(k) summary focused on demonstrating substantial equivalence to a predicate. The 75 samples mentioned are for the comparison study.

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

As there's no explicitly described "training set" in the context of the method comparison in this document, the method for establishing its ground truth is not provided. If we interpret "training set" loosely as the data used to develop the IMMULITE® Pyrilinks®-D assay itself, the ground truth would have been established through internal validation studies using reference methods or characterized samples during assay development by Diagnostic Products Corporation. This information is usually not part of the 510(k) summary review.

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Osteomark is a urinary assay that provides a quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) as an indicator of human bone resorption. Elevated levels of urinary NTx indicate elevated human bone resorption. Measurement of NTx is intended for use in:

A. Predicting skeletal response (bone mineral density) to hormonal antiresorptive therapy in postmenopausal women.

B. Therapeutic monitoring of:

• 1. antiresorptive therapies in postmenopausal women
• 2. antiresorptive therapies in individuals diagnosed with osteoporosis
• 3. antiresorptive therapies in individuals diagnosed with Paget's disease of bone

4. estrogen-suppressing therapies

C. Assessing the relative risk for loss of spinal bone mass after one year if not treated with hormonal antiresorptive therapy

Osteomark is a competitive enzyme-linked immunosorbent assay (ELISA) which utilizes a horseradish peroxidase labeled monoclonal antibody directed against the cross-linked N-telopeptides (NTx) present in urine specimens. An Osteomark® kit is comprised of the following reagents:

Antigen Coated 96-Well Plate Calibrators: 1 nM BCE 30 nM BCE 100 nM BCE 300 nM BCE 1000 nM BCE 3000 nM BCE Antibody Conjugate Concentrate Antibody Conjugate Diluent Level I and Level II Urine Controls 30X Wash Concentrate Buffered Substrate Chromogen Reagent Stopping Reagent

The solid phase utilizes microwells onto which NTx has been adsorbed. NTx in the specimen or Calibrator competes with the solid phase NTx for antibody binding sites. The resulting amount of Antibody Conjugate bound to the solid phase is indirectly proportional to the amount of NTx in the specimen or Calibrator. The quantity of NTx in the specimen is determined from a standard calibration curve using reagents supplied in the kit. Assay values are standardized to an equivalent amount of bone collagen, and are expressed in nanomole bone collagen equivalents per liter (nM BCE). BCE reflects the amount of immunoreactive NTx, as measured by Osteomark, liberated from human bone collagen following digestion with bacterial collagenase, as measured by hydroxyproline by high performance liquid chromatography (HPLC).

Here's an analysis of the provided text, outlining the acceptance criteria and the studies performed for the Osteomark® device:

Acceptance Criteria and Device Performance Study for Osteomark®

The Osteomark® device is a urinary assay designed to quantitatively measure N-telopeptides of type I collagen (NTx) as an indicator of human bone resorption. The provided documentation details several performance characteristics and studies that likely served as the basis for acceptance criteria.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria with defined pass/fail thresholds for a regulatory submission. Instead, it presents performance characteristics and reference ranges derived from studies. Based on the "Performance Characteristics" section, we can infer the following:

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