(264 days)
The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.
Alinity i Total ß-hCG Reagent Kit
The Alinity i Total ß-hCG assay is a two-step immunoassay for the quantitative and qualitative determination of ß-hCG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.
Alinity i System
The Alinity i System (also known as the Alinity i analyzer) uses chemiluminescent microparticle immunoassay (CMIA) detection technology to measure the concentration of analytes in samples. The modular design of the Alinity family of analyzers allows multiple processing modules, which perform all sample processing activities, to be physically joined to form a single workstation or system. The selection of processing module(s) determines the configuration of the system.
Each Alinity analyzer, regardless of type, consists of a System Control Module (SCM), Reagent and Sample Manager (RSM), and processing module.
Here's an analysis of the provided information, structured according to your request:
Device: Alinity i Total ß-hCG Reagent Kit and Alinity i System
Intended Use: The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.
1. A table of acceptance criteria and the reported device performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Within-Laboratory Precision (Total Imprecision) | ≤ 10 %CV for the Low, Medium, and High Controls (target range from 25 to 5000 mIU/mL). | Panel 1 (25.35 mIU/mL): 5.1% CV (within range of 4.6-5.5%) |
| Panel 2 (765.76 mIU/mL): 1.9% CV (within range of 1.5-2.3%) | ||
| Panel 3 (4971.95 mIU/mL): 2.2% CV (within range of 1.7-2.7%) | ||
| Calibrator B (5.33 mIU/mL): 7.6% CV (within range of 7.1-8.2%) | ||
| Calibrator C (165.16 mIU/mL): 2.9% CV (within range of 2.7-3.3%) | ||
| Calibrator D (9421.08 mIU/mL): 2.8% CV (within range of 2.2-3.5%) | ||
| Calibrator E (13069.37 mIU/mL): 3.2% CV (within range of 2.8-3.6%) | ||
| All reported %CV values are within the ≤10% criterion. | ||
| Linearity | The assay is linear across the measuring interval of 2.42 to 15,000 mIU/mL. | The assay was linear across the range of 2.42 to 15,000 mIU/mL. |
| Limit of Detection (LoD) | Implicit: LoD should be sufficiently low for early pregnancy detection. The predicate's stated analytical sensitivity is ≤ 1.2 mIU/mL. The Alinity i LoD ranged from 0.16 to 0.67 mIU/mL, with the highest observed LoD value being 0.67 mIU/mL. | The highest observed LoD value was 0.67 mIU/mL (IU/L). |
| Limit of Quantitation (LoQ) | LoQ is defined as the lowest concentration at which a maximum Total Error allowable (TEa) of 25% was met. | The highest observed LoQ value at 25% TEa was 2.42 mIU/mL (IU/L). The LoQ ranged from 1.10 to 2.42 mIU/mL. |
| Measuring Interval | Defined as the range of values in mIU/mL (IU/L) which meets the limits of acceptable performance for bias, imprecision, and linearity. | The measuring interval of the Alinity i Total ß-hCG assay is 2.42 to 15,000.00 mIU/mL (2.42 to 15,000.00 IU/L). |
| Analytical Specificity (Cross-Reactivity) | Cross-reactivity calculated as a percent interference for samples with a ß-hCG concentration > 25 mIU/mL (> 25 IU/L) was shown to be less than 10% for each cross-reactant. | Cross-reactivity was within or equal to ±10% for FSH (≤ 500 mIU/mL), LH (≤ 500 mIU/mL), TSH (≤ 100 μIU/mL), and hCG alpha subunit (≤ 500 mIU/mL). |
| Potentially Interfering Substances | Potential interference from bilirubin, hemoglobin, total protein, and triglycerides showed a difference in measured concentration of ß-hCG within or equal to ±10%. | Difference in measured concentration of ß-hCG was within or equal to ±10% for Bilirubin (≤ 20 mg/dL), Hemoglobin (≤ 500 mg/dL), Total Protein (≤ 12 g/dL), and Triglycerides (≤ 3000 mg/dL). Similar results for various exogenous substances. |
| Within-Assay Sample Carryover | Carryover from a sample containing 1,000,000 mIU/mL ß-hCG to an adjacent 0 mIU/mL ß-hCG sample was less than 7.5 mIU/mL ß-hCG. | The difference between the protected sample and the unprotected sample was 0.22 mIU/mL, which is well below the 7.5 mIU/mL criterion. |
| Method Comparison (Quantitative) | Comparison to ARCHITECT Total ß-hCG assay to show substantial equivalence, typically assessed by correlation coefficient, slope, and intercept. | Correlation Coefficient: 1.00 |
| Intercept: 0.12 | ||
| Slope: 1.01 | ||
| Concentration Range: 2.40 – 14,866.03 mIU/mL | ||
| These values demonstrate excellent agreement with the predicate. | ||
| Method Comparison (Qualitative Concordance) | High concordance with the ARCHITECT Total ß-hCG assay across different concentration categories (Positive ≥ 25.00, > 5.00 - 60 replicates of low-analyte level samples for LoD; n ≥ 60 replicates of low-analyte level samples for LoQ. |
- Analytical Specificity (Cross-Reactivity): Number of samples not explicitly stated, but "samples with a ß-hCG concentration > 25 mIU/mL" were used.
- Potentially Interfering Substances: Number of samples not explicitly stated, but "test samples containing potentially-interfering endogenous substances to reference samples" were used.
- Within-Assay Sample Carryover: 1 sample containing high ß-hCG and 1 adjacent 0 mIU/mL ß-hCG sample tested.
- Method Comparison (Quantitative): 210 serum samples.
- Method Comparison (Qualitative): 381 Alinity i Total ß-hCG qualitative results.
- Tube Type Equivalency (Matrix Comparison): 43 unique positive pregnant donor's serum specimens, supplemented into 45 unique female non-pregnant whole blood specimens.
- Expected Values Non-Pregnant (Reference Range): 128 pre-menopausal, 140 peri-menopausal, and 137 post-menopausal human serum specimens.
- Isoform Recognition: Pooled normal human female serum (ß-hCG concentrations less than 1.2 mIU/mL) supplemented with 6 different ß-hCG isoforms and 1 alpha subunit. (Number of replicates not specified).
- Verification of Auto-Dilution: 25 samples created by supplementing ß-hCG stock solution into normal male serum.
Data Provenance: The document does not specify the country of origin of the data or explicitly state whether the studies were retrospective or prospective, though the nature of laboratory studies often implies prospective data collection for the specific tests being performed. The samples used for method comparison and expected values are "human serum specimens."
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 device is an in-vitro diagnostic (IVD) assay that measures the concentration of a biomarker (ß-hCG). The "ground truth" for such assays is typically established by reference methods, certified calibrators, and well-characterized samples, rather than human experts interpreting images or complex clinical scenarios.
- Calibrators: Manufactured gravimetrically and referenced to the World Health Organization (WHO) 4th International Reference Standard 75/589 for ß-hCG. This WHO standard serves as the "ground truth" or reference, established by an international consensus of experts in biochemistry and endocrinology related to hCG.
- Predicate Device: The ARCHITECT Total ß-hCG assay (K983424) and ARCHITECT i System (K983212) serve as the comparator ("ground truth" for method comparison studies), implying their performance has been previously validated and accepted.
- Precision and LoD/LoQ samples: These are laboratory-prepared samples or characterized controls with known concentrations.
- Reference Intervals: Based on human serum specimens from specific demographic groups.
Therefore, direct "human experts" for establishing ground truth in the context of diagnostic interpretation (like radiologists for imaging) are not applicable here. The ground truth is rooted in established metrological traceability to international standards and performance against a cleared predicate device.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Adjudication methods like 2+1 or 3+1 are typically used in studies where human readers provide subjective interpretations (e.g., in medical imaging) and disagreements need to be resolved. This is not applicable to an automated IVD assay where results are quantitative or qualitative based on pre-defined cutoffs and analytical measurements. The assay itself provides a numerical result or a positive/negative/indeterminate classification, which is then compared against established reference values or a 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
No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for evaluating improvements in human reader performance (e.g., radiologists, pathologists) when assisted by an AI system. The Alinity i Total ß-hCG assay is an automated diagnostic test that directly measures a biomarker concentration. There is no human "reader" in the loop needing assistance from the device in the way an AI would assist in image interpretation.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the studies described are, by nature, standalone performance evaluations of the algorithm/device. The Alinity i Total ß-hCG assay and Alinity i System operate without human intervention once the samples are loaded and the test is initiated. The "performance" refers to the analytical accuracy, precision, linearity, and other parameters of the automated system itself, comparing its output to expected values or to a predicate device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for this device is based on several elements:
- International Reference Standards: The calibrators are traceable to the World Health Organization (WHO) 4th International Reference Standard 75/589 for ß-hCG.
- Predicate Device: The ARCHITECT Total ß-hCG assay and ARCHITECT i System serve as the established "ground truth" comparator for method comparison studies, demonstrating substantial equivalence.
- Known Concentrations: For precision, linearity, LoD, LoQ, cross-reactivity, and interference studies, the ground truth is samples with known or spiked concentrations of ß-hCG or interfering substances.
- Clinical Groupings: For "Expected Values Non-Pregnant," the ground truth is the categorization of individuals (pre-menopausal, peri-menopausal, post-menopausal) based on their clinical status.
There is no "pathology" or "outcomes data" as a direct ground truth in these analytical performance studies.
8. The sample size for the training set
The document describes premarket notification (510(k)) studies for a diagnostic assay, primarily focused on analytical validation and comparison to a predicate. It does not mention a "training set" in the context of machine learning or AI development. The device is a "chemiluminescent microparticle immunoassay (CMIA)" system, meaning its principles are based on established biochemical reactions, not on learning from a dataset in the way an AI algorithm would be "trained."
9. How the ground truth for the training set was established
As there is no "training set" for an AI algorithm mentioned for this device, a ground truth for a training set was not established. The device operates based on the inherent chemical and biological characteristics of the assay and the optical detection system, calibrated against known standards.
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.