(101 days)
The Free Testosterone AccuBind® ELISA Test System is an Enzyme Immunoassay (EIA) for the quantitative measurement of free testosterone in human serum. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in males and in females; hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries and androgenital syndromes.
The kit consists of seven (7) vials of serum reference calibrators for Free Testosterone with two (2) controls (one low and one high); one (1) vial of Testosterone (Analog)-horseradish peroxidase (HRP) conjugate in a protein stabilizing matrix; one 96-well testosterone antibody-coated microplate; one (1) vial of concentrated wash solution; two (2) vials for tetramethy(benzidine (TMB) substrate solution preparation; and one (1) vial of stop reaction solution.
The provided document describes the analytical performance of the Monobind Inc. Free Testosterone AccuBind® ELISA Test System, an in vitro diagnostic device, rather than an AI/ML-driven device. Therefore, many of the requested criteria often associated with AI/ML device studies (e.g., number of experts for ground truth, MRMC studies, human-in-the-loop performance, training set details) are not applicable to this type of medical device.
However, I can extract the relevant information regarding the device's acceptance criteria and the study that proves it meets them as presented in the document.
Here's the breakdown:
1. Table of Acceptance Criteria and Reported Device Performance
For this type of in-vitro diagnostic device, "acceptance criteria" are typically defined by regulatory standards and good laboratory practices (e.g., CLSI guidelines). The document presents analytical performance data against these established industry benchmarks rather than explicit numerical acceptance criteria beyond what is internally defined for successful assay development and validation (e.g., precision specifications).
| Performance Metric | Acceptance Criteria (Implicit from Industry Standards/Good Practice) | Reported Device Performance (Representative Lot / Combined Lot) |
|---|---|---|
| Precision | Low %CV for within-run and total precision across concentrations. | Within-Run CV: 3.6-7.9% (Representative Lot), 4.23-5.95% (Combined Lot) |
| Total CV: 7.8-12.4% (Representative Lot), 7.20-9.43% (Combined Lot) | ||
| Linearity (Accuracy) | High correlation coefficient (R) and slope close to 1. | y = 1.0149x - 0.6028, R = 0.9888 (Excellent linearity) |
| Recovery | Percent recovery close to 100% for spiked samples. | 98.7% - 105.2% (Across 5 patient samples) |
| Reagent/Kit Stability | Demonstrates stability for stated shelf life and open-vial stability. | 2 years (unopened kit), 61 days (open kit, calibrators, controls, enzyme reagent, TMB, plate) |
| Sample Stability | Demonstrates stability for specified storage conditions. | 61 days (serum at 2-8°C), 31 days (frozen serum at -20°C) |
| Detection Limits | Defined LOB, LOD, LOQ based on CLSI EP17-A. | LoB: 0.0295 pg/ml; LoD: 0.0519 pg/ml; LoQ: 0.0519 pg/ml |
| Cross-Reactivity | Generally low cross-reactivity (10% difference) observed. | |
| Method Comparison | Strong correlation with predicate device (high R, slope near 1, low intercept). | y = 1.017x - 0.244, Correlation Coefficient = 0.997 (Excellent agreement) |
| Interferences | No significant interference at specified concentrations for various substances. | Most substances showed no significant interference at the tested concentrations. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: For the representative lot, 3 control samples were tested, with 80 measurements per sample (duplicate, two times per day for 20 days). 3 serum pools were also tested in the same manner (N=32 readings for the representative lot table, N=80 for combined lot table). For the combined lot precision, 3 controls and 3 patient samples (serum pools) were used, with a total of 80 measurements per sample.
- Data Provenance: Not explicitly stated, but typical for in vitro diagnostic device validation, these would be controlled laboratory studies using clinical samples (serum pools and control materials). No mention of country of origin or retrospective/prospective clinical data for the performance evaluation (this differs from the reference range determination).
- Linearity Study: 11 concentrations of sample preparations.
- Recovery Study: 5 serum samples (containing different levels of endogenous testosterone).
- Reference Range Determination: 261 male and female serum samples.
- Data Provenance: Not specified for the 261 samples, but typically these samples are collected under ethical guidelines from a relevant population.
- Cross-Reactivity Study: Specific compounds were tested with male serum spiked samples and blank serum spiked samples. No specific number of replicates per compound is given, but "aliquots from pool of human serum" are mentioned for testosterone cypionate and undecanoate.
- Method Comparison Study: 137 samples.
- Data Provenance: Not explicitly stated, but these would be clinical samples with varying testosterone levels.
- Interferences Study: Charcoal-stripped human serum spiked with known concentrations of interferent.
3. Number of Experts Used to Establish the Ground Truth and Qualifications of Experts
- Not Applicable. For an in-vitro diagnostic assay for quantitative measurement of an analyte like Free Testosterone, the "ground truth" is established by the analytical method itself (the assay's ability to accurately measure the target analyte) and validated against reference methods or calibrated materials. There are no human "experts" establishing image-based ground truth as would be the case for AI/ML diagnostic tools. The predicate device serves as a comparative "ground truth" for method comparison.
4. Adjudication Method for the Test Set
- Not Applicable. This is an in-vitro diagnostic assay, not an AI/ML system requiring human adjudication of results. The results are quantitative measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. This is an in-vitro diagnostic assay, not an imaging AI/ML device that assists human readers. Therefore, an MRMC study is not relevant or performed.
6. Standalone (Algorithm Only) Performance
- Yes (inherently). The device itself is the "standalone" measurement system. Its performance (precision, linearity, recovery, sensitivity, specificity, interference) is evaluated on its own. There isn't a separate "human-in-the-loop" component as would be found in an AI-assisted diagnostic workflow.
7. The Type of Ground Truth Used
The ground truth for this device's performance validation is established through:
* Known Concentrations: For precision (control materials with known values), linearity (prepared concentrations), recovery (spiked samples with known additions), detection limits (analyzing blanks and low-concentration samples).
* Reference Methods/Predicate Device: For method comparison, the predicate device (EiAsy Free Testosterone EIA) serves as the comparator.
* Established Analytical Principles: The fundamental biochemical reactions and measurement principles of the ELISA platform.
* CLSI Guidelines: Adherence to established Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP06-A, C28-A3, EP17-A, EP07-A2) for validation studies provides the framework for defining acceptable performance.
8. The Sample Size for the Training Set
- Not Applicable. This is an in-vitro diagnostic assay, not an AI/ML device that requires a distinct "training set" in the context of machine learning model development. The development and optimization of the assay's reagents and protocol are analogous to "training" in a general sense, but no specific numerical sample size is defined as a training set for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As above, there is no AI/ML "training set." The "ground truth" for developing such an assay comes from fundamental biochemical understanding, chemical synthesis of reagents, and iterative optimization of assay conditions to achieve desired analytical performance characteristics. This involves standard laboratory development practices common to IVD manufacturing.
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.