(125 days)
The IMMULITE® ACTH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE ACTH assay on the IMMULITE 2000 systems
The Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LACCVM1 contains processed bovine protein matrix with preservatives. LACCVM2, LACCVM3 and LACCVM4 contain low, intermediate and high levels of ACTH respectively, in processed bovine protein based matrix with preservatives.
Here's a breakdown of the acceptance criteria and study details for the IMMULITE® 2000 ACTH Calibration Verification Material, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline Criteria % difference to assigned dose) | Acceptable Dose Range (pg/mL) | Reported Performance (Implied from meeting criteria) |
|---|---|---|---|
| LACCVM1 | ≤5.00 | ≤5.00 | Met criteria (as study claims success) |
| LACCVM2 | ±10 | 19.62 - 23.98 | Met criteria (as study claims success) |
| LACCVM3 | ±10 | 214.20 - 261.80 | Met criteria (as study claims success) |
| LACCVM4 | ±10 | 1092.6 - 1335.40 | Met criteria (as study claims success) |
| Review Limits (Secondary Acceptance Criteria): Controls are within 2SD of target from stability calibrator curve. |
Note: The document states "Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use." This implies that the reported device performance met these acceptance criteria, though specific numerical results within the ranges are not explicitly provided.
Study that Proves the Device Meets the Acceptance Criteria:
The study conducted was a stability study designed to validate the shelf life claim for the IMMULITE® 2000 ACTH Calibration Verification Material (CVM).
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Description: The document refers to the CVM study protocols being run as part of calibrator stability testing. The CVMs (test samples) were run in duplicate (as a minimum) at specified time points.
- Sample Size for Stability Testing:
- For the stability study, CVM levels (LACCVM1, LACCVM2, LACCVM3, LACCVM4) were tested at time points: Day 1, Day 182, Day 548, and Day 730. The quantity of "samples" at each time point is "duplicate (as a minimum)".
- For the Expected Values/Reference Range establishment, which involved testing of each CVM level to define the target mean and SD, there were "a total of 27 replicates; 9 runs and 3 replicates per run."
- Data Provenance: The data is internally generated from a non-clinical performance testing which makes it retrospective in nature. No country of origin is explicitly mentioned other than the submitter's address in Tarrytown, NY, USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This is not applicable as the "ground truth" for this device, a calibration verification material, is established through a precise, gravimetrically prepared reference standard and an internal value assignment process, not through expert human interpretation.
4. Adjudication Method for the Test Set:
Not applicable. The "ground truth" (assigned dose) is determined through instrumental and gravimetric methods, not through human adjudication. The acceptance criteria include two parts: a guideline percentage difference to the assigned dose and a review limit of controls within 2SD. If the result is not within the acceptable dose range of ±10%, then additional data review is performed using the part 2 acceptance criterion. This implies a hierarchical review process, but not expert adjudication in the traditional sense of diagnostic imaging or clinical assessment.
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, an MRMC comparative effectiveness study was not conducted. This device is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Not applicable. This device is a chemical assay control material, not a software algorithm. Its "performance" is its ability to maintain its intended value and characteristics over time, which is assessed through laboratory testing.
7. The Type of Ground Truth Used:
The ground truth for the IMMULITE® 2000 ACTH Calibration Verification Materials is based on traceability to internal assigned reference calibrators prepared using ACTH antigen stock solution that are gravimetrically prepared. This represents a form of measurement standard/reference material ground truth.
8. The Sample Size for the Training Set:
The concept of a "training set" is not directly applicable in the conventional sense for this type of device (calibration verification material). However, the value assignment process for the CVMs, which establishes their target values, involved extensive testing:
- The CVMs were tested on 27 replicates in total (comprised of nine runs and three replicates per run) on eight systems and four different reagent kit lots.
- Additionally, two levels of commercially available controls, and 40 patient samples (5 normal patients samples and 35 spiked normal patients samples) are used to validate CVM value assignments.
This extensive testing serves a similar purpose to establishing robust targets in a training phase.
9. How the Ground Truth for the Training Set Was Established:
As noted above, "training set" isn't a direct fit. However, the ground truth for the CVM's assigned values (which could be considered the "ground truth" for its utility) was established through:
- Traceability: The CVMs are traceable to internal assigned reference calibrators.
- Gravimetric Preparation: These reference calibrators are prepared using ACTH antigen stock solution that is gravimetrically prepared (i.e., measured by weight for high accuracy).
- Internal Value Assignment Procedures: The IMMULITE calibrators (and thus CVMs) are value-assigned using these assigned reference calibrators.
- Validation Studies: Value assignments are validated using commercially available controls and 40 patient samples (5 normal, 35 spiked normal).
- Extensive replicate testing used to establish the target mean and standard deviation for each CVM level.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.