(267 days)
The Abbott m2000 system is intended for in vitro diagnostic use in performing FDA cleared and approved nucleic acid testing in clinical laboratories. It comprises the Abbott m2000sp and the Abbott m2000rt instruments. The Abbott m2000sp is an automated system for performing sample preparation for nucleic acid testing. The Abbott m2000rt is an automated system for performing fluorescence-based PCR to provide quantitative and qualitative detection of nucleic acid sequences.
The Abbott m2000 System is an instrument platform that automates steps to perform nucleic acid amplification assays from sample processing through amplification, detection, and data reduction. The Abbott m2000 System comprises the m2000sp and m2000rt instruments, which are operated with separate System Control Center (SCC) workstations. Each instrument contains an independent software application; one for the m2000sp and a second for the m2000rt. The m2000sp instrument is a floor standing, automated sample preparation system. The three main components of the m2000sp are the: Instrument, Cabinet, System Control Center (SCC). The m2000rt instrument is a real-time PCR thermal cycler/reader instrument system. The two main components of the m2000rt are the: Instrument, System Control Center (SCC). The Abbott m2000 System software processes sample preparation and amplification/detection protocols based on pre-determined, assay-specific parameters that are contained in individual assay application specification files that are installed on the SCC. The Abbott m2000sp reads and processes bar coded primary sample tubes and processes up to 96 specimens, controls, and calibrators in batch mode. The m2000 System is capable of processing samples from various matrices, depending on the specific assay application, including plasma, serum, endocervical swabs, urethral swabs, vaginal swabs, and urine. At the completion of the automated sample preparation protocol, the operator seals and manually transfers the PCR plate to the Abbott m2000rt for nucleic acid detection. Bar code and m2000sp data is transferred to the m2000rt electronically.
The Abbott m2000 System is an automated instrument platform intended for in vitro diagnostic use in performing FDA-cleared and approved nucleic acid testing in clinical laboratories. This includes the Abbott m2000sp (automated sample preparation) and m2000rt (automated fluorescence-based PCR for quantitative and qualitative detection of nucleic acid sequences). The system was evaluated in conjunction with the Abbott RealTime CT/NG assay.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
While explicit "acceptance criteria" are not presented as a direct table in the provided document, the study aims to demonstrate substantial equivalence to predicate devices and establish performance characteristics. The key performance metrics reported are sensitivity and specificity for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).
| Metric | Acceptance Criteria (Implicit - based on predicate device performance and clinical relevance) | Reported Device Performance (Abbott RealTime CT/NG assay) |
|---|---|---|
| Overall CT Sensitivity | High sensitivity, comparable to predicate NAATs | 95.2% |
| Overall CT Specificity | High specificity, comparable to predicate NAATs | 99.3% |
| Overall NG Sensitivity | High sensitivity, comparable to predicate NAATs | 97.5% |
| Overall NG Specificity | High specificity, comparable to predicate NAATs | 99.7% |
| CT LOD (95% Probability) | Detectable at very low copy numbers | 21 copies/assay (95% CI 18 - 28) |
| nvCT LOD (95% Probability) | Detectable at very low copy numbers | 29 copies/assay (95% Cl 24 - 41) |
| NG LOD (95% Probability) | Detectable at very low copy numbers | 149 copies/assay (95% CI 130 - 176) |
| Carryover Rate | Minimal to no cross-contamination | 0.91% (5 false positive, 1 equivocal out of 656 negative samples) |
2. Sample Size Used for the Test Set and the Data Provenance
- Test Set (Clinical Study):
- 3,832 male and female, asymptomatic and symptomatic subjects.
- 3,832 subjects provided urine, endocervical swabs, self-collected vaginal swabs, and clinician-collected vaginal swabs (females) or urine and urethral swabs (males).
- A total of 6,555 CT results and 6,569 NG results were used in the analysis after excluding subjects for whom patient infected status could not be determined (4 for CT, 7 for NG).
- Data Provenance: Prospective, multi-center clinical study conducted in the United States. Specimens were collected from 16 geographically diverse sites, including physician private practices, public and private STD clinics, and a hospital emergency room.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document does not explicitly state the number or qualifications of experts who established the ground truth in the traditional sense (e.g., radiologists interpreting images). Instead, the ground truth was established through a reference standard composed of multiple commercially available nucleic acid amplification tests (NAATs) and culture for NG.
- For CT or NG infection in females: A minimum of two positive results (at least one from each reference NAAT).
- For CT in females (urine/swab discrepancy): Positive urine and negative endocervical swab from both reference assays resulted in categorization as infected for urine but not for swab specimens.
- For CT or NG infection in males: A minimum of two positive results were reported.
- For NG infection (regardless of NAAT) if NG culture positive: If the reference NG culture assay result was positive, the subject was categorized as infected regardless of NAAT results.
- For non-infection in females: At least one of the reference NAATs reported negative results for all sample types AND if the NG culture assay result was negative.
- For non-infection in males: A total of at least two negative results reported by the reference NAATs AND if the NG culture assay result was negative.
Therefore, the "ground truth" was established by a consensus of FDA-cleared diagnostic assays rather than individual expert interpretation.
4. Adjudication Method for the Test Set
The adjudication method for determining "patient infected status" (ground truth) was a composite reference standard based on the results of two commercially available NAATs and culture for NG. It essentially used a "2 out of 2" or "2 out of 3" (for NG cases with culture) positive rule for infection, and a "negative across multiple tests" rule for non-infection. In cases of internal discrepancy, specific rules were applied (e.g., for female CT urine vs. swab).
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 involving human readers and AI assistance was not mentioned. This device is an automated in vitro diagnostic system, not an AI-powered diagnostic imaging or interpretation tool designed to assist human readers. Its performance is evaluated as a standalone diagnostic.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the clinical study primarily evaluated the standalone performance of the Abbott RealTime CT/NG assay on the Abbott m2000 System. The reported sensitivity and specificity values are for the assay and system independent of human interpretation beyond typical lab procedures and result reporting.
7. The Type of Ground Truth Used
The ground truth used was a composite reference standard based on the results of:
- Two commercially available nucleic acid amplification tests (NAATs) for CT and NG.
- Culture for NG.
This is a frequently used method for establishing ground truth for infectious disease diagnostics when a single "gold standard" may not always be definitive. It combines multiple reliable diagnostic methods to increase confidence in the true infection status.
8. The Sample Size for the Training Set
The document does not explicitly specify a "training set" size for the Abbott RealTime CT/NG assay and m2000 system. For in vitro diagnostic devices like this, the development process (which would involve data akin to training) is typically extensive and proprietary, focusing on analytical performance and robustness. The clinical study described would be analogous to an independent validation or test set.
9. How the Ground Truth for the Training Set Was Established
Since a dedicated "training set" with ground truth establishment in the AI/machine learning sense is not detailed, this question applies less directly. However, the development of the assay would inherently involve:
- Analytical studies: Determining Limit of Detection (LOD), analytical sensitivity (serovars, isolates), cross-reactivity, and interference using well-characterized samples (e.g., quantified pure cultures, spiked samples). The ground truth for these analytical studies is based on known concentrations of targets and the presence/absence of interfering substances or cross-reactants. These studies are detailed in Section 9.0 "Summary of Non-Clinical Testing."
§ 862.2570 Instrumentation for clinical multiplex test systems.
(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.