(17 days)
The new TAS PT-NC Controls are intended to be used with the TAS Analyzer and PT-NC test cards to provide a method for quality control of the system. The controls produce clotting times which must be within accepted, standard ranges, to indicate that the analyzer and test cards are functioning properly and thereby help assure the accuracy of PT-NC test card results. These controls were designed to allow CVDI's point of care customers to maintain accepted laboratory standards and requirements. These controls also can be used to determine system (TAS Analyzer and PT-NC test cards) precision. The controls are substantially equivalent in Intended use to other control materials used in coagulation tests.
The controls for TAS PT-NC test cards consist of two separate vials. One was designed to mimic a sample from a normal individual, and the second to mimic a sample from a patient with an abnormally prolonged clotting time due to a deficiency of extrinsic coagulation factors. These controls are made with human plasma screened for antibodies to and antigens of hepatitis and Human Immunodeficiency viruses. To make the controls as easy to use as possible for point-of-care testing, we chose the patented packaging system of EDITek (Burlington, NC). This consists of a closed, crushable glass ampoule containing lyophilized plasma which is inside a plastic sleeve. The sleeve contains water for diluent and has a capped dropper top with a filter in the tip (to remove glass shards from the sample). The entire assembly is shrink wrapped with a label and plastic seal. To use, the ampoule is crushed inside the plastic sleeve, which allows the diluent to mix with the lyophilized plasma. The mixture is reconstituted by shaking or vortexing the capped vial. The plastic seal and cap are removed and three drops of plasma suspension are discarded into a biohazard waste container (to eliminate the dilution effect of the diluent that is contained in the filter). A drop of the plasma suspension is added to a TAS PT-NC test card in an analyzer. The rest of the test procedure and the manner of signal production is identical to that for a patient sample.
Here's an analysis of the provided text to extract information about the device's acceptance criteria and the study proving it, formatted as requested:
Device: TAS PT-NC Controls
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a numerical, pass/fail format for the performance studies. However, it implicitly uses a comparison to a predicate device and stability/precision metrics as indicators of acceptable performance. The "normal ranges" for the within-day precision essentially serve as the expected performance.
| Characteristic | Acceptance Criteria (Implicit/Stated Goal) | Reported Device Performance |
|---|---|---|
| Intended Use | Assure performance of system by functional testing (comparison to predicate) | Substantially equivalent to predicate, produces clotting times within set limits. |
| Stability (Room Temp) | At least 13 weeks of storage at room temperature (20-25°C) | Stable for at least 13 weeks. |
| Stability (Refrigerator) | Probable refrigerator stability of at least one year | Probable refrigerator stability of at least one year (inferred from room temp stability). |
| Stability (Frozen) | Little to no effect on performance at -80°C | No significant difference in mean or CV compared to refrigerated vials. |
| Stability (High Temp) | Not explicitly stated as a pass/fail, but adverse effect noted. | Heating to 37°C for several days causes an increase in mean clotting time. |
| Within Day Precision (Normal Control) | Clotting time like that of a normal individual; expected range 9.3 - 11.0 sec | Mean: 10.1 sec, SD: 1.4, CV: 4.1% (within 9.3 - 11.0 range) |
| Within Day Precision (Abnormal Control) | Responds like a patient with extrinsic coagulation factor deficiency; expected range 40.4 - 55.6 sec | Mean: 43.3 sec, SD: 2.9, CV: 6.6% (within 40.4 - 55.6 range for 5-10 drops) |
| Overall CV (Abnormal Control - "first drop") | Expected CV ~7% for QA testing in the field | Overall CV for abnormal control (all days, all experiments, "first drop" analysis): 7% |
| Lot-to-Lot Precision (Normal Control) | Not directly stated numerically, but expected to be low variation. | Mean (sec): 10.1, 11.9, 12.2; CV (%): 4.2, 5.8, 6.1 (for 3 lots) |
| Lot-to-Lot Precision (Abnormal Control) | Not directly stated numerically, but expected to be low variation. | Mean (sec): 43.5, 41.4, 41.8; CV (%): 6.9, 8.3, 9.1 (for 3 lots) |
| Field Study (Normal Control) | (Comparison to predicate/internal lab results) | Site A: Mean 10.7, CV 9.9; Site B: Mean 10.5, CV 6.3 |
| Field Study (Abnormal Control) | (Comparison to predicate/internal lab results) | Site A: Mean 45.2, CV 13.6; Site B: Mean 49.7, CV 8.0 |
2. Sample Size for the Test Set and Data Provenance
- Sample Size:
- Within-day precision: "Most of these studies were done with five to ten drops from the same vial." The tables show "mean ranges" for normal and abnormal controls, implying multiple measurements. For lot-to-lot precision,
n = 40 eachis stated, referring to individual measurements for each lot. - Field study: "tested at least in duplicate each day for 20 days" at each site. This means a minimum of 40 measurements per control type per site (2 measurements/day * 20 days).
- Within-day precision: "Most of these studies were done with five to ten drops from the same vial." The tables show "mean ranges" for normal and abnormal controls, implying multiple measurements. For lot-to-lot precision,
- Data Provenance: Retrospective (implicitly, as the studies are completed before submission).
- Country of Origin: United States (Cardiovascular Diagnostic, Inc. is in Raleigh, NC; EDITek is in Burlington, NC; clinical study sites are not explicitly named with country, but the submission is to FDA, implying US studies).
- Type of Study: Laboratory studies for stability and precision, and a multi-site field study for variation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
Not applicable. This device is a quality control material, not a diagnostic device that interprets clinical data or images requiring expert consensus for ground truth. Its "ground truth" is its measured clotting time characteristics, stability, and precision when run on the TAS Analyzer.
4. Adjudication Method for the Test Set
Not applicable for a quality control device's performance study. The "ground truth" is the empirically measured clotting time.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC study was not done. This device is a quality control material intended to verify instrument and test card function, not a diagnostic tool requiring human interpretation or assistance.
6. If a Standalone (algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are essentially standalone performance evaluations of the TAS PT-NC Controls themselves, measuring their inherent characteristics (stability, precision) when used with the TAS Analyzer and PT-NC test cards. There is no human interpretation component of the control material's result that would be assisted by an "algorithm." The algorithm is embedded within the TAS Analyzer for determining the clotting time from the sample.
7. The Type of Ground Truth Used
The ground truth for this device (a quality control material) is based on:
- Empirical Measurement: Directly measured clotting times in seconds using the TAS Analyzer system.
- Comparison to Predicate: Performance is compared to the established TAS PT controls.
- Physiological Mimicry: The controls are designed to mimic a normal individual or a patient with an abnormally prolonged clotting time due to extrinsic coagulation factor deficiency.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning or algorithm development. The device is a physical control material. The data presented are for validation/testing the performance of the manufactured control materials.
9. How the Ground Truth for the Training Set Was Established
Not applicable as there is no mention of a "training set" for an algorithm. The ground truth for the development of the control material itself would involve careful formulation, characterization, and comparison to known clinical samples or established reference materials, but this information is not detailed in the summary provided.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.