(42 days)
The modified CEDIA® DAU PCP Assay is a homogeneous enzyme immunoassay for the in vitro qualitative and semiquantitative assay of PCPs in human urine. Measurements are used as an aid in the diagnosis and treatment of PCP use or overdose.
The CEDIA DAU PCP assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. This assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. In the assay, drug in the sample competes with drug conjugated to one inactive fragment of B-galactosidase for antibody binding site. If drug is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If drug is not present in the sample, antibody binds to drug conjugated on the inactive fragment, inhibiting the reassociation of inactive B-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are proportional to the amount of drug present in the sample.
Here's a breakdown of the acceptance criteria and study information for the CEDIA DAU PCP Assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Feature | Acceptance Criteria (Implicit from Predicate & Comparison) | Modified CEDIA DAU PCP Performance (Test Device) | Predicate CEDIA DAU PCP Performance |
|---|---|---|---|
| Precision (25 ng/mL Cutoff, 19 Concentration Level) | At least equivalent to predicate (238.4 mA/min Total, 4.3% CV Total) | 281.1 mA/min Total, 1.5% CV Total | 238.4 mA/min Total, 4.3% CV Total |
| Precision (25 ng/mL Cutoff, 25 Concentration Level) | At least equivalent to predicate (276.4 mA/min Total, 5.3% CV Total) | 323.1 mA/min Total, 1.5% CV Total | 276.4 mA/min Total, 5.3% CV Total |
| Precision (25 ng/mL Cutoff, 31 Concentration Level) | At least equivalent to predicate (316.3 mA/min Total, 5.0% CV Total) | 370.4 mA/min Total, 1.4% CV Total | 316.3 mA/min Total, 5.0% CV Total |
| Qualitative Sensitivity (25 ng/mL Cutoff) | At least equivalent to predicate (1.7 ng/mL) | 1.05 ng/mL | 1.7 ng/mL |
| Semiquantitative Sensitivity (25 ng/mL Cutoff) | (Not explicitly stated for predicate in quantitative terms, but implied to be effective) | 0.96 ng/mL | N/A (Not reported quantitatively for predicate) |
| Accuracy (25 ng/mL Cutoff Sensitivity) | At least equivalent to predicate (99.1% vs. Commercially available EIA Assay) | 96.9% (Vs. CEDIA PCP Assay) | 99.1% (Vs. Commercially available EIA Assay) |
| Specificity | 100.0% | 100.0% | 100.0% |
| Interfering Substances (Acetone) | Less than 10% error at 1 g/dL | Less than 10% error at 1 g/dL | Less than 10% error at 1 g/dL |
| Interfering Substances (Ascorbic Acid) | Less than 10% error at 1.5 g/dL | Less than 10% error at 1.5 g/dL | Less than 10% error at 1.5 g/dL |
| Interfering Substances (Creatinine) | Less than 10% error at 0.5 g/dL | Less than 10% error at 0.5 g/dL | Less than 10% error at 0.5 g/dL |
| Interfering Substances (Ethanol) | Less than 10% error at 1 g/dL | Less than 10% error at 1 g/dL | Less than 10% error at 1 g/dL |
| Interfering Substances (Galactose) | Less than 10% error at 10 mg/dL | Less than 10% error at 10 mg/dL | Less than 10% error at 10 mg/dL |
| Interfering Substances (y-globulin) | Less than 10% error at 0.5 g/dL | Less than 10% error at 0.5 g/dL | Less than 10% error at 0.5 g/dL |
| Interfering Substances (Glucose) | Less than 10% error at 3 g/dL | Less than 10% error at 3 g/dL | Less than 10% error at 3 g/dL |
| Interfering Substances (Hemoglobin) | Less than 10% error at 0.3 g/dL | Less than 10% error at 0.3 g/dL | Less than 10% error at 0.3 g/dL |
| Interfering Substances (Human Serum Albumin) | Less than 10% error at 0.5 g/L | Less than 10% error at 0.5 g/L | Less than 10% error at 0.5 g/L |
| Interfering Substances (Oxalic Acid) | Less than 10% error at 0.1g/dL | Less than 10% error at 0.1g/dL | Less than 10% error at 0.1g/dL |
| Interfering Substances (Riboflavin) | Less than 10% error at 7.5 mg/dL | Less than 10% error at 7.5 mg/dL | Less than 10% error at 7.5 mg/dL |
| Interfering Substances (Sodium Chloride) | Less than 10% error at 6 g/dL | Less than 10% error at 6 g/dL | Less than 10% error at 6 g/dL |
| Interfering Substances (Urea) | Less than 10% error at 3 g/dL (for predicate, modified specifies 5 g/dL) | Less than 10% error at 5 g/dL | Less than 10% error at 3 g/dL |
| Specificity (PCP Compounds) | Multiple PCP compounds detected | Multiple PCP compounds detected | Multiple PCP compounds detected |
Explanation of Acceptance Criteria: The acceptance criteria are implicitly defined by demonstrating "substantial equivalence" to the predicate device (CEDIA DAU PCP Assay, K935650). This means the new device's performance characteristics should be comparable to or better than the predicate's, with any differences not raising new questions of safety or effectiveness. For precision, the modified device shows better or equivalent %CV. For sensitivity, the modified device shows better performance. For accuracy, it's compared to the predicate, which in turn was compared to a commercially available EIA. Interfering substances are shown to have similar, acceptable interference levels.
2. Sample Size Used for the Test Set and Data Provenance
- Precision (Test Set):
- For the modified CEDIA DAU PCP, at each concentration level (19, 25, 31 ng/mL): N = 126.
- For the predicate CEDIA DAU PCP, at each concentration level (19, 25, 31 ng/mL): N = 120.
- Accuracy (Test Set): The sample size for the accuracy comparison (96.9% sensitivity for the modified device vs. the predicate, and 99.1% for the predicate vs. a commercial EIA) is not explicitly stated in terms of number of samples.
- Data Provenance: The document does not specify the country of origin of the data. It is a submission to the FDA, suggesting the studies were conducted to meet US regulatory requirements, but the origin of the samples is not mentioned. The studies appear to be prospective, as performance characteristics are being generated for a new device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. The studies described are analytical performance studies of an in vitro diagnostic device, not studies involving human interpretation or clinical outcomes adjudicated by experts.
4. Adjudication Method for the Test Set
This information is not applicable as the studies are analytical and do not involve human adjudication of results. The results are quantitative measurements and comparisons of sensitivity, specificity, and precision.
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. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The entire study described is a standalone performance evaluation of the device (assay), without human-in-the-loop performance being a relevant factor for this type of test. The device itself performs the measurement.
7. The Type of Ground Truth Used
The ground truth for the performance characteristics appears to be established by:
- Analytically determined concentrations: For precision, samples were prepared at specific concentrations (19, 25, 31 ng/mL).
- Comparison to a predicate device: For accuracy, the modified device was compared against the existing CEDIA DAU PCP Assay, and the predicate itself was compared against a "Commercially available EIA Assay." This implies that the predicate assay's results, or the commercial EIA's results, served as a reference standard (ground truth) for establishing accuracy.
- Known concentrations of interfering substances and PCP compounds: For interfering substances and specificity, the ground truth would be the known concentration of the substance and the presence of specific PCP compounds.
8. The Sample Size for the Training Set
This information is not applicable/not provided. The CEDIA DAU PCP Assay is a homogeneous enzyme immunoassay based on recombinant DNA technology. It is not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The "training" of this system is inherent in its biochemical design and optimization during development, rather than through data-driven machine learning.
9. How the Ground Truth for the Training Set was Established
This information is not applicable as there is no "training set" for this type of in vitro diagnostic device in the context of machine learning. The principles of its operation (enzyme immunoassay) are based on established biochemical reactions, and optimization would involve laboratory experiments to determine optimal reagents and conditions, rather than a "ground truth" derived from expert consensus or pathology on a training dataset.
N/A