(133 days)
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COATEST APC RESISTANCE V or V S test is based on the use of activated protein C in an APTT clotting assay, as was the original test kit.
1. Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implied) | Reported Device Performance (COATEST APC™ RESISTANCE V or V S) |
|---|---|
| Improved sensitivity for Factor V mutation (FV:Q506) compared to original device. | "considerably increased sensitivity for the mutation in factor V." "greater than 99 % sensitivity for FV:Q506." |
| High discrimination for FV:Q506. | "high discrimination for FV:Q506." "clear and complete discrimination is obtained for FV:Q506 by both instruments." |
| Correlation with the original COATEST® APC™ RESISTANCE method (K945940). | Good correlation (R=0.74 in one study) between the new and original methods. |
| Applicability on different clot detection instruments. | Successfully utilized on Thrombolyzer, MLA/Electra 900C, ACL 300, and ST-4 instruments. |
| Appropriate results for patients on: - Oral anticoagulants (OAC) - Normal or low molecular weight (LMW) heparin - Phospholipid antibody syndrome | "appropriate results are obtained on analysis of plasmas from patients receiving oral anticoagulants, normal or low molecular weight (LMW) heparin or patients with the phospholipid antibody syndrome." Specific data show correct classification for genotyped patients on heparin and those with phospholipid antibody syndrome. |
| Ability to provide normal APT times on heparin up to 1 IU/mL. | "provides normal APT times to at least 1 IU/mL of normal heparin." |
| Similar repeatability and reproducibility to the original device. | "provides a similar repeatability and reproducibility as Coatest APC Resistance." |
| Determination of a narrower APC Ratio range for normal Factor V genotype individuals compared to the original kit. | "significantly narrower range is obtained with COATEST APC® RESISTANCE V or V S compared to the original Coatest APC Resistance kit." |
| Stability of V-DEF Plasma and other reconstituted reagents. | Data supports assigned stabilities in the package insert for reconstituted V-DEF plasma. Similar stability for 3mL and 4mL vials. Whole blood and plasma can be stored for at least 7 hours at room temperature. |
2. Sample Size Used for the Test Set and Data Provenance
The provided text describes several studies that collectively form the basis of the test set.
- Study 1 (Correlation and Discrimination):
- Sample Size: 218 acutely ill patients with suspected venous thrombosis or pulmonary emboli and family members.
- Data Provenance: Retrospective (implied, as patients are "acutely ill" suggesting existing conditions) and likely from clinical settings where these patients were managed. No specific country of origin is mentioned.
- Study 2 (Correlation and Discrimination):
- Sample Size: 399 plasmapheresis donors.
- Data Provenance: Retrospective (implied, as donors would have already provided samples). No specific country of origin is mentioned.
- Instrument Studies:
- Thrombolyzer: 97 patients with myocardial infarction and 132 healthy controls.
- MLA/Electra 900C: 50 thrombotic patients or family members.
- ACL 300 & ST-4 (OAC patients): 147 patients on OAC therapy (ACL 300) and 129 patients on OAC therapy (ST-4).
- ACL 300 & ST-4 (Healthy Controls): 61 healthy controls (ACL 300) and 62 healthy controls (ST-4).
- Heparin Patients: Implied within the OAC/healthy control groups, all genotyped for Factor V.
- Phospholipid Antibody Syndrome Patients: Samples from these patients were also tested, but no specific number is provided.
- Data Provenance for Instrument Studies: Retrospective, as these are existing patient samples and controls. No specific country of origin is mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The text does not explicitly state the number or qualifications of experts used to establish the ground truth for the test sets.
4. Adjudication Method for the Test Set
The text does not describe any adjudication method like 2+1 or 3+1. The ground truth appears to be solely based on Factor V gene nucleotide determination (FV:Q506 mutation).
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 conducted. This device is a diagnostic assay, not an AI-assisted interpretation tool for human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are standalone performance evaluations of the COATEST APC™ RESISTANCE V or V S assay. The device itself performs the measurement and provides a result (APC ratio), which is then interpreted against established cut-off values. There is no human-in-the-loop performance described in the context of improving the device's output.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The primary ground truth used for the test sets was Factor V gene nucleotide determination specifically for the FV:Q506 mutation at position 1691. This is a genetic-level diagnostic certainty.
8. The Sample Size for the Training Set
The document does not separately describe a distinct "training set." The studies appear to be validation or test sets. It's possible that the initial development and optimization of the assay (which would involve some form of "training") utilized samples, but those are not clearly delineated as a separate training set with specific numbers in this summary.
9. How the Ground Truth for the Training Set Was Established
As no distinct training set is identified, the method for establishing its ground truth is not specified. However, by extension, if any samples were used for initial assay development, their ground truth would likely also be based on Factor V gene nucleotide determination, similar to the test sets.
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CHROMOGENIX AB
510(k) Application COATEST APC™ RESISTANCE
DEC 23 1996
510(k) SUMMARY
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
APC resistance is a newly detected abnormality in hemostasis, which appears to be prevalent in 20 % to 50 % of patients with deep venous thrombosis. This abnormality appears to be at least 10 times more common than inherited deficiencies of any of the other anticoagulant proteins.
APC resistance reflects an impairment of the expression of activated protein C (APC) activity in an individual's plasma and will result in a reduced ability to stop thrombin formation. The original device COATEST® APC™ RESISTANCE C / COATEST® APC™ RESISTANCE SC received 510(K) clearance for diagnosis of the APC resistance phenotype on August 8, 1995 (K945940). The new device COATEST APC™ RESISTANCE V / COATEST APC™ RESISTANCE V S contains a supplementary component, (factor) V-DEF Plasma. The present documentation intends to show the applicability of V-DEF Plasma in a modification of the original COATEST® APC™ Resistance kit and the sensitivity for the mutation in coagulation factor V is considerably increased. 90 to 95% of all cases with APC resistance are explained by a mutation in the factor V protein rendering the activated form of factor V less susceptible to degradation by APC. The documentation shows the applicability of V-DEF Plasma in a modification of the original COATEST APC® RESISTANCE kit with a considerably increased sensitivity for the mutation in factor V.
COATEST APC RESISTANCE V or V S test is based on the use of activated protein C in an APTT clotting assay, as was the original test kit. Two studies support the substantially equivalency of COATEST APC™ RESISTANCE V or V S (modified method) with COATEST APC® RESISTANCE (original method, K945940).
The first study shows a correlation (R= 0.74) between the two methods and their discrimination for FV:Q666 on analysis of plasma from 218 acutely ill patients with suspected venous thrombosis or pulmonary emboli and from family members. The second study showed a similar correlation and discrimination for FV:Q56, noted above, between the two methods on analysis of plasma from 399 plasmapheresis donors. Thus, the data supports COATEST" APC" RESISTANCE V or V S Substantial Equivalency to the predicated device COATEST® APC RESISTANCE C (K945940) and there is a high discrimination for FV:Q506.
The new method, CQATEST APC RESISTANCE V or V S, correlated well with regard to cases with thrombosis and with homo- or heterozygous factor V mutation. All showed pronounced APC resistance. The homozygous cases were properly discriminated from the heterozygous cases which were separated from the rest.
The safety and efficacy of CONTEST APC® RESISTANCE V or V S is further supported by studies which show that this kit can be utilized on instruments with different clot detection principles and that appropriate results are obtained on analysis of plasmas from patients receiving oral anticoagulants, normal or low molecular weight (LMW) heparin or patients with the phospholipid antibody syndrome.
Thrombolyzer and MLA/Electra 900C, were utilized for samples of plasma from patients with myocardial infarction (97) and from healthy controls (132) in the former instrument; and on plasma from thrombotic patients or family members (50), in the latter instrument. The factor V gene nucleotide at
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CHROMOGENIX AB
510(k) Application COATEST APC™ RESISTANCE
position 1691 was determined in almost all individuals. A clear and complete discrimination is obtained for FV:Q566 by both instruments and an improvement is obtained as compared to the original kit method. This is illustrated for the patient group. Evaluation of the 50 family members by the MLA/Blectra 900C showed that for normal Factor V genotype an APC ratio of 2.4 - 3.4 was obtained, for the Heterozygous genotype 1.6 - 1.9 and for the Homozygous 1.2 to 1.3.
COATEST® APC® RESISTANCE V or V S was used for analysis of plasma from 147 patients on OAC therapy and 61 healthy controls by the ACL 300 and of plasma from 129 patients on OAC therapy and 62 healthy controls by the ST-4 instrument. The factor V gene nucleotide at position 1691 was determined in all.
Results show a clear discrimination obtained for the FV:Q46 mutation on both ACL and ST-4. Similar ranges of APC ratios are obtained for healthy controls vs patients on OAC, for individuals with a normal factor V genotype, and with heterozygosity and homozygosity for FV:Q566, respectively. Results from the ACL and ST-4 instruments for plasmas from patients on unfractionated and low molecular weight (IMW) heparin at concentrations < 1 IU/mL show that in contrast to the original method COATEST APC® RESISTANCE V or V S provides normal APT times to at least 1 IU/mL of normal heparin. All samples from factor V genotyped patients receiving normal heparin were correctly classified as well as all of the genotyped IMN samples. The data also supports that a correct classification with regard to the factor V genotype is obtained for patients with the phospholipid antibody syndrome.
COATEST APC RESISTANCE V or V S provides a similar repeatability and reproducibility as Coatest APC Resistance. Similar results were obtained on the four instruments (Thrombolyzer, MLA/Electra 900, ST-4, ACL 300) included in the studies.
Calibration and Determination of the Cut-Off Value for the APC Ratio was performed with the CONTEST APC RESISTANCE V or V S with three instruments in a population of normal factor V genotype males and females. The results illustrate that a significantly narrower range is obtained with COATEST APC® RESISTANCE V or V S compared to the original Coatest APC Resistance kit. Further, based on the data presented and analyzed in the same manner as the original Kit, the results support the fact that the COATEST APC RESISTANCE V or V S has a greater than 99 % sensitivity for FV:Q06.
Reagent V-DEF Plasma and the stability of other reconstituted reagent was determined through the effect of storage at different temperatures on the APT time and the APC ratio on the analysis of plasmas containing factor V of different genotype origin. The above noted data support the assigned stabilities in the package insert of reconstituted V-DEF plasma. Further, a similar stability is obtained for 3 mL and 4 mL vials. Further, the data supports that whole blood and plasma can be stored for at least 7 hours at room temperature.
Erich A. Hausmann.
RONALD G. LEONARDI, Ph. D.
August 9, 1996
§ 864.7925 Partial thromboplastin time tests.
(a)
Identification. A partial thromboplastin time test is a device used for primary screening for coagulation abnormalities, for evaluation of the effect of therapy on procoagulant disorders, and as an assay for coagulation factor deficiencies of the intrinsic coagulation pathway.(b)
Classification. Class II (performance standards).