Search Results

The AncestryDNA Factor V Leiden Genetic Health Risk Test for Hereditary Thrombophilia uses qualitative genotyping to detect clinically relevant variants in genomic DNA isolated from human saliva collected from individuals 18 years and older with the AncestryDNA Saliva Collection Kit for the purpose of reporting and interpreting Genetic Health Risks (GHR).

The AncestryDNA Factor V Leiden Genetic Health Risk Report for Hereditary Thrombophilia is indicated for reporting of the Factor V Leiden variant in the F5 gene. This report describes if a person has variants associated with a higher risk of developing harmful blood clots, but it does not describe a person's overall risk of developing harmful blood clots. This test is most relevant for people of European descent.

A user's saliva is self-collected using the AncestryDNA Saliva Collection Kit, which consists of a sealable collection tube containing a stabilizing buffer solution. Once the sample is collected, it is shipped to one of two Clinical Laboratory Improvement Amendments (CLIA) certified laboratories for processing.

DNA is isolated from the saliva, quantified, and tested in a multiplex assay using a customized genotyping chip and instrumentation manufactured by Illumina. The multiplex assay simultaneously tests for more than 500,000 variants, including those for the indication proposed herein.

The raw data is generated using Illumina GenomeStudio software, and then sent to Ancestry Genomics (the Manufacturer). The data are analyzed using the Manufacturer's proprietary GHR software, and a genotype is determined for each tested variant. The results for the Factor V Leiden variant are used to generate personalized reports for users that provide information about the disease associated with the detected variant.

Personalized reports are generated for each user that provide results of the testing performed. These reports tell the user which variant(s) has/have been detected in their sample and provide information on the risk of disease associated with the variant(s). If no variant was detected, that information is also provided. The personalized reports are designed to present scientific concepts to users in an easy-to-understand format. The reports provide scientifically valid information about the risks associated with the presence of a particular variant. The reports are designed to help users understand the meaning of their results and any appropriate actions that may be taken based on their results.

Here is a summary of the acceptance criteria and the study that proves the device meets the acceptance criteria, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details

2. Sample Size and Data Provenance (Test Set):

• Reproducibility/Precision:
  • Total replicates: 2,340 genotyping events (combining all replicates from Lab 1, Lab 2, inter-laboratory, by site/operator team, by site/instrument, and by site/reagent lot).
  • Donors: 9 donors with known Factor V Leiden genotypes (3 homozygous common, 3 heterozygous, 3 homozygous rare).
  • Provenance: Samples were collected using AncestryDNA Saliva Collection Kits (SCKs) and tested at two CLIA-certified laboratories (Lab 1 and Lab 2). The study was prospective in nature for data collection.
• Analytical Sensitivity:
  • Saliva Study: 15 donors (5 homozygous common, 5 heterozygous, 5 homozygous rare). 450 replicates tested.
  • Cell Line Study: 4 cell lines. 216 data points per cell line for dilutions, and 855 blank replicates.
  • Provenance: Saliva samples collected using Oragene® Dx Collection Device and AncestryDNA SCK. Cell lines. Data collected prospectively for the study.
• Interfering Substances (Endogenous):
  • Donors: 10 saliva donors. 450 initial genotyping attempts (3 replicates for each of 10 donors per interferent + 30 control replicates).
  • Provenance: Saliva samples collected using Oragene® Dx Collection Device. Data collected prospectively for the study.
• Interfering Substances (Exogenous):
  • Donors: 10 non-smokers and 10 smokers. 594 data points.
  • Provenance: Saliva samples collected using AncestryDNA SCKs. Data collected prospectively for the study.
• Interfering Substances (Microbial):
  • Cell Lines: 6 human cell lines (4 homozygous common, 1 heterozygous, 1 homozygous rare). 432 genotyping results.
  • Provenance: Human cell lines. Data collected prospectively for the study.
• Accuracy / Method Comparison:
  • Donors: 209 donors with known Factor V Leiden genotypes (73 homozygous common, 69 heterozygous, 67 homozygous rare). 198 samples passed QC.
  • Provenance: Saliva samples collected using Oragene Dx Ogd-500.001 (OGD) and AncestryDNA SCK. Data collected prospectively for comparison.
• User Comprehension (Study 1):
  • Participants: 378 individuals (N=96, N=86, N=106, N=90 for each of four study arms).
  • Provenance: Participants were recruited from the U.S. matching demographics for education, age, sex/gender, and race/ethnicity, and geographic diversity across four U.S. Census regions. Performed in-person. Prospective study.
• User Comprehension (Study 2):
  • Participants: 213 individuals (N=103 for "1 Variant", N=110 for "Result Not Determined").
  • Provenance: Participants were recruited from the U.S., matching demographics and geographic diversity as in Study 1. Performed via live televideo interviews. Prospective study.

3. Number of Experts and Qualifications for Ground Truth (Test Set):
For analytical studies (Reproducibility, Analytical Sensitivity, Interfering Substances, Accuracy/Method Comparison), the ground truth for Factor V Leiden genotype was primarily established using bi-directional sequencing analysis at a third-party laboratory. The specific qualifications of the experts performing the bi-directional sequencing were not detailed in the provided text.

For User Comprehension Studies, the materials were reviewed by a Certified Genetic Counselor to confirm that the materials met specific criteria for explaining test concepts.

4. Adjudication Method (Test Set):
The text does not explicitly describe an adjudication method like 2+1 or 3+1 for the analytical studies. Instead, direct comparison was made between the device's genotype calls and the ground truth established by bi-directional sequencing. Any discrepancies would presumably be investigated, though the method is not detailed. For User Comprehension studies, a questionnaire was administered by a trained interviewer/moderator to assess comprehension.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not performed. This device is a genetic health risk test (an in vitro molecular diagnostic system), not an imaging device typically associated with MRMC studies in the context of human reader performance improvements with AI.

6. Standalone Performance:
Yes, standalone performance (algorithm only) was done. The studies described (reproducibility, analytical sensitivity, interfering substances, and accuracy/method comparison) evaluate the performance of the device itself (AncestryDNA Factor V Leiden GHR Test) in determining genotype status, independent of human interpretation of raw data. The "AncestryDNA GHR software" processes data from the instrumentation and generates the final analytical genotype information for each sample, which is then used to generate personalized reports.

7. Type of Ground Truth Used (Test Set):
The primary ground truth used for determining the Factor V Leiden genotype in analytical studies was bi-directional sequencing analysis.

8. Sample Size for the Training Set:
The document does not explicitly specify a "training set" sample size for the AncestryDNA Factor V Leiden Genetic Health Risk Test in the context of its 510(k) submission. For molecular diagnostic systems like this, the "training" aspect often refers to the development and optimization of the assay and software algorithms. The document instead focuses on analytical validation studies (test sets) for device performance. If the AncestryDNA GHR software performs certain control checks and analyses (as described in section "P. SYSTEM DESCRIPTION" - "Software"), the underlying algorithms would have been developed and potentially "trained" or optimized during the device's development phase, but specific training set sizes are not provided.

9. How the Ground Truth for the Training Set was Established:
Since a specific training set sample size is not explicitly mentioned for the reported studies, the method for establishing ground truth for a training set is also not detailed. However, for any developmental work or optimization, it is highly probable that the ground truth would have been established using bi-directional sequencing or other highly accurate, established reference methods, similar to how the ground truth for the test sets was established.

Ask a specific question about this device