Genomic testing within the NHS Flashcards
What are two major changes launched by NHS England?
Restructuring genetics service and the national genomic test directory
Why has the National genomic test directory been created?
To remove the variation in the approach to the commissioning and funding of genomic tests across England
The National test directory identify as the most appropriate test for each clinical indication and the resting methodology by which it should be delivered.
What else does it include?
Who developed it?
The eligibility criteria document sets out which patients should be considered for testing under that indication
The requesting specialties is a list of the clinical specialties who would be expected to request the test
Developed by a panel of clinicians, scientists, health economists, policy experts, public representatives and patient organizations
Only tests in the Test Directory are commissioned and paid for by the NHS and they must be delivered by a Genomic Laboratory Hub
True or false
True
Genomic testing at the NHS is pursed for….
Rare and inherited disorders
Cancer
Genomic testing at the NHS involves what?
Single genes to whole genome sequencing
Genomic tests are divided into what?
Core genomic tests – high volume tests that will be provided by all GLHs
Specialist genomic tests – specialist tests that will be delivered only by the GLHs that have the required quality and expertise
What does the test directory specify?
Clinical indication name
Testing criteria (description of the patients who should receive the test)
Requesting specialties (i.e. clinical genetics)
Specialist service group that covers the clinical indication (i.e. Cardiology, Eyes, Immunology etc)
The test directory specifies what associated tests?
Optimal family structure
i.e. singleton, trio, parents only
Scope
i.e. small nucleotide variant, insertion-deletion, copy number variant and structural variant detection to exon or genome wide resolution, short tandem repeat analysis, methylation analysis
Target type
i.e. genome-wide, targeted panel of genes, single genes
Target name
names of genes in which the variant type should be detected
Test method
i.e. Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), targeted panels, single gene sequencing, Multiplex ligation-dependent probe amplification (MLPA), microarray, karyotyping, Fluorescence In Situ Hybridization (FISH), Non-invasive Prenatal Diagnosis (NIPD)
What is the motivation for genomic testing?
- Diagnostic testing for known mutation(s)
Patient clinically affected with specific disorder where:
- The familial mutation(s) have already been identified in a relative OR
- There is a recurrent mutation for the disorder that is likely to be causative OR
- There is a founder mutation for the disorder that is likely to be causative OR
- A mutation has been identified in the patient during somatic testing that is likely to be causative
Molecular confirmation of the diagnosis is required to guide management (i.e. advice on treatment options, to make an informed decision)
- Predictive testing for known familial mutation(s)
- Patient requiring predictive testing for specific disorder where the familial mutation(s) have already been identified in a relative - Carrier testing for known familial mutation(s)
- Patient requiring carrier testing for specific disorder where the familial mutation(s) have already been identified in a relative
-To confirm the potential
inheritance pattern of a disease-causing variant in a family member
What is the purpose of seeking consent?
To ensure that a person understands the nature and purpose of the procedure or intervention
What is the aim of the ‘patient choice’ consent process?
To enable patients to make an informed decision about having clinical genomic testing in the NHS, as well as make a clear and distinct decision about being part of any research (requires explicit consent).
What does the Royal College of Pathologists provides guidance on>
The retention and storage of pathological reports and specimens
- DNA (and RNA) samples are to be retained for at least 30 years if needed for family studies in those with genetic disorders
- Stored samples can be used in the future for further genomic tests after taking appropriate consent from the patient, or as a control sample when testing family members of that patient.
What are the implications of giving consent?
Discussion on results:
Test may not yield any significant finding
- Uncertainty of genomic information (interpretation and knowledge)- Variants of uncertain significance
- Main findings – may or may not affect current/future care
- Incidental findings (including family relationships)
- Results will not inform all health conditions
Implications for the patient:
- Onward referrals
- Psychosocial impact
- Family planning
- Relatives could have access to preventative screening, predictive testing
- Discussion on sharing results with family members
What are examples of over diagnosis?
- Predictive or carrier testing:
Symptom-free people with associated variant defined as ‘having the disease“ albeit they are not clinically unwell
Uncertainty in most genetic conditions about if and when the person will become ill- This may lead to preventive “treatment” even if the patient is not ill
- Diagnostic testing:
A variant is found and reported back to the patient but its relationship to the disease in question is uncertain (variants of uncertain significance)- Testing without a family history
A variant is found that is associated with
milder level of dysfunction- Not clear how the finding should affect how the patient should be treated
