Evaluation of new genetic tests for NHS services
Recommendations to the March 2015 Clinical & Scientific Advisory Group (CSAG)
Key messages
11 new tests recommended for NHS serviceOf the new tests recommended 7 are expected to have less than 50 index cases per annum
In addition to the clinical genetics specialty/CRG the tests range across:
- 11 specialties
- 9 Clinical Reference Groups (CRG)
- 1 Highly Specialised Service (HSS)
- £20,786 is required for medical genetics
- £30,921is required for prescribed specialised services (excluding medical genetics & HSS)
- £57,712 from medical genetics
- £142,576 from prescribed specialised services (excluding medical genetics & HSS)
Context
Criteria for evaluation by UKGTN: any genetic test provided by a UKGTN member laboratory for NHS service provision for rare disorders that usually affect fewer than 1 in 2000 as described in the UK Rare Disease Strategy.
The burden of rare diseases was recognised in the Chief Medical Officer report 2009 stating that rare diseases, when considered collectively, are common and that “a diagnosis of a rare disease has a huge impact, not just on the individual but also on their family. There are potential efficiencies in treatment if repetition of tests is avoided every time the patient sees another consultant.” These efficiencies are evidenced in the care pathway of the submissions to UKGTN for new genetic tests.
The update to the Strategy for UK Life Sciences (2012) championed genetic testing “The UK has led the world in genetic and genomic science, and the Government is determined to provide a supportive environment, to ensure that the UK remains at the forefront of new innovations in this field, capitalising on this leadership for the benefit of UK patients, the NHS, and the UK economy.” This has led to the establishment of Genomics England to deliver whole genome sequencing in
collaboration with NHS England. In December 2014 the first 11 Genomic Medicine Centres were announced by NHS England.
The UK Strategy for Rare Diseases was published in December 2013. The strategy aims todrive forward understanding of rare disease and work to increase the prospects of finding effective and
sustainable treatments and therapies and earlier diagnosis. It sets out 51 commitments. Implementation of these commitments is the responsibility of the four countries in the UK. A stakeholder forum has been established to oversee progress on implementation.
Recommendations to March 2015 CSAG for new genetic tests for commissioning year 2016/17
The UKGTN recommendations contained in this paper to introduce new genetic tests would not be evaluated by NICE as they are outside the selection criteria due to their rarity.
The UKGTN Genetic Test Evaluation Working Group, in the periodAugust 2014 to February 2015:
- evaluated20gene dossiers
- recommends 11new tests of which for NHS England:
- 10are prescribed servicesand1is within Highly Specialised Services
(The contract for the test for the HSS is for England and Scotland only).
To be noted:
- all 11recommendations are panel tests that use Next Generation Sequencing (NGS)
- of the 11 new tests using NGS, 3 have a number of sub panel tests
- 7 were evaluated through the very rare disease process (less than 20 index cases a year and less than £5000 annual costs for index cases)
The cost implications of the UKGTN recommendations for new tests are detailed in Appendix 1.
The clinical utility and consequences for patients if the tests were not available are included in the embedded document here:
The number of new tests by specialtiesare indicated in the chart on page 3. It would be appropriate for Consultant Clinical Geneticists to request all the new tests but 2 have Consultant Clinical Geneticists as the only referrer.
Based on the types of referrers for each test and the nature of each disorder it is expected that the new tests would fall within 9 prescribed specialised services in addition to medical genetics CRG and Highly Specialised Services. The number of tests by CRG and HSS is shown in the chart on page 3.
Clinical Outcomes
UKGTN is assessing the benefits to patient outcomes as a result of new genetic tests. The categories for clinical utility are summarised below and the embedded document details the expected outcomes for each test.
- Genetic testing alerts significant clinical co-morbidities
- Reduced mortality/saves lives
- Avoids diagnostic invasive procedures/tests and associated in patient episodes
- Confirms targeted therapy
- Earlier diagnosis avoiding multi hospital appointments/procedures
- Avoids irreversible harm
- Enables access to educational and social support
- At risk family members that test negative for a familial mutationcan be discharged from follow up
- At risk family members that test positive for a familial mutation have appropriate follow up.
Funding for new genetic tests for NHS service from 2016/17
The table of new test recommendations shows estimated funding required for clinical genetics separately from the funding requirements for specialties outside of clinical genetics and for Highly Specialised Services. This has been calculated based on expected activity for testing from the genetics specialty and expected activity from mainstream specialties.
For the whole of the UK for:INVESTMENT
clinical genetics activity ONLY:£20,786
CRG specialties activity EXCLUDING clinical genetics: £30,921
HSS activity ONLYcost neutral
TOTAL£51,707
Three tests are provided on a cost neutral basis as they have the potential to replace other diagnostic tests and procedures that would be at a similar cost to provide the genetic test.
There are three tests that show both costs and cost savings/ efficiencies. This occurs when there are savings for index cases (usually due to a decrease in other tests required to diagnose if the genetic test is introduced earlier in the diagnostic care pathway or because the NGS test replaces sequential testing) but new costs as there is an expectation that a greater number of at risk family members could have testing due to an increase in the number of index cases identified (due to a wider breadth of genes analysed).
All the tests are NGS panels and all of them have a number of genes on the panel that are already available for testing as either single gene or multi gene tests using Sanger Sequencing. In some cases the panel tests replace these and in other cases they work alongside them. For the latter scenario this would usually be where the clinical phenotype is obvious for a condition and the single gene Sanger test would remain the preferred option.
Tests that cost less than the current diagnostic tests can be introduced at cost saving. The net savings are:
For the whole of the UK for:NET SAVINGS
clinical genetics activity ONLY:£36,926
CRG specialties activity EXCLUDING clinical genetics: £111,655
HSS activity ONLYcost neutral
TOTAL£148,581
The net savings for England and the Devolved Countries for medical genetics CRG, all other CRGs, and HSS activity is shown in table 1. It is recognised that CRGs apply to commissioning in England only and it is suggested that devolved nations use these categories as a proxy to apply to the equivalent commissioning bodies in Scotland, Northern Ireland and Wales.
Table 1. Estimated net savings for new UKGTN recommended testing services across all specialised services (including clinical genetics and HSS) for all UK countries
NET SAVINGSCountry / POPULATION / Medical Genetics only / CRGs excluding medical genetics / HSS only
England / 53,107,169 / £31,060 / £93,916 / Cost neutral
Wales / 3,006,430 / £1,758 / £5,317 / Cost neutral
Scotland / 5,200,000 / £3,041 / £9,196 / Cost neutral
Northern Ireland / 1,824,000 / £1,067 / £3,226 / Cost neutral
The total estimated net savings for new UKGTN recommended tests for England for the clinical genetics specialty only are listed by region in Table 2. The net savingsacross allspecialised services (including clinical genetics and HSS) are listed in Table 3.
Table 2. Estimated net savings for new UKGTN recommended testing services for Clinical Genetics specialty for England.
Country & Region (England) / POPULATION / NET SAVINGSEngland / 53,107,169 / £31,060
North / 15,086,775 / £8,823
Midlands and East / 16,117,771 / £9,426
London / 8,204,407 / £4,800
South / 13,698,216 / £8,011
Table 3. Estimated net savings for new UKGTN recommended testing services across all specialised services (including clinical genetics and HSS)for England.
Country & Region (England) / POPULATION / NET SAVINGSEngland / 53,107,169 / £124,976
North / 15,086,775 / £35,504
Midlands and East / 16,117,771 / £37,930
London / 8,204,407 / £19,306
South / 13,698,216 / £32,236
The total estimated investment, savings and net savings across all funding streams for each devolved nation is shown in table 4.
Table 4. Estimated investment, savings and net savings for all activity across the home nations
Home NationEngland / Scotland / Northern Ireland / Wales
Investment / £43,493 / £4,259 / £1,493 / £2,462
Savings / £168,469 / £16,496 / £5,786 / £9,537
Net Savings / £124,976 / £12,237 / £4,293 / £7,075
Costs have not been provided for testing for those laboratories that have requested to be an additional provider as the resource is already available for these tests.
Services to be commissioned from 1st April 2016. The new test service information will be available from the website
Trend Analysis
The figures shown in the above trend chart are indicating the total investment per annum for the genetic tests that would require investment to implement. Some tests would not require investment as they release savings and/or cost efficiencies in the diagnostic pathway. These savings have not been offset from the investment figures above. Tests introduced from 2014/15 also show the total savings.
Background
The Gene Dossier provides a standardised format for the evaluation of the key information about a genetic test. A UKGTN multidisciplinary Working Group performs the evaluation of these applications and one of its key objectives is to confirm the clinical utility of a proposed genetic test. In the embedded document on page 2, the Working Group has included brief details about the clinical impact of each genetic test and the clinical consequences of not providing the test for NHS patients.
Every Gene Dossier submitted has to include Testing Criteria for the test. The UKGTN developed the concept of Testing Criteria as part of the Gene Dossier application process. Testing Criteria defines the appropriateness of a genetic test referral, and it is intended that the test is only carried out in accordance with the criteria set out in the Gene Dossier and approved by the UKGTN Clinical and Scientific Advisory Group. Testing Criteria should include only those data that are specifiedwithin the Gene Dossier, and should not be confused with any other information that a provider laboratory may wish to have for research or any other reasons. The additional benefit of these criteria is that they can inform clinicians’ decisions about which investigations are suitable for their patients. A summary of the Genetic Test Evaluation process is provided below.
Genetic Test Evaluation Process
The Genetic Test Evaluation process (previously referred to as the Gene Dossier process) was developed by the UKGTN in 2003 as a tool to evaluate whether a proposed laboratory genetic test for a specific genetic disease is to be recommended for inclusion on the NHS Directory of Genetic Disorders/Genes for Diagnostic Testing (previously NHS Directory for Genetic Testing). Once a test is on the Directory it is recommended to be considered for funding under local commissioning arrangements. The Directory lists disease and gene combinations for which tests are available, that have been agreed as appropriate for clinical use, from member laboratories. The testing services provided and the laboratories providing them are available from the online database on the UKGTN website. The purpose of the Directory is to allow equity in access to genetic testing across the NHS. The process ensures that the decision regarding the recommendation of a test is explicit, transparent and based on evidence. The Genetic Test Evaluation documents (Gene Dossier and Additional Provider forms) and a description of the process can be found at
A gene dossier must be submitted to the UKGTN for any new genetic test that a UKGTN laboratory member wishes to provide and have listed on the NHS Directory of Genetic Disorders/Genes for Diagnostic Testing. For the UKGTN genetic test evaluation purposes, prior to April 2013, a genetic test was defined as any test for NHS service provision by a UKGTN member laboratory which required funding by specialised commissioning arrangements as supporting provision of clinical genetics services as defined in the national definition set for medical genetics services. Since April 2013, the definition of genetic testing has been expanded to include tests for any prescribed specialised service.
For diseases that are currently listed on the NHS Directory of Genetic Disorders/Genes for Diagnostic Testing or UKGTN website an additional provider form must be submitted.
It is recommended that a gene dossier is completed by the UKGTN laboratory in collaboration with clinical colleagues. The dossier is submitted by the laboratory director to the UKGTN and the UKGTN Genetic Test Evaluation Working Group (previously Gene Dossier working group) undertakes the evaluation of the dossier. The membership of this group includes professionals from clinical genetics, clinical laboratory genetics, public health, commissioning and patient groups.
The evaluation is based on agreed evaluation criteria. A template has been developed including the criteria and is part of the Gene Dossier. The evaluation criteria are summarised below:
(1)The seriousness of the condition
(2) The prevalence of the condition
(3)The purpose of the test – diagnosis, treatment, prognosis and management, presymptomatic testing, risk assessment
(4) The technical details of the test
(5) The context in which the test is to be used – defined population groups
(6)The characteristics of the test – the clinical sensitivity, specificity and predictive value
(7)The clinical utility of the test – how it adds to patient management and the availability of alternative diagnostic procedures
(8) Ethical, legal and social considerations
(9) The price of the test
The evaluation process includes both quantitative and qualitative information. The evaluations carried out so far have focused on molecular tests for rare genetic disorders. In many cases this results in limited test data and service information being available.
The results of the evaluation are reported to the UKGTN Clinical and Scientific Advisory Group (previously UKGTN Steering Group). Those disorders for which testing has been recommended by the working group and endorsed by the Clinical and Scientific Advisory Group are recommended to NHS commissioners for funding as NHS services and added to the NHS Directory of Genetic Disorders/Genes for Diagnostic Testing.
Prior to 2014 the process was carried out annually and recommendations made to the September CSAG meeting. From 2014 the process became biannual. Consequently from 2015 recommendations are made to both the March and September CSAG meetings. The two deadlines for gene dosser submissions to UKGTN are 31st January (for recommendations made to the September CSAG within the same year) and 31st July (for recommendations made to the March CSAG in the following year).
The Genetic Test Evaluation Working Group also reviews a number of the tests that are already on the NHS Directory of Genetic Testing in order to develop testing criteria for these tests. The UKGTN project team organises conferences/workshops on specific disorders (e.g. Cystic Fibrosis, Marfan and Fragile X) for scientists, clinicians and public heath consultants. Consensus testing criteria is produced so that all genetic laboratories are able to use them. This ensures a consistent approach to genetic test provision for these conditions throughout the UK.
The UKGTN has established a process to monitor the number of tests performed for all approved tests and will compare these figures to the predicted level of testing. If there is a significant difference then the UKGTN will investigate to establish the reasons for this.
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Appendix 1
Evaluationnumber asassignedduring theprocess / TestName / Clinicalcollaborator / Laboratory / Costpertestforindexcases / Costpertestforfamilymembers / Expectedannualreferralsforindexcases / Expectedannualreferralsforfamilymembers / Typesofreferrersontestingcriteria / SplitofactivitybasedonCRGandequivantgroups/specialitiesindevolvednations / Estimateoftotal annualcosts / Estimateoftotal annualsavings / Estimateofannualcostsforclinicalgenetics / Estimateofannualcostsformainstream specialtyoutsideofclinicalgenetics / Estimateofannualsavingsforclinicalgenetics / EstimateofannualsavingsformainstreamspecialtyoutsideofclinicalgeneticsRECOMMENDATIONSTOBECONSIDEREDFORFUNDING
#255 / EndocrineDisordersPanelTest(includes14subpanels) / DrBijayVaidya / ExeterRGC / £750 / £100 / 785 / 555 / ConsultantClinicalGeneticistConsultantEndocrinologist
ConsultantPaediatrician/NeonatologistConsultantPaediatricEndocrinologists / E01.MedicalGenetics(I=345,F=400)
A03.SpecialisedEndocrinology(I=350,F=145)
E03.PaediatricMedicine(inlcudepaediatricendocrinology)
(I=80,F=10)
E08.NeonatalCriticalCare(I=10,F=0) / £14610
(Costsapplytoclinicalgeneticsandadultendocrinologyonlyasonly3subpanelshavecostsandforallthreeonlygeneticistsandendocrinologistsarereferrers) / £0 / £7,965 / A03:£6645 / £0 / £0
#256 / EyeMovementDisorders8GenePanelTest / DrNicholasGutowski / ExeterRGC / £750 / £100 / 20 / 10 / ConsultantClinicalGeneticistConsultantOphthalmologistConsultantPaediatricNeurologistConsultantAdultNeurologist / E01.MedicalGenetics(I=10,F=10)
E09.PaediatricNeurosciences(I=3,F=0)
D04.Neurosciences(I=2,F=0)
D12.SpecialisedOphthalmologyServices
(I=5,F=0) / Costneutral / Costneutral / Costneutral / Costneutral / Costneutral / Costneutral
#257 / Holoprosencephaly6GenePanelTest / DrJulieRankin / ExeterRGC / £750 / £100 / 5 / 10 / ConsultantClinicalGeneticist / E01:MedicalGenetics / Costneutral / Costneutral / Costneutral / n/a / Costneutral / n/a
#258 / PontocerebellarHypoplasia12GenePanelTest / DrJulieRankin / ExeterRGC / £750 / £100 / 10 / 15 / ConsultantClinicalGeneticistConsultantPaediatricNeurologist / E01MedicalGenetics
E09.PaediatricNeurosciences / £9,000 / £0 / £5,250 / £3,750 / £0 / £0
#259 / SpondylocostalDysostosis5GenePanelTest / DrPeterTurnpenny / ExeterRGC / £750 / £100 / 10 / 5 / ConsultantClinicalGeneticist / E01:MedicalGenetics / £3,600 / £0 / £3,600 / n/a / £0 / £0
#260 / PeroxisomeDisorders24GenePanelTest / ProfessorSYap / SheffieldRGC / £950 / £105 / 50 / 70 / ConsultantClinicalGeneticistConsultantinMetabolicDiseasesConsultantPaediatricianConsultantNeonatologist / E06Metabolicdisorders(I=25,F=25)
E03PaediatricMedicine(I=13,F=10) / £9,862 / £0 / £1,381 / E06:£4931
E03:£2564E08:£592 / £0 / £0
ConsultantNeurologist / E08Neonatalcriticalcare / D04:£394
(I=3,F=0)
E01MedicalGenetics
(I=7,F=35)
D04Neurosciences
(I=2,F=0)
#261 / FattyAcidMetabolismDisorders22GenePanelTest / DrMJSharrard / SheffieldRGC / £950 / £105 / 35 / 30 / ConsultantPaediatricianConsultantNeurologistConsultantinMetabolicMedicineConsultantClinicalGeneticist / E01MedicalGenetics(I=5,F=10)
E03PaediatricMedicine(I=10,F=3) / £525 / £18,781 / £175 / E03:£52
E06:£263D04:£35 / £2,683 / E03:£5366
E06:£8049D04:£2683
E06Metabolicmedicine
(I=15,F=15)
D04Neurosciences
(I=5,F=2)
#262 / Hyperammonaemia/UreaCycleDisorders14GenePanelTest / ProfessorSYap / SheffieldRGC / £800 / £105 / 48 / 80 / ConsultantClinicalGeneticist
ConsultantinMetabolicDiseases(PaediatricAdult)
ConsultantPaediatricianConsultantNeonatologistConsultantNeurologistConsultantHepatologist / E01MedicalGenetics(I=5,F=35)
E06MetabolicDisorders(I=35,F=45)
E03Paediatricmedicine(I=3,F=0)
E08NeonatologyCriticalCare(I=1,F=0)
A02HepatobiliaryPancreas(I=1,F=0)
E09Paediatricneurosciences(I=3,F=0) / £9,985 / £0 / £1,040 / E06:£7281
E03:£624E08:£208A02:£208E09:£624 / £0 / £0
#263 / Rhabdomyolysis/MetabolicMyopathies30GenePanelTest / DrRQuinlivan / SheffieldRGC / £950 / £105 / 175 / 35 / ConsultantClinicalGeneticistConsultantinMetabolicMedicineConsultantPaediatricianConsultantNeurologist / E01MedicalGenetics(I=20,F=10)
E06MetabolicDisorders(I=50,F=8) / £2,625 / £61,507 / £750 / E03:£150
E06:£600D04:£1125 / £7,029 / E03:£5272
E06:£17574D04:£31632
E03Paediatricmedicine
(I=15,F=2)
D04Neurosciences
(I=90,F=15)
Evaluationnumber asassignedduring theprocess / TestName / Clinicalcollaborator / Laboratory / Costpertestforindexcases / Costpertestforfamilymembers / Expectedannualreferralsforindexcases / Expectedannualreferralsforfamilymembers / Typesofreferrersontestingcriteria / SplitofactivitybasedonCRGandequivantgroups/specialitiesindevolvednations / Estimateoftotal annualcosts / Estimateoftotal annualsavings / Estimateofannualcostsforclinicalgenetics / Estimateofannualcostsformainstream specialtyoutsideofclinicalgenetics / Estimateofannualsavingsforclinicalgenetics / Estimateofannualsavingsformainstreamspecialtyoutsideofclinicalgenetics
#267 / CongenitalMuscularDystrophy31GenePanelTest / ProfessorFranescoMuntoni / LondonSouthEastRGCGSTT / £1,000 / £160 / 100 / 100 / ConsultantpaediatricneurologistConsultantneurologistConsultantclinicalgeneticist / HSSforresidentsinEnglandandScotland
(I=90,F=90)
Wales/IrishactivityClinicalGenetics(I=2,F=8)
Wales/IrishactivityPaediatricNeurology(I=7,F=1)
Wales/IrishactivityAdultNeurology(I=1,F=1) / Costneutral / Costneutral / Costneutral / Costneutral / Costneutral / Costneutral
#277 / DisordersofSexualDevelopment26GenePanelTest / DrKatherineLachlanDrJustinDavies / SalisburyRGC / £900persub
panel / £175 / 200 / 24 / ConsultantclinicalgeneticistConsultantPaediatricEndocrinologistConsultantAdultEndocrinologistConsultantGynaecologist / E01MedicalGenetics
E03PaediatricMedicine(forpaediatricendocrinology)
A03SpecialisedEndocrinology(Adult)E10.ComplexGynaecologicalServices / £1,500 / £120,000 / £625 / E03:£625
A03:£125E10:£125 / £48,000 / E03:£48000
A03:£12000E10:£12000
TOTAL / £51,707 / £200,288 / £20,786 / £30,921 / £57,712 / £142,576
GENEDOSSIERSSUBMITTEDBUTRESUBMISSIONSREQUESTEDANDNOTCOMPLETEDWITHINYEAR
#276 / NF1Rasopathy13GenePanelTest / SalisburyRGC
#271 / Epilepsy31GenePanelTest / Cardiff
#272 / CorticalMalformations37GenePanelTest / Cardiff
GENEDOSSIERSNOTAPPROVED
#264 / DDG2P(DevelopmentDelay)1335GenePanelTest / LondonSouthEastRGCGSTT
#265 / RenalWES220GenePanelTest / LondonSouthEastRGCGSTT
#266 / SkeletalDysplasiaWES223GenePanelTest / LondonSouthEastRGCGSTT
#270 / OrofacialClefting13GenePanelTest / Liverpool
GENEDOSSIERSCONVERTEDTOADDITIONALPROVIDERS
#279 / MarfanTAAD19GenePanelTest / SalisburyRGC
GENEDOSSIERWASNOTREQUIREDASCHANGEOFTECHNOLOGYONLY
#278 / FamilialBreastandOvarianCancer2GenePanelTest / SalisburyRGC
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