Molecular genetic test activity rates in the United Kingdom Key messages 26 laboratories submitted data on 152,866 reports 88,890 test reports met the inclusion criteria for analysis 61% of test reports analysed were requested from specialties outside of clinical genetics Summary Genetic test report rates per 100,000 population for data analysed Age Standardised Crude England 143 136 Scotland 219 204 Northern Ireland 157 155 Wales unavailable 127 UK 145 142 This paper reports on the data collection of genetic test activity by UK Genetic Testing Network member laboratories. The purpose of the data collection is to gain information on the access to genetic testing provided by UKGTN member laboratories for NHS patients. Laboratories were asked to submit information on genetic tests issued for the period 1 st April 2011 to 31 st March 2012. In addition, the laboratories were asked to flag tests for Huntington s disease, breast cancer and Fragile X. Twenty six of the 27 member laboratories in the constituent countries of the UK submitted data for the period ; Wales RGC was not able to submit data for this period due to technical difficulties. However to ensure UK activity could be analysed, Wales RGC data for 2010/2011 were used on the assumption that there has not been a significant change in volume and/or nature of activity. Key findings include that the total activity for the United Kingdom from all UKGTN member laboratories was 152,866 test reports of which 88,890 (58%) met the inclusion criteria and were analysed for this report. Of the reports that met the inclusion criteria, the majority (71%) were referred by medical specialties other than clinical genetics. It was necessary to use criteria to ensure the data being analysed were comparable for all areas. This report for the first time presents the rate of molecular genetic test activity across the United Kingdom on a population basis and includes details for England, Scotland, Wales and Northern Ireland. Compared to data submissions, evidence suggests that there has been a slight decrease in the quality of the reporting of valid resident postcodes. The analysis indicates that valid resident postcodes were obtained for 90.1% in compared with 91.1% in of the records submitted by UK laboratories. However, for test reports it has been possible to derive valid resident postcodes from patients NHS/CHI numbers received from the laboratories increasing the total percentage of valid postcodes to 94.3%. The remaining records had invalid or no postcodes. For laboratories in England, resident postcodes were obtained for 95.2% of tests submitted for, 96.3% in Scotland and 97.5% in Northern Ireland (including postcodes derived from NHS/CHI numbers). Among member laboratories in the constituent countries the completeness of valid resident postcodes ranged from 82.2% to 99.8%. The results show wide variation between devolved countries in report rates that met inclusion criteria. Test report rates are higher in Scotland (219 per 100,000 population). Test report rates are 157 and 143 per 100,000 population for Northern Ireland and for England respectively. In addition, there is significant variation between health commissioning areas within the devolved countries. In, there was a wide difference in directly age standardised rates between areas by almost a factor of 4. Shetland health board recorded the highest test report rates (414 per 100,000 population) and North Yorkshire and The Humber the lowest (107 per 100,000 population). For the 1
same year, the differentials between areas were even larger for the three test types. The testing of breast cancer, Huntington s disease and Fragile X varied between areas by factors of 15, 12 and 8 respectively. The results presented in this report should assist healthcare commissioners and laboratory providers in assessing the needs of their population with regards to access to and provision of genetic testing services. Introduction The UKGTN aims to promote high quality, equitable laboratory services based on clinical need for patients and their families who require genetic advice, diagnosis and management within the NHS. In order to measure the genetic test activity by member laboratories, the UKGTN Steering Group (from September 2011 the UKGTN Clinical & Scientific Advisory Group) agreed to data collection using the genetic test report as the unit of activity. The UKGTN received approval from the Caldicott Guardian of the hosting organisation of the UKGTN to perform this work, and received approval for the London Health Observatory (now part of Public Health England) to analyse the data on their behalf. Methods In September 2012, UKGTN member laboratories (molecular genetic) were asked to submit information on genetic tests conducted during the period 1 st April 2011 to 31 st March 2012 to the UKGTN and the London Health Observatory. The laboratories were asked to provide details about the genetic test activity requested by clinical genetics and separately for all other medical specialities. In addition to the postcode or NHS number for each test report, the date of birth for each report was collected to enable age standardisation of report rates. As in the data collection, the excluded tests were: 1. Banking reports / DNA storage 2. Tests conducted for research purposes 3. Molecular rapid aneuploidy tests 4. All non-uk and non-nhs private referrals 5. Somatic / acquired molecular oncology tests (JAK2, KRAS, EGFR, BRAF MPL, FLT3, NPM1, SML, ALL etc) including MSI studies for HNPCC 6. Thrombophilia tests (Factor V Leiden, Prothrombin) 7. Haemochromatosis tests 8. Haemophilia and Haemoglobinopathy (Sickle Cell and Thalassaemia) tests 9. Testing as part of population screening programme (e.g CF Newborn screening) 10. ArrayCGH and MLPA tests for genomic imbalance / microdeletions In order to be able to compare testing activity accurately and consistently across populations it was necessary to apply exclusion criteria for the data collection. This was to ensure that the analysis was restricted to activity from services that were only provided by UKGTN member molecular genetic laboratories and comparable across all areas. Molecular rapid aneuploidy tests, arraycgh and MLPA tests for genomic imbalance / microdeletions were excluded as these tests are often provided by cytogenetics laboratories (not currently part of the data collection process). Somatic/acquired molecular oncology tests ( for example, JAK2, KRAS, EGFR, BRAF MPL, FLT3, NPM1, SML, ALL ), MSI studies for HNPCC, Thrombophilia tests (Factor V Leiden, Prothrombin), Haemochromatosis tests, Haemophilia and Haemoglobinopathy (Sickle Cell and Thalassaemia) tests are sometimes provided in pathology laboratories within the UK and were also excluded. 2
DNA storage, tests for research or as part of a national screening programme were also excluded alongside all non UK and private referrals. In addition, the laboratories were asked to flag tests for breast cancer, Huntington s disease and Fragile X. In a few cases, laboratories were asked to clarify items of information that did not conform to the specification. The London Health Observatory (LHO) entered the datasets into a database, restructured any irregular postcodes into the required 8-character format, and postcodes were validated using the August 2012 release of the National Statistics Postcode Directory. Those test report records that contained an invalid or no postcode but did have information in the NHS number field were extracted. These records were then separated into two files according to the information present in the NHS number field. The file with records containing NHS numbers was subsequently sent to Guy s and St Thomas NHS Foundation Trust. The file with Scottish Community Health Index (CHI) numbers was despatched to NHS National Services in Scotland. Staff at these institutions employed lookup tables to identify the postcodes corresponding to the NHS/CHI numbers and date of birth, and added them to the records. After their return to LHO, the new information was appended to the records in the main database. In the final stage of data processing, the Postcode Directory was used to add health area codes PCTs, Area Teams, and Regions (England), Local Health Boards (Wales), Health Boards (Scotland), and Commissioning Groups (Northern Ireland) to the individual records. For all outcome measures of interest, directly age-standardised rates and their 95 % confidence intervals were calculated. For England data it was not possible to perform analyses for clinical commissioning group areas because at the time of analysis postcode look up files for these new commissioning organisations were not available. PCT rates were calculated to provide data for sub Area Team commissioning areas. Results Twenty-six laboratories submitted data for to the UKGTN. This number represents an increase of four participating laboratories compared with (London ION, London Retinoblastoma, Dundee and Belfast). Indeed, all laboratories in the network with any test reports that met the inclusion criteria provided data for the current collection year apart from Wales RGC which was experiencing major technical issues at the time the data were due to be compiled and despatched. In an attempt to minimise the impact of the missing data, the Wales RGC records for were added to the main dataset. However, because date of birth was not collected in, age-standardised rates cannot be calculated from the earlier data. Therefore, and because a majority of genetic tests conducted for Wales residents are analysed at the Wales RGC laboratory, age-standardised test report rates for Welsh Local Health Boards are not included in the figures and tables in this report. The information on reports issued for all molecular activity and reports that met the inclusion criteria is summarised in Table 1. Key findings include that the total activity for the United Kingdom from all UKGTN member laboratories was 152,866 test reports of which 88,890 (58%) met the inclusion criteria and were analysed in this report. Of the reports that met the inclusion criteria the majority (71%) were referred by medical specialties other than clinical genetics. This was the case in the data for all countries in the United Kingdom. 3
Table 1 Reported total molecular activity and reports that met the inclusion criteria for genetic and other speciality requests, by laboratory Laboratory Total Genetic speciality requests Other speciality requests Reports issued for all molecular activity Reports that met inclusion criteria** Reports issued for all molecular activity Reports that met inclusion criteria** Reports issued for all molecular activity Reports that met inclusion criteria** N N % N % of all N % of met N % of all N % of met (a) (b) (c) (d) (e) (f) (g) (h) (i) (j) (k) (b/a) (d/a) (f/b) (h/a) (j/b) Birmingham 15,580 6,327 41 4,057 26 3,062 48 11,523 74 3,265 52 Birmingham Biochem 1,269 613 48 184 14 112 18 1,085 86 501 82 Bristol 11,247 3,716 33 1,036 9 624 17 10,211 91 3,092 83 Cambridge 5,164 3,508 68 nr 1,159 33 nr 2,349 67 Exeter 5,882 3,659 62 1,474 25 674 18 4,408 75 2,985 82 Leeds 4,786 3,072 64 nr 2,089 68 nr 983 32 Liverpool 6,329 3,323 53 906 14 732 22 5,423 86 2,591 78 London GOSH 8,794 5,420 62 2,601 30 1,785 33 6,193 70 3,635 67 London GSTT^ 10,917 6,651^ 61 3,112 29 2,727^ 41 7,805 71 3,924^ 59 London ION 2,528 1,189 47 126 5 25 2 2,402 95 1,164 98 London KGC 5,348 3,241 61 nr 1,210 37 nr 2,031 63 London Retinoblastoma 183 120 66 85 46 72 60 98 54 48 40 London St Georges 3,298 3,298 100 1,961 61 2,067 63 1,236 39 1,231 37 London UCLH Biochem 91 91 100 nr 54 59 nr 37 41 Manchester RGC 7,147 5,204 70 2,017 27 1,597 31 5,130 69 3,607 69 Newcastle 14,497 7,631 53 3,084 21 2,716 36 11,413 79 4,915 64 Nottingham 3,917 3,032 77 1,389 35 1,106 36 2,528 65 1,926 64 Oxford RGC 7,291 6,346 87 3,627 50 3,157 50 3,664 50 3,189 50 Salisbury RGC 7,929 4,746 60 3,450 44 2,369 50 4,479 56 2,377 50 Sheffield 8,484 3,907 46 1,916 23 1,459 37 6,568 77 2,448 63 Cardiff SAS Porphyria 157 131 83 66 42 58 44 91 58 73 56 Wales RGC Aberdeen 3,114 2,632 85 1,562 50 1,335 51 1,552 50 1,297 49 Dundee 2,275 2,197 97 649 29 626 28 1,626 71 1,571 72 Edinburgh 2,884 2,054 71 1,457 51 1,320 64 1,427 49 734 36 Glasgow 8,122 3,801 47 nr 1,534 40 nr 2,267 60 Belfast 5,324 2,985 56 1,757 33 733 25 3,567 67 2,252 75 England 130,990 75,088 57 31,025 27* 28,796 38 84,166 64* 46,298 62 Wales 157 131 83 66 42 58 44 91 58 73 56 Scotland 16,395 10,686 65 3,668 44* 4,815 45 4,605 28* 5,869 55 Northern Ireland 5,324 2,985 56 1,757 33 733 25 3,567 67 2,252 75 All UK laboratories 152,866 88,890 58 36,516 28* 34,402 39 92,429 71* 54,485 61 ** These figures are taken from the total records in the Genetic and Non Genetic data collection sheets submitted to UKGTN. For 19 of the 26 labs, these figures were the same as the total number of reports that met the inclusion criteria record in the Totals sheet. nr = Not reported * Numbers and percentages exclude labs that did not provide figures for all molecular activity disaggregated by speciality. ^ London GSTT an error in the submitted data for reports that met the inclusion criteria was identified post data analysis. Correct data indicates the number of eligible report is over estimated by 35%. 4
Data quality Valid postcodes were obtained for 94.3 % of all UK laboratory test reports submitted for the year. This figure comprises both the valid postcodes received (90.1 %) and those that were derived from NHS or CHI numbers (4.2 %). For laboratories in the devolved countries, the overall totals ranged from 79.1 % to 95.2, 96.3 and 97.5 % for Wales, England, Scotland and Northern Ireland respectively. It should be noted, however, that 206 records with no or invalid postcodes contained Northern Ireland NHS numbers and such numbers are absent from the NHS number lookup table that the UKGTN had access to. These records constitute a very small proportion (0.23%) of the total number of report records received in (88,890) and only 14 % of this small proportion of these records was submitted by the Belfast laboratory. Figure 1 provides additional details on the quality of the data submitted by laboratories based in the four devolved countries. Although comparisons with the results for are limited by the fact that the number of laboratories that sent data differed and because postcode lookup tables for NHS/CHI numbers were not available in, key changes are apparent. The most encouraging development is the increase in the proportion of Scottish test reports that were sent to UKGTN with valid postcodes from 79.5 % in to 88.8 % in. In contrast, the change for England was in the opposite direction dropping from 94.0 % of records received in to 91.2 % in. However, when records with postcodes derived from NHS numbers are added, the valid postcode total is slightly higher than the figure for. Figure 2 shows the same data quality information for individual laboratories and the input figures for this and Figure 1 are given in Appendix 1 Table A. 5
Figure 1 Percentage distributions of genetic test records according to information provided by UKGTN member laboratories, and All UK laboratories England laboratories Wales laboratories Scotland laboratories Northern Ireland laboratory 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Per cent of all genetic test records received Valid postcodes received Valid postcodes derived from NHS/CHI number ( only) NHS/CHI number provided but postcode lookup not available ( only) Invalid postcodes No postcodes ( excludes cases where NHS/CHI number is provided) Valid postcodes NHS/CHI number Invalid postcodes No postcodes Total Received Derived from NHS/CHI number provided, but postcode lookup not available ( only) ( excludes cases where NHS/CHI number is provided) % All UK laboratories 2010/2011 91.3 n/a 2.9 1.6 4.2 100.0 2011/2012 90.1 4.2 n/a 0.6 5.2 100.0 England laboratories 2010/2011 94.0 n/a 1.9 1.3 2.7 100.0 2011/2012 91.2 3.9 n/a 0.4 4.4 100.0 Wales laboratories* 2010/2011 76.2 n/a 3.2 1.7 19.0 100.0 2011/2012 76.1 3.0 n/a 1.6 19.3 100.0 Scotland laboratories 2010/2011 79.5 n/a 12.0 3.6 4.9 100.0 2011/2012 88.8 7.5 n/a 0.6 3.1 100.0 Northern Ireland 2010/2011 2011/2012 96.3 1.2 n/a 1.1 1.4 100.0 n/a Not applicable * Includes test reports from Cardiff SAS Porphyria and Wales RGC laboratories. 6
Figure 2 Percentage distributions of genetic test records according to information provided by UKGTN member laboratories, and Lab and Year (Sorted in descending order of total valid postcodes in ) Aberdeen Birmingham Nottingham London RMCGL London KGC London St Georges Belfast Edinburgh Sheffield London ION Manchester RGC Oxford RGC Cambridge London GSTT Leeds Birmingham Biochem Glasgow Liverpool Salisbury RGC Newcastle Dundee London GOSH Cardiff SAS Porphyria Service Bristol London UCLH Biochem Exeter Wales RGC 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Per cent of all genetic test records received Valid postcodes received Valid postcodes from NHS/CHI number ( only) NHS/CHI number provided but postcode lookup not available ( only) Invalid postcodes No postcodes ( excludes cases where NHS/CHI number is provided) Total valid postcodes All UK laboratories 7
Genetic test activity rates Age Standardised Rates The total age-standardised genetic test report rates per 100,000 population for high level commissioning health areas in England, Scotland and Northern Ireland are presented in Figures 3 and 4, and by referrals from clinical genetics in Figure 5 and referrals from all other specialties (excluding clinical genetics) in Figure 6. The rates presented are only for reported UKGTN member laboratory activity. The genetic test reports rates for Scotland are consistently significantly higher than the UK rates across all the analyses. There is also significant variation within countries for genetic test report rates from clinical genetics and both within and between countries for genetic test report rates for other medical specialties. Further details about the genetic test report rates are presented in Table B in the Appendix. In Shetland had the highest genetic testing report rate per 100,000 population at 413.5, and North Yorkshire and the Humber had the lowest rate (106.6). This is a range of 306.9 between areas and a differential of almost 4 times. Appendix 1 Table B also shows the percentage change in crude test rates between and. All countries of the UK have seen an increase in test rates, with the largest increases in Northern Ireland and Scotland. The main contribution to these changes is the improvement in the data submission from these countries. Within England, some health areas have seen an increase in genetic testing, whereas some have seen a decrease. Devon, Cornwall and the Isles of Scilly had the largest increase (60%) and Shropshire and Staffordshire the largest decrease (-11%). These changes could be due to improved data submission or actual changes in provision or a mixture of both factors. Appendix 2 presents age standardised rates per 100,000 by each PCT with PCTs grouped into each Area Team. Appendix 3 provides a graph showing an overview of the rates for all the PCTs in England ordered from the highest to lowest rates. 8
Figure 3 Age-standardised report rates per 100,000 population for all activity that met the inclusion criteria, by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Orkney Lothian Tayside Forth Valley Western Isles Dumfries and Galloway Shetland NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 50 100 150 200 250 300 350 400 450 Directly age standardised genetic test report rate per 100,000 population * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 9
Figure 4 Age-standardised report rates per 100,000 population for all activity that met the inclusion criteria, by high level commissioning health areas in the United Kingdom, 10
Figure 5 Age-standardised report rates per 100,000 population for tests requested from clinical genetics, by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Orkney Lothian Tayside Forth Valley Western Isles Dumfries and Galloway Shetland NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 50 100 150 200 250 Directly age standardised genetic test report rate per 100,000 population * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 11
Figure 6 Age-standardised report rates per 100,000 population for tests requested from medical specialities excluding clinical genetics, by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Orkney Lothian Tayside Forth Valley Western Isles Dumfries and Galloway Shetland NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 50 100 150 200 250 Directly age standardised genetic test report rate per 100,000 population * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 12
Figure 7 Number of test reports disaggregated by clinical speciality and high level commissioning health areas United Kingdom Commissioning health area England *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire *{ North East London *{ North West London *{ South London Bath, Gloucestershire, Swindon and Wiltshire *Bristol, N. Somerset, Somerset and S. Glos. Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex Scotland Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Orkney Lothian Tayside Forth Valley Western Isles Dumfries and Galloway Shetland Northern Ireland Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Clinical genetics (CG) Medical specialities (excl CG) * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). 13
Genetic test activity rates for breast cancer, Huntington Disease and Fragile X Figures 8-12 show the rate of genetic testing reports in by high level commissioning area for breast cancer, Huntington s disease and Fragile X respectively. The rates presented are only for reported UKGTN member laboratory activity. The genetic test reports rates for Scotland are consistently significantly higher than the UK rates across all the analyses. There is also variation within countries which is significant in England. In, the testing of breast cancer, Huntington s disease and Fragile X varied between areas in the UK by factors of 15, 12 and 8 respectively. The variations between areas in England were by factors of 6, 7 and 5 for breast cancer, Huntington s disease and Fragile X respectively. These figures especially that for breast cancer, are larger than the differential in overall test rates. In, the reporting of test rates varied between areas by factors of 2, 5 and 2 for breast cancer, Huntington s disease and Fragile X respectively. The variations between areas in were in England and Wales only. In this most recent time period, Orkney had the highest test report rate for breast cancer (94.5 per 100,000 population) and Belfast for Huntington s disease (52.3 per 100,000 population) and Shetland for Fragile X (87.5 per 1,000,000 population). Devon, Cornwall and Isle of Scilly (6.2) had the lowest test report rate for breast cancer, North East London (4.3) for Huntington s disease and Cheshire, Warrington and Wirral (10.6) for Fragile X. 14
Figure 8 Age-standardised breast cancer test report rates per 100,000 women aged 15 and over by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Orkney Lothian Tayside Forth Valley Dumfries and Galloway NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 20 40 60 80 100 Directly age standardised breast cancer test report rate per 100,000 women aged 15 and over * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). Note: Data for 2 Scottish Health Boards have been suppressed to protect the confidentiality of individuals. The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 15
Figure 9 Age-standardised breast cancer test report rates per 100,000 women aged 15 and over by high level commissioning health areas in the United Kingdom, 16
Figure 10 Age-standardised Huntington s disease test report rates per million population by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Lothian Tayside Forth Valley NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 20 40 60 80 100 Directly age standardised Huntington's disease test report rate per million population * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). Note: Data for 5 Scottish Health Boards have been suppressed to protect the confidentiality of individuals. The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 17
Figure 11 Age-standardised Fragile X test report rates per 100,000 population by high level commissioning health areas in the United Kingdom, ENGLAND (all Area Teams) North Region *Cheshire, Warrington and Wirral Durham, Darlington and Tees Greater Manchester Lancashire Merseyside *Cumbria, Northumberland, Tyne and Wear North Yorkshire and The Humber *South Yorkshire and Bassetlaw West Yorkshire Midlands and East Region Arden, Herefordshire and Worcestershire *Birmingham and the Black Country Derbyshire and Nottinghamshire *East Anglia Essex Hertfordshire and the South Midlands *Leicestershire and Lincolnshire Shropshire and Staffordshire London Region *{ North East London *{ North West London *{ South London South Region Bath, Gloucestershire, Swindon and Wiltshire *Bristol, North Somerset, Somerset and South Gloucestershire Devon, Cornwall and Isles of Scilly Kent and Medway *Surrey and Sussex Thames Valley *Wessex SCOTLAND (all Health Boards) Ayrshire and Arran Borders Fife Greater Glasgow and Clyde Highland Lanarkshire Grampian Lothian Tayside Forth Valley Dumfries and Galloway Shetland NORTHERN IRELAND (all Commissioning Groups) Belfast Commissioning Group Northern Commissioning Group Southern Commissioning Group South Eastern Commissioning Group Western Commissioning Group United Kingdom 0 20 40 60 80 100 120 140 Directly age standardised Fragile X test report rate per 100,000 population * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT for specialised services). Note: Data for 2 Scottish Health Boards have been suppressed to protect the confidentiality of individuals. The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 18
Figure 12 Age-standardised Fragile X test report rates per 100,000 population by high level commissioning health areas in the United Kingdom, 19
Discussion This report for the first time presents the rate of molecular genetic test activity across the United Kingdom on a population basis and includes details for England, Scotland, Wales and Northern Ireland. The results show considerable variation in the molecular genetic test report activity rates between countries and by health commissioning area. The genetic test reports rates for Scotland are consistently significantly higher than the UK rates across all the analyses. However, there are a number of factors that need to be taken into consideration when interpreting these data. First, a proportion of records (4.8% of records for laboratories in England, 3.7% in Scotland and 2.5% in Northern Ireland in ) were excluded from the resident based analysis as they did not include a valid postcode or NHS number from which to derive the health area of residence. This is not expected to contribute significantly to the variation identified. In addition, Wales RGC did not submit data for and although efforts were made to minimise the effect of this by using previous year s data submission, the details of test reports produced in and the effect the data would have on resident based analysis is unknown. The key assumption for this analysis in the report is that there has not been a significant increase in the total or a change in the types of genetic testing performed by Wales RGC between these years. In, test reports from Wales RGC constituted 8% of the total test reports received from participating laboratories in the UK. For London GSTT, an error in the submitted data for reports that met the inclusion criteria was identified post data analysis. Correct data indicates the number of eligible reports is over estimated by 35%. This over-estimate will affect a number of PCT and Area Team rates and these have been highlighted in the laboratory and commissioner reports. The actual size of the impact on these PCT and Area Team rates could not be established. This difference contributed to a non-significant variation at England (3%) and UK (2.5%) levels. Of the total activity reported by laboratories only 58% of reports met the inclusion criteria and were analysed. Therefore the detailed analyses and results are limited to this activity only. The data is limited to UKGTN member laboratories and the impact of NHS genetic testing activity performed by non-member laboratories is unknown. It is likely that there is variation in the non-member laboratory provision of genetic tests in some areas. The additional feature in the analysis of the 2011/2012 data is the inclusion of the date of birth for submitted reports which enabled the calculation of age standardised rates. These rates provide more robust data for comparison purposes. Also the breakdown of the results by activity referred by clinical genetics and other medical specialties provides an understanding of the referral flows for genetic testing for defined populations. The results show significant variation in genetic test activity for health commissioning areas both between and within devolved countries. This variation will include both warranted and unwarranted variation in genetic test activity. Unwarranted variation in healthcare has been defined as variation that cannot be explained on the basis of illness, medical evidence, or patient preference. It is not possible in this analysis to identify the nature and contribution of all the significant factors for the variation in the rates presented. Additional factors to be considered include variation in the capacity and funding of molecular genetic testing, variation in the incidence and prevalence of inherited conditions in the different populations and variation in clinical practice. Commissioners of healthcare working with their local molecular genetic laboratories and clinical services can investigate their data further to better understand the variation of genetic testing activity for their populations. The results presented in this report provide further details regarding the provision of molecular genetic testing for the NHS by UKGTN members. The quality of the data has improved significantly since the first report on genetic test activity for 2007/08 however further work is required to 20
maintain and improve the data quality to the standard necessary for direct commissioning purposes. The UKGTN Laboratory Membership and Audit Working Group (LMA) has been consulted throughout this work programme including this report and its findings. This report has been circulated to UKGTN member laboratories for information, data check and feedback. In addition, a specific laboratory summary report will be provided to each laboratory and separate commissioning reports for each Area Team in England responsible for specialised services commissioning; examples are presented in Appendix 4 and 5 respectively. In conclusion, the results presented in this report should assist healthcare commissioners and laboratory providers in reviewing and addressing the needs of their population with regards to access to and provision of genetic testing services. Recommendations 1. Exclusion criteria should be reviewed to ensure the maximum possible proportion of data submitted is available for analysis 2. Commissioning organisations should be requested to feedback the local interpretation of the genetic test activity results. This will highlight any causes or explanations for the variation identified and enable future analyses to be corrected for errors in reporting and data collection. This will also provide valuable intelligence to assist in the interpretation of future results. 3. With the greater integration of molecular and cytogenetic laboratories, cytogenetic laboratory activity data should also be collected and analysed. 4. A formal review to establish the possible contributing factors to genetic test activity variation should be undertaken in collaboration with public health intelligence experts. Authors Mark Kroese, Jane Deller (UK Genetic Testing Network) Anne Scott, Robel Feleke, Justine Fitzpatrick (London Health Observatory now Public Health England) The London Health Observatory (now Public Health England) was commissioned by the UKGTN to provide analysis of the data and to document findings in this report. 21
Appendix 1 Table A: Genetic test reports sent to UKGTN by laboratory and year: total eligible test reports, percentages of records with valid postcodes, and other recorded details Total eligible test reports % Valid postcodes Valid postcode s received Invalid No postcodes (Excludes Total eligible % Valid Valid postcode cases where NHS/CHI test reports postcodes postcode s number is provided) s received NHS/CHI number provided but postcode lookup not available Valid postcodes derived from NHS/CHI number Invalid No postcodes postcode s Birmingham 7,526 97.4 7,333 18 21 154 6327 99.6 6,285 15 * * Birmingham Biochem 744 98.7 734 0 10 0 613 95.1 560 23 * * Bristol 3,291 97.2 3,198 48 45 0 3716 90.4 3,011 349 12 344 Cambridge 3,150 98.0 3,088 0 62 0 3508 95.9 3,319 45 112 32 Exeter 1,865 87.1 * * * * 3659 82.2 2,290 716 * * Leeds 2,518 96.9 2,441 28 18 31 3072 95.5 2,885 49 * * Liverpool 3,443 83.7 2,883 326 46 188 3323 94.4 2,863 275 8 177 London GOSH 5,415 99.4 5,385 24 6 0 5420 92.5 4,691 325 * * London GSTT 4,430 93.1 4,123 29 92 186 6651^ 95.8 6,241 130 24 256 London ION 1189 96.6 1,042 107 33 7 London KGC 2,998 98.8 2,961 18 19 0 3241 99.0 3,179 28 * * London Retinoblastoma 120 99.2 119 0 * * London St Georges 3,086 95.1 2,935 16 35 100 3298 97.8 3,183 41 6 68 London UCLH Biochem 38 94.7 * * * 0 91 89.0 71 10 * * Manchester RGC 6,062 90.6 5,492 26 162 382 5204 96.6 4,986 39 20 159 Newcastle 6,614 90.2 5,967 69 89 489 7631 94.2 7,134 52 21 424 Nottingham 3,049 97.9 2,985 28 36 0 3032 99.4 2,946 68 * * Oxford RGC 5,797 98.5 5,708 35 54 0 6346 96.5 6,031 93 7 215 Salisbury RGC 5,183 94.2 4,880 13 98 192 4746 94.3 4,436 41 43 226 Sheffield 3,583 81.5 2,920 489 49 125 3907 97.0 3,250 539 6 112 Wales RGC 6,417 75.8 * 206 * 1,240 6417 78.8 4,873 184 95 1265 Cardiff SAS Porphyria Service 121 95.9 * 0 * 0 131 91.6 109 11 * * Aberdeen 1,943 97.5 1,895 0 48 0 2632 99.8 * * * 0 Dundee 2197 93.3 2,039 10 50 98 Edinburgh 2,236 69.1 1,545 271 54 366 2054 97.2 * * * * Glasgow 3,323 76.0 2,527 629 167 0 3801 95.0 3,111 500 13 177 Belfast 2985 97.5 2,875 35 33 42 England 68,792 94.0 64,694 1,326 922 1,850 75,094 95.2 68,522 2,945 325 3,302 Wales 6,538 76.2 4,979 206 113 1,240 6,548 79.1 4,982 195 105 1,266 Scotland 7,502 79.5 5,967 900 269 366 10,684 96.3 9,486 798 69 331 Northern Ireland 2,985 97.5 2,875 35 33 42 All laboratories 82,832 91.3 75,640 2,432 1,304 3,456 95,311 94.3 85,865 3,973 532 4,941 Notes (1) Wales RGC could not supply data for and therefore the previous year s data were taken as the best available substitute. (2) Tests for residents outside the UK have been excluded. No test reports received or * Figures suppressed to protect confidentiality of individuals. ^ London GSTT an error in the submitted data for reports that met the inclusion criteria was identified post data analysis. Correct data indicates the number of eligible report is over estimated by 35%. 22
Table B Crude and age-standardised genetic test report rates and disaggregation by clinical speciality, high level commissioning health areas Crude rate Directly standardised rate Reports~ per 100,000 population % change Total Requests from: Total Clinical Medical per Clinical Medical genetics specialities 100,000 to genetics specialities (excl. CG) (CG) (excluding CG) N % % United Kingdom 142 17 145 54 91 84,619 39 61 England 136 11 143 52 91 69,980 38 62 *Cheshire, Warrington and Wirral 100 2 109 40 69 1,187 39 61 Durham, Darlington and Tees 186 31 202 80 121 2,158 42 58 Greater Manchester 128 4 137 36 101 3,451 28 72 Lancashire 115 0 129 32 97 1,645 27 73 Merseyside 134 12 142 43 99 1,562 32 68 *Cumbria, Northumberland, Tyne and Wear 176 17 191 73 118 3,342 40 60 North Yorkshire and The Humber 94 7 107 43 63 1,586 44 56 *South Yorkshire and Bassetlaw 134 19 146 50 95 1,933 35 65 West Yorkshire 110 4 117 43 74 2,425 38 62 Arden, Herefordshire and Worcestershire 132 5 144 44 101 2,100 33 67 *Birmingham and the Black Country 144 6 149 55 94 3,430 38 62 Derbyshire and Nottinghamshire 118 13 132 47 84 2,298 38 62 *East Anglia 127 6 131 50 80 2,830 41 59 Essex 106 6 114 49 64 1,776 46 54 Hertfordshire and the South Midlands 135 7 140 51 89 3,540 38 62 *Leicestershire and Lincolnshire 150 3 169 62 108 2,572 39 61 Shropshire and Staffordshire 108 11 121 47 74 1,655 42 58 *{ North East London 129 3 131 49 82 3,977 38 62 *{ North West London 136 19 139 47 92 2,630 35 65 *{ South London 163 44 163 64 99 4,925 41 59 Bath, Gloucestershire, Swindon and Wiltshire 140 9 144 47 96 1,907 34 66 *Bristol, N. Somerset, Somerset and S. Glos. 164 6 166 62 104 2,202 37 63 Devon, Cornwall and Isles of Scilly 202 60 211 81 130 3,098 38 62 Kent and Medway 144 42 146 56 90 2,311 41 59 *Surrey and Sussex 130 25 141 55 86 3,482 42 58 Thames Valley 134 2 134 50 84 2,589 39 61 *Wessex 131 8 145 51 94 3,369 37 63 Scotland 204 57 219 95 124 10,636 46 54 Ayrshire and Arran 182 40 199 76 123 662 41 59 Borders 156 71 177 88 89 175 53 47 Fife 182 72 202 88 114 664 45 55 Greater Glasgow and Clyde 206 30 218 85 133 2,476 41 59 Highland 171 69 194 108 86 529 57 43 Lanarkshire 164 32 174 74 100 918 45 55 Grampian 266 43 276 166 110 1,459 62 38 Orkney 188 52 188 121 68 38 66 34 Lothian 185 44 202 84 118 1,555 45 55 Tayside # 295 362 332 107 225 1,192 34 66 Forth Valley 187 88 200 88 112 545 48 52 Western Isles # 314 292 330 82 248 82 22 78 Dumfries and Galloway 171 70 192 79 114 251 47 53 Shetland 404 89 414 212 202 90 54 46 Northern Ireland # 155 293 157 49 108 2,746 32 68 Belfast Commissioning Group # 159 300 166 53 113 526 33 67 Northern Commissioning Group # 136 291 138 47 91 611 35 65 Southern Commissioning Group # 180 316 181 56 125 644 31 69 South Eastern Commissioning Group # 137 282 137 46 91 468 36 64 Western Commissioning Group # 170 271 169 41 128 497 25 75 * Area Team responsible for specialised services; *{ London integrated regional operating model (no single AT responsible for specialised services). # The per cent change of over 100% for Tayside, Western Isles and Northern Ireland Commissioning Groups is due to data submission by Dundee and Belfast labs in and not in. ~These are test reports that met the inclusion criteria. The proportion of clinical genetics and medical specialities are given as a percentage of test reports that met the inclusion criteria. Reports without a valid postcode have been excluded. 23
Appendix 2 North of England 24
25
26
27
28
29
30
Midlands and East of England 31
32
Age Standardised report rates per 100,000 population for all activity that met inclusion criteria by Area Team in Derbyshire and Nottinghamshire by PCT, Derbyshire and Nottinghamshire Nottinghamshire County Teaching PCT Nottingham City PCT Derby City PCT Derbyshire County PCT 0 40 80 120 160 200 Directly age standardised report rates per 100,000 population 33
34
35
36
37
London 38
39
40
South of England 41
42
43
44
45
Appendix 3 Age standardised report rates per 100,000 population for all activity that met inclusion criteria by PCT, UK Primary Care Trusts (PCTs) 0 50 100 150 200 250 300 Directly age standardised genetic test report rate per 100,000 population The UK rate excludes test reports from Wales RGC which is a major provider of genetic testing for Wales residents. In, test reports from Wales RGC comprised 8% of the entire data collected for the UK, although only 23 laboratories provided data in that year out of 27. Therefore the UK rate, shown as a comparator, is an underestimate. 46
Appendix 4 Molecular genetic test rates: Summary report for Oxford RGC laboratory Total test reports that met the inclusion criteria and percentage distributions of reports according to geographical information provided, to Oxford RGC laboratory Year Tests Valid Received* postcodes 5,797 98.5% 6,346 96.5% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% * Test reports that met the inclusion criteria Per cent of all genetic test reports received Valid postcodes received Valid postcodes from NHS/CHI number ( only) NHS/CHI number provided but postcode lookup not available ( only) Invalid postcodes No postcodes ( excludes cases where NHS/CHI number is provided) Distribution of clients of Oxford RGC laboratory (whose reports for and had valid postcodes) by Area Team of residence Elsewhere (clients from other areas where there are less than 3% in each area) 45% Thames Valley 25% Hertfordshire and the South Midlands 16% East Anglia 3% Wessex 4% Bath, Gloucestershire, Swindon and Wiltshire 7% 47
Distribution by PCT of residence of clients of Oxford RGC laboratory in and whose test reports had valid postcodes, top 12 PCTs Oxfordshire PCT 11.0% Northamptonshire PCT 8.8% Buckinghamshire PCT 5.3% Elsewhere 50.6% Milton Keynes PCT 4.8% Berkshire West PCT 4.6% Berkshire East PCT 4.1% Gloucestershire PCT 1.2% Devon PCT 1.3% Hertfordshire PCT 1.4% Wiltshire PCT 1.8% Swindon PCT 3.2% Hampshire PCT 2.1% Laboratories that provided testing services to Thames Valley and Wessex specialised commissioning area (previously referred to as South Central SHA) residents (with valid postcodes) for tests conducted in and 21 other labs 18% Manchester RGC 3% London GOSH 3% Salisbury RGC 43% Wales RGC 4% Oxford RGC 29% 48