Appendix 1: Detailed break-down of test costs according to micro-costing 1. Cell culture cytotoxin neutralization assay (CCNA) List price (£) Pack size Unit cost (£) Resource use per test Cost per test (£) Universal container (Sterilin) 57.99 400 0.14 1.00 0.14 Phosphate buffered saline 81.00 1000 ml 0.08 10.00 ml 0.81 Micro plate (confluent layer of Vero cells in maintenance medium containing HEPES) incl. lid 58.00 50 1.16 0.02 0.02 20 µl Clostridium sordelli antitoxin 60.00 500000 µl 0.0001 20.00 µl 0.0024 Pipette or swab 4.40 500 0.01 1.00 0.01 Pipette tip (20 µl) 31.79 2000 0.02 2.00 0.03 Tissue culture flasks (75 cm2) 211.41 100 2.11 0.01 0.01 Other reagents 0.50 1 0.50 1.00 0.50 Foetal bovine serum 30.00 500 0.06 0.30 0.02 Tissue culture media (HEPES) 17.40 1000 0.02 0.30 0.01 Gloves 4.87 100 0.05 0.25 0.01 Resource Comment Source Consumables and reagents: one flask for 4 plates (152 samples), 2 wells per sample includes continuous line of cells and its maintenance and positive control one flask (30 ml) makes 4 plates (152 samples) one flask (30 ml) makes 4 plates (152 samples) glove change every 4 samples assumed http://www.sterilin.co.uk (September 2011) Purchasing Singelton Hospital, Swansea, UK Purchasing Singleton Hospital, Swansea, UK http://www.sterilin.co.uk (September 2011) http://www.sterilin.co.uk (September 2011) Head of laboratory and purchasing Singleton Hospital, Swansea, UK Purchasing Singleton Hospital, Swansea, UK http://www.sigmaaldrich.com (September 2011) Purchasing Singleton Hospital, Swansea, UK £1.57 Total (consumables and reagents): Material waste made onsite, readymade price used 96 wells, 2 per test needed + positive and negative controls 5 ml bottle, diluted 1:100, 20 µl/test http://www.sterilin.co.uk (September 2011) http://www.sigmaaldrich.com (September 2011) 0.08 (5% of total consumable 0.0023 0.0002 on average 34 samples received per day, materials for 38 Head of Virology, laboratory staff cost) prepared, 5% wasted Capital and overheads: Overheads 2.00 Estimate (includes space needed, cell culture, lighting, electricity, cleaning, maintenance) 5 year lifespan assumed, 10,000 samples a year, assumption made that only used for CCNA Estimate Purchasing Singleton Hospital, Swansea, UK Hospital statistics Centrifuge (Sorval Legend RT) 6804.00 50000 0.14 1.00 0.14 Maintenance contract Centrifuge 210.00 10000 0.02 1.00 0.02 £ 210 per year Purchasing Singleton Hospital, Swansea, UK Purchasing Singleton Hospital, Swansea, UK Hospital statistics Purchasing Singleton Hospital, Swansea, UK Class 1 microbiological safety cabinet (Leec) 10000.00 50000 0.20 1.00 0.20 5 year lifespan assumed, 10,000 samples a year, assumption made that only used for CCNA Maintenance contract safety cabinet 72.00 10000 0.01 1.00 0.01 £ 72 per year 5 year lifespan assumed, 10,000 samples a year, assumption made that only used for CCNA 5 year lifespan assumed, 10,000 samples a year, assumption made that only used for CCNA Purchasing Singleton Hospital, Swansea, UK Hospital statistics Vortex (Whirlimixer) 500.00 50000 0.01 1.00 0.01 Incubator (Leec Research CO2) 5000.00 50000 0.10 1.00 0.10 Maintenance contract microscope 54.00 10000 0.01 1.00 0.01 £ 54 per year Purchasing Singleton Hospital, Swansea, UK 0.10 5 year lifespan assumed, 10,000 samples a year, assumption made that only used for CCNA Purchasing Singleton Hospital, Swansea, UK Hospital statistics Band 2 (£ 15,194) Laboratory staff and Microscope 5000.00 50000 0.10 1.00 Purchasing Singleton Hospital, Swansea, UK Hospital statistics £2.58 Total (overhead and capital): Staff costs: Sample labelling 7.69/hour 60 mins 0.13/min 2.00 mins 0.26 Sample preparation 7.69/hour 60 mins 0.13/min 4.50 mins 0.58 Tidying up 7.69/hour 60 mins 0.13/min 0.50 mins 0.06 Cataloguing 7.69/hour 60 mins 0.13/min 0.50 mins 0.06 Sample reading (18 hours) 14.91/hour 60 mins 0.25/min 5.00 mins 1.24 Sample reading (48 hours) 14.91/hour 60 mins 0.25/min 5.00 mins 1.24 Reporting of results 14.91/hour 60 mins 0.25/min 2.00 mins 0.50 Staff training (preparation, trainee time) 7.69/hour 60 mins 0.13/min 0.19 0.02 Staff training (preparation, trainer time) 14.91/hour 60 mins 0.25/min 0.19 0.05 Staff training (reading, trainee time) 14.91/hour 60 mins 0.25/min 0.19 0.05 Staff training (reading, trainer time) 14.91/hour 60 mins 0.25/min 0.19 0.05 20.27 mins £ 4.11 Total (staff): Repeat samples Total cost/test CCNA: 9.00 (approx. test cost) 0.06 0.51 £8.78 Band 2 (£ 15,194), 45 mins for 10 samples Band 2 (£ 15,194), 5 mins for 10 samples Band 2 (£ 15,194), 5 mins for 10 samples Band 6 (£ 29,464), 30 mins for 6 samples Band 6 (£ 29,464), 30 mins for 6 samples Band 6 (£ 29,464), 30 mins for 6 samples Band 2 (£ 15,194), assumed 4 days a year = 32 hours = 1920 minutes per 10,000 samples Band 6 (£ 29,464), assumed 4 days a year = 32 hours = 1920 minutes per 10,000samples Band 6 (£ 29,464), assumed 4 days a year = 32 hours = 1920 minutes per 10,000samples Band 6 (£ 29,464), assumed 4 days a year = 32 hours = 1920 minutes per 10,000samples 59/1034 samples positive PCR but negative CCNA; would be sent again = 5.7 % of samples personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Clinical study data [17] 2. Xpert C. difficile rtPCR List price (£) Pack size Unit cost (£) Resource use/test Cost per test (£) PCR kit (incl. cartridge and reagents) 333.50 10 33.35 1.00 33.35 Sterile swab 14.91 100 0.15 1.00 0.15 Gloves 4.87 100 0.05 0.13 0.01 Resource Comment Source Glove change every 8 samples assumed Cepheid (no discount applied) http://www.sterilin.co.uk (September 2011) Purchasing Singleton Hospital, Swansea, UK one repeat sample per 31 samples Clinical trial data (33 repeats in 1051 samples) [17] Consumables and reagents: £33.51 Total (consumables and reagents): Material waste 33.51 0.03 1.08 Capital and overheads: Overheads 0.02 Cepheid GeneXpert PCR (16-8) 63600.00 100000 0.64 1.00 0.64 Maintenance contract (16-8) 18221.00 50000 0.36 1.00 0.36 adjusted according to space taken up in comparison to CCNA 10 year life span = 124000 samples (mean 10,000 per year) 5 year warranty = 62000 samples (mean 10,000 per year) Estimate Cepheid and ABMUHB statistics (assumption as machine only on market since 2006 Cepheid and ABMUHB statistics £1.02 Total (overhead and capital): Staff costs: Sample labelling 7.69/hour 60 mins 0.13/min 1.00 min 0.13 Sample preparation and test start 7.69/hour 60 mins 0.13/min 1.50 mims 0.19 Tidying up and entry on Masterlab 7.69/hour 60 mins 0.13/min 0.60 mins 0.08 Staff training (preparation, trainee time) 7.69/hour 60 mins 0.13/min 0.01 mins 0.001 Band 2 (£ 15,194), 1 mins per sample Band 2 (£ 15,194), 1.5 mins per sample Band 2 (£ 15,194), 0.6 mins per sample Band 2 (£ 15,194), assumed 0.2 days a Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department year = 1.6 hours = 96.0 minutes per 10,000 samples = 0.0096 mins per sample Band 6 (£ 29,464), assumed 0.2 days a year = 1.6 hours = 96.0 minutes per 10,000 samples = 0.0096 mins per sample Staff training (preparation, trainer time) 14.91/hour 60 mins 0.25/min 0.01 mins 0.002 Results check 14.91/hour 60 mins 0.25/min 0.20 mins 0.05 Band 6 (£ 29,464) Reporting of results 14.91/hour 60 mins 0.25/min 0.50 mins 0.12 Band 6 (£ 29,464) 3.82 mins £ 0.57 Total (staff): Total cost/test PCR: £36.18 Laboratory staff and personnel department Laboratory staff and personnel department Laboratory staff and personnel department Appendix 2: Calculation of potential cost savings of rtPCR compared to routine CCNA Parameter Value Comment Calculation (1) Samples/year by routine CCNA 10,769 Number of samples tested in ABMUHB 2011 n/a (2) Positive patients/year (CCNA) 289 Number of positives (all ages) in ABMUHB 2011 n/a (2a) Percentage of positive samples 0.0268 (3) Negative samples/year 10,480 Percentage of positive samples in ABMUHB in 2011 Number of negative samples per year 5,240 Assumption made that negative CCNA tests will be repeated once per patient2 94,502.67 Assumption made that initially negative CCNA tests need to be repeated once per patient2 (5) Cost testing PCR (all samples); £ 200,040.21 Only half of negative samples tested i.e. every patient tested once2 (6) Incremental cost PCR; £ 105,537.54 (3a) Negative patients/year (4) Cost testing CCNA (all samples); £ (7) Positives earlier discharge; days (8) Negatives earlier discharge; days 4.88 7.03 (9) Bed days saved positives 1,410.32 (10) Bed days saved negatives 36,837.20 Mean study result PCRCCNA Mean study result PCRCCNA Mean bed days saved in 2011 for all positive patients by using PCR instead of CCNA Mean bed days saved in 2011 for all negative patients by using PCR instead of CCNA; assumed all patients Source ABMUHB laboratory statistics Mandatory Surveillance Report, Public Health Wales for 20111 Positives(2)/Samples(1) Samples(1) – positives(2) Hospital statistics suggest high rate of repeat samples for CCNA Cost/test CCNA [£8.78]* samples(1) (Cost/test PCR [£36.18]* positives(1))+(Cost/test PCR [£36.18]* negatives(3a)) Cost PCR(5) - cost CCNA(4) ABMUHB laboratory statistics and microcosting ABMUHB laboratory statistics and microcosting Mean difference according to study result Mean difference according to study result Positives earlier discharge(7)*positives(2) Negatives earlier discharge(8)*negative patients(3a) (11) Cost per bed day; £ 334.17 (12) Cost savings/positive; £ 1,630.75 (13) Cost savings/negative; £ 2,349.22 (14) Savings all positives; £ 470,649.34 (15) Savings all negatives; £ 12,310,346.16 (16) Total savings; £ 12,780,995.50 (17) Total net savings; £ 12,675,457.96 (18) Cost savings per patient; £ 2292.62 tested twice with CCNA2 Weighted for speciality and activity Potential cost saving per positive patient by using PCR instead of CCNA Potential cost saving per negative patient by using PCR instead of CCNA Total potential cost savings for all positive samples in ABMUHB in 2011 if PCR is used instead of CCNA Total potential cost savings for all negative samples in ABMUHB in 2011 if PCR is used instead of CCNA NHS reference costs 20113 Positives earlier discharge(7)*cost per bed day(11) Negatives earlier discharge(8)*cost per bed day(11) Bed days saved positive(9)*cost per bed day(11) Bed days saved negative(10)*cost per bed day(11) Savings positive(14) +savings negative(15) Total potential net savings of PCR compared to CCNA in ABMUHB in 2011 Potential cost savings of PCR compared to CCNA in ABMUHB in 2011 per patient Total savings(16) incremental cost PCR(6) Net savings(17)/ (positives(2) + negative patients(3a)) 1 Welsh Healthcare Associated Infection Programme. Clostridium difficile. Mandatory Surveillance Report. Abertawe Bro Margannwg University Health Board. Public Health Wales. 2012: page 8 [19]. 2For the calculations it was assumed that negative CCNA samples would be repeated twice per patient while negative PCR samples would only be done once. This assumption is based on a high rate of repeat samples for CCNA testing according to ABMUHB laboratory statistics and recent literature suggesting a significant drop in repeat samples after introduction of PCR [37] 3Department of Health. NHS reference costs 2010-2011. Department of Health 2012, United Kingdom [18].