Lay summary of adjuvant bisphosphonates financial modelling Developed by Breast Cancer Now in collaboration with Professor Rob Coleman Cost of treatment and of potential savings taken from business case and financial modelling by South Yorkshire Cancer Strategy Group, Feb 2016 A B C D E Patient population Pathway scenarios Cost-savings elsewhere Total cost versus total savings Cost savings and lives saved per UK nation A Patient population European consensus guidance This says that bisphosphonates should be used as part of routine clinical practice in the prevention of metastases in patients with low levels of female sex hormones - age 55 and over and/or postmenopausal. Entire patient population: 35,700 in UK every year 1 Regarding risk-guided selection, it says: There was strong consensus that the data supported the use of adjuvant bisphosphonates in postmenopausal (whether natural or induced) women, with some experts (58%) suggesting further restriction to those considered at intermediate or high risk of recurrence rather than unselected use across all risk groups. 2 Prof Rob Coleman/ Sheffield pathway This says to give routinely to all patients who are postmenopausal AND either having chemotherapy, or with adverse prognostic factors of >12% 10 year risk of breast cancer death. The South Yorkshire Cancer Strategy Group outline in their business case that it is expected that [around] two thirds of postmenopausal women diagnosed with breast cancer [age 55 and over and/or postmenopausal] will be considered at sufficient level of risk for recurrence of breast cancer to benefit from the introduction of bisphosphonates. Risk-guided patient population: approximately 20,000 women in UK every year 3 B Pathway scenarios 4 All zoledronic acid (IV) Scenario 1 having chemotherapy: 4mg x 3 during chemotherapy at approx. 5 each (incurs drug cost only) = 15 then 6 doses at 91 each - 6,12,18,24,30,36 months (includes drug cost and consultant time including follow-up) = 546 561
2 Scenario 2 not having chemotherapy: 7 doses at 91 each 0,6,12,18,24,30,36 months = 637 IV then oral ibandronate 5 Scenario 3 (having chemotherapy) 4mg x 3 during chemotherapy at approx. 5 each (incurs drug cost only) = 15 then daily tablet at 0.34 per tablet from 6-36 months: 2.5 years/ 30 months: 365+365+182.5 = 912.5, x 0.34 = 310.25 325.25 All oral ibandronate Scenario 4 (not having chemotherapy) daily tablet at 0.34 per tablet from 0-36 months: annual cost: 0.34 x 365 = 124.10 3 years/ 36 months: 124.10 x 3 = 372.30 Switching between IV and oral ibandronate Scenario 5 Use unit costing above to calculate bespoke figure C Cost-savings elsewhere Reduced need for DEXA bone scans The unit cost of a DEXA bone scan is 63.82 The current pathway assumes that all post-menopausal women with invasive breast cancer (35,700 in UK every year) require 3 DEXA bone scans over a three year period (at 0, 18, and 36 months). 63.82 x 3 = 191.46, x 35,700 = 6,835,122 (per annual cohort) (i) European consensus The new pathway recommended by the European consensus guidance would mean that the entire patient population (i.e. all post-menopausal women with invasive breast cancer) would receive a bisphosphonate. This would negate the need for any of these patients to have DEXA bone scans. This amounts to savings of 6.84m (per annual cohort) (ii) South Yorkshire (risk-guided) Alternatively, the new pathway being implemented in South Yorkshire assumes that around 20,000 patients per annual cohort would receive a bisphosphonate and therefore no longer need DEXA bone scans, whilst the remainder (15,700) would not receive a bisphosphonate
3 and therefore remain on the current pathway of 3 DEXA bone scans over a three year period (at 0, 18, and 36 months). 6 In addition to this, South Yorkshire s pathway assumes that, of the patients which are still having scans, one third will be found to need treatment for low BMD and will start a bisphosphonate and not need further DEXA scans. To model this we have made the assumption that this third will start a bisphosphonate at their 18 month appointment and not need further DEXA scans, thereby reducing these patients from 3 DEXA scans to 2. So, of 15,700 patients, two thirds (10,467) on the current pathway and one third (5,233) on a reduced pathway: 63.82 x 3 = 191.46, x 10,467 = 2,004,011.8 63.82 x 2 = 127.64, x 5,233 = 333,970.06 2,004,011.8 + 333,970.06 = 2,337,981.8 6,835,122-2,337,981.8 = 4,497,140.2 This is a reduction to 34% of previous activity/ spend Which amounts to savings of around 4.5m (per annual cohort) Less women developing secondary breast cancer In the longer term, the costs are offset by a reduction in the number of women developing secondary breast cancer. It is possible to calculate the reduction in secondary breast cancer cases for any patient population size. You can do this as follows: The EBCTCG meta-analysis showed that, of the women who took a bisphosphonate, 17.9% developed secondary breast cancer within 10 years. Of the women who didn t take a bisphosphonate, 21.2% developed secondary breast cancer within 10 years. 7 To work out the reduction in secondary breast cancer cases in the total UK patient population of 35,700, you take the difference between 21.2% and 17.9% (3.4%) 8 and calculate 3.4% of 35,700 which is 1,213.8 (1,214). There is no comprehensive up-to-date estimate of the total cost of a secondary breast cancer patient to the NHS. The best estimate currently available is 12,500 and this, from 2004, is likely to be a gross underestimate. 9 (i) European consensus However, given this figure, routine implementation would save at least 15,172,500 ( 15.17m) per annual cohort for the NHS in the UK. This assumes that you give a bisphosphonate to the whole patient population (of 35,700), thereby reducing the number of secondary breast cancer cases by 1,214 per year. (1,213.8 x 12,500 = 15,172,500) (ii) South Yorkshire (risk-guided) In the South Yorkshire risk-guided patient population, lives saved can be calculated in the same way as above 10 : Reduction in number of secondary breast cancer cases: 680 Therefore, cost savings are: 680 x 12,500 = 8,500,000 ( 8.5m) per annual cohort
4 D Total cost versus total savings Average cost of treatment: 561 + 637 + 325.25 + 372.3 = 1,895.55, /4 = 473.8875 Cost per day for 1 patient: 473.8875 / (365 x 3) = 0.43 (i) European consensus Total cost of treatment: 473.8875 x 35,700 = 16,917,783 16,917,783-6,835,122-15,172,500 = - 5,089,839 5.09m net savings per annual cohort (ii) South Yorkshire (risk-guided) Total cost of treatment: 473.8875 x 20,000 = 9,477,750 9,477,750-4,497,140.2-8,500,000 = - 3,519,390.2 3.52m net savings per annual cohort E Cost savings and reduction in secondary breast cancer cases per UK nation Assuming the whole cohort are treated UK Patient population (all post-menopausal women with invasive breast cancer): 35,700 Reduction in number of secondary breast cancer cases per year: 1,214 Cost of treatment = 473.8875 x 35,700 = 16,917,783 Savings from no longer needing to take DEXA scans (assuming the entire 35,700 are treated): 63.82 x 3 = 191.46, x 35,700 = 6,835,122 1,213.8 x 12,500 = 15,172,500 16,917,783-6,835,122-15,172,500 = - 5,089,839 5.09m net savings per annual cohort England Patient population (all post-menopausal women with invasive breast cancer): 29,600 11 Reduction in number of secondary breast cancer cases per year: 1,006.4 (1,006) Cost of treatment = 473.8875 x 29,600 = 14,027,070 Savings from no longer needing to take DEXA scans (assuming the entire 29,600 are treated): 63.82 x 3 = 191.46, x 29,600 = 5,667,216
5 1,006.4 x 12,500 = 12,580,000 14,027,070-5,667,216-12,580,000 = - 4,220,146 4.22m net savings per annual cohort Scotland Patient population (all post-menopausal women with invasive breast cancer): 3,200 12 Reduction in number of secondary breast cancer cases per year: 108.8 (109) Cost of treatment = 473.8875 x 3,200 = 1,516,440 Savings from no longer needing to take DEXA scans (assuming the entire 3,200 are treated): 63.82 x 3 = 191.46, x 3,200 = 612,672 108.8 x 12,500 = 1,360,000 1,516,440-612,672-1,360,000 = - 456,232 456k net savings per annual cohort Wales Patient population (all post-menopausal women with invasive breast cancer): 1,900 13 Reduction in number of secondary breast cancer cases per year: 64.6 (65) Cost of treatment = 473.8875 x 1,900 = 900,386.25 Savings from no longer needing to take DEXA scans (assuming the entire 1,900 are treated): 63.82 x 3 = 191.46, x 1,900 = 363,774 64.6 x 12,500 = 807,500 900,386.25-363,774-807,500 = - 270,887.75 271k net savings per annual cohort Northern Ireland Patient population (all post-menopausal women with invasive breast cancer): 890 14 Reduction in number of secondary breast cancer cases per year: 30.26 (30) Cost of treatment = 473.8875 x 890 = 421,759.87 Savings from no longer needing to take DEXA scans (assuming the entire 890 are treated):
6 63.82 x 3 = 191.46, x 890 = 170,399.4 30.26 x 12,500 = 378,250 421,759.87-170,399.4-378,250 = - 126,889.53 127k net savings per annual cohort 1 This is based on the annual average number of breast cancer (ICD10 C50) cases diagnosed in females aged 55 and over in the UK between 2011-2013. Information provided by CRUK, 16 May 2016. The average age for women to reach the menopause in the UK is actually 51, meaning that 35,700 is a modest estimate of the number of women who would be eligible to take bisphosphonates each year. Breast cancer incidence figures were only available in 5 year intervals (50-54; 55-59 and so on), so we have taken the more modest estimate. http://www.nhs.uk/conditions/menopause/pages/introduction.aspx 2 Hadji, P; Coleman, R (2016): Adjuvant bisphosphonates in early breast cancer: Consensus guidance for clinical practice from a European Panel Annals of Oncology 27 (3), 379-390; For the EBCTCG metaanalysis, see: Early Breast Cancer Trialists' Collaborative Group (2015): Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials, The Lancet 386 (10001), 1353 1361. 3 Estimated by Professor Rob Coleman, 18 May 2016. Prof Coleman commented that it is not that there would be no benefit in lower risk patients but that the numbers needed to treat to prevent one recurrence or death are much lower in patients with high risk disease compared with low risk disease. 4 This modelling is based on zoledronic acid/zoledronate and ibandronic acid/ibandronate only. This is because, although clodronate has been shown to have a similar survival benefit to ibandronic acid, it is more expensive. 5 Although the European consensus panel recommended either intravenous zoledronic acid or oral clodronate, a number of trials have shown similar outcomes from clodronate and ibandronate, whilst ibandronate is much cheaper than clodronate. 6 DEXA scans to monitor for bone loss are recommended every 1-2 years. Prof Coleman scans every 2 years and therefore advised to model an average of 1 scan every 18 months, so 3 scans over 3 years. 7 Early Breast Cancer Trialists' Collaborative Group (2015): Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials, The Lancet 386 (10001), 1353 1361. 8 The discrepancy is acknowledged difference presumed to be due to rounding of figures, see appendix of published paper for details. 9 Remak, E; Brazil, L (2004): Cost of managing women presenting with stage IV breast cancer in the UK, British Journal of Cancer 91, 77-83. 10 The bisphosphonate trials largely recruited higher risk patients, so the application of this method seems reasonable. 11 55 and over in England between 2011-2013. 12 55 and over in Scotland between 2011-2013. 13 55 and over in Wales between 2011-2013. 14 55 and over in Northern Ireland between 2011-2013.
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