Ross et al. (2004 HTA report)

Full bibliographic referenceRoss, J. R., Y. Saunders, et al. (2004). “A systematic review of the role bisphosphonates in metastatic disease.” Health Technology Assessment 8(4): iii–139.
Source of fundingHTA
Economic study typeCost-effectiveness and cost-utility analysis using markov modelling.
Population, country & perspectiveUK. NHS and social care perspective for breast cancer patients with bone metastases.
Comparison(s)Pamidronate (90mg) vs. no treatment
Source of effectiveness data
  • Median survival (from placebo arm) – 18 months (Lipton et al, 2000; Hultborn et al,1999)
  • (No bisphosphonate arm) monthly incidence of SREs (vertebral fracture, non-vertebral fracture, hypercalcaemia, RT and orthopaedic surgery) (Lipton et al, 2000)
  • (Bisphosphonate arm) monthly incidence of SREs for no-bisphosphonate arm multiplied by an estimated relative risk which was calculated for each SRE by random effects meta-analysis.
  • Reduction in bone pain (1 in 7 patients would have bone pain fully alleviated each month) (Wong and Wiffen, 2002)
  • QALY estimates (Dranitsaris and Hsu, 1999) – adjusted to account for a longer treatment duration
Cost componentsUK £ Stirling. Cost year 2000/1.
  1. cost to the hospital of providing bisphosphonate therapy;
  2. inpatient and outpatient hospital costs associated with treating SREs, fractures, hypercalcaemia, surgery and RT;
  3. community health service costs associated with palliation of bone pain;
  4. community health service costs associated with the longer term care of patients;
Costs to patients and their families were not included in line with the costing perspective taken.
Time horizon, discount rate48 months (to be consistent with the longest time horizon of the studies examined in the literature).
Costs - 6%, benefits 1%. Also investigate use of different discount rates in sensitivity analysis. The results are not sensitive to the discount rates.
Results – costThe incremental cost of bisphosphonate use was estimated to be £444 per patient.
Results – effectivenessIt was estimated that for every 100 patients treated with bisphosphonates (pamidronate), 179 SREs would be averted – 54 non-vertebral fractures, 16 vertebral fractures, 34 episodes of hypercalcaemia, 64 episodes of RT and 12 episodes of surgery.
Results – adverse eventsThe cost of treating side-effects from the drug was not included because of the rarity of serious side-effects. The cost of treating SCC was not estimated because there is not good evidence of a reduction in incidence associate with the use of bisphosphonates.
Results –incremental cost-effectivenessIt was estimated that the use of bisphosphonates in this context costs £250 per SRE averted or £1645 per fracture avoided.
Incremental cost per QALY gained was £1340.
Results-uncertaintyUnivariate sensitivity analyses were performed. The results were not sensitive to the survival rate, the inclusion of SCC or the assumption of constant event rates. Costs and cost- effectiveness were sensitive to the price of bisphosphonates, the probability of averting an event and the unit costs associated with events. Whilst the incremental cost per SRE averted in the baseline analysis is £250, the results of the sensitivity analysis show the cost per SRE averted could lie anywhere between being cost-saving and costing £13,153. The most sensitive parameter was the relative risk of SREs which, using the higher confidence limit of this value, represent a cost of £7,383 per SRE averted.

In a separate sensitivity analysis including an analysis of possible cost-savings from prevention of fracture, the authors conclude that inclusion of such savings may mean that use of pamidronate is cost-saving to the NHS.
General commentsThis analysis is the most relevant for this guideline in that it takes a UK NHS and social care perspective and is the most independent assessment of the UK economic appraisals found as part of this review.

From: Chapter 6, Management of specific problems

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
National Collaborating Centre for Cancer (UK).
Copyright © 2009, National Collaborating Centre for Cancer.

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