Manufacturers' Models
For proprietary alendronate, compared with no treatment, the manufacturer's model resulted in an incremental cost-effectiveness ratio (ICER) of 3135 pounds sterling per quality-adjusted life year (QALY) gained for 70-year-old women with a T-score below -1.6 standard deviation (SD).
For etidronate, compared with no treatment, the manufacturer's model provided an ICER of 18,634 pounds sterling per QALY gained for 70-year-old women with a T-score below −2.5 SD.
For risedronate, compared with no treatment, the manufacturer provided data from two models. The ICER derived from the manufacturer's own model was 577 pounds sterling per QALY gained for women aged 74 years. In the second model provided by the manufacturer, which was commissioned from an external body, the ICER was higher, varying from 35,800 pounds sterling per QALY gained in women aged 60 years to 4800 pounds sterling per QALY gained in women aged 80 years, for women with a prior vertebral osteoporotic fragility fracture and a T-score of −2.5 SD. For women at slightly higher risk of fracture, the ICERs were 18,600 pounds sterling per QALY gained or less for all age groups.
For raloxifene, compared with no treatment, the manufacturer provided data for different age groups and different risk levels. All of the analyses included the breast cancer benefits. It was not clear how the different risk levels were defined. The ICERs ranged from 12,000 pounds sterling to 22,000 pounds sterling per QALY gained.
For strontium ranelate, compared with no treatment, the manufacturer provided two models: one developed in-house and the other commissioned from an external body. The first model showed that, for women aged over 75 years with previous fractures and a T-score of −2.5 SD, strontium ranelate was cost-effective at a maximum acceptable incremental cost-effectiveness ratio of 30,000 pounds sterling per QALY gained. The second model resulted in an ICER of 6341 pounds sterling per QALY gained for 70-year-old women with a previous vertebral fracture and a T-score of −2.5 SD, decreasing to 5002 pounds sterling per QALY gained in women aged 80 years.
For teriparatide, compared with no treatment, the manufacturer provided ICERs for women aged 69 years. For women with fractures that had occurred more than 6 months previously (historical fracture), the ICER was 35,400 pounds sterling per QALY gained and for women with a more recent fracture the ICER was 28,863 pounds sterling per QALY gained.
The Assessment Group's Model
The Assessment Group provided a cost–utility model with two components (described in detail in the 2005 Strontium Ranelate Assessment Report). As a first step, the model calculated absolute fracture risk from the epidemiological literature on a number of independent clinical risk factors. As a second step, the model applied relative risk (RR) reductions for fracture taken from the meta-analysis carried out by the University of Sheffield, School of Health and Related Research (ScHARR) in 2006. A single estimate of efficacy was used for alendronate and risedronate based on pooled data for these two drugs. Following advice from the Osteoporosis Guideline Development Group (see www.nice.org.uk) it was assumed that RRs remained constant across all ages, T-scores and fracture status.
The Assessment Group's Model: Results for Alendronate
For alendronate priced at 53.56 pounds sterling per year (once-weekly treatment), and when assuming that 24% of women in the first treatment month and 3.5% of women thereafter experienced bisphosphonate-related side effects, the model produced the following results:
- A strategy of risk assessment, dual-energy X-ray absorptiometry (DXA) scanning, and treatment with alendronate resulted in an ICER of less than 30,000 pounds sterling per QALY gained for all women aged 55 years or older with confirmed osteoporosis (that is, a T-score of –2.5 SD), and for postmenopausal women aged 50 to 54 years with confirmed osteoporosis and two independent clinical risk factors for fracture.
In a sensitivity analysis for alendronate priced at 53.56 pounds sterling per year, acid-suppressive medication was assumed to affect fracture risk. This sensitivity analysis produced the following results:
- A strategy of risk assessment, DXA scanning, and treatment with alendronate in women younger than 55 years resulted in an ICER of more than 30,000 pounds sterling per QALY gained.
- A strategy of risk assessment, DXA scanning and treatment with alendronate resulted in an ICER of less than 30,000 pounds sterling per QALY gained for all women aged 65 years or older with confirmed osteoporosis (that is, a T-score of –2.5 SD or below), for postmenopausal women aged 60 to 64 years with confirmed osteoporosis and one independent clinical risk factor for fracture, and postmenopausal women aged 55 to 59 years with confirmed osteoporosis and two independent clinical risk factors for fracture.
For alendronate priced at 108.20 pounds sterling per year (daily treatment), and when assuming that 24% of women were experiencing bisphosphonate-related side effects in the first treatment month and 3.5% of women thereafter, the model produced the following results:
- A strategy of risk assessment, DXA scanning, and treatment with alendronate in women younger than 55 years resulted in an ICER of more than 30,000 pounds sterling per QALY gained.
- A strategy of risk assessment, DXA scanning and treatment with alendronate resulted in an ICER of less than 30,000 pounds sterling per QALY gained for women aged 65 years or older with confirmed osteoporosis (that is a T-score of –2.5 SD or below), for postmenopausal women aged 60 to 64 years with confirmed osteoporosis and one independent clinical risk factor for fracture, and for postmenopausal women aged 55 to 59 years with confirmed osteoporosis and two independent clinical risk factors.
The Assessment Group's Model: Results for Other Drugs
For risedronate, raloxifene, strontium ranelate, and teriparatide, analyses were conducted to explore identification and treatment strategies that could be cost effective for these interventions when compared with no intervention. All results showed less favourable cost effectiveness than non-proprietary alendronate.
Consideration of the Evidence
Alendronate
The Committee concluded that alendronate (based on the price of 53.56 pounds sterling per year for once-weekly treatment) would be an appropriate use of National Health Service (NHS) resources for secondary preventative treatment in postmenopausal women with fragility fractures and confirmed osteoporosis (that is, a T-score of –2.5 SD or below).
Considerations for the Other Drugs under Appraisal
The Committee noted that risedronate, etidronate, raloxifene and strontium ranelate were dominated by alendronate (based on the price of 53.56 pounds sterling per year for alendronate); that is, these drugs have a higher acquisition cost than alendronate, but are not more efficacious.
The Committee concluded that risedronate could be recommended for women who are unable to comply with the special instructions for the administration of alendronate, or have a contraindication to or are intolerant of alendronate, and who have a T-score of –2.5 SD or below plus a combination of age and number of independent clinical risk factors for fracture where treatment with risedronate resulted in an ICER of less than 30,000 pounds sterling per QALY gained without the consideration of identification costs.
The Committee decided that etidronate should not be recommended in preference to risedronate. However, the Committee agreed that guidance on the use of etidronate should be included in the recommendations, and concluded that etidronate can be recommended as an alternative treatment option for women who cannot take alendronate.
The Committee concluded that strontium ranelate could be recommended for women who are unable to comply with the special instructions for the administration of alendronate and either risedronate or etidronate, or have a contraindication to or are intolerant of alendronate and either risedronate or etidronate, and who have a T-score of −2.5 SD or below plus a combination of age and number of independent clinical risk factors for fracture where treatment with strontium ranelate resulted in an ICER of less than 30,000 pounds sterling per QALY gained, without the consideration of identification costs.
The Committee concluded that, the possible benefits in addition to fracture prevention meant that, in cases where women are unable to comply with the special instructions for the administration of alendronate and either risedronate or etidronate, or have contraindications to or are intolerant of alendronate and either risedronate or etidronate, raloxifene could be recommended for the same groups of women for whom treatment with strontium ranelate resulted in an ICER of less than 30,000 pounds sterling per QALY gained without the consideration of identification costs.
The Committee concluded that a change from the recommendations for teriparatide in NICE technology appraisal 87 for women aged 65 years and older is not warranted. Furthermore, the Committee considered that the updated modelling indicated that women aged 55 to 64 years who have a T score of –4 SD or below and more than two fractures could be cost-effectively treated with teriparatide.
See section 4.2 and 4.3 of the original guideline document for a detailed discussion of the cost-effectiveness analysis.