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In final draft guidance published today, NICE is recommending the use of mifamurtide (Mepact, Takeda) in combination with postoperative multi-agent chemotherapy as an option for treating high-grade resectable non-metastatic osteosarcoma (bone cancer), when it's made available at a reduced cost to the NHS under a patient access scheme. NICE has not yet issued final guidance to the NHS.

Following a clarification from the NICE Board on how discounting is applied (which involves assessing the way in which health benefits are valued and calculated over a very long period of time) the independent Appraisal Committee has re-examined the evidence for this appraisal. The evidence indicated that mifamurtide, when added to the usual treatment with surgery and chemotherapy, increases the number of patients who are effectively cured of their cancer. Although the number of additional patients who would benefit in this way is small and uncertain, the treatment effects are both substantial in restoring health and sustained over a very long period - the patients who are cured continue to benefit for the rest of their lives. The clarification from the Board provided guidance on how discount rates can be applied in this circumstance.

In considering the evidence, the Committee's view was that health-related quality of life may not have been adequately captured in the economic analysis, and they were also mindful of the innovative nature of the drug for a rare disease. Having noted the Board clarification, and taken all other aspects into account, including the price discount that the drug's manufacturer has agreed with the Department of Health, the Committee concluded that mifamurtide could be accepted as a cost-effective use of NHS resources. The draft guidance includes additional recommendations supporting further research into the size of the effect of mifamurtide when combined with the type of chemotherapy typically used in UK clinical practice, as well as further collection of quality of life data from people who are cured.

Sir Andrew Dillon, NICE Chief Executive, said: "The independent appraisal committee has re-examined the evidence for this appraisal, following clarification from the NICE Board on how discounting should by applied in cases where treatment benefits are realised over a very long time period.

"This clarification, along with a revised patient access scheme, means that the extra cost per unit of health gained that the NHS will be asked to pay for mifamurtide is now lower than previously determined, but still above the normal range. The Committee looked again very carefully in every way possible at whether there might be a case for accepting this higher than normally accepted extra cost per unit of health gained (the incremental cost-effectiveness ratio, ICER) for mifamurtide. This included considering the curative potential of the drug for some people, that this is a small patient population with a rare disease, and whether the change in health-related quality of life had been inadequately captured in the economic analysis. After further careful consideration, and taking all of these factors into account, the Committee was able to recommend mifamurtide for osteosarcoma.

"This appraisal has raised some important methodological issues, so we thank the Board for their consideration of these points, which has helped us progress this work in the most appropriate way."

This draft guidance is available at: http://guidance.nice.org.uk/TA/Wave17/11 and consultees and commentators have until 21 September 2011 if they wish to appeal it. Until final guidance is issued, NHS organisations should make decisions locally on the funding of specific treatments.

Ends

Notes to Editors

About the Appraisal

1. The full recommendation is: "Mifamurtide in combination with postoperative multi-agent chemotherapy is recommended within its licensed indication as an option for the treatment of high-grade resectable non-metastatic osteosarcoma after macroscopically complete surgical resection in children, adolescents and young adults and when mifamurtide is made available at a reduced cost to the NHS under the patient access scheme."

2. The evidence indicates that use of mifamurtide in the circumstance covered by the recommendation can increase overall survival on average by an extra 7 people for every 100 people treated. It's estimated that around 60 people could be treated under this draft recommendation.

3. Noting the clarification to the ‘Guide to the methods of technology appraisal' issued in July 2011 by the Board of NICE, resulted in a manufacturer's best-case probabilistic ICER (incremental cost-effectiveness ratio) of £36,000 per QALY gained.

4. NICE produced final draft guidance in October 2010 which was unable to provisionally recommend mifamurtide for NHS use in combination with post-operative chemotherapy drugs for the treatment of high-grade non-metastatic, surgically treatable osteosarcoma. At that point, the most plausible probabilistic ICER was £56,700 per QALY gained.

5. The manufacturer (Takeda) submitted a revised patient access scheme to the Department of Health, the details of which are confidential as requested by the manufacturer.

About the Board's clarification to the Guide to the Methods of Technology Appraisal

6. Following additional in-depth consideration of the evidence by the independent Appraisal Committee, the Guidance Executive at NICE (which acts on behalf of the Board in approving draft and final guidance for publication) subsequently referred the appraisal to the Institute's Board for advice on the methodological issues raised whilst appraising this topic. In particular, the Board was asked to provide clarification on aspects of the Institute's Guide to the Methods of Technology Appraisal, as it applies in this case.

7. At the NICE Board meeting on 20 July, the Board considered the use of discounting, which involves assessing the way in which health benefits are valued and calculated over a very long period of time. The Board considered whether it would be helpful to the appraisal committees to clarify paragraph 5.6.2 in the Guide to the Methods of Technology Appraisal which refers to the use of discounting. The Board considered the matter and issued a clarification to the Guide, in the following way:

"5.6.2 The need to discount to a present value is widely accepted in economic evaluation, although the specific rate is variable across jurisdictions and over time. The Institute considers it appropriate to normally discount costs and health effects at the same rate. The annual rate of 3.5%, based on recommendations of the UK Treasury for the discounting of costs, should be applied to both costs and health effects. Where the Appraisal Committee has considered it appropriate to undertake sensitivity analysis on the effects of discounting because treatment effects are both substantial in restoring health and sustained over a very long period (normally at least 30 years), the Committee should apply a rate of 1.5% for health effects and 3.5% for costs."

The clarification has immediate effect and has been published on the Institute's website.

About osteosarcoma

8. Although rare, osteosarcoma is the most common form of bone cancer. Around 150 new cases are diagnosed each year in the UK. Tumours can grow anywhere in the skeleton, but the most common places are in the legs or upper arm. Common symptoms include pain, redness and swelling in the affected area

9. At present, treatment for osteosarcoma involves chemotherapy first to shrink the tumour, then surgery to remove the part of the bone or limb affected, followed by further chemotherapy after surgery to destroy any remaining cancer cells. Mifamurtide has a marketing authorisation for use after surgery, in combination with post-operative chemotherapy drugs.

About NICE

10. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health

11. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

12. NICE produces standards for patient care:

• quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
• Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients

13. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.