Soft tissue sarcoma - trabectedin: appraisal consultation document

Trabectedin for the treatment of advanced soft tissue sarcoma

The Department of Health has asked the National Institute for Health and Clinical Excellence (NICE) to produce guidance on using trabectedin in the NHS in England and Wales. The Appraisal Committee has considered the evidence submitted by the manufacturer and the views of non-manufacturer consultees and commentators, and clinical specialists and patient experts.

This document has been prepared for consultation with the consultees. It summarises the evidence and views that have been considered, and sets out the draft recommendations made by the Committee. NICE invites comments from the consultees and commentators for this appraisal (see appendix B) and the public. This document should be read along with the evidence base (the evaluation report), which is available from www.nice.org.uk

Note that this document is not NICE's final guidance on this technology. The recommendations in section 1 may change after consultation.

After consultation:

  • The Appraisal Committee will meet again to consider the evidence, this appraisal consultation document and comments from the consultees.
  • At that meeting, the Committee will also consider comments made by people who are not consultees.
  • After considering these comments, the Committee will prepare the final appraisal determination (FAD).
  • Subject to any appeal by consultees, the FAD may be used as the basis for NICE’s guidance on using trabectedin in the NHS in England and Wales.

For further details, see the ‘Guide to the technology appraisal process’.

 

The key dates for this appraisal are:

Closing date for comments: 21 July 2009

Second Appraisal Committee meeting: 4 August 2009

Details of membership of the Appraisal Committee are given in appendix A, and a list of the sources of evidence used in the preparation of this document is given in appendix B.

 

1 Appraisal Committee’s preliminary recommendations

1.1 Trabectedin is not recommended as a treatment option for people with advanced soft tissue sarcoma.

1.2 People who are currently being treated with trabectedin for advanced soft tissue sarcoma should have the option to continue their therapy until they and their clinicians consider it appropriate to stop.

2 The technology

2.1 Trabectedin (Yondelis, PharmaMar) is an alkylating agent, which affects cancer cells by damaging DNA. Trabectedin has a UK marketing authorisation for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. The marketing authorisation was granted ‘under exceptional circumstances’. The summary of product characteristics (SPC) states that ‘efficacy data are based mainly on liposarcoma and leiomyosarcoma patients’.

2.2 Trabectedin is contraindicated in people who have hypersensitivity to trabectedin or to any of the excipients, in those with concurrent serious or uncontrolled infection, in women who are breast-feeding, and in combination with yellow fever vaccine. The SPC states that trabectedin is not indicated for use in children and adolescents, and that creatinine phosphokinase, hepatic function and haematological parameters should be monitored regularly during treatment. The SPC lists precautions for use of trabectedin in people with liver or kidney impairment. The SPC reports that the most common adverse reactions are nausea, fatigue, vomiting, weight loss (anorexia), neutropenia, thrombocytopenia, and increases in enzymes indicating abnormal liver function. Fatal adverse reactions have occurred in 1.9% of patients. For full details of adverse events and contraindications, see the SPC.

2.3 The SPC for trabectedin states that ‘the recommended dose is 1.5 mg/m2 body surface area, administered as an intravenous infusion over 24 hours with a 3-week interval between cycles.’ The SPC also states that administration of trabectedin through a central venous line is ‘strongly recommended’. Anti-emetic prophylaxis with intravenous dexamethasone (20 mg) must be administered to all patients 30 minutes before trabectedin treatment. Dexamethasone also has hepatoprotective effects. The acquisition cost of trabectedin is £363.00 for a 250-microgram vial and £1366.00 for a 1-mg (1000-microgram) vial (excluding VAT; 'British national formulary' [BNF] edition 56). At a dose of 1.5 mg/m2, approximately 2.5 mg trabectedin would be needed per cycle for a patient with a body surface area of 1.7 m2. One such infusion (using two 1-mg vials and two 250-microgram vials of trabectedin) would cost £3458. The cost of treatment would also depend on the number of cycles used. Costs may vary in different settings because of negotiated procurement discounts.

3 The manufacturer’s submission

3.1 The Appraisal Committee (appendix A) considered evidence submitted by the manufacturer of trabectedin and a review of this submission by the Evidence Review Group (ERG; appendix B).

3.2 The manufacturer’s submission included a phase II randomised trial (STS-201) evaluating the efficacy of trabectedin in participants with locally advanced or metastatic soft tissue sarcoma and whose disease had relapsed or become refractory after treatment with at least an anthracycline and ifosfamide, given either in combination or in sequence. The trial randomised participants to one of two trabectedin dosing regimens. One group received the dosage of trabectedin specified in the marketing authorisation (1.5 mg/m2 every 3 weeks as a 24-hour intravenous infusion, n = 136) whereas the other group (n = 134) received trabectedin at a dosage of 0.58 mg/m2 every week as a 3-hour intravenous infusion. All participants had liposarcomas or leiomyosarcomas (L-sarcomas) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In addition, three uncontrolled phase II trials of trabectedin were presented in the manufacturer’s submission. These included a total of 194 participants with soft tissue sarcoma, of whom 104 had L-sarcomas. Participants in all of these studies had an ECOG performance status of 0 or 1. In the absence of relevant comparator data in the included trials, the manufacturer reported historical control data for patients receiving treatments considered to be equivalent to best supportive care (BSC; see sections 3.7 to 3.9). These data were derived from studies in the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) database.

3.3 The primary outcome of the STS-201 trial was time-to-progression (time between randomisation and the first documentation of disease progression or death as a result of progressive disease, TTP); secondary outcomes included progression-free survival (PFS), overall survival (OS) and best overall response (BSR). According to the manufacturer, treatment with trabectedin continued as long as therapeutic benefit was derived, until disease progression, or for at least two courses of therapy beyond confirmed response. Crossover was allowed for participants in either arm who experienced disease progression. The manufacturer acknowledged that the crossover design of the study affected OS.

3.4 Intention-to-treat median TTP was statistically significantly longer (hazard ratio [HR] 0.734, p = 0.032) for the licensed dosage of trabectedin, with a TTP of 3.7 months (95% confidence interval [CI] 2.1 to 5.4) compared with 2.3 months (95% CI 2.0 to 3.5) for the comparator dosage of trabectedin. Median OS was 13.9 months (95% CI 12.5 to 18.6) for the licensed dosage of trabectedin compared with 11.8 months (95% CI 9.9 to14.9) for the comparator trabectedin regimen. Median PFS at 3 and 6 months was 51.5% (95% CI 43.0 to 60.1) and 35.5% (95% CI 27.1 to 43.9) respectively for the licensed dosage of trabectedin, compared with 44.7% (95% CI 36.0 to 53.3) and 27.5% (95% CI 19.4 to 35.5) for the comparator trabectedin regimen. The manufacturer reported that in a pre-planned subgroup analysis, efficacy outcomes appeared to be more favourable in patients with liposarcomas than in those with leiomyosarcomas, regardless of the study arm.

3.5 The manufacturer reported that the main treatment-related severe (grades 3 and 4) adverse events observed in all studies were transient, reversible and non-cumulative neutropenia and transaminase elevations without clinical consequences. Grade 3 or 4 nausea and vomiting were also observed in some participants. The manufacturer stated that unlike other commonly used cytotoxic agents, no cardiotoxicity or neurotoxicity was observed with trabectedin.

3.6 No health-related quality of life data were presented for patients with advanced soft tissue sarcoma and the manufacturer stated that none were obtained from the trials.

3.7 Historical control data were used to approximate BSC, with the manufacturer acknowledging the limitations of this approach. For OS estimates, data for those in whom treatment with ifosfamide had failed, for those receiving dacarbazine, and for those receiving etoposide were taken from an unpublished analysis of four phase II studies in the EORTC STBSG database of adults with advanced pre-treated soft tissue sarcoma. For estimates of PFS, data for the comparators were taken from a publication reporting on phase II studies from the EORTC STBSG. The studies included in the analysis varied in the treatment given to patients during and before entering the trials, and so the manufacturer selected the pre-treated populations that they considered to be most relevant.

3.8 The manufacturer reported that the median OS of historical control patients treated with ifosfamide was 6.6 months from start of therapy (95% CI 5.0 to 9.0); a further figure was stated by the manufacturer, but was marked as academic-in-confidence and therefore cannot be presented in this document. The manufacturer reported that the median OS for those treated with dacarbazine was 6.6 months (95% CI 4.3 to 8.4) and 6.3 months (95% CI 4.4 to 8.9) for those treated with etoposide.

3.9 The manufacturer reported that the mean PFS of historical control patients treated with inactive regimens[1] (n = 234) was 21% (standard error [SE] ± 3%) and 8% (SE ± 2%) at 3 and 6 months, respectively. The corresponding figures for historical control patients treated with active regimens comprising ifosfamide and dacarbazine (n = 146) were 39% (SE ± 4%) and 14% (SE ± 3%), respectively.

[1] Inactive regimens include treatment with mitozolomide, nimustine, fotemustine, miltefosine, liposomal muramyl tripeptide phosphatidylethanolamide, temozolamide, etoposide, tomudex or gemcitabine.

3.10 The manufacturer developed its own economic evaluation, comprising a two-arm state-transition model. The first arm was designed to capture the costs and outcomes associated with treatment with trabectedin; the second arm was designed to capture the costs and outcomes associated with treatment with BSC. Administration of other chemotherapies in addition to BSC was explored in a sensitivity analysis. The model included four mutually exclusive health states: progression-free after treatment with trabectedin; progressive disease after treatment with trabectedin; progressive disease with BSC; and death. People treated with trabectedin entered the model in the progression-free state, whereas people treated with BSC entered the model in the progressive disease state. The model cycle length was 1 month with a time horizon of 5 years.

3.11 The model used the effectiveness data from the STS-201 trial of trabectedin, which included only participants with L-sarcomas after they had been treated with a regimen containing at least an anthracycline and ifosfamide (combined or sequential). Effectiveness data from participants receiving a 24-hour infusion of trabectedin every 3 weeks were selected to represent the base case. As a sensitivity analysis, the pooled effectiveness from the three initial phase II uncontrolled studies of trabectedin was also modelled. Transition probabilities for the trabectedin arm were estimated from Weibull parameters derived from the patient-level data for TTP from the STS-201 trial. Weibull curves were fitted to Kaplan–Meier curves for TTP and OS. The Weibull estimates were considered by the manufacturer to be sufficiently comparable to the Kaplan–Meier curves. Following a request by the ERG arising because of differences in patient characteristics between the treatment and BSC arms, Weibull curves for trabectedin were re-calculated using age, gender and severity as covariates.

3.12 The effectiveness data for patients who receive BSC after failure of anthracyclines and ifosfamide were estimated from pooled data from four previously published trials obtained from the EORTC STBSG database. The EORTC STBSG data were used in the same manner as the STS-201 data to estimate the transition probabilities (in this case, only from progression to death). In response to requests for clarification, the manufacturer submitted a revised model in which the survival curves were adjusted for the differences in patient characteristics between the trabectedin and BSC arms.

3.13 Because no studies of quality of life in patients with soft tissue sarcoma were identified, the manufacturer used health-state utilities for non-small-cell lung cancer as proxies, following discussion with their clinical experts on the comparable prognosis and stages of disease. Health-state utilities in progression-free (PF) and progressive disease (PD) states were assumed to be similar for all patients, irrespective of treatment. The utility for PF and PD was assumed to be 0.653 and 0.473, respectively. Admission to hospital as a result of adverse events associated with trabectedin treatment was associated with a utility of 0.61, which was equal to that associated with nausea and vomiting. This was assumed to last 1 month and equated to a quality-adjusted life year (QALY) decrement of 0.004. The utility associated with developing grade 3 or 4 neutropenia was 0.56. This was assumed to last 1 week and equated to a QALY decrement of 0.002. Adverse events were assumed to occur only during the first cycle of trabectedin treatment, and no disutility associated with adverse events was modelled for patients receiving BSC.

3.14 Following concerns raised by the ERG about the calculation of the average cost per patient, the manufacturer revised- the methodology used to estimate the acquisition cost of the drug. Patient-level data from the STS 201 trial were used to calculate the average number of 1-mg and 250-microgram vials used for each patient and the proportion of patients receiving trabectedin in each cycle. The ERG stated that the manufacturer’s revised response reported a cost per patient of £23,719 with administration costs excluded, and £25,986 with administration costs and a pre-treatment injection of dexamethasone included. Management costs for patients in PD were extracted from a cost of illness study, and costs of PF were assumed, in the absence of data, to be half the costs for PD. Additional costs were included when a patient died. Costs of hospitalisation were average costs and were dependent on patient diagnoses. No costs were included for neutropenia, adverse events in the BSC arm or for patient monitoring.

3.15 With discounting at 3.5% per annum, the manufacturer’s revised base-case cost effectiveness results gave an incremental cost-effectiveness ratio (ICER) of £56,985 per QALY gained for trabectedin compared with BSC, based on an incremental cost of £27,145 and an incremental QALY gain of 0.476. The manufacturer explored uncertainty in one-way sensitivity and probabilistic sensitivity analysis. The ICER appeared most sensitive to changes in utility estimates.

3.16 Results for additional scenarios were presented by the manufacturer:

  • Using pooled effectiveness for trabectedin from three uncontrolled phase II trials was associated with an ICER of £50,017 per QALY gained.
  • Assuming that 33% and 100% of patients receiving BSC receive further chemotherapy was associated with an ICER of £62,044 and £80,279 per QALY gained, respectively.

3.17 The ERG stated that the revised method used to estimate the cost of trabectedin was, in general, appropriate. It noted, however, that the cost of trabectedin may be underestimated because a few participants were still being treated at the end of the follow-up period and were assumed not to incur future cost in the model. The ERG also identified a number of errors in the revised model submitted by the manufacturer. These errors were corrected by the ERG and were shown to have limited impact on the results. The ERG’s corrections to the manufacturer’s model (see section 3.15) resulted in an ICER of  £56,949 per QALY gained for the base case and of £49,992 per QALY gained for the pooled analysis (from the three phase II uncontrolled studies of trabectedin).

3.18 The ERG expressed strong concerns over the model structure in that people treated with trabectedin entered the model in the PF health state, whereas those treated with BSC entered in the PD health state, noting that the PD health state assumed a lower estimate of associated utility than did the PF state. The manufacturer conducted a revised sensitivity analysis (based on the revised method to estimate the cost of trabectedin) which assumed that the utility for PF (in the BSC arm) was 0.653 for the first cycle and followed a linear decline over the next four cycles to reach the utility for PD (0.473). This manufacturer’s analysis was associated with an ICER of £61,064 per QALY gained.

3.19 The ERG also noted the following uncertainties in the cost-effectiveness estimates presented in the manufacturer’s submission:

  • It is unclear how the estimated ICER would relate to patients with types of soft tissue sarcoma other than L-sarcomas, because the STS-201 trial included only participants with L-sarcomas.
  • The comparability of the BSC and trabectedin arms is unclear. The ERG believed that participants in the STS-201 trial were highly selected and would probably be expected to have a high rate of survival at the time of inclusion.
  • The data based on historical sources were uncertain in themselves and natural history data may not be appropriate for patients who have contraindications for or are intolerant of ifosfamide and/or anthracyclines.
  • The ERG was unsure about the comparability of the utility values for patients with soft tissue sarcoma and those with lung cancer; noting that cost-effectiveness results were shown to be sensitive to changes in health-state utilities.

Full details of all the evidence are in the manufacturer’s submission and the ERG report, which are available from www.nice.org.uk/TAXXX

4 Consideration of the evidence

4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of trabectedin, having considered evidence on the nature of advanced soft tissue sarcoma and the value placed on the benefits of trabectedin by people with the condition, those who represent them, and clinical specialists. It also took into account the effective use of NHS resources.

Clinical effectiveness

4.2 The Committee considered the UK treatment pathway for patients with advanced soft tissue sarcoma and noted that trabectedin is licensed for patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. The Committee heard from the patient experts and clinical specialist that there have been no major changes in the treatment of advanced soft tissue sarcoma in the past 20 years and that treatment with trabectedin represents an option for those patients who would otherwise have no licensed treatment options. The Committee heard from the clinical specialist that trabectedin treatment would be managed by specialists in sarcoma units and would usually be administered in an outpatient setting, within existing care structures.

4.3 The Committee noted the clinical effectiveness evidence presented by the manufacturer from the pivotal STS-201 trial which compared two dose regimens for trabectedin and included no alternative treatment as a comparator. The Committee was aware that because soft tissue sarcoma is a rare condition the evidence base for the comparative effectiveness of trabectedin was limited. The Committee noted that trabectedin was granted a marketing authorisation from the European Medicines Agency (EMEA) under ‘exceptional circumstances’ based on evidence from a randomised, uncontrolled phase II trial of trabectedin in patients with L-sarcomas. The Committee also noted that there were three uncontrolled phase II trials that included patients with other types of sarcomas. The Committee heard from the clinical specialist that response to treatment varies according to sarcoma type, with some sarcomas being more sensitive to treatment with trabectedin. The Committee was aware that as part of the regulatory process for trabectedin the manufacturer is committed to exploring the subtypes of soft tissue sarcoma that may best respond to treatment.

4.4 The Committee then considered whether the evidence from the ‘historical’ trials suggested by the manufacturer was representative of BSC. Although the Committee was aware of the limitations of historical control data, it noted the ‘exceptional circumstances’ of the marketing authorisation regarding the difficulties of conducting adequately powered randomised controlled trials against BSC in this patient group and of exploring factors associated with response to treatment within a reasonable timeframe. The Committee also heard from the clinical specialist that the patients in the ‘historical’ trials of BSC had been recruited relatively recently, that the general management of these patients had not changed significantly and that the timeframe was comparable with the trabectedin trial. The Committee therefore concluded that the use of historical controls was appropriate for this disease area but nevertheless needed to be considered with caution.

4.5 The Committee noted that there were differences among the patient populations in the randomised trabectedin trial (STS-201) and the ‘historical’ trials of BSC, mainly with regard to previously received treatment, sarcoma type and ECOG performance status. The clinical specialist informed the Committee that the three other uncontrolled phase II trials of trabectedin had included patients who were similar to the patients in the ‘historical’ trials. The Committee therefore accepted that the results could be cautiously generalised to the wider population of patients with advance soft tissue sarcoma.

4.6 The Committee considered the clinical effectiveness data presented by the manufacturer, and noted the median overall survival for patients receiving the licensed dosage of trabectedin to be higher than that for patients receiving BSC. For progression-free survival, patients receiving the licensed dosage of trabectedin did better than those patients receiving an active regimen of BSC (see sections 3.4 and 3.9). The Committee noted that there was no evidence on the effectiveness of trabectedin for patients with contraindications for ifosfamide or anthracyclines. The Committee heard from the clinical specialist, however, that an inability to receive either ifosfamide or anthracyclines because of cardiac or liver impairment would not prevent a patient receiving trabectedin.

4.7 The Committee understood that most adverse effects associated with trabectedin were minor, reversible and non-cumulative. They heard from the clinical specialist and patient experts that there were fewer, less severe and less frequent adverse reactions associated with trabectedin than with the other chemotherapy agents used to treat soft tissue sarcoma. Based on the clinical effectiveness evidence and the testimony from the clinical specialist and patient experts, the Committee concluded that trabectedin is a clinically effective treatment for advanced soft tissue sarcoma in patients in whom both anthracyclines and ifosfamide have failed, or who are unsuited to receive these agents, allowing for reservations about the use of historical control trials.

Cost effectiveness

4.8 The Committee considered evidence on the cost effectiveness of trabectedin for the treatment of advanced soft tissue sarcoma. The Committee noted that the key factors driving the economic model were overall survival, the acquisition cost of the drug and the utility estimates. It heard from the ERG that the modelled overall survival estimates fitted the data well, and that given the limited evidence available, the methods used by the manufacturer appeared robust and appropriate. It heard that the administration costs of trabectedin did not greatly affect the outcome of the model.

4.9 The Committee discussed the utility estimates used in the model. It accepted the ERG’s comment that the model was inappropriate in its assignment of different utility values to the initial health state of patients depending on the treatment to be received (trabectedin or BSC). The Committee heard from the ERG that the revised scenario analysis presented by the manufacturer was more appropriate, in which the PD health state in the BSC arm was assigned an initial utility value identical to that of the PF health state which then declined linearly over the first four cycles of the model. The Committee agreed that this scenario represented the most plausible base-case estimation of the ICER. The Committee noted that the ICER of trabectedin compared with BSC was £61,000 per QALY gained for this scenario.

4.10 The Committee next considered the appropriateness of the use of utilities associated with non-small-cell lung cancer as proxies for those associated with advanced soft tissue sarcoma, given that no utility values exist for advanced soft tissue sarcoma. The Committee heard from the clinical specialist and patient experts that it is not uncommon for patients with advanced soft tissue sarcoma to maintain a quality of life relatively undiminished by the disease for some time, experiencing a rapid decline of quality of life in the final weeks of life, rather than experiencing continued gradual decline over an extended period of time. It heard from the clinical specialist that it may be reasonable to assume that for some proportion of time, patients with advanced soft tissue sarcoma may therefore experience a higher quality of life than patients with non-small-cell lung cancer at a comparable stage of disease. The Committee accepted that these differences could be associated with a different utility profile for patients with soft tissue sarcoma than for those with non-small-cell lung cancer. The Committee heard from the ERG that if the model was adjusted to reflect these possible differences in utility by extending the period of time over which the linear decline in utility happened, the ICER would be expected to decrease. Conversely, it heard that if these differences were instead modelled as a longer period of higher utility followed by rapid decline at the end of life, this could be expected to increase the ICER.

4.11 The Committee also heard from the clinical expert that modelling alternative chemotherapy as having no benefit at all in this clinical situation was implausible, and that 10% of patients might derive some benefit. Taking this and the points in section 4.10 together, the Committee concluded that the most plausible ICER for trabectedin compared with BSC remained at approximately £61,000 per QALY gained; but, in view of the weak evidence base, the Committee agreed that there remained considerable uncertainty around this estimate.

4.12 The Committee then considered the supplementary advice from NICE that should be taken into account when appraising treatments that may extend the life of patients with short life expectancy and that are licensed for indications that affect small numbers of people with incurable illnesses. For this advice to be applied, all the following criteria must be met:

  • The treatment is indicated for patients with a short life expectancy, normally less than 24 months.
  • There is sufficient evidence to indicate that the treatment offers an extension to life, normally of at least an additional 3 months, compared with current NHS treatment.
  • No alternative treatment with comparable benefits is available through the NHS.
  • The treatment is licensed or otherwise indicated for small patient populations.

In addition, when taking these criteria into account, the Committee must be persuaded that the estimates of the extension to life are robust and that the assumptions used in the reference case economic modelling are plausible, objective and robust.

4.13 The Committee discussed whether the benefit provided by trabectedin for the treatment of advanced soft tissue sarcoma fulfilled the criteria for consideration as a life-extending, end-of-life treatment. The Committee understood that the total number of people with advanced soft tissue sarcoma in England and Wales was approximately 500–600. Noting the limitations of analyses based on data from historical control trials, the Committee considered that life expectancy with BSC alone was likely to be approximately 6 months. The Committee considered the evidence from the trabectedin trial (STS-201) and noted the median overall survival for the licensed dosage was 13.9 months, although the Committee was not convinced that this value had not been overestimated. The Committee did, however, agree that trabectedin provided an improvement in the treatment of advanced soft tissue sarcoma and that it was likely that trabectedin would increase overall survival by more than 3 months. The Committee, despite its reservations about the weakness of the evidence base for the cost effectiveness of trabectedin, took the view that the parameter estimates informing its preferred ICER estimate were sufficiently robust enough to conclude that trabectedin meets the criteria for being a life-extending, end-of-life treatment.

4.14 The Committee then considered the most plausible ICER for trabectedin (£61,000 per QALY gained) in light of the end-of-life considerations. It considered that the magnitude of additional weight that would need to be assigned to the original QALY benefits in this patient group for the cost effectiveness of the drug to fall within the current threshold range would be too great. Therefore the Committee concluded that trabectedin as a treatment for people with advanced soft tissue sarcoma would not be a cost-effective use of NHS resources.

5 Implementation

5.1 The Secretary of State and the Welsh Assembly Minister for Health and Social Services have issued directions to the NHS on implementing NICE technology appraisal guidance. When a NICE technology appraisal recommends use of a drug or treatment, or other technology, the NHS must provide funding and resources for it within 3 months of the guidance being published. If the Department of Health issues a variation to the 3-month funding direction, details will be available on the NICE website. The NHS is not required to fund treatments that are not recommended by NICE.

5.2 NICE has developed tools to help organisations put this guidance into practice (listed below). These are available on our website (www.nice.org.uk/TAXXX). [NICE to amend list as needed at time of publication]

  • Slides highlighting key messages for local discussion.
  • Costing report and costing template to estimate the savings and costs associated with implementation.
  • Implementation advice on how to put the guidance into practice and national initiatives that support this locally.
  • A costing statement explaining the resource impact of this guidance.
  • Audit support for monitoring local practice.

6 Proposed recommendations for further research

6.1 The Committee recommends that a study estimating utilities using directly observed health-related quality of life values (such as EQ–5D scores) in people with soft tissue sarcoma is conducted.

7 Related NICE guidance

Published

  • Cancer Service Guidance Sarcoma: Improving outcomes in people with sarcoma. (2006). Available from www.nice.org.uk/CSGSarcoma

8 Proposed date for review of guidance

8.1 NICE proposes that the guidance on this technology is considered for review by the Guidance Executive in October 2012. NICE welcomes comment on this proposed date. The Guidance Executive will decide whether the technology should be reviewed based on information gathered by NICE, and in consultation with consultees and commentators.

David Barnett
Chair, Appraisal Committee
June 2009

Appendix A: Appraisal Committee members and NICE project team

A. Appraisal Committee members

The Appraisal Committee is one of NICE’s standing advisory committees. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets three times a month except in December, when there are no meetings. The Committee membership is split into three branches, each with a chair and vice chair. Each branch considers its own list of technologies, and ongoing topics are not moved between the branches.

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website.

Professor Keith Abrams
Professor of Medical Statistics, University of Leicester

Dr Ray Armstrong
Consultant Rheumatologist, Southampton General Hospital

Dr Jeff Aronson
Reader in Clinical Pharmacology, University Department of Primary Health Care, University of Oxford

Dr Darren Ashcroft
Reader in Medicines Usage and Safety, School of Pharmacy and Pharmaceutical Sciences, University of Manchester

Professor David Barnett (Chair)
Professor of Clinical Pharmacology, University of Leicester

Dr Peter Barry
Consultant in Paediatric Intensive Care, Leicester Royal Infirmary

Professor John Cairns
Professor of Public Health and Policy, London School of Hygiene and Tropical Medicine

Dr Mark Chakravarty
External Relations Director – Pharmaceuticals & Personal Health, Oral Care Europe

Dr Martin Duerden
Medical Director, Conwy Local Health Board

Ms Sally Gooch
Independent Nursing and Healthcare Consultant

Mrs Eleanor Grey
Lay member

Mr Sanjay Gupta
Former Service Manager in Stroke, Gastroenterology, Diabetes and Endocrinology, Basildon and Thurrock University Hospitals Foundation NHS Trust

Mr Terence Lewis
Lay member, Mental Health Consultant, National Institute for Mental Health in England

Professor Gary McVeigh
Professor of Cardiovascular Medicine, Queen’s University, Belfast

Dr John Pounsford
Consultant Physician, Frenchay Hospital, Bristol

Dr Stephen Saltissi
Consultant Cardiologist, Royal Liverpool University Hospital

Dr Lindsay Smith
General Practitioner, East Somerset Research Consortium

Mr Roderick Smith
Finance Director, West Kent Primary Care Trust

Mr Cliff Snelling
Lay member

Professor Ken Stein (Vice Chair)
Professor of Public Health, Peninsula Technology Assessment Group (PenTAG), University of Exeter

Professor Andrew Stevens
Professor of Public Health, Department of Public Health and Epidemiology, University of Birmingham

Dr Rod Taylor
Associate Professor in Health Services Research, Peninsula Medical School, Universities of Exeter and Plymouth

Ms Nathalie Verin
Health Economics Manager, Boston Scientific UK and Ireland

Dr Colin Watts
Consultant Neurosurgeon, Addenbrooke’s Hospital, Cambridge

Mr Tom Wilson
Director of Contracts and Information Management and Technology, Milton Keynes Primary Care Trust

 

B. NICE project team

Each technology appraisal is assigned to a team consisting of one or more health technology analysts (who act as technical leads for the appraisal), a technical adviser and a project manager.

Whitney Miller
Technical Lead

Joanna Richardson
Technical Adviser

Jeremy Powell
Project Manager

This page was last updated: 30 March 2010

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Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.