Mesothelioma - pemetrexed disodium: Appraisal consultation document


Appraisal Consultation Document

Pemetrexed disodium for the treatment of malignant pleural mesothelioma

The Department of Health and the National Assembly for Wales have asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct an appraisal of pemetrexed disodium for the treatment of malignant pleural mesothelioma and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of pemetrexed disodium for the treatment of malignant pleural mesothelioma.

This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website,

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.

The process the Institute will follow after the consultation period is summarised below. For further details, see the Guide to the Technology Appraisal Process (this document is available on the Institute's website,

  • The Appraisal Committee will meet again to consider the original evidence and this Appraisal Consultation Document in the light of the views of the formal consultees.
  • At that meeting, the Committee will also consider comments made on the document by people who are not formal consultees in the appraisal process.
  • After considering feedback from the consultation process, the Committee will prepare the Final Appraisal Determination (FAD) and submit it to the Institute.
  • Subject to any appeal by consultees, the FAD may be used as the basis for the Institute's guidance on the use of the appraised technology in the NHS in England and Wales.

The key dates for this appraisal are:
Closing date for comments: 26 April 2006
Second Appraisal Committee meeting: 10 May 2006

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.

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.


1 Appraisal Committee's preliminary recommendations
1.1 Pemetrexed disodium is recommended for the treatment of malignant pleural mesothelioma only as part of ongoing or new clinical trials that compare it with current best practice or other promising treatments.
1.2 Patients currently receiving pemetrexed disodium should have the option to continue therapy until they and their consultants consider it appropriate to stop.


2 Clinical need and practice
2.1 Malignant pleural mesothelioma (MPM) is a type of cancer that occurs in the pleura, the mesothelium (membranous lining) surrounding the lungs. MPM is a rapidly progressive malignancy of insidious onset. .
2.2 Approximately 90% of cases of MPM are linked to asbestos exposure. When asbestos fibres are inhaled or swallowed, they can cause scarring of the lung tissues, cancer of the bronchial tree (lung cancer) and sometimes cancers in the pleura and peritoneum. A wide range of occupations, notably shipbuilding, railway engineering and asbestos product manufacture, are associated with an increased risk of MPM. Family members of people whose work clothes were contaminated with asbestos fibres have also developed MPM. The condition is significantly more common in men, with a male:female ratio of 5:1. Age at presentation is usually between 60 and 79 years
2.3 MPM usually develops 20–50 years after exposure to asbestos. Data from 2004 suggest that about 1700 people in the UK are diagnosed with MPM each year. It is estimated that the number of people diagnosed with MPM in the UK will increase to a peak of more than 2000 cases each year between 2011 and 2015, reflecting a lag from the highest use of asbestos in the 1970s. An estimated 65,000 cases are expected to occur between 2002 and 2050. The use of asbestos was banned in the UK in 1999.
2.4 Most patients present with chest pain and dyspnoea and have pleural effusions evident on examination. Fatigue, profuse sweating, weight loss, anorexia and difficulty in swallowing become common as the disease progresses. Presentation and diagnosis often occur at an advanced stage and the prognosis for most patients is extremely poor. Median survival from diagnosis varies in studies, with a range of 9–13 months. Age, tumour histology, tumour stage at diagnosis and performance status have been shown to be independent prognostic factors.
2.5 Staging provides prognostic information and can help to determine an appropriate treatment strategy. However, staging is complex and surgical intervention is required to practice it fully. There is no universally accepted staging system, but the traditional Butchart staging system is gradually being replaced with a tumour nodes metastases (TNM) system developed by the International Mesothelioma Interest Group.
2.6 There is no standard treatment pathway for MPM in the UK. The clinical management of MPM is multimodal and a patient may receive a combination of treatments. Extrapleural pneumonectomy is an option for the small proportion of patients (1–5%) whose tumours are at stage 1 or 2.
2.7 For the majority of patients (for whom surgery is not indicated) treatment is aimed at improving symptoms and maintaining quality of life for as long as possible and often does not involve treating the tumour with chemotherapy. Treatment that does not include a specific anti-cancer therapy is referred to as active symptom control (ASC) or best supportive care (BSC). For people with MPM, this may include interventions to manage pain and dyspnoea and to address psychosocial problems. Treatments may include draining excess fluid from the pleural cavity and applying a talc pleurodesis (the insertion of talc to prevent further fluid accumulation), palliative radiotherapy, analgesics, steroids, appetite stimulants and bronchodilators.
2.8 There is no standard chemotherapy treatment for MPM. Pemetrexed in combination with cisplatin is the only chemotherapy regimen that is currently licensed for this indication. However, a variety of single-agent and combination regimens, such as the mitomycin C, vinblastine and cisplatin combination (MVP) or vinorelbine, are used. To date there have been no reported randomised controlled trials (RCTs) comparing survival and symptom control in patients receiving chemotherapy with those receiving ASC/BSC. It is therefore uncertain whether chemothe
3 The technologies
3.1 Pemetrexed disodium (Eli Lilly and Company Limited) is licensed, in combination with cisplatin, for the treatment of chemotherapy-naive patients with unresectable malignant pleural mesothelioma. The licensed dose is 500mg/m2 body surface area, to be administered as a 10-minute intravenous infusion on the first day of a 21-day cycle. It is followed approximately 30 minutes later by cisplatin (recommended dose 75 mg/m2 body surface area) infused over 2 hours. In order to reduce toxicity, patients treated with pemetrexed must receive folic acid and vitamin B12 supplementation. To reduce the incidence and severity of skin reactions, patients are pre-medicated with a corticosteroid.
3.2 Pemetrexed disodium is a multi-targeted folate antagonist that inhibits DNA replication. Cisplatin is a platinum-based chemotherapeutic agent that has antitumour activity, either as a single agent or in combination, for a number of different cancers.
3.3 Adverse effects commonly associated with pemetrexed include nausea, vomiting, fatigue and neutropenia. Skin rash, mucositis and liver function abnormalities have also been reported. Cisplatin causes nausea and vomiting in the majority of patients. This is controllable in 50–80% of patients by anti-emetic drugs. Serious toxic effects of cisplatin on the kidneys, bone marrow and ears are common, and serum electrolyte disturbances, hyperuricaemia, allergic reactions and cardiac abnormalities have also been reported. For full details of side effects and contraindications, see the Summary of Product Characteristics.
3.4 Pemetrexed disodium costs £800 for a 500 mg vial (excluding VAT, ’British National Formulary’ (BNF) 50th edition). The cost per patient, assuming an average of five treatment cycles and a body surface area of 2 m2, is approximately £8000. Costs may vary in different settings because of negotiated procurement discounts.


4 Evidence and interpretation

The Appraisal Committee considered evidence from a number of sources (see appendix B).

4.1. Clinical effectiveness

A single RCT of pemetrexed was identified. The EMPHACIS study compared pemetrexed plus cisplatin with cisplatin alone. This was a single-blind, international multicentre trial in 448 patients. To be eligible, patients were required to have a minimum life expectancy of 12 weeks, uni- or bi-dimensionally measurable disease, a Karnofsky performance status of greater than or equal to 70, and to be 18 years or older. Patients who had had prior chemotherapy, those with a second primary malignancy or brain metastases, and patients unable to interrupt non-steroidal anti-inflammatory drugs, were excluded.


Patients in the intervention arm (n = 226) received pemetrexed at a dose of 500mg/m2 followed 30 minutes later by cisplatin at a dose of 75 mg/m2. Patients in the control arm (n = 222) received normal saline followed 30 minutes later by cisplatin at a dose of 75 mg/m2. In both arms, treatment was administered on the first day of each 21-day cycle. The median number of cycles given was 6 (range 1–12) in the pemetrexed plus cisplatin arm and 4 (range 1–9) in the cisplatin arm. Median length of follow-up was 10 months.

4.1.3 During the early stages of the trial, a high incidence of severe toxicity (including drug-related death, neutropenia, febrile neutropenia and diarrhoea) occurred in the combination arm. Therefore, folic acid and vitamin B12 supplementation were added to the trial protocol, in both treatment arms to preserve blinding. With effect from the date of the protocol change, all patients received supplementation, resulting in three patient subgroups defined by supplementation status: never supplemented (n = 70), partially supplemented (n = 47) and fully supplemented (n = 331). The primary analysis was performed on all patients who were randomised and treated (intention to treat [ITT] population). A subgroup analysis was performed on fully supplemented patients. Further (apparently post-hoc) subgroup analyses were performed on fully supplemented patients with advanced disease (stage 3/4) as it was thought that most patients presenting to clinicians would fall into this category.
4.1.4 The primary endpoint of the EMPHACIS trial was survival. A statistically significant survival benefit was observed in patients randomised to pemetrexed plus cisplatin versus those receiving cisplatin alone. In the ITT population, median survival was 12.1 months (95% confidence interval [CI], 10.0 to 14.4) in the pemetrexed plus cisplatin arm versus 9.3 months (95% CI, 7.8 to 10.7) in the cisplatin arm (hazard ratio [HR] 0.77; 95% CI, 0.61 to 0.96; log-rank p value 0.02). In fully supplemented patients, median survival was 13.3 months (95% CI, 11.4 to 14.9) in the combination arm versus 10 months (95% CI, 8.4 to 11.9) in the cisplatin arm (HR 0.75; 95% CI, 0.57 to 1.00; log-rank p value 0.051). In fully supplemented patients with advanced disease, median survival was 13.2 months (95% CI, 9.3 to 14.9) in the combination arm versus 8.4 months (95% CI, 6.8 to 10.2) in the cisplatin arm (HR 0.63; 95% CI, 0.46 to 0.86; log-rank p value 0.003).

Secondary endpoints included 1-year survival, time to progressive disease and tumour response rate. Pemetrexed plus cisplatin demonstrated statistically significant benefits versus cisplatin alone for all of these outcomes. This was the case in all subgroups.


Quality of life was evaluated using the Lung Cancer Symptom Scale–Meso instrument. Several aspects of quality of life were evaluated, including pain, dyspnoea, fatigue, anorexia and cough. At 18 weeks, patients treated with pemetrexed plus cisplatin demonstrated statistically significant symptomatic improvements when compared with those who received cisplatin alone. This was the case in both the ITT and fully supplemented populations.

4.1.7 Grade 3/4 adverse events were statistically significantly more frequent in patients receiving pemetrexed plus cisplatin than in those receiving cisplatin alone. The most commonly reported grade 3/4 toxicities in patients receiving pemetrexed plus cisplatin were: neutropenia (27.9%), leukopenia (17.7%), nausea (14.6%) and vomiting (13.3%). Supplementation with folic acid and vitamin B 12 resulted in a consistent partial reduction in the severity and incidence of toxicities (except for dehydration) in the pemetrexed plus cisplatin arm. The most common severe adverse events in fully supplemented patients randomised to pemetrexed plus cisplatin were: neutropenia (23.2%), leukopenia (14.9%), nausea (11.9%) and vomiting (10.7%).
  Summary of the evidence on clinical effectiveness
4.1.8 The results of the EMPHACIS trial suggest that pemetrexed plus cisplatin confers a survival benefit of approximately 3 months, compared with cisplatin alone. The combination treatment also appears to demonstrate advantages in terms of 1-year survival, time to progressive disease, tumour response rate and quality of life. Pemetrexed plus cisplatin appears to offer a greater benefit (versus cisplatin) in patients with advanced disease.

4.2 Cost effectiveness
4.2.1 Estimates of cost effectiveness were provided by the manufacturer and by the Assessment Group. A review of the published literature identified a single cost-effectiveness study. This was a conference presentation/abstract that was a forerunner of the manufacturer’s submission.

4.2.2 Two cost-effectiveness models were submitted by the manufacturer. Model 1 compared pemetrexed plus cisplatin with cisplatin alone. Model 2 compared pemetrexed plus cisplatin with what the manufacturer considered to be standard care. Both models had a 29-month time horizon (reflecting the trial follow-up period) and took a health service perspective. Both considered outcomes in terms of life years gained (LYGs) and quality adjusted life years (QALYs). No discounting was applied to costs, as they were all incurred within 1 year. Outcomes were discounted at 3.5%.

4.2.3 Model 1 was based on individual patient data from the EMPHACIS trial. The model considered four subgroups: fully supplemented patients; fully supplemented patients with advanced disease; fully supplemented patients with good performance status; and fully supplemented patients with advanced disease and good performance status. Resource use was taken from the trial and unit costs from Department of Health reference costs or official drug price lists (BNF, MIMS 2005). Mean survival was estimated from the trial data using Kaplan-Meier curves. Utility scores were taken from an ongoing observational study in patients with non-small cell lung cancer who completed the EQ-5D health-related quality of life questionnaire before chemotherapy. The utility scores were similar for both arms: 0.68 for the pemetrexed plus cisplatin arm and 0.69 for the cisplatin arm. A range of one-way and two-way sensitivity analyses was performed.
4.2.4 The incremental cost-effectiveness ratio (ICER) was £68,598 per QALY in the fully supplemented population. The ICER was more favourable in fully supplemented patients with advanced disease (£53,314), fully supplemented patients with good performance status (£48,099), and fully supplemented patients with advanced disease and good performance status (£47,567).
4.2.5 Model 2 indirectly compared pemetrexed plus cisplatin with MVP, vinorelbine (with or without platinum) and ASC/BSC. Costs and outcomes for pemetrexed plus cisplatin were taken from the fully supplemented population in model 1. For the comparators, resource use data were gathered from market research surveys of oncologists, commissioned by the manufacturer. Zero cost was assumed for ASC/BSC, because it was reasoned that participants in chemotherapy trials would have received a similar level of ASC/BSC to patients receiving ASC/BSC alone. Median survival estimates were taken from a review of the published literature. Mean values for use in the cost-effectiveness analysis were derived by calculating a weighted average of reported medians and assuming the same mean:median ratio as that observed in the cisplatin arm of the EMPHACIS trial. The same utility values were used as in model 1, with the utility for cisplatin (0.69) being applied to all comparators in model 2. A range of one-way and two-way sensitivity analyses was performed.
4.2.6 The incremental cost per QALY for pemetrexed plus cisplatin was £21,731 versus MVP, £28,391 versus vinorelbine with or without platinum and £32,066 versus ASC/BSC.
4.2.7 When the Assessment Group corrected the survival estimate for MVP for performance status, an ICER of £47,972 was obtained for pemetrexed plus cisplatin versus MVP. The Assessment Group also noted that an increase in survival of about 1% for vinorelbine would result in an ICER in excess of £30,000 for pemetrexed plus cisplatin versus vinorelbine. Using more favourable survival estimates and taking the number of cycles of chemotherapy from the literature rather than the manufacturer’s market research survey, the ICERs versus MVP and vinorelbine were both above £60,000. Using survival estimates for ASC taken from a meta-analysis designed to consider prognostic factors in MPM resulted in an ICER of £48,779 for pemetrexed plus cisplatin versus ASC/BSC.
4.2.8 The Assessment Group carried out its own economic analysis of pemetrexed plus cisplatin compared with cisplatin alone. The four subgroups considered in the manufacturer’s model 1 were analysed. Mean costs were derived from the individual patient data in model 1. Costs were not discounted. To derive mean effectiveness estimates, Weibull distributions were fitted to the Kaplan‑Meier survival curves from the EMPHACIS trial, in order to model the survival distribution of patients at the end of the follow-up period. Mean survival was estimated using the weighted least squares method and a discount rate of 3.5% was applied. In both arms, the Assessment Group used mean utility values of 0.51–0.54 for each subgroup. These values were calculated based on an initial utility of 0.65, falling to 0.40 during a 100-day terminal period. A probabilistic sensitivity analysis was carried out.
4.2.9 The Assessment Group’s analysis resulted in an ICER of £60,561 per QALY in the fully supplemented population. The results were more favourable in fully supplemented patients with advanced disease (£49,051), fully supplemented patients with good performance status (£50,357) and fully supplemented patients with advanced disease and good performance status (£37,664). The probability that pemetrexed plus cisplatin is cost effective at a maximum acceptable ICER of £30,000 per QALY was less than 20% for all subgroups.
  Summary of the evidence on cost effectiveness
4.2.10 The economic analyses carried out by the manufacturer and the Assessment Group both indicate a cost per QALY of greater than £60,000 when pemetrexed plus cisplatin is compared with cisplatin alone in the fully supplemented population. Pemetrexed plus cisplatin appears to be more cost effective in patients with advanced disease and/or good performance status but the cost per QALY versus cisplatin remains above £30,000 in all subgroups. An indirect comparison submitted by the manufacturer indicates more favourable cost effectiveness of pemetrexed plus cisplatin versus MVP, vinorelbine and ASC/BSC. However, the assumptions underpinning this model are subject to high levels of uncertainty. When the assumptions were modified to reflect performance status, adjusted survival, and resource use based on published data, the ICERs were in line with those of pemetrexed plus cisplatin versus cisplatin alone.
4.3 Consideration of the evidence
4.3.1 The Committee reviewed the data available on the clinical and cost effectiveness of pemetrexed disodium for the treatment of MPM, having considered evidence on the nature of the condition and the value placed on the benefits of pemetrexed disodium by patient representatives and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.
4.3.2 The Committee heard from the experts that pemetrexed plus cisplatin is valued as a potential treatment option in a disease area where it has demonstrated survival and quality of life advantages in a RCT and where there is incomplete evidence on the efficacy of alternative treatments.
4.3.3 The Committee discussed the relevance of cisplatin as a comparator for pemetrexed plus cisplatin in terms of clinical and cost effectiveness. Clinical experts advised that cisplatin would not normally be used to treat MPM in clinical practice in England and Wales due to a lack of evidence for its effectiveness and its relatively unfavourable adverse-effect profile. The Committee heard that there is no standard care pathway for MPM. Although some patients receive chemotherapy treatment, notably with MVP and vinorelbine, many patients receive ASC/BSC only. However, the Committee was also aware that there had been no RCTs of MVP or vinorelbine in MPM, either versus ASC/BSC or against each other. The Committee noted that an ongoing trial of chemotherapy (MVP and vinorelbine) versus ASC/BSC (the MSO1 trial) is shortly due to achieve its target recruitment and that publication of results is anticipated in 2007. The Committee observed that pemetrexed was not included as a comparator in this study and heard that the manufacturer had not sanctioned its use. The Committee agreed that this was unfortunate, because a direct comparison of the efficacy of pemetrexed versus other chemotherapy treatments and ASC/BSC would be a critical addition to the evidence base.
4.3.4 The Committee discussed what inferences could be made when the comparative evidence was limited to pemetrexed and cisplatin. The Committee concluded that the survival benefit demonstrated by pemetrexed plus cisplatin in the EMPHACIS trial was likely to be robust because cisplatin was likely to be at least as effective as placebo or ASC/BSC. However, in terms of quality of life, the Committee thought that cisplatin could not be considered to be equivalent to placebo or ASC/BSC as it is likely to have adverse effects that may be detrimental to health-related quality of life. The Committee also noted that cisplatin was likely to have higher costs than placebo or ASC/BSC and that this would affect the results of cost-effectiveness analysis.
4.3.5 Notwithstanding its reservations regarding the appropriateness of cisplatin as a comparator in terms of cost effectiveness, the Committee discussed the estimates of the cost effectiveness of pemetrexed plus cisplatin versus cisplatin produced by the manufacturer and the Assessment Group. The Committee observed that these were above conventional cost-effectiveness thresholds for all subgroups. The Committee noted that the cost effectiveness was most favourable in a subgroup of patients who had both advanced disease and good performance status, but that even in these patients the ICER was in excess of £30,000 per QALY.
4.3.6 The Committee discussed whether pemetrexed should be recommended over other treatments for MPM and considered the indirect comparisons submitted by the manufacturer. It discussed the plausibility of the result that pemetrexed plus cisplatin was more cost effective when compared with MVP, vinorelbine and ASC/BSC than when it was compared with cisplatin alone. The Committee noted the high degree of uncertainty surrounding the assumptions underpinning the model and observed that the survival estimates had been taken from relatively small, non-randomised phase II and observational studies. It also noted that the study populations were unlikely to be comparable, particularly in terms of performance status, a key independent determinant of survival. The Committee also noted that resource use estimates for MVP and vinorelbine (based on the number of cycles of chemotherapy derived from the manufacturer’s market research surveys) were higher than those reported in the studies from which the effectiveness estimates were taken, and considered the possibility that comparator costs may have been overestimated. The Committee saw that when the model assumptions were amended to incorporate more favourable survival estimates and resource use taken from the literature, incremental cost-effectiveness ratios were significantly higher. On balance, the Committee concluded that pemetrexed plus cisplatin was very unlikely to be cost effective when compared with MVP, vinorelbine or ASC/BSC.
4.3.7 The Committee discussed the possibility of making subgroup recommendations for patients with both advanced disease and good performance status, as this group had demonstrated the most favourable cost effectiveness versus cisplatin alone. However, having heard from the experts that patients are not routinely staged in clinical practice due to the complexity and invasiveness of this procedure, the Committee concluded that a recommendation based on stage was likely to be unworkable in practice. The Committee discussed whether a subgroup recommendation could be made based on good performance status alone, as this was more easily measurable in clinical practice. The Committee concluded, however, that the evidence from the economic analyses did not support such a recommendation.
4.3.8 The Committee noted that MPM is a rare and aggressive malignancy caused by occupational exposure and for which limited treatment options are available. However, the Committee thought that there was insufficient evidence to demonstrate that pemetrexed plus cisplatin was superior to other, far less costly treatment regimens. The Committee recalled that the results of the MS01 trial, which compares ASC/BSC against MVP and vinorelbine, were likely to be published in 2007 and agreed that this would be extremely important in determining the effectiveness of these chemotherapy regimens. The Committee also suggested that studies comparing pemetrexed plus cisplatin against MVP and vinorelbine should be conducted to clarify their relative efficacies.


5 Proposed recommendations for further research

The MS01 study of ASC/BSC with and without chemotherapy (MVP or vinorelbine) in MPM is due to complete recruitment in early 2006 and results are anticipated in 2007.

5.2 The Committee identified a need for RCTs comparing alternative chemotherapy regimens in MPM. Specifically, the Committee recommended that trials be conducted in which pemetrexed is compared with current standard care (notably MVP and vinorelbine) in order to determine its effectiveness relative to treatments that are commonly used in clinical practice in England and Wales. The Committee also recommended that comparative trials of pemetrexed versus other promising treatments be conducted



Preliminary views on the resource impact for the NHS


The NICE Costing Unit is currently developing this section. A costing template and report will be available at the time of publication of the final guidance.

7 Proposals for implementation and audit

This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in section 1..


NHS organisations and clinicians caring for people who have malignant pleural mesothelioma should review their current practice and policies to take account of the guidance set out in section 1.


Pemetrexed disodium is used for the treatment of malignant pleural mesothelioma only as part of ongoing or new clinical trials that compare it with current best practice or other promising treatments.

7.3 Patients who are currently receiving pemetrexed disodium have the option to continue therapy until they or their consultants consider it appropriate to stop
8 Related guidance

There is no related guidance for this technology.



9 Proposed date for review of guidance

The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators.

9.2 It is proposed that the guidance on this technology is considered for review in May 2008. The Institute would particularly welcome comment on this proposed date.


Andrew Stevens

Chair, Appraisal Committee

March 2006


Appendix A. Appraisal Committee members

The Appraisal Committee is a standing advisory committee of the Institute. 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 regularly and membership is split into two branches, with the chair, vice-chair and a number of other members attending meetings of both branches. 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.


Dr Darren Ashcroft
Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical Sciences, University of Manchester

Professor David Barnett
Professor of Clinical Pharmacology, University of Leicester
Dr Peter Barry
Consultant in Paediatric Intensive Care, Leicester Royal Infirmary

Mr Brian Buckley
Vice Chairman, InContact
Professor John Cairns
Public Health and Policy, London School of Hygiene and Tropical Medicine
Professor Mike Campbell
Statistician, University of Sheffield
Professor David Chadwick
Professor of Neurology, Walton Centre for Neurology and Neurosurgery
Dr Mark Chakravarty
Head of Government Affairs and NHS Policy, Procter and Gamble Pharmaceuticals ( UK) Ltd
Dr Peter I Clark
Honorary Chairman, Association of Cancer Physicians
Dr Mike Davies
Consultant Physician, University Department of Medicine & Metabolism, Manchester Royal Infirmary
Mr Richard Devereaux-Phillips
Public Affairs Manager, Medtronic Ltd
Professor Jack Dowie
Health Economist, London School of Hygiene
Dr Fergus Gleeson
Consultant Radiologist, The Churchill Hospital, Oxford
Ms Sally Gooch
Former Director of Nursing & Workforce Development, Mid Essex Hospital Services NHS Trust
Mr Sanjay Gupta
Stroke Services Manager, Basildon and Thurrock University Hospitals NHS Trust
Professor Philip Home
Professor of Diabetes Medicine, University of Newcastle upon Tyne
Dr Peter Jackson
Clinical Pharmacologist, University of Sheffield
Professor Peter Jones
Professor of Statistics & Dean Faculty of Natural Sciences, Keele University
Dr Mike Laker
Medical Director, Newcastle Hospitals NHS Trust
Dr George Levvy
Lay representative
Ms Rachel Lewis
Nurse Advisor to the Department of Health
Mr Terence Lewis
Mental Health Consultant, National Institute for Mental Health in England
Professor Jonathan Michaels
Professor of Vascular Surgery, University of Sheffield
Dr Neil Milner
General Medical Practitioner, Sheffield
Dr Ruairidh Milne
Senior Lecturer in Health Technology Assessment, National Coordinating Centre for Health Technology
Dr Rubin Minhas
General Practitioner, Primary Care Cardiovascular Society
Mr Miles Scott
Chief Executive, Bradford Teaching Hospitals NHS Foundation Trust
Dr Lindsay Smith
General Practitioner, East Somerset Research Consortium
Dr Ken Stein
Senior Lecturer, Peninsula Technology Assessment Group (PenTAG), University of  Exeter
Professor Andrew Stevens (Chair)
Professor of Public Health, University of Birmingham


NICE Project Team

Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute.

Kate Burslem
Technical Lead, NICE project team
Janet Robertson
Technical Advisor, NICE project team

Emily Marschke
Project Manager, NICE project team


Appendix B. Sources of evidence considered by the Committee

The assessment report for this appraisal was prepared by The Liverpool Reviews and Implementation Group (LRiG), Department of Pharmacology and Therapeutics, University of Liverpool:

Dundar Y, Bagust A, Dickson R, Dodd S, Green J, Haycox A, Hill R, McLeod C, Walley T. Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation, December 2005.


The following organisations accepted the invitation to participate in this appraisal. They w ere invited to make submissions and comment on the draft scope and assessment report. They are also invited to comment on the Appraisal Consultation Document and consultee organisations are provided with the opportunity to appeal against the Final Appraisal Determination.

I Manufacturers/sponsors:

  • Eli Lilly and Company Ltd (pemetrexed disodium)

II Professional/specialist and patient/carer groups:

  • Association of Cancer Physicians
  • Association for Palliative Medicine of Great Britain
  • British Mesothelioma Interest Group (BMIG)
  • British Oncology Pharmacy Association
  • British Psychosocial Oncology Society
  • British Thoracic Society (Lung Cancer and Mesothelioma Working Party)
  • Cancer Research UK
  • National Lung Cancer Forum for Nurses
  • Royal College of Nursing
  • Royal College of Physicians of Edinburgh
  • Royal College of Physicians’ Intercollegiate Lung Cancer Group
  • Royal College of Physicians’ Medical Oncology Joint Special Committee
  • Royal College of Radiologists
  • Royal College of Surgeons
  • Royal Pharmaceutical Society
  • Society of Radiographers
  • Asbestos Awareness Wales/UK
  • Asbestos Diseases UK
  • Cancer BACUP
  • Cancer Voices
  • June Hancock Mesothelioma Research Fund
  • Long Term Medical Conditions Alliance
  • Macmillan Cancer Relief
  • National Cancer Alliance
  • National Council for Palliative Care
  • Occupational and Environmental Diseases Association
  • Ridings Asbestos Support and Awareness Group (RASAG)
  • Roy Castle Lung Cancer Foundation
  • Tenovus Cancer Information Centre Department of Health
  • Hartlepool PCT
  • North Birmingham PCT
  • Welsh Assembly Government

III Commentator organisations (without the right of appeal):

  • Mayne Pharma plc (cisplatin)
  • Bristol-Myers Squibb Pharmaceuticals Ltd (cisplatin)
  • Approved Prescription Services Ltd (cisplatin)
  • British National Formulary
  • GMB Union
  • Transport & General Workers Union
  • Medicines and Healthcare products Regulatory Agency (MHRA)
  • National Public Health Service for Wales
  • NHS Confederation
  • NHS Purchasing and Supplies Agency
  • NHS Quality Improvement Scotland
  • Liverpool Reviews and Implementation Group
  • National Coordinating Centre for Health Technology Assessment
  • National Collaborating Centre for Cancer
  • British Thoracic Oncology Group
  • MRC Clinical Trials Unit
  • National Cancer Research Institute

The following individuals were selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups. They participated in the Appraisal Committee discussions and provided evidence to inform the Appraisal Committee’s deliberations. They gave their expert personal view on pemetrexed disodium for malignant pleural mesothelioma by attending the initial Committee discussion and/or providing written evidence to the Committee. They are invited to comment on the Appraisal Consultation Document.

  • Dr Mary O’Brien, Consultant Medical Oncologist, Institute of Cancer Research – clinical expert nominated by the Institute of Cancer Research.
  • Dr Robin Rudd, Consultant Physician, British Thoracic Society – clinical expert nominated by the British Thoracic Society.
  • Ms Liz Darlison, Consultant Nurse, Mesothelioma UK – patient expert nominated by June Hancock Mesothelioma Research Fund.


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