The Department of Health and the Welsh Assembly Government have asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct an appraisal of cinacalcet hydrochloride for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy 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 cinacalcet hydrochloride.

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, www.nice.org.uk).

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, www.nice.org.uk).

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: 13 July 2006
Second Appraisal Committee meeting: 25 July 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.

Appraisal Committee's preliminary recommendations

Cinacalcet hydrochloride is not recommended for the routine treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy.

Clinical need and practice

The parathyroid glands produce parathyroid hormone (PTH), which controls the levels of calcium in the blood. Excessive production of this hormone is called hyperparathyroidism. When this is caused by another condition, it is called secondary hyperparathyroidism. Secondary hyperparathyroidism is a common complication of impaired renal function. Almost all people with end-stage renal disease (ESRD) have secondary hyperparathyroidism. Two UK studies have estimated the annual incidence of ESRD to be 132 and 148 per million population. A high proportion of people with ESRD receive dialysis; it is estimated that approximately 100 people per million population begin dialysis each year.

The development of secondary hyperparathyroidism in people with impaired renal function is complicated. It occurs as a result of failure of the excretory function of the kidney (impaired excretion of phosphate and impaired reabsorption of calcium) and of the endocrine function of the kidney (reduced hydroxylation of inactive forms of vitamin D to the active form, calcitriol). In the early stages of renal impairment, phosphate excretion is reduced. Initially, this does not lead to high levels of phosphate in the blood (hyperphosphataemia) because increased secretion of PTH stimulates the kidneys to excrete more phosphate. When renal impairment progresses to the moderate stage, the kidneys can no longer eliminate more phosphate in response to increased PTH secretion and phosphate levels begin to rise. Hyperphosphataemia suppresses the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol. Low levels of calcitriol lead to reduced intestinal absorption of calcium, leading in turn to hypocalcaemia. Hypocalcaemia, low calcitriol levels and hyperphosphataemia all independently stimulate PTH synthesis and secretion. As these chronic stimuli persist, the parathyroid glands become enlarged and begin to function autonomously, continuing to secrete PTH even if hypocalcaemia is corrected. PTH levels become extremely elevated and this causes further quantities of calcium and phosphate to be released from bone. Hyperphosphataemia is exacerbated and hypercalcaemia may occur. When the parathyroid no longer adequately responds to calcium levels, the condition is referred to as ‘tertiary’ or ‘refractory’ hyperparathyroidism. At this advanced stage, the hyperparathyroidism is refractory to medical treatment.

Secondary hyperparathyroidism is associated with clinical complications involving the bones and other tissues. Bone disease (renal osteodystrophy) is present in about 70% of people starting dialysis. It is a multifactorial disease but secondary hyperparathyroidism is an important contributor to its development. Renal osteodystrophy manifests as bone pain, bone deformity and pathological fracture and is a major cause of disability in people with ESRD. A study conducted in the USA including 40,538 people on haemodialysis found that serum phosphorous concentration was statistically significantly related to hospitalisation for fracture. Time on dialysis was also strongly associated with hospitalisation for fracture.

People with kidney disease have a much higher risk of cardiovascular disease and associated mortality than the general population. This is a result of multiple factors, but derangements in calcium and phosphate homoeostasis appear to contribute. Hyperphosphataemia and elevated calcium phosphorus product (the multiple of the serum levels of calcium and phosphorus) are associated with cardiovascular calcification, including the aorta, carotid and coronary arteries, the cardiac valves, and myocardial muscle.

Calcification can also be seen in other soft tissues including the lung, the conjunctiva, periarticular tissues, and the breast. Calciphylaxis (calcific uraemic arteriolopathy) is a rare but serious complication that can occur in people with ESRD. It appears as painful, red cutaneous nodules (singular or numerous) that can often progress rapidly to ulceration, necrosis and sepsis. On biopsy, arteriolar calcification of the subcutaneous fat and dermis is seen. Mortality is high; rates of between 45% and 65% have been reported in people with this complication.

The aim of treatment in secondary hyperparathyroidism is to re-establish normal levels of phosphate, PTH and calcium. Conventional therapy includes dietary modification to reduce phosphate intake, the use of phosphate binders, hydroxylated vitamin D sterols (calcitriol, alfacalcidol) or the synthetic vitamin D analogue paricalcitol, and modification of the dialysis regimen. In severe hyperparathyroidism, total or partial surgical removal of the parathyroid glands may be required.

Reducing phosphate in the diet is difficult to achieve while maintaining adequate nutritional intake, because many sources of protein are also high in phosphate. Phosphate binders can be taken with meals to reduce phosphate absorption from the gut. In the past, aluminium hydroxide was commonly used as a phosphate binder, but concern about aluminium toxicity in people receiving dialysis means that it is no longer widely used for this purpose. Calcium acetate and calcium carbonate are the most commonly used phosphate binders, but calcium salts are contraindicated in hypercalcaemia. Sevelamer is a non-calcium containing phosphate-binding agent.

Vitamin D compounds that do not require renal hydroxylation for activation have been used in the treatment of secondary hyperparathyroidism in ESRD. However, doses that are capable of suppressing PTH secretion may lead to hypercalcaemia and a decline in renal function. By increasing intestinal absorption of calcium and phosphate, the risk of vascular calcification may be increased.

Improved phosphate clearance can be achieved by intensifying the dialysis regimen. The most usual haemodialysis prescription is for 4 hours three times per week. Slow prolonged dialysis (over 8 hours or more at night) or more frequent (daily) dialysis improves phosphate loss. Limitations on the availability of dialysis facilities mean that this option may be feasible only for some patients on home dialysis.

Surgical parathyroidectomy can be subtotal, total, or total with some parathyroid tissue reimplanted in a site such as the arm. Perioperative risk is greater in people with renal failure than in people with normal renal function, and there is the additional risk that any remaining parathyroid tissue will become hyperplastic and require repeat surgery.

The technology

Cinacalcet hydrochloride (Amgen) is a calcimimetic agent, that is, it increases the sensitivity of the calcium-sensing receptor to extracellular calcium ions, thereby inhibiting the release of PTH. It is licensed for treatment of secondary hyperparathyroidism in patients with ESRD on maintenance dialysis therapy. It may be used as part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate. It is initiated at a dose of 30 mg once daily, titrated every 2–4 weeks against intact or biointact PTH levels to a maximum of 180 mg once daily.

Because cinacalcet hydrochloride lowers calcium levels, it is contraindicated when serum calcium is below the lower limit of the normal range. The most commonly reported adverse effects in clinical trials were nausea and vomiting. These were mild to moderate in nature and transient in most cases. For full details of side effects and contraindications, see the summary of product characteristics.

The drug costs of treatment with cinacalcet hydrochloride are between £1646 and £9110 per year depending on the dose administered (excluding VAT ‘British national formulary’ edition 51). Costs may vary in different settings because of negotiated procurement discounts.

Evidence and interpretation

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

Clinical effectiveness

The systematic review carried out by the Assessment Group (see appendix B) identified seven published reports of randomised controlled trials (RCTs) of cinacalcet hydrochloride versus standard care in people with hyperparathyroidism secondary to ESRD who were receiving dialysis. Most of these publications reported on one or more of four RCTs sponsored by the manufacturer of cinacalcet hydrochloride, although three smaller RCTs were also identified. In addition, the manufacturer submitted information on an unpublished study relating to an RCT designed to evaluate optimal levels of concomitant vitamin D and phosphate binders in patients receiving standard care with or without cinacalcet hydrochloride. All studies were designed to assess biochemical endpoints (namely changes in serum PTH, calcium, phosphate and calcium phosphorus product [Ca x P]). One small study (n = 14) also reported on bone mineral density. Seven of the RCTs had a duration of 26 weeks or less, with dose titration phases of between 12 and 16 weeks and efficacy assessment phases of between 6 and 14 weeks). The remaining study was 52 weeks long (a 24-week dose titration period followed by a 28-week efficacy assessment).

Improvements in mean levels of PTH, calcium, phosphate and Ca x P observed in the trials were statistically significantly greater in the cinacalcet hydrochloride groups in most of the studies that reported these endpoints. Generally, patients receiving cinacalcet hydrochloride achieved decreases from baseline for all four measures, with placebo-treated patients experiencing increases or, in some cases, decreases of lower magnitude. However, in two studies that reported change in serum phosphate levels, differences in change between the groups were not statistically significant. In one study (n = 48) patients receiving placebo had a greater reduction in phosphate than those receiving cinacalcet hydrochloride, in the other study (n = 71) the change in serum phosphate favoured cinacalcet hydrochloride.

A pooled analysis of the three largest RCTs (n = 1136) showed that 40% of patients randomised to cinacalcet hydrochloride achieved target mean intact PTH levels versus 5% of patients receiving placebo (p < 0.001). In these studies target intact PTH was defined as a level below 26.5 pmol/litre (250 pg/ml). It is unclear why this threshold was chosen, although it does fall within the target range recommended in the US National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines. Similar results were seen in another two studies that measured this endpoint. In these studies the proportions of patients achieving this endpoint were 53% versus 6% (n = 48, statistical significance not reported) and 44% versus 20% (n = 71, p = 0.029).

Statistically significantly more patients who were treated with cinacalcet hydrochloride achieved a reduction of at least 30% in mean intact PTH levels compared with those receiving standard care alone in all RCTs that reported this outcome. In the pooled analysis of the three largest studies, 62% of patients treated with cinacalcet hydrochloride achieved this target, versus 11% in the placebo arm (p = 0.029). This endpoint was reported in two other studies, which also favoured cinacalcet hydrochloride over standard care. In these studies the proportions of patients achieving this endpoint were 38% versus 8% (n = 78, p = 0.001) and 53% versus 23% (n = 71, p = 0.009).

A post-hoc analysis of pooled data from four RCTs designed to investigate changes in biochemical markers (n = 1184) assessed the effect of cinacalcet hydrochloride on the clinical outcomes of fracture, cardiovascular hospitalisation, all-cause hospitalisation, parathyroidectomy and mortality compared with placebo. No statistically significant difference was seen in overall mortality or all-cause hospitalisation. However, statistically significant differences were observed in fracture (relative risk [RR] 0.46, 95% confidence interval [95% CI] 0.22–0.95), cardiovascular hospitalisation (RR 0.61, 95% CI 0.43–0.86), and parathyroidectomy (RR 0.07, 95% CI 0.01–0.55) based on follow-up of 6–12 months.

The same analysis also reported combined data on health-related quality of life, based on the SF-36 instrument. At baseline in both treatment groups, the scores on the eight domains of the scale were approximately half to one standard deviation below the general population mean. For the physical component summary score there was a 0.5-unit improvement in the cinacalcet hydrochloride arms compared with a 0.8-unit decrease in the control arms (p = 0.01), for bodily pain scale there was a 0.6-unit improvement in the cinacalcet hydrochloride arms compared with a 1.0-unit decrease in the control arms (p = 0.03) and for the general health perception scale there was a 0.2-unit improvement in the cinacalcet hydrochloride arms compared with a 1.0-unit decrease in the control arms (p = 0.02). No statistically significant differences were found for the other domains.

The Assessment Group reported subgroup analyses by baseline intact PTH, serum Ca x P, serum calcium, serum phosphate and dialysis duration for a variety of biochemical endpoints. However, most of these did not indicate statistically significant differences. The Assessment Group noted that some results suggested that cinacalcet hydrochloride may be more effective in less advanced disease, but were cautious in interpreting these findings.

The manufacturer’s submission reported unpublished results of an open-label post-marketing study (n = 552) that randomised participants to standard care with or without cinacalcet hydrochloride. The primary endpoint was the proportion of patients achieving a mean intact PTH level of 31.8 pmol/litre (300 pg/ml). In contrast to previous trials, this study allowed the adjustment of doses of vitamin D sterols and phosphate binders in accordance with treatment algorithms (doses were held constant in other RCTs to minimise the potential for confounding). The primary endpoint was achieved by 71% of patients in the cinacalcet hydrochloride arm versus 22% of patients receiving standard care alone (p < 0.001). Although the proportion of patients taking vitamin D sterols increased in both arms (66% to 81% in the standard care arm, 68% to 73% in the cinacalcet hydrochloride arm), the mean relative dose of vitamin D sterol decreased by 22% in the cinacalcet hydrochloride arm, whereas a 3% increase occurred in the standard care arm.

The systematic review carried out by the Assessment Group did not identify any published cost-effectiveness studies relevant to the scope of this appraisal. An economic model and separate cost–consequence analysis were submitted by the manufacturer of cinacalcet hydrochloride and the Assessment Group developed their own economic model. Both models were cost–utility analyses comparing cinacalcet hydrochloride in addition to standard care (using vitamin D and phosphate binders) with standard care only in patients with secondary hyperparathyroidism (PTH > 31.6 pmol/litre) who were receiving dialysis. Both analyses adopted the perspective of the NHS, and generally similar cost and resource use assumptions were used. There were, however, differences between the models with regard to the assumptions driving effectiveness.

The model submitted by Amgen incorporated health states reflecting patients’ status in relation to adverse events associated with secondary hyperparathyroidism. Clinical events included in the analysis were cardiovascular hospitalisations, fractures (major and minor), parathyroidectomies and death. The effect of cinacalcet hydrochloride on the relative risks for these outcomes was based on pooled results of four clinical trials. The manufacturer’s model resulted in an incremental cost-effectiveness ratio (ICER) of £35,600 per quality adjusted life year (QALY) gained. Subgroup analyses in patients with moderate (PTH 31.6 to 84.2 pmol/litre) and severe (PTH > 84.2 pmol/litre) secondary hyperparathyroidism resulted in ICERs of £30,400 and £48,300 per QALY gained respectively. A range of one-way sensitivity analyses were conducted. The results of these indicated that the ICER was most sensitive to variations in the dose of cinacalcet hydrochloride.

The Assessment Group adopted a different approach to the manufacturer in that they modelled the effect of treatment on PTH levels and then related this intermediate endpoint to clinical events. In the base-case analysis, patients in both arms were stratified by PTH levels (as controlled [PTH ≤ 32 pmol/litre], uncontrolled [PTH 33 to 84 pmol/litre] or very uncontrolled [PTH ≥ 85 pmol/litre]) and, within the very uncontrolled group, according to whether or not they had undergone parathyroidectomy (with or without adverse surgical events). Clinical events included cardiovascular events, fractures and death, and the probabilities of these occurring at different PTH levels were derived based on a variety of different sources, mostly large cohort studies. These rely on a number of assumptions and are subject to uncertainty. The reduction in utility associated with an adverse event was greater in the 3 months after the event. For subsequent cycles of the model utility increased, but to a level that was lower than the utility before the event. A wide range of sensitivity analyses were conducted. The costs of dialysis were excluded in the base-case analysis and included in a sensitivity analysis.

The results of the base-case analysis found that the ICER was £61,900 per additional QALY. One-way sensitivity analyses carried out by the Assessment Group indicated that the model was most sensitive to the cost of cinacalcet hydrochloride, the relative risk of mortality for people with very uncontrolled PTH versus those with controlled PTH and the inclusion of costs associated with dialysis. The inclusion of dialysis costs increased the ICER by over £10,000 per QALY.

The Assessment Group also modelled two further scenarios. In the first of these the intermediate marker of PTH level was removed and a direct effect of treatment on clinical outcomes was simulated. This permitted a more direct comparison with the manufacturer’s submission and, as far as possible, effectiveness data were taken from the same source (pooled data from four RCTs). This analysis resulted in an ICER of £43,000 excluding dialysis costs. The second additional analysis assumes that the effect of cinacalcet hydrochloride is mediated by levels of both PTH and Ca x P. This produced an ICER of £38,900 per QALY gained, excluding dialysis costs.

In an additional analysis conducted after the submission of the assessment report, the Assessment Group examined the cost effectiveness of two strategies of discontinuing cinacalcet hydrochloride in people whose PTH levels were not controlled by treatment. In the first scenario it was assumed that people with ‘very uncontrolled’ PTH levels (≥ 85 pmol/litre) after 3 months of treatment with cinacalcet hydrochloride (titration phase) would discontinue cinacalcet hydrochloride and receive standard care only. In this scenario, the ICER reduced to £57,400 per QALY. In the second scenario it was assumed that only those achieving target PTH levels of 32 pmol/litre would continue treatment. In this scenario the ICER was £44,000 per QALY.

The Committee reviewed the data available on the clinical and cost effectiveness of cinacalcet hydrochloride, having considered evidence on the nature of the condition and the value placed on the benefits of cinacalcet hydrochloride by people with hyperparathyroidism secondary to ESRD, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.

The Committee noted that the clinical trials of cinacalcet hydrochloride showed that it was effective in reducing levels of PTH and other biochemical markers including serum calcium and phosphate. It acknowledged that a reduction in adverse clinical outcomes associated with raised PTH levels, such as bone fracture and cardiovascular hospitalisation, had been observed in a post-hoc analysis of pooled safety data from several trials. However, it noted that these trials were not designed to demonstrate the clinical benefits of treatment in terms of reduction in adverse effects and also noted that there was a lack of data relating to long-term treatment with cinacalcet hydrochloride. The Committee was aware of observational evidence to suggest that there was a relationship between levels of PTH, calcium and phosphate and adverse clinical outcomes. However it noted that there was considerable uncertainty in the extent to which intervening to correct derangements in the levels of PTH, calcium and phosphate (in particular by lowering PTH levels) was effective in reducing the risk of the adverse outcomes. The Committee also noted that people on dialysis have many other factors that contribute to their increased risk of serious adverse events, and that these add to the uncertainty in predicting clinical benefits from changes in surrogate markers.

In addition to the possible risk of major adverse events associated with raised PTH levels, the Committee heard from the clinical and patient experts at the meeting that the biochemical disturbances associated with secondary hyperparathyroidism produced symptoms, such as pruritus, pain and muscle weakness, that were detrimental to quality of life and could interfere with sleep and daily activities. However, the Committee heard that while cinacalcet hydrochloride could help reduce the severity of these symptoms, it did not replace the need for dietary restrictions and the use of other medications such as phosphate binders and vitamin D sterols.

Although acknowledging the uncertainties involved with using surrogate markers, the Committee accepted the approach taken by the Assessment Group in using PTH levels as a marker of risk of adverse events in its cost-effectiveness analysis. The Committee also agreed that the additional complexity of the model in incorporating additional states to reflect different degrees of control of PTH provided the best characterisation of the course of the disease. Furthermore, this approach allowed the incorporation of health-related utilities to reflect a reduction in quality of life due to symptoms of very uncontrolled hyperparathyroidism. The Committee accepted the validity of the Assessment Group’s approach to incorporating the reduction in health-related quality of life associated with an adverse event, followed by some degree of recovery. On the basis of the cost-effectiveness analyses submitted, the Committee concluded that cinacalcet hydrochloride was unlikely to be a cost-effective use of NHS resources in the treatment of secondary hyperparathyroidism.

The Committee discussed whether cinacalcet hydrochloride could be used cost-effectively if a stopping rule for non-responders were applied. However, in the light of the additional analysis performed by the Assessment Group, it was not persuaded that the cost effectiveness would be sufficiently improved.

The Committee heard from the experts that there may be a very small subgroup of people with refractory or ‘tertiary’ hyperparathyroidism for whom cinacalcet hydrochloride may be an alternative to surgical parathyroidectomy. This option may be particularly useful where surgical risk is considered to be high. However, there was insufficient clinical evidence on the effectiveness of cinacalcet hydrochloride in this subgroup, and there was no evidence on the clinical effectiveness of cinacalcet hydrochloride compared with surgical parathyroidectomy. In addition, cost-effectiveness analysis suggested that cinacalcet hydrochloride was less cost effective in people with very uncontrolled hyperparathyroidism, although the extent to which this analysis reflected the population with refractory disease was not clear. The Committee therefore concluded that there was insufficient evidence to enable it to recommend cinacalcet hydrochloride in this group.

The Committee considered the comments of consultees relating to the use of cinacalcet hydrochloride in subgroups of people with particular clinical needs. These groups included people awaiting kidney transplants from living donors, people with calciphylaxis, people with recurrent hyperparathyroidism after parathyroidectomy, and people in whom surgical parathyroidectomy is contraindicated. However in the absence of evidence on clinical and cost effectiveness in these groups, the Committee concluded that cinacalcet hydrochloride could not be recommended.

Implementation

The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in ‘Standards for better health’ issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals.

'Healthcare Standards for Wales’ was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 that requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months.

NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website (www.nice.org.uk/TA XXX). [Note: tools will be available when the final guidance is issued]

Proposed recommendations for further research

The Committee identified a need for long-term clinical studies that are designed to evaluate the effect of cinacalcet hydrochloride on clinical outcomes (in particular, fracture and cardiovascular events). Studies to establish the multivariate relationship between biochemical disruption in SHPT and these clinical outcomes were also recommended.

The Committee also noted a paucity of evidence on the effect of cinacalcet hydrochloride in people with ESRD with particular clinical needs, specifically people with tertiary or refractory SHPT, people awaiting kidney transplants from living donors, people with calciphylaxis, people with recurrent hyperparathyroidism after parathyroidectomy, and people in whom surgical parathyroidectomy is contraindicated.

Related guidance

NICE has issued the following related technology appraisal guidance.

Renal failure: home versus hospital haemodialysis. NICE technology appraisal no. 48 (2002). Available from: www.nice.org.uk/TA048

NICE is in the process of producing the following clinical guideline.

Kidney disease: early identification and management of adults with chronic kidney disease in primary and secondary care (publication expected September 2008).

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.

It is proposed that the guidance on this technology is considered for review in December 2009. The Institute would particularly welcome comment on this proposed date.

David Barnett

Chair, Appraisal Committee

June 2006

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 twice a month except in December, when there are no meetings. The Committee 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 Jane Adam
Radiologist, St George's Hospital, London

Professor A E Ades
MRC Senior Scientist, MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol

Dr Tom Aslan
General Practitioner, Stockwell, London

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

Mrs Elizabeth Brain
Lay Representative

Dr Karl Claxton
Health Economist, University of York

Dr Richard Cookson
Senior Lecturer in Health Economics, School of Medicine Health Policy and Practice, University of East Anglia

Mrs Fiona Duncan
Clinical Nurse Specialist, Anaesthetic Department, Blackpool Victoria Hospital, Blackpool

Professor Christopher Eccleston
Director, Pain Management Unit, University of Bath

Dr Paul Ewings
Statistician, Taunton and Somerset NHS Trust, Taunton

Professor John Geddes
Professor of Epidemiological Psychiatry, University of Oxford

Mr John Goulston
Director of Finance, Barts and the London NHS Trust

Mr Adrian Griffin
Health Outcomes Manager, Johnson & Johnson Medical Ltd

Ms Linda Hands
Consultant Surgeon, John Radcliffe Hospital

Dr Elizabeth Haxby
Lead Clinician in Clinical Risk Management, Royal Brompton Hospital

Dr Rowan Hillson
Consultant Physician, Diabeticare, The Hillingdon Hospital

Dr Catherine Jackson
Clinical Lecturer in Primary Care Medicine, University of Dundee

Professor Richard Lilford
Professor of Clinical Epidemiology, Department of Public Health and Epidemiology, University of Birmingham

Dr Simon Mitchell
Consultant Neonatal Paediatrician, St Mary's Hospital, Manchester

Ms Judith Paget
Chief Executive, Caerphilly Local Health Board, Wales

Dr Katherine Payne
Health Economist, The North West Genetics Knowledge Park, The University of Manchester

Dr Ann Richardson
Independent Research Consultant

Dr Stephen Saltissi
Consultant Cardiologist, Royal Liverpool University Hospital

Mr Mike Spencer
General Manager, Clinical Support Services, Cardiff and Vale NHS Trust

Professor Andrew Stevens (Vice Chair)
Professor of Public Health, University of Birmingham

Dr Cathryn Thomas
General Practitioner, and Associate Professor, Department of Primary Care and General Practice, University of Birmingham

Simon Thomas
Consultant Physician, General Medicine and Clinical Pharmacology, Newcastle Hospitals NHS Trust

Dr Norman Vetter
Reader, Department of Epidemiology, Statistics and Public Health, College of Medicine, University of Wales, Cardiff

Professor Mary Watkins
Professor of Nursing, University of Plymouth

Dr Paul Watson
Medical Director, Essex Strategic Health Authority

B. 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

Louise Longworth
Technical Advisor, NICE project team

Janet Robertson
Technical Advisor, NICE project team

Alana Miller
Project Manager, NICE project team

Appendix B. Sources of evidence considered by the Committee

The assessment report for this appraisal was prepared by Peninsula Technology Assessment Group.

Garside R, Pitt M, Anderson R, et al. ’The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation’, 16 March 2006.

The following organisations accepted the invitation to participate in this appraisal. They were 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.     Manufacturer/sponsors:

• Amgen Ltd (cinacalcet HCl)

II    Professional/specialist and patient/carer groups:

• British Kidney Patient Association
• British Thyroid Foundation
• Kidney Alliance
• Long Term Medical Conditions Alliance
• National Kidney Federation
• Association of Renal Industries
• Association of Renal Technologists
• British Dietetic Association
• British Renal Society
• British Thyroid Association
• National Kidney Research Fund
• Renal Association
• Renal Pharmacy Group
• Royal College of Nursing
• Royal College of Pathologists
• Royal College of Physicians
• Royal College of Surgeons
• Royal Pharmaceutical Society
• Society for DGH Nephrologists
• Society for Endocrinology
• Department of Health
• Huntingdonshire PCT
• North Eastern Derbyshire PCT

III     Commentator organisations (without the right of appeal):

• NHS Confederation
• NHS Purchasing and Supplies Agency
• NHS Quality Improvement Scotland
• British National Formulary
• Welsh Assembly Government

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 Cinacalcet HCI for the treatment of hyperparathyroidism secondary to impaired renal function 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 Neil Gittoes, Consultant Endocrinologist, Royal College of Physicians – clinical expert
• Dr Alastair Hutchison, Consultant Renal Physician, Royal College of Physicians – clinical expert
• Christopher Payne, National Kidney Federation – patient expert
• Steve Rowe, National Kidney Federation – patient expert