Report of evidence-based assessments from Scottish Health Technologies Group August 2009

Transcription

1 Report of evidence-based assessments from Scottish Health Technologies Group August 2009 HTA Programme: Report no HSRE/SHTG/EBA Report/2009/003A Health Services Research & Effectiveness Unit

2

3 CONTENTS AND APPRAISALS OF NOTE Introduction... 1 NICE multiple and single technology appraisals... 2 MTAs (drug)... 2 Bevacizumab, sorafenib, sunitinib and temsirolimus for RCC... 2 STAs published April 2009 June Rivaroxaban for the prevention of VTE after total hip or total knee replacement Lenalidomide for the treatment of multiple myeloma Cetuximab for recurrent and/or metastatic squamous cell cancer of the head/neck... 4 NICE implementation support... 5 Sunitinib for the first-line treatment of advanced and/or metastatic RCC... 5 Imminent NICE multiple and single technology appraisals... 7 Forthcoming MTAs... 7 STAs due for publication July 2009 December NHS QIS HTA programme Evidence Notes Is patient self-monitoring of OAT safe, efficacious and cost-effective? Other UK and International HTAs Diagnostic strategies using DNA testing for hereditary haemochromatosis EECP for the treatment of stable angina and heart failure Octaplas versus FFP to reduce the risk of transmitting lipid-enveloped viruses Pharmaceutical and non-pharmaceutical interventions in Alzheimer s disease Centre for Evidence-based Purchasing reports Redsense blood loss detection device for venous needle dislodgment monitoring Implantable cardiac devices with remote monitoring facilities SIGN guidelines NHS Health Scottish perspectives on NICE public health guidance NICE interventional procedures Abbreviations Glossary... 30

4

5 Introduction This report provides summaries of: National Institute for Health and Clinical Excellence (NICE) technology appraisals published since April 2009 and information on all forthcoming multiple technology appraisals (MTAs) currently on the NICE work programme to enable forward planning NHS Quality Improvement Scotland (NHS QIS) HTA programme and related implementation activity Other UK and international HTAs Centre for Evidence-based Purchasing (CEP) reports Scottish Intercollegiate Guidelines Network (SIGN) guidelines NHS Health Scotland Scottish perspectives on NICE public health guidance NICE interventional procedures. For MTAs produced by NICE, the NHS QIS HTA programme, other UK and international HTAs and CEP reports, summaries outline the technology under consideration, patient and comparator groups and highlight the key clinical and cost effectiveness results and any patient/safety issues. Summaries conclude by providing background on Scottish context and directing SHTG members to existing sources of evidence. NICE MTAs are processed by NHS QIS to establish whether the recommendations are valid for Scotland. For such MTAs, NHSScotland should take account of the NICE guidance and ensure that recommended drugs and treatment are made available to meet clinical need. NICE has provided costing statements and audit support tools to support implementation in England. These are summarised to assist implementation in Scotland. All other sections of the report are for information only. At the meeting SHTG members may request further evidence-based assessments or implementation support. Actions will be reported and on completion of additional work by National Procurement (NP) or NHS QIS outputs will be published on the SHTG pages on the NHS QIS website A list of key terms/acronyms included in this report is provided on pages SHTG Report HSRE A (approved ).doc 1

6 NICE multiple and single technology appraisals Since April 2009 NICE has published one drug MTA and three STAs. This section summarises the MTA and STAs, including comparing the decisions from NICE with those from SMC where relevant. MTAs (drug) TA number Date published Drug NICE decision SMC decision Implications for NHSScotland 178 August 2009 Bevacizumab (firstline), sorafenib (firstand second-line), sunitinib (second-line) and temsirolimus (first-line) for the treatment of advanced and/or metastatic renal cell carcinoma. Bevacizumab, sorafenib and temsirolimus are not recommended as first-line treatment options for people with advanced and/or metastatic renal cell carcinoma. Sorafenib and sunitinib are not recommended as second-line treatment options for people with advanced and/or metastatic renal cell carcinoma. No submission made to SMC for the first-line use of Bevacizumab, therefore it is not recommended for use in Scotland. No advice from SMC on temsirolimus. Sorafenib (2006) is not recommended for second-line use within NHSScotland. Sunitinib (2007) is not recommended for second-line use within NHSScotland. No important differences were identified for this NICE appraisal and NHS QIS advises that the recommendations are as valid for Scotland as for England and Wales. This guidance supersedes the existing SMC advice on these medicines. SHTG Report HSRE A (approved ).doc 2

7 STAs published April 2009 June 2009 Not valid in Scotland and for information only. TA number Date published Drug NICE decision SMC decision Implications for NHSScotland 170 April 2009 Rivaroxaban for the prevention of venous thromboembolism (VTE) after total hip or total knee replacement in adults. Rivaroxaban, within its marketing authorisation, is recommended as an option for the prevention of VTE in adults having elective total hip replacement surgery or elective total knee replacement surgery. Rivaroxaban is accepted for use within NHSScotland for the prevention of VTE in adult patients undergoing elective hip or knee replacement surgery. NHSScotland should continue to adhere to the SMC advice. There is no material difference between the recommendations of the NICE STA and SMC advice. 171 June 2009 Lenalidomide for the treatment of multiple myeloma in people who have received at least one prior therapy. Lenalidomide in combination with dexamethasone is recommended, within its licensed indication, as an option for the treatment of multiple myeloma only in people who have received two or more prior therapies, and with the condition that the drug cost of lenalidomide (excluding any related costs) for people who remain on treatment for more than 26 cycles (each Lenalidomide is not recommended for use within NHSScotland in combination with dexamethasone for the treatment of multiple myeloma in patients who have received at least one prior therapy. NHSScotland should continue to adhere to SMC advice. There is a material difference between the recommendations of the NICE STA and SMC advice. The NICE STA is based upon the application of both a Department of Health agreed Patient Access Scheme 1 and consideration of the medicine as a lifeextending, end of life SHTG Report HSRE A (approved ).doc 3

8 TA number Date published 172 June 2009 Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck. Drug NICE decision SMC decision Implications for NHSScotland of 28 days; normally a period of 2 years) will be met by the manufacturer. treatment 2. A process has been agreed to consider Patient Access Schemes for NHSScotland. The manufacturer of Lenalidomide has indicated their intention to provide a resubmission to SMC for Cetuximab in combination with platinum-based chemotherapy is not recommended for people with recurrent and/or metastatic squamous cell cancer of the head and neck. In the absence of a submission from the holder of the marketing authorisation, Cetuximab is not recommended for use within NHSScotland for the treatment of patients with squamous cell cancer of the head and neck in combination with platinum based chemotherapy for recurrent and/or metastatic disease. further consideration. NHSScotland should continue to adhere to the SMC advice. There is no material difference between the recommendations of the NICE STA and SMC advice. 1 Schemes proposed by a pharmaceutical company and agreed by the Department of Health (with input from NICE) for NHS England, or by a PAS steering group for NHS Scotland, in order to improve the cost-effectiveness of a drug ( 2 Treatments which may be life-extending for patients with short life expectancy, are licensed for indications affecting small numbers of patients with incurable illnesses, and which may offer demonstrable survival benefits over current NHS practice, but which have an incremental cost effectiveness ratio (ICER) in excess of the upper end of the range normally accepted by a NICE Appraisal Committees ( SHTG Report HSRE A (approved ).doc 4

9 NICE implementation support This section summarises the implementation support produced by NICE to help the NHS in England implement recently published MTAs. NICE TA 169 Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma A summary of the NICE guidance (published in March 2009) was included in the June 2009 EBA report and is repeated below. NICE decision Sunitinib is recommended as a first-line treatment option for people with advanced and/or metastatic renal cell carcinoma who are suitable for immunotherapy and have an Eastern Cooperative Oncology Group performance status of 0 or 1. SMC decision Not recommended for use within NHSScotland as a first or second line therapy for advanced and/or metastatic renal cell carcinoma (2007). Implications for NHSScotland NHS QIS advised that the recommendations made in the NICE guidance are as valid for Scotland as for England and Wales. The NICE guidance supersedes the SMC advice. This MTA guidance was based upon the application of a price discount scheme and incorporated the use of NICE extended end-of-life modifiers. Costing statement The average daily cost of sunitinib per patient is 74.74, with an average 6-week cycle of treatment costing 3,139. The manufacturer of sunitinib (Pfizer) has agreed a patient access scheme with the Department of Health, in which the first treatment cycle of sunitinib is free to the NHS. Costs of subsequent treatment cycles may vary in different settings because of negotiated procurement discounts. The estimated cost of fully implementing this guidance per 100,000 population is 79,000 in the first year, with recurrent annual costs of 149,000. These costs are based on the total cost of treatment, less existing spend and manufacturer s total refund. Immunotherapy is currently considered as a treatment option to relieve physical symptoms and for maintenance of function. As a result there may be some offset in costs as patients move from immunotherapy to sunitinib. The number of patients thought to be affected is small and over time all newly diagnosed patients may receive sunitinib. Audit support NICE recommended that a sample of patients with advanced and/or metastatic renal cell carcinoma should be audited using the following criteria to support implementation of the guidance. Criterion 1: The percentage of patients offered evidence-based written information about: their illness or condition the treatment and care they should be offered, including being made aware of the Understanding NICE guidance booklet SHTG Report HSRE A (approved ).doc 5

10 the service providing their treatment and care. Criterion 2: The percentage of people with advanced and/or metastatic renal cell carcinoma where sunitinib was recommended as a first line treatment option providing they: are suitable for immunotherapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Criterion 3: The percentage of people who are currently being treated with sunitinib for advanced and/or metastatic renal cell carcinoma, who do not meet the guidance criteria 1, but who have been given the option to continue sunitinib treatment until they and their clinicians consider it appropriate to stop. Re-audit is recommended until the results meet the standards; that is 100% compliance with all criteria. SHTG Report HSRE A (approved ).doc 6

11 Imminent NICE multiple and single technology appraisals Forthcoming MTAs To enable forward planning within NHSScotland, all ongoing NICE MTAs are listed below. When an MTA is published, the advice supersedes any existing SMC advice. NHSScotland should take account of the NICE MTA advice and ensure recommended drugs and treatments are made available to meet clinical need. Small cell lung cancer (SCLC) -second-line topotecan Anticipated publication: November 2009 Background information: Estimated population: 3,300 6,600 new cases of SCLC for England and Wales. Usual treatment: first-line therapy is multi-drug platinum-based chemotherapy. Second-line chemotherapy to be offered at relapse only if no response to first-line. Supportive and palliative care is given concurrently. SMC advice: a) Oral: accepted for restricted use as monotherapy for adults with relapsed SCLC for whom re-treatment with first-line regimen is inappropriate. Manufacturers estimated budget impact for Scotland is 163,000 in year one rising to 187,000 in year five. b) IV (before oral formulation was available in UK): is not recommended for adults with relapsed SCLC for whom re-treatment with the first-line regimen is not appropriate. Chronic myeloid leukaemia - dasatinib and nilotinib Anticipated publication: April 2010 Background information: Estimated population: 600 people with chronic myeloid leukaemia diagnosed each year in England and Wales. Usual treatment: imatinib but 10 40% of patients become resistant to the drug. SMC advice: Both drugs have been accepted by SMC for restricted use in this indication. Given this restriction to chronic phase SMC determined the budget impact for dasatinib would be less than the manufacturer s estimate of 119,000 in year one rising to 122,000 in year five. Growth failure in children - human growth hormone (HGH) (review) Anticipated publication: May 2010 Background information: Estimated population: there are several syndromes and deficiencies that can give rise to short stature. The annual incidence could be around 5% of births. Usual treatment: HGH is currently recommended by NICE for children with proven diagnosis of most of the syndromes. There are seven licensed drugs available for the various indications. SMC advice: No SMC advice available. Discussions with a Scottish expert suggest very few additional children will be treated under any extension of the recommended indications. SHTG Report HSRE A (approved ).doc 7

12 Rheumatoid arthritis (RA) - drugs for treatment after failure of a TNF inhibitor (including review of TA126 (rituximab) and TA141 (abatacept) Anticipated publication: June 2010 Background information: Estimated population: 400,000 people in England and Wales have RA of whom 60,000 (15%) have severe disease. Usual treatment: non-steroidal anti-inflammatory agents (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and corticosteroids. DMARDs include TNF inhibitors. NICE TA36 recommended first-line use of etanercept and infliximab after the failure of two conventional DMARDs. Neither were recommended for use after the failure of a TNF inhibitor. TA130 replaced the first-line component of TA36, additionally recommending adalimumab for first-line treatment after the failure of two conventional DMARDs. TA130 does not address sequential use of agents, except where a TNF inhibitor is discontinued owing to an adverse event. TA126 recommended rituximab in combination with methotrexate for treatment of adults with severe active RA and inadequate response or intolerance to other DMARDs including one or more TNF inhibitor. In TA141 abatacept was not recommended for treatment of RA. SMC advice: a) Etanercept: treatment of moderate to severe active RA in adults, alone or in combination with methotrexate when response to DMARDs has been inadequate; treatment of severe, active and progressive RA in adults not previously treated with methotrexate. b) Rituximab: in combination with methotrexate for treatment of adults with severe active RA who have had an inadequate response or intolerance to other DMARDs including one or more TNF inhibitor. c) Abatacept: not recommended for use in combination with methotrexate to treat moderate to severe RA in patients who have had an inadequate response to DMARDs including one or more TNF inhibitor. d) No advice issued on adalimumab or infliximab for RA. Budget impact: rituximab - the impact is likely to be less than the manufacturer s estimate of 1.8 million, 2.2 million, 1.5 million, 1.9 million and 3.5 million in years one five; abatacept - manufacturer s estimate 798,000 to 1.76 million in year one rising to 1.17 million to 2.57 million in year five depending on uptake. Etanercept, infliximab, and adalimumab for the treatment of psoriatic arthritis (PsA) (part review of TA104 and TA125) Anticipated publication: July 2010 Background information: Estimated population: prevalence estimated at 50, ,000 people in England and Wales. Usual treatment: Alternative TNF inhibitors and conventional management strategies for PsA that have responded inadequately to DMARDs. NICE TA104 and TA125 recommended etanercept or adalimumab when a person has severe peripheral arthritis which has not responded to at least two other DMARDs. TA104 also recommended infliximab if the person cannot use etanercept. SMC advice: a) Etanercept to treat active and progressive psoriatic arthritis. b) Infliximab: no submission. SHTG Report HSRE A (approved ).doc 8

13 c) Adalimumab to treat active, progressive psoriatic arthritis when the response to previous DMARDs has been inadequate. Manufacturers estimated budget impact of treating all eligible patients with adalimumab: 3.8 million in year one then 3.3 million per year up to year five. Multiple myeloma (first line) - bortezomib and thalidomide Anticipated publication: September 2010 Background information: Estimated population: there were about 3,500 new cases of multiple myeloma in England and Wales in 2005, predominantly in people aged between years. Elderly patients and those patients who are not well enough to withstand high-dose chemotherapy plus bone marrow transplant using the patient s own cells are given less intensive chemotherapy using one drug or a combination of drugs. Recently either bortezomib or thalidomide, have been added to the alkylating agent and corticosteroid combination. SMC advice: a) Bortezomib monotherapy is not recommended for use within NHSScotland for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation; no advice issued on combination therapy. b) Thalidomide is accepted for use within NHSScotland in combination with melphalan and prednisone, as first line treatment of patients with untreated multiple myeloma, aged 65 years or over or ineligible for high dose chemotherapy. Budget impact is likely to be around 3 million per annum. Vascular disease - clopidogrel and dipyridamole (review) Anticipated publication: September 2010 Background information: Protocol not yet available. SMC advice: a) Clopidogrel is accepted for restricted use within NHSScotland for patients with ST segment elevation acute myocardial infarction (MI), in combination with aspirin, in medically treated patients eligible for thrombolytic therapy. Maximum budget impact would be 158,000. b) Clopidogrel is accepted for restricted use for treatment of acute coronary syndrome (without ST-segment elevation) in combination with aspirin. c) Diprydamole: no advice issued. Peginterferon alpha and ribavarin for the treatment of chronic hepatitis C (HCV) (part review of current NICE guidance TA106) Anticipated publication: October 2010 Background information: Estimated population: 200, ,000 people are infected with HCV in England and Wales, the majority of whom are asymptomatic. In 2005, Department of Health estimated only 47,000 had been diagnosed and 7,000 treated. Prevalence is estimated to be 50% in intravenous drug users attending clinics. Usual treatment: combination therapy of ribavarin and peginterferon alpha. Since NICE TA75 and TA106, the licensed indications for some forms of peginterferon alpha have been extended. SMC advice: SMC has accepted: a) Pegylated interferon alpha 2b in combination with ribavirin in adults with chronic HCV who have failed previous treatment. SHTG Report HSRE A (approved ).doc 9

14 b) Pegylated interferon alfa 2a for adults with chronic HCV. Manufacturers estimated budget impact for pegylated interferon alpha 2b: 287,000 in year one rising to 546,000 in year five. Age-related macular degeneration - photodynamic therapy Anticipated publication: November 2010 Background information: Protocol not yet available. SMC advice: Non-drug treatment so no SMC advice will be issued. Bone metasteses from solid tumours and multiple myeloma - denosumab Anticipated publication: March 2011 Background information: Protocol not yet available. SMC advice: SMC: no advice issued for denosumab. Crohn s disease - infliximab (review), certolizumab, natalizumab and adalimumab Anticipated publication: tbc Background information: Estimated population: between 3,000 6,000 people diagnosed with Crohn s each year in the UK. Usual treatment: aminosalicylates, antimetabolites, corticosteroids, immunosuppressive drugs, antibiotics, or dietary or surgical intervention. All four drugs are only licensed for use when conventional treatment has failed. NICE approved use of infliximab to treat people with severe, active Crohn s disease when treatment with immunomodulators and corticosteroids has not worked and surgery would not be appropriate. SMC advice: SMC has not recommended infliximab or adalimumab in adults but did recommend infliximab for paediatrics. The potential budget impact for Scotland of NICE accepting these drugs could be several million pounds. Gastro-intestinal stromal tumours (GISTs) (unresectable/ metastatic) - imatinib (review) Anticipated publication: tbc Background information: The number of new cases of unresectable and/or metastatic GISTs is estimated to be less than 240 per year in England and Wales. Usual treatment: best supportive care. Current NICE guidance (TA86) recommends imatinib 400 mg/day for first-line management; an increase in the dose is not recommended for those who develop progressive disease after initially responding. SMC advice: No advice issued for imatinib. SHTG Report HSRE A (approved ).doc 10

15 STAs due for publication July 2009 December 2009 Not valid in Scotland and for information only. SMC advice supercedes STA guidance. STA Anticipated SMC decision publication date Colorectal cancer (first line) - August 2009 Not recommended cetuximab Eczema (chronic) - alitretinoin August 2009 Recommended Gastrointestinal stromal tumours - September 2009 Not recommended sunitinib Lung cancer (non-small-cell, first September 2009 Not recommended line treatment) - pemetrexed Psoriasis - ustekinumab September 2009 Decision awaited Rheumatoid arthritis - tocilizumab October 2009 Decision awaited Soft tissue sarcoma - trabectedin October 2009 Not recommended Acute coronary syndrome - prasugrel Cervical cancer (recurrent) - topotecan Myelodysplastic syndromes - azacitidine October 2009 October 2009 November 2009 Decision awaited Recommended for restricted use with cisplatin Decision awaited SHTG Report HSRE A (approved ).doc 11

16 NHS QIS HTA programme This section summarises the NHS QIS HTA Programme, to include HTAs, Systematic Reviews and Evidence Notes published. Evidence Notes Evidence Note 27: Is patient self-monitoring (including self-testing and self-management) of oral anticoagulation therapy safe, efficacious and cost-effective?; May 2009 Description: Patient self-testing of oral anticoagulation therapy (OAT) involves the patient pricking a finger with a lancet device, applying a drop of blood to a reagent strip and inserting it into a portable point of care (POC) meter that measures the blood clotting time. The patient sends the result to a physician who interprets it and recommends adjustment to the OAT dose as necessary. In self-management the patient interprets the result and adjusts the dose. Patient group(s): Patients at increased risk of thrombosis taking oral anticoagulation therapy (mainly warfarin in the UK). Comparators: Usual care/no self-monitoring. Clinical effectiveness: Three recent systematic reviews of RCTs have found selfmonitoring to be as safe and effective as monitoring in specialist clinics and more effective than usual care provided in primary care. The generalisability of these findings to the UK setting is uncertain. Cost effectiveness: A model populated largely with UK trial data estimated the cost per QALY gained by self-monitoring at 122,365 over five years and 63,655 over 10 years. At a cost per QALY threshold of 30,000 the probability that self-monitoring would be cost-effective was 44% over 10 years. From a Canadian health care perspective self-testing using POC devices in clinics was cost saving compared to conventional laboratory testing, but not cost-effective (ICER approximately 32,000 per QALY). The generalisabilty of the findings from both of these studies to Scottish care settings is unclear. Patient/safety issues: The MHRA has issued a medical device alert highlighting the potential for needlestick injuries and transmission of infection associated with lancet devices. The NPSA has issued patient safety alerts highlighting anticoagulants as sources of preventable harm and admission to hospital. Resource impact: The POC meter most commonly used in Scotland costs ; total expenditure on test strips was 215,000 in Scottish context: Is there existing advice in Scotland? Yes No SIGN 36: Antithrombotic therapy (1999; Patient self-management of oral anticoagulation requires further study. Current practice: National service regional service NHS board service NHS boards are advised: For selected and well-trained patients self-monitoring is safe, more effective than primary care-based usual care and as effective as clinicbased monitoring. Self-monitoring and self-testing has been shown not to be costeffective compared to clinic-based monitoring. However, the applicability of the available evidence to the UK is uncertain. Decision makers in Scotland should compare annual costs of self-monitoring and training to the potential avoided costs of clinicbased usual care in order to judge cost-effectiveness in their own setting. SHTG Report HSRE A (approved ).doc 12

17 Other UK and International HTAs This section summarises recent non-drug HTAs published by the healthcare agencies of England, Belgium, Canada, Australia and New Zealand. These agencies provided HTAs in English and consider clinical and cost effectiveness evidence. Diagnostic strategies using DNA testing for hereditary haemochromatosis in atrisk populations: a systematic review and economic evaluation. UK NIHR HTA Programme, Southampton; April 2009 Description: Hereditary haemochromatosis (HHC) results from a genetic disorder of iron metabolism that leads to excessive intestinal absorption of iron and a progressive abnormal deposition of iron in the liver, heart, pancreas and other vital organs. DNA testing can be used to identify individuals with a particular gene mutation which predisposes them to develop this condition. 4 3 Patient group(s): Individuals suspected on the basis of clinical presentation and disturbed iron parameters of having HHC, and family members of those diagnosed with HHC. Comparators: For clinical validity, a control population. For clinical utility, any case identification strategy not involving DNA testing. Clinical effectiveness: Based upon the most relevant studies identified, the sensitivity of the gene mutation for HHC was found to range from %. The specificity ranged from %. No studies were identified which examined the clinical utility of the test. Cost effectiveness: Two economic models were developed to compare the costs and consequences of diagnostic strategies with and without DNA testing: one for people suspected of having HHC and the other for family members of diagnosed patients. For people suspected of having HHC, the DNA strategy was found to be cost saving compared with the baseline strategy of using liver biopsy (cost saved per case detected 123). The results were most sensitive to the specificity of the transferrin saturation (TS) test, the cost of the liver biopsy test and the proportion of people with a positive DNA test for the gene mutation and raised serum ferritin. Regarding family members, the DNA strategy was found to be cost saving for testing offspring compared to a baseline biochemical strategy. However, it was not cost saving for testing siblings, unless the cost of the DNA test fell from 100 to 60. For testing offspring, the cost saved per case detected varied between 4,144 and 11,786 for changes in the frequency of monitoring. For testing siblings, the additional cost per case detected varied between 94 and 305 for changes in the price of the DNA test Patient/safety issues: Limited psychosocial literature was identified which indicated that genetic testing for HHC is well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The economic evaluation did not consider potential benefits of reassurance and reduction in anxiety resulting from DNA testing, which could have an impact on the long-term cost-effectiveness of DNA testing in siblings. Resource impact: Not specified. SHTG Report HSRE A (approved ).doc 13

18 Scottish context: Is there existing advice in Scotland? Yes No Current practice: National service regional service NHS board service In Scotland testing is undertaken through the Scottish Genetics Laboratory Consortium, a centrally funded national service. However subsequent advice and counseling is provided through local genetic services. Screening for haemochromatosis does not currently meet the National Screening Committee (NSC) criteria for a national screening programme. A draft report prepared in response to an NSC policy review of screening for this condition, proposes that the criteria are still not met. NHS boards are advised: DNA testing should be used in conjunction with testing iron parameters when there is a clear clinical indication of suspicion of being at risk for haemochromatosis because of biochemical criteria or when being at familial risk for haemochromatosis. The use of a molecular genetic laboratory network, as is in place in Scotland, can reduce the cost of DNA testing through rationalising the use of resources. SHTG Report HSRE A (approved ).doc 14

19 Enhanced External Counterpulsation (EECP) for the treatment of stable angina and heart failure: a systematic review and economic analysis. UK NIHR HTA Programme, York; April 2009 Description: An electrocardiogram (ECG) monitor controls inflation and deflation of pressure cuffs wrapped around the patients calves and thighs, which increases cardiac output and decreases cardiac workload. Treatment normally comprises 35 one-hour sessions over a period of seven weeks. Patient group(s): Patients with refractory stable angina or mild heart failure. Comparators: Usual care including drugs, cardiac rehabilitation and revascularisation. Clinical effectiveness: One RCT compared EECP with sham EECP in patients with angina (mostly Class I or II disease). EECP reduced the time to exercise-induced ischaemia (mean difference [MD] 41 seconds; 95% CI ) but change in exercise duration, daily use of nitroglycerin and angina episodes were not significantly different. More patients in the EECP group experienced adverse events (RR 2.13; 95% CI ). A non-randomised comparison of registry data found similar rates of allcause mortality at one-year between EECP and elective percutaneous coronary intervention. One RCT compared EECP with drug therapy in patients with mild to moderate heart failure. At six months the proportion of patients whose exercise duration increased by at least 60 seconds was higher in the EECP group (RR 1.39; 95% CI ), as was the proportion with improved New York Heart Association (NYHA) classification (RR 2.25; 95% CI ); the clinical significance of this is uncertain. More patients in the EECP group withdrew due to adverse events (RR 1.05; 95% CI ). Cost effectiveness: A decision analytic model was developed to assess the costeffectiveness of EECP compared to no treatment for adults with chronic stable angina in the UK NHS. The model included costs for the standard 35-hour EECP treatment sessions and repeat procedures over time. It also assumed that EECP has no differential effect on the risk of developing CVD or death. The long-term maintenance of HRQoL benefits of EECP is central to the estimate of its cost-effectiveness: if the benefits last for only one year the ICER is 63,072 for each additional QALY; if they are sustained over a lifetime the ICER is 5,831. In the base case analysis (based on expert opinion on the sustainability of benefits) the ICER of EECP was 18,643, with a probability of being cost-effective of 0.44 at a cost per QALY threshold of 20,000 and 0.70 at 30,000. Patient/safety issues: Timing between EECP sessions can vary in clinical practice, depending on patient preference and tolerance for the therapy. The standard treatment regimen has been developed empirically. Adverse effects reported include leg and back pain, skin abrasion, bruising, blistering, oedema and paraesthesia. Resource impact: Not provided. Scottish context: Is there existing advice in Scotland? Yes No SIGN 95: Management of stable angina (2007; states that initial treatment for patients with refractory angina should follow an educative, rehabilitative then cognitive behavioural approach prior to considering other interventions such as EECP. Current practice: National service regional service NHS board service Not currently in use in Scotland. NHS boards are advised: Currently there is insufficient evidence to inform firm conclusions on the clinical effectiveness of EECP for refractory stable angina or heart failure. EECP is cost-effective if the HRQoL benefits are assumed to continue throughout a patient s lifetime however the long-term effects of EECP remain uncertain. SHTG Report HSRE A (approved ).doc 15

20 Octaplas compared to fresh frozen plasma to reduce the risk of transmitting lipid-enveloped viruses: an economic analysis and budget impact analysis. Canadian Agency for Drugs and Technologies in Health; April 2009 This is a revised version of the original CADTH HTA published in March Revisions were made by CADTH in response to concerns raised by experts and the manufacturer (Octapharma AG). The original assessment was summarised in the SHTG August 2008 EBA. The major change to this report is that the conclusions drawn now suggest reduced (rather than increased) disease burden from the decision to use Octaplas versus fresh frozen plasma. This decision is still associated with increased costs, as in the previous report. Description: Octaplas, a solvent/detergent treated fresh frozen plasma (SD-FFP), is a pooled blood product treated with the aim of reducing the risk of transmitting lipidenveloped viruses (HBV and HCV) and transfusion related acute lung injury (TRALI). Patient group(s): Patients undergoing transfusion therapy. Comparators: Fresh Frozen Plasma (FFP). Clinical effectiveness: Not covered in this review. Cost effectiveness: Cost effectiveness and cost utility decision analytic models were prepared which showed that Octaplas is more costly than FFP ( 314 versus 223) but produces more QALYs ( versus ) and more life years ( versus ). The incremental cost per QALY gained for Octaplas was 43,855 and incremental cost per life-year gained was 53,033. The most important drivers of costeffectiveness were found to be the cost per unit of Octoplas and the risk of TRALI. Patient/safety issues: Octaplas reduces the risk of transmitting major viruses. However this risk is already very low as a result of other safety measures adopted. Resource impact: A switch to Octoplas from FFP in the Canadian health care system would incur a yearly net loss of about 7.48 million. (Based on Canadian population 33.4 million). Scottish context: Is there existing advice in Scotland? Yes No SNBTS Provision of Pathogen Reduced Plasma Components by SNBTS for all patients aged 16 and under. (POL Cat: Vir-inac). Prices and virus prevalence in the UK differ from Canada. In the UK efforts are made to provide male plasma only which largely ameliorates the problems of TRALI associated with FFP. To further reduce the risk of vcjd transmission, the advisory committee on the Safety of Blood Tissues and Organs (SABTO) has recently recommended that all plasma should be imported from low risk countries and pathogen inactivated. (Dr C Prowse, SNBTS, Personal Communication, 21 August 2009) Current practice: National service regional service NHS board service Central funding via SNBTS to purchase Octaplas (3000 units annually) for use in thrombotic thrombocytopenic purpura (TTP) patients receiving plasma exchange. NHS boards are advised: Octaplas is associated with a reduced disease burden at a higher cost than standard FP or FFP. The cost-effectiveness of Octaplas will be determined by a decision maker s willingness to pay for a QALY. SHTG Report HSRE A (approved ).doc 16

21 Pharmaceutical and non-pharmaceutical interventions in Alzheimer s disease, a rapid assessment. Belgian Health Care Knowledge Centre; July 2009 Description: Current drug and non-drug treatment interventions target the symptoms of Alzheimer s disease, aiming to improve patient and caregiver QOL and attenuate patient behavioural problems. Patient group(s): Patients with Alzheimer s disease. Comparators: Placebo, alternative drugs and usual care. Clinical effectiveness: Evidence was derived from recent HTA reports and systematic reviews. Key recommendations: the use of antipsychotics is associated with increased mortality and should be restricted; use of acetylcholinesterase inhibitors in hospitalised medically unstable patients is associated with increased early mortality and needs careful judgment. The effect of memantine on cognitive function is small. Evidence that Ginkgo biloba is beneficial is inconsistent and unreliable. There is a lack of high quality evidence to support the use of technological support interventions and nonpharmaceutical interventions targeting patients. There is some evidence of positive effects from non-pharmaceutical interventions for care givers, but conclusions across studies are inconsistent. Cost effectiveness: Published cost-effectiveness evaluations of pharmaceutical and non-pharmaceutical interventions are heterogeneous and unreliable. Efficacy studies with long-term follow-up to populate cost-effectiveness models are lacking. One UK trial has indicated that group-based cognitive stimulation sessions for patients with mild to moderate dementia in day care or care homes might be cost-effective. Patient/safety issues: Typical and atypical antipsychotics are associated with increased mortality in patients with dementia. The rate of adverse events (anorexia, nausea, vomiting and diarrhoea) with acetylcholinesterase inhibitors is dosedependent. Resource impact: Not provided. Scottish context: Is there existing advice in Scotland? Yes No NICE TA111: Alzheimer's disease - Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer s disease (amended 2007; Donepezil, galantamine and rivastigmine (acetylcholinesterase inhibitors) are recommended as options in the management of patients with Alzheimer s disease of moderate severity only; only specialists should initiate treatment; patients should be reviewed every six months and carers views sought. Memantine is not recommended as a treatment option for patients with moderately severe to severe Alzheimer s disease outside of well-designed clinical studies. SIGN 86: Management of patients with dementia (2006; Donepezil ( 5 mg/d), galantamine ( 16 mg/d) and rivastigmine ( 6 mg/d) can be used to treat cognitive decline and in the management of associated symptoms in patients with Alzheimer s disease. In people with dementia, behaviour management may be used to reduce depression, cognitive stimulation should be offered and recreational activities should be introduced. Current practice: National service regional service NHS board service NHS boards are advised: To continue to follow existing NICE MTA and SIGN guidance. SHTG Report HSRE A (approved ).doc 17

22 Centre for Evidence-based Purchasing reports This section summarises recent reports of note from CEP. Further information is available from the CEP section of the NHS Purchasing and Supply Agency website ( Redsense blood loss detection device for venous needle dislodgment monitoring in haemodialysis. Evidence review; March 2009 Description: The Redsense device monitors dislodgement of the venous needle through which blood is returned from the dialysis machine to the patient during haemodialysis. An alarm unit transmits infrared light through an optical fibre to a sensor patch placed over the needle access site. Blood leakage interrupts the infrared signal, which activates a warning light and audible alarm; it does not stop the venous blood pump. Patient group(s): Patients undergoing haemodialysis. Comparators: None identified. Clinical effectiveness: The available evidence on the use of venous needle dislodgement monitors was limited to one uncontrolled study of its use in Sweden, articles discussing needle dislodgement incidents and an ECRI medical devices safety report. Venous needle dislodgement occurs in less than 0.001% of dialyses in England and Wales and the risk of fatality is low (2/12 incidents of venous needle dislodgement reported to the MHRA over five years were fatal, seven serious and three minor). CEP concluded that the Redsense monitor may be of value in patients at increased risk of needle dislodgement, including restless patients and those receiving dialysis at home or in isolation units. Cost effectiveness: Cost-effectiveness was not assessed. Cost impact analysis indicated that using Redsense for all patients receiving dialysis in the UK would cost approximately 8.6 million per year ( 2.89 per dialysis session). Use of the Redsense monitor in patients receiving dialysis at home would add around 450 per patient to the annual cost of treatment (cost of home dialysis 20,764 per patient per year). Patient/safety issues: Venous needle dislodgement is rare and the risk of death from undetected needle dislodgement is low (2/12 reported incidents over five years were fatal). Resource impact: The cost of using Redsense for all patients in the UK receiving home dialysis would be approximately 180,000 per year. Scottish context: Is there existing advice in Scotland? Yes No Current practice: National service regional service NHS board service NHS boards are advised: The limited evidence available suggests that the Redsense monitor may be of value in patients at high risk of needle dislodgement. The additional cost of using Redsense in patients on home dialysis would be approximately 450 per patient per year. Although Redsense will detect blood leakage as soon as the venous needle dislodges it will not stop the blood pump, therefore vigilance and adherence to good practice recommendations is required to prevent serious injury or death. NHS National Services Scotland has added the purchase of the Redsense monitor as a supplement to the haemodialysis contract. SHTG Report HSRE A (approved ).doc 18

23 Implantable cardiac devices with remote monitoring facilities. Evidence Review; April 2009 Description: Implanted cardiac devices such as pacemakers, cardiac resynchronisation therapy devices (CRTs) and implantable cardioverter defibrillators (ICDs) have been developed which have the ability to transmit periodic messages, or in some cases, patient activated messages via telephone or satellite networks. The data can then be viewed by clinicians on secure websites enabling them to monitor the functioning of the device and the patient s condition. Patient group(s): Patients with disorders of the hearts conductive system, who require to have implanted cardiac devices to stimulate the heart, resynchronise contractions or deliver intracardiac shocks to terminate lethal rhythms. Comparators: Standard care without remote monitoring. Clinical effectiveness: No RCTs were identified. Evidence, mainly from observational or retrospective studies, indicated that early detection of atrial fibrillation, ventricular arrhythmias and device failure by remote monitoring provided improved patient management and allowed earlier detection of device malfunction. Cost effectiveness: A cost analysis, assuming no impact on health outcomes of remote monitoring but an impact on healthcare resource use, predicted no savings in the lifetime of an implantable cardiac device unless the number of outpatient visits was reduced to a maximum of one per year. A further cost effectiveness analysis which assumed that remote monitoring could reduce the incidence of stroke as well as impact on healthcare resource use, showed that the incremental cost effectiveness ratio for remote monitoring versus routine outpatient care would fall below 30,000 if the incidence of stroke was reduced by 5% or more. However, there is currently little robust data to support this assumption. The results were found to be most sensitive to the cost of strokes and post-stroke follow up, and the costs of the implantable device. Patient/safety issues: There is currently insufficient evidence to determine the impact on patient safety if remote monitoring was used to increase the interval between clinic visits. Two observational studies indicated that remote monitoring was well accepted by patients. Resource impact: Manufacturers are moving towards building the cost of the remote monitoring technology into the purchase price of the implant. Scottish context: Is there existing advice in Scotland? Yes No Current practice: National service regional service NHS board service NHS boards are advised: NHS National Services Scotland are currently in the process of renewing the contract for implantable cardiac devices for NHSScotland and will take the information contained within this report into account. SHTG Report HSRE A (approved ).doc 19

24 SIGN guidelines The table below summarises forthcoming SIGN guidelines and notes those where NHS QIS is working on resource impact reports. Guideline Anticipated publication date Parkinson s disease November 2009 Sore throat (selective update) November 2009 Management of obesity (review) December 2009 NHS QIS costing work underway Non-pharmacological management of depression January 2010 Attention deficit hyperactivity disorder (selective update) January 2010 Diabetes update (to incorporate new evidence in the following areas: type 1 diabetes, cardiovascular disease drug therapy for type 2 diabetes, foot disease, lifestyle, pregnancy, renal disease and retinopathy) March 2010 NHS QIS costing work underway Leg ulcer (selective update) March 2010 Early rheumatoid arthritis (selective update) April 2010 Stroke rehabilitiation (selective update) April 2010 Germ cell tumours (selective update) April 2010 Venous thromboembolism October 2010 Antithrombotic therapy October 2010 SHTG Report HSRE A (approved ).doc 20

25 NHS Health Scottish perspectives on NICE public health guidance NICE produces two types of guidance on public health topics: public health intervention guidance (interventions being defined as involving single measures, eg GP advice to patients to be more active) and public health programme guidance (on broader activities, eg strategies for smoking cessation). In Scotland, such guidance has no formal status but attracts interest and provides a useful source of reviewed evidence. NHS Health Scotland has introduced the Scottish Perspectives series following helpful feedback on the previously-produced Commentaries and Statements on NICE public health guidance. These are intended to help organisations, professionals and others make use of the guidance, adapted as appropriate to fit the Scottish context. They do not in themselves constitute formal guidance or guidelines. This section summarises the first two Scottish perspectives published. Further information is available from the Evidence section of the NHS Health Scotland website ( Topic Mental wellbeing and older people - occupational therapy and physical activity interventions to promote the mental wellbeing of older people in primary care and residential care Maternal and child nutrition - improving the nutrition of pregnant and breastfeeding mothers and children in low-income households Publication date July 2009 July 2009 Forthcoming Scottish perspectives; Topic Identifying and supporting people most at risk of dying prematurely - reducing the rate of premature deaths from cardiovascular disease and other smoking-related diseases finding and supporting those most at risk and improving access to service Promoting physical activity for children and young people - promoting physical activity, active play and sport for pre school and school-age children in family, pre-school, school and community settings Promoting young people's social and emotional wellbeing in secondary education - guidance promoting young people's social and emotional wellbeing in secondary education Promoting mental wellbeing at work - guidance for employers on promoting mental wellbeing through productive and healthy working conditions Anticipated publication date August 2009 August 2009 January 2010 February 2010 SHTG Report HSRE A (approved ).doc 21