British Geriatrics Society

Transcription

1 Healthcare professional group/clinical specialist statement Thank you for agreeing to give us a statement on your organisation s view of the technology and the way it should be used in the NHS. Healthcare professionals can provide a unique perspective on the technology within the context of current clinical practice which is not typically available from the published literature. To help you in making your statement, we have provided a template. The questions are there as prompts to guide you. It is not essential that you answer all of them. Please do not exceed the 8-page limit. About you Your name: Dr Martin James Name of your organisation (if applicable): British Geriatrics Society Are you (tick all that apply): - a specialist in the treatment of people with the condition for which NICE is considering this technology? - a specialist in the clinical evidence base that is to support the technology (e.g. involved in clinical trials for the technology)? - an employee of a healthcare professional organisation that represents clinicians treating the condition for which NICE is considering the technology? If so, what is your position in the organisation where appropriate (e.g. policy officer, trustee, member etc.)? I am not an employee of the healthcare professional organisation (The British Geriatrics Society) but I have been nominated by them to act on their behalf in representing clinicians treating the condition. - other? (please specify) 1

2 What is the expected place of the technology in current practice? How is the condition currently treated in the NHS?. Is there significant geographical variation in current practice? Are there differences of opinion between professionals as to what current practice should be? What are the current alternatives (if any) to the technology, and what are their respective advantages and disadvantages? Are there any subgroups of patients with the condition who have a different prognosis from the typical patient? Are there differences in the capacity of different subgroups to benefit from or to be put at risk by the technology? In what setting should/could the technology be used for example, primary or secondary care, specialist clinics? Would there be any requirements for additional professional input (for example, community care, specialist nursing, other healthcare professionals)? If the technology is already available, is there variation in how it is being used in the NHS? Is it always used within its licensed indications? If not, under what circumstances does this occur? Please tell us about any relevant clinical guidelines and comment on the appropriateness of the methodology used in developing the guideline and the specific evidence that underpinned the various recommendations. The technology (alteplase for thrombolysis in acute ischaemic stroke) is already available for NHS patients since the product was granted a conditional European licence in Spring The only currently available alternative treatment is conventional treatment without thrombolysis. Treatment without the use of alteplase avoids the most significant complication of thrombolysis, that of symptomatic intracranial haemorrhage, what had an absolute risk of about 6% in the randomised controlled trials (RCTs). There have been persistent differences of opinion since the publication of the first alteplase trial in the US in 1995 regarding the interpretation of the main trial findings, although this has largely been laid to rest by the latest re-analysis of these studies (The ATLANTIS, ECASS and NINDS rt-pa Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS and NINDS rt-pa stroke trials. Lancet 2004; 363: ). There is considerable variation in the extent to which alteplase is used, with relatively few acute hospitals providing the treatment (probably no more than 40 centres in the UK at present, although that number is gradually increasing). As a general rule, centres that use alteplase are restricting use to within its licenced indications, of which the most significant restrictions are the time from symptom onset to initiation of treatment (limited to 3 hours), and the upper age limit of 80 years. A recent systematic review of alteplase treatment in patients older than 80 years has observed that such patients are under-represented in the available RCT data, and the review concluded that treated patients older than 80 years had a less favourable outcome than those less than 80, possibly due to imbalances in baseline predictors such as stroke severity, but that the risk of the major complication of treament (symptomatic intracranial haemorrhage) was not higher among older subjects (Engelter et al. Intravenous thrombolysis in stroke patients of >80 versus <80 years of age a systematic review across cohort studies. Age & Ageing 2006; 35: ). Research studies (principally the third International Stroke Trial, IST-3) are currently in progress to explore the evidence outside the current limitations of the licence, and such studies 2

3 are vital to address the age inequality in access to the treatment under the existing conditions of the licence. Clinical Guidelines on the use of alteplase in the UK are available from the Intercollegiate Working Party of the Royal College of Physicians of London the National Clinical Guidelines for Stroke, most recently updated in 2004 (available at These state that thrombolysis should only be given within 3 hours of stroke onset provided that haemorrhage has been excluded, the conditions set out in the licence have been met, and the centre is registered with the Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST). The SITS-MOST European monitoring database identifies the UK as one of the countries with the lowest proportional use of alteplase for acute ischaemic stroke in Europe in the 3½ years since licencing. The advantages and disadvantages of the technology NICE is particularly interested in your views on how the technology, when it becomes available, will compare with current alternatives used in the UK. Will the technology be easier or more difficult to use, and are there any practical implications (for example, concomitant treatments, other additional clinical requirements, patient acceptability/ease of use or the need for additional tests) surrounding its future use? If appropriate, please give your view on the nature of any rules, informal or formal, for starting and stopping the use of the technology; this might include any requirements for additional testing to identify appropriate subgroups for treatment or to assess response and the potential for discontinuation. If you are familiar with the evidence base for the technology, please comment on whether the use of the technology under clinical trial conditions reflects that observed in clinical practice. Do the circumstances in which the trials were conducted reflect current UK practice, and if not, how could the results be extrapolated to a UK setting? What, in your view, are the most important outcomes, and were they measured in the trials? If surrogate measures of outcome were used, do they adequately predict longterm outcomes? What is the relative significance of any side effects or adverse reactions? In what ways do these affect the management of the condition and the patient s quality of life? Are there any adverse effects that were not apparent in clinical trials but have come to light subsequently during routine clinical practice? There is no currently available comparator treatment to alteplase. Patients who are not thrombolysed receive conventional acute care, which should include care on a multidisciplinary stroke unit (although in fact only 46% of stroke patients even receive this level of specialist care see Implementation Issues ). The widespread introduction of alteplase would therefore represent a dramatic change in the management of suspected acute stroke (see Implementation Issues below). 3

4 There has been concern following licencing of alteplase for acute ischaemic stroke by the FDA in the United States in 1996, that acute centres who do not adhere strictly to the eligibility criteria and protocols described in the original research studies had higher levels of complications of treatment, principally acute intracranial haemorrhage (Katzan et al. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 2000;283: ). It will be difficult for many acute centres in the UK to replicate the level of acute care and monitoring that was a feature of the trials in the US, and this may affect rates of complications of treatment. Following licencing in Canada, and amidst concerns that inexperience with the use of alteplase would lead to higher than expected rates of complications, a 2½ year national audit was conducted that demonstrated that low volume centres did not have higher complication rates than high volume centres, and that the overall rate of the most serious complication, symptomatic intracranial haemorrhage, was no higher (at 4.6%) than was seen in the original RCTs - although when it occurred, 75% of intracranial heamorrhages were fatal (Hill et al. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005; 172: ). The Canadian study did, however, identify a significant risk (1.3%) of orolingual angioedema which was not identified by the original RCTs. Any additional sources of evidence Can you provide information about any relevant evidence that might not be found by a technology-focused systematic review of the available trial evidence? This could be information on recent and informal unpublished evidence, or information from registries and other nationally coordinated clinical audits. Any such information must include sufficient detail to allow a judgement to be made as to the quality of the evidence and to allow potential sources of bias to be determined. One condition of the granting of the European licence for alteplase in Spring 2003 was the establishment of the monitoring database SITS-MOST. Of 6483 patients entered in the database until April 2006, only 327 (5.5%) were from the UK, one of the lowest rates per population in Europe. Data on safety has not yet been definitively published, but may be available from the Study Co-ordinator Dr Nils Wahlgren, Professor of Neurology at the Karolinska University Hospital, Stockholm (nils.wahlgren@karolinska.se). The primary outcome measure in SITS-MOST is safety, principally symptomatic intracranial haemorrhage. Implementation issues The NHS is required by the Department of Health and the Welsh Assembly Government to provide funding and resources for medicines and treatments that have been recommended by NICE technology appraisal guidance. This provision has to be made within 3 months from the date of publication of the guidance. If the technology is unlikely to be available in sufficient quantity, or the staff and facilities to fulfil the general nature of the guidance cannot be put in place within 3 months, NICE may advise the Department of Health and the Welsh Assembly Government to vary this direction. 4

5 Please note that NICE cannot suggest such a variation on the basis of budgetary constraints alone. How would possible NICE guidance on this technology affect the delivery of care for patients with this condition? Would NHS staff need extra education and training? Would any additional resources be required (for example, facilities or equipment)? The widespread introduction of alteplase would represent a dramatic change in the management of suspected acute stroke: all patients with suspected acute stroke will need to be referred immediately to hospital via the 999 service rather in the same manner as patients with suspected myocardial infarction are currently. This will lead to a large rise in the numbers of patients attending Emergency Departments for the assessment of a variety of neurological symptoms. Many of these departments do not have the infrastructure, particularly the CT scanning access, to assess these patients in the sort of timeframes that are necessary to achieve treatment within 3 hours of onset. There is a significant gap in the training and experience of the majority of clinicians (particularly acute/emergency physicians and nurses, but also radiologists) in assessing patients and administering this treatment. The round-the-clock availability of alteplase depends to a large extent on the provision of emergency access to CT brain imaging and its interpretation. This is not available in many acute centres, often due to a shortage of appropriately trained radiographers. Provision of alteplase outside of normal working hours may have to be made in fewer, larger centres, and ambulance trusts will need special arrangements to drive by local Emergency departments to reach eligible centres more quickly. This might be guided by the use of pre-hospital screening instruments for acute stroke such as the FAST test or ROSIER scale (Nor AM et al. The Recognition of Stroke in the Emergency Room scale: development and validation of a stroke recognition instrument. Lancet Neurology 2005; 4: ). The medical specialty of Stroke Medicine is still in its infancy, with a considerable shortfall in the availability of Physicians trained and experienced in the management of acute stroke and a tiny number of training posts in Stroke Medicine for Specialist Registrars. For the equitable provision of emergency treatments for acute stroke such as thrombolysis with alteplase, there will need to be much greater availability of physicians trained and experienced in the use of this potentially hazardous treatment. It is very unlikely that these gaps in the provision of infrastructure affecting ambulance services, Emergency and Radiology departments and medical and nursing personnel and training could be closed within three months if NICE approves the widespread use of alteplase. It is also vital that any attempt to bridge such a gap does not jeopardise services that need to be available for all stroke patients, most significantly Stroke Unit multidisciplinary care. In the latest round of the National Sentinel Audit of Stroke 2004 (publisher: Royal College of Physicians of London, 2005) only 46% of patients with stroke were treated in a Stroke Unit at any point during their stay in hospital. Any change in the priority given to emergency stroke treatment, however appropriate, must not detract from the urgent need to improve the proportion of all patients with stroke with access to specialist services for acute care and rehabilitation. 5