Select Committee on Health Written Evidence


Evidence submitted by the Alzheimer's Society (NICE 70)

EXECUTIVE SUMMARY

  The Alzheimer's Society welcomed the establishment of NICE and supports its role of ensuring fair access to clinically effective treatment. We have been extensively involved in the development of two technology appraisals as well as the dementia clinical guideline.

  There are four drug treatments licensed for the treatment of Alzheimer's disease. Their clinical efficacy has been confirmed by gold-standard Cochrane systematic reviews. Benefits extend well beyond outcomes commonly captured in clinical trials such as stabilisation of illness and improvements in function and cognition; and include other key benefits such as being more aware and more active, calmer, taking more interest in things, improved conversation, better quality of life and restored confidence.

Why NICE's Decisions are Increasingly Being Challenged

  NICE are challenged when it is felt their decisions are poor because they are a very powerful body and their decisions have a huge impact on people's lives. Two key reasons for challenges are:

NICE do not give sufficient weight to patient/professional evidence

  Health economic analysis must be placed in the context of people's lives and real life clinical practice. In the experience of the Alzheimer's Society, little weight is given to evidence submitted by people with experience of the drugs. NICE failed to consider that the evidence from patients and carers might be considered on its own merits rather than as pointers for the committee to consider further published research. In addition, the knowledge and experience of clinicians with expertise in the disease area has also been ignored, resulting in guidance that does not translate easily to clinical practice. Methods for incorporating patient evidence into the appraisal process should be developed.

Issues with transparency of decision-making

  Challenges are likely where there is inadequate explanation as to how the appraisal committee arrived at a decision. During the appraisal of Alzheimer's drugs it has been impossible to understand how a number of decisions have been reached.

Whether Public Confidence in the Institute is Waning and If So Why

  Frequent, high profile challenges to NICE will undermine the Institute's authority and reputation. Given the important role of NICE, we believe the Institute must respond to this by seriously addressing the criticisms raised by stakeholders. The failure of guidance to reflect the views of people with experience of treatments and clinicians with expertise in the area damages public confidence in the Institute.

NICE's Evaluation Process and Whether any Particular Groups are Disadvantaged by the Process

  There are specific methodological challenges in using QALYs in dementia. These include:

    —  Difficulties in measuring quality of life in dementia

    —  Capturing benefits to carers

    —  Complexities of funding in dementia care

    —  Capturing the benefits of the drug treatments.

  Unless the wider benefits of the technology are given more weight and the QALY estimates less in cases where QALY estimates are not robust, we believe people with dementia and their carers will be strongly disadvantaged. There is precedent for this—in the 2001 appraisal of Alzheimer's drugs QALY estimates were considered unreliable by the appraisal committee and given little weight.

Appeal Process

  The Alzheimer's Society recommends an independent appeals process is developed and more detail on how the appeal panel reach decisions is provided to appellants.

1.  INTRODUCTION

  The comments we make in this memorandum are chiefly concerned with the technology appraisal process. The memo addresses:

    —  Background to the drug treatments and our involvement with NICE.

    —  Why NICE's decisions have been increasingly challenged.

    —  Whether public confidence in the Institute is waning and why.

    —  NICE's evaluation process and whether any particular groups are disadvantaged by the process.

    —  The appeal process.

2.  BACKGROUND

  2.1  The impact of dementia is vast and as our population ages the numbers of people with dementia will rise rapidly from 700,000 today to over 1 million by 2025.[24] Alzheimer's disease is the most common cause of dementia. There is no known cure, however drug treatments have been developed that significantly improve symptoms in some people. Donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) all work in a similar way and are known as acetylcholinesterase inhibitors. Another drug, memantine (Ebixa), works in a different way and is the only drug licensed for the severe stages of Alzheimer's disease.

  2.2.  The clinical effectiveness of all four drugs has been confirmed by over 30 clinical trials and Cochrane systematic reviews of the trials.[25], [26]People with experience of the treatments report benefits in terms of happiness, awareness and confidence, as well as effects on memory and activities of daily living. NICE agrees that the acetylcholinesterase inhibitors are clinically effective for a significant proportion of people. NICE data show that 34% of people using donepezil in the mild stages of Alzheimer's are responders (according to the 2001 NICE guidance definition of response), compared to 31% in the moderate stage.[27] However, NICE questions the cost-effectiveness of the acetylcholinesterase inhibitors in the mild stages of Alzheimer's. NICE also questions the clinical efficacy of Ebixa, which is particularly puzzling in that it contradicts the findings of the gold standard Cochrane review. Because NICE queried the clinical effectiveness of Ebixa, its cost-effectiveness analysis of the drug was not thorough.

  2.3  The Society was involved as a consultee in the first appraisal of the acetylcholinesterase inhibitors in 2001 and has been extensively involved in the review of that guidance which was extended to include Ebixa. The current review began in 2004 and the Final Appraisal Determination was published in May 2006.  Five appeals were lodged against this guidance, from patient groups, professional bodies and manufacturers. The key points of the Society's appeal were:

    —  NICE's failure to take important benefits of the drugs into account, particularly benefits to carers and reduced need for harmful neuroleptic drugs.

    —  Failures in the economic model, for example it does not measure quality of life of people with dementia properly.

    —  The decision is contrary to good practice in dementia care—treatment in the early stages is what people want.

  2.4  These appeals were unsuccessful and permission has been given for a judicial review of the decision. The Alzheimer's Society has registered as an interested party in this judicial review. We have also acted as consultees in the development of the NICE/SCIE clinical guideline on dementia and Society representatives were members of the Guideline development group.

3.  WHY NICE'S DECISIONS ARE INCREASINGLY BEING CHALLENGED

  3.1  NICE is challenged because it is a very powerful body. Its decisions have an enormous impact on people's lives. However, it is important to note that NICE is not challenged because patient organisations simply dislike its decisions. Groups such as the Alzheimer's Society are challenging NICE because they believe the decision making process was flawed.

NICE do not give sufficient weight to patient/professional evidence

  3.2  NICE has difficult decisions to make and it has developed sophisticated but complex mechanisms to arrive at estimates of cost effectiveness. However, health economic analysis must be placed in the context of clinical practice and the lives of the people who are prescribed the drug treatments. NICE's final decision to allow access to Alzheimer's drugs only in moderate stages is completely out of step with what carers and people with dementia want and the recent direction of dementia policy—early diagnosis and treatment. The knowledge and experience of clinicians with expertise in the disease area has also been ignored, resulting in guidance that does not translate easily to clinical practice. It is therefore not surprising that there was such a huge outcry.

  3.3  NICE was certainly made aware of the strength of feeling of patients, carers and clinicians during the Alzheimer's appraisal via it's arrangements for consulting with stakeholders. However, it is questionable whether this has influenced appraisal committee deliberations.

  3.4  In response to the comments from stakeholders NICE did look at different approaches to estimating costs effectiveness and a range of factors that should be included in the economic analysis. However, there is limited formal data around many of these issues and based on this NICE concluded there was no evidence that factoring in these considerations would make the drug treatments cost-effective. NICE failed to consider that the evidence from patients, carers and professional might be considered on its own merits rather than as pointers for the committee to consider further published research.

  3.5  Patient groups put significant resource towards participating in NICE appraisals and the number of responses received from individuals show that the public is also keen to input. It is essential that NICE examines whether it is putting the information it gathers to effective use. We would welcome a debate around how NICE uses patient evidence, both when there is a lack of formal published data and when patient evidence contradicts the published evidence. Firstly, methods should be developed to incorporate the evidence into the economic analysis. Consensus methodology such as Delphi (a technique which aims to find a reliable consensus opinion from a group of experts) is a potential way of doing this. Secondly, when there is uncertainty around cost per QALY estimates, patient evidence must be given more weight. In our experience, the balance between the weight given to results of a much-criticised economic model and the evidence of people with dementia, carers and professionals has been wrong.

Issues with transparency of decision-making

  3.6  Challenges are also likely where there is inadequate explanation as to how the appraisal committee arrived at a decision. During the appraisal of Alzheimer's drugs it has been impossible to understand how a number of decisions have been reached. Proper explanation must be provided so that consultees can either understand a decision, or challenge the basis of that decision. For example, the Alzheimer's Society was very concerned that withdrawing access to licensed Alzheimer's drug treatments would increase the prescription of dangerous neuroleptic treatments, which increase falls and stroke and can reduce quality of life through over-sedation. We argued strongly that the costs associated with increased prescription of these drugs should be factored into the economic analysis. NICE responded to this by saying: "it was not convinced that inclusion of an element of harm in the economic analysis from further prescribing of antipsychotics as a result of their recommendations was appropriate." (ACD2 and FAD para 4.3.10.4) No explanation was given as to why it was considered inappropriate, making it impossible for us to engage with NICE on this point. If a more constructive dialogue around points of disagreement could take place during the development of guidance it might be that appeals and challenges could be avoided.

  3.7  The lack of depth of explanation in ACDs and FADs is a particular problem given that it is difficult to enter into a dialogue with NICE outside of the consultation process. If a consultee is not satisfied that an argument has been understood or properly considered, there is little opportunity to discuss this with NICE. When we have had specific questions we have been told to put those questions in our comments to the next consultation. While clearly NICE have to control dialogue with stakeholders in order to keep the appraisal process manageable, it would be helpful to have an opportunity to raise questions outside of the consultation process.

  3.8  These problems can leave no option but to follow the appeal process. This is a hugely costly process for patient groups, which any organisation would want to avoid if possible. We believe more transparency in the decision making process could help reduce the number of appeals and we would recommend the following to enable this:

    —  Representatives of patient groups should be able to act as non-speaking observers at appraisal committee meetings at which a relevant technology is discussed.

    —  A full minute of the meeting should be available, with sufficient detail so that it is possible to understand how decisions were reached. We did request a record of the appraisal committee meeting through a freedom of information act request, but this was refused.

    —  Fuller explanations should be provided as to how a decision was reached in FADs and ACDs. "Considered not appropriate" is not good enough.

4.  WHETHER PUBLIC CONFIDENCE IN THE INSTITUTE IS WANING AND IF SO WHY?

  4.1  Frequent, high profile challenges to NICE will undermine the Institute's authority and reputation. Given the important role of NICE, we believe the Institute must respond to this by seriously addressing the criticisms raised by stakeholders.

  4.2  We believe the failure of guidance to reflect the views of people with experience of treatments seriously damages public confidence in the Institute. Little weight has been given to the evidence of these individuals in the Alzheimer's drugs appraisal. This is extremely concerning given that NICE's decisions have such serious implications. The experience of people living with the condition should be the starting point of any technology appraisal.

  4.3  If clinicians are to have full confidence in NICE, guidance needs to be both evidence based and workable in clinical practice. The guidance on Alzheimer's drugs fails in this respect and therefore it is not surprising that the Royal Colleges of Nursing and of Psychiatry and the British Geriatric Society appealed against the final decision. In addition, implementation of the NICE guidance on Alzheimer's drugs means that the UK is virtually the only country in Europe that does not allow access to the drug treatments in the mild stages of illness.

5.  NICE'S EVALUATION PROCESS AND WHETHER ANY PARTICULAR GROUPS ARE DISADVANTAGED BY THE PROCESS

  5.1  NICE have developed a complex evaluation process that is primarily based on generating a cost per quality adjusted life year (QALY). NICE use this generic measure to allow comparative judgements across diseases. We understand the need for NICE to be consistent, however there are specific methodological challenges in using QALYs in dementia, many of which are also found in other long-term conditions. Unless in these cases the wider benefits of the technology are given more weight and the QALY estimates less, we believe people with dementia and their carers will be strongly disadvantaged. There is precedent for this—in the 2001 appraisal of Alzheimer's drugs QALY estimates were considered unreliable by the appraisal committee and given little weight.

  5.2  The problems of applying traditional health economics to dementia include:

Measuring quality of life in dementia

  5.3  The calculation of cost per QALY relies on the measurement of health related quality of life (HRQL) in different disease states. Although key symptoms such as functional ability strongly correlate with quality of life and could be used as a proxy measure, there are currently no validated methods of measuring HRQL in Alzheimer's disease. NICE used an unvalidated method. This fundamental problem seriously compromises the robustness of NICE's model.

  5.4  Furthermore, as the individual begins to lose capacity as dementia progresses, proxy judgements of the person's quality of life are used. This is far from ideal. There is no consensus on who is the best proxy—the literature suggests that professionals may be better proxies than carers on some subscales and family carers better on others.[28]

Benefits to carers

  5.5  Family carers are the mainstay of support for people with Alzheimer's disease. Although providing this support is something that most carers gladly do, it is extremely stressful, and takes a large toll on people's physical and mental health. If a drug means that the person they care for can, for example, be left alone in the house, regains a sense of humour, cooperates in tasks like bathing, the benefits to carers are immense.

  5.6  While NICE's evaluation processes are focused on the individual receiving the intervention NICE do acknowledge that benefits to carers should be incorporated. However, in our experience, NICE have not adequately incorporated these benefits.

  5.7  Despite the deluge of evidence from carers that effective drug treatment benefits carers as much as individuals with dementia, NICE chose to rely on the very limited and weak published evidence around carer quality of life at different stages of dementia. This suggested carers' quality of life does not vary significantly as a person's disease progresses. Based on this NICE chose to assign the very small utility gain of 0.01 to carers when calculating a cost per QALY. We believe NICE should not have accepted this finding unquestioningly, particularly given the strength of evidence from carers contradicting this. NICE must address how to properly incorporate benefits to carers if they are to produce equitable evaluations of interventions. Certainly, in the case of treatments for Alzheimer's disease NICE's evaluation methods have failed carers.

Costs of dementia care

  5.8  The exclusion of costs outside those borne by the NHS and social services is also likely to disadvantage groups where the individual and their family meet a considerable proportion of costs. Unlike other illnesses, people with dementia are disadvantaged by the current system of health care in the UK. The vast majority of formal care is provided by social services and is therefore means tested. In addition, the cost of informal care provided by family members and other unpaid carers makes up one third of the £17 billion that dementia costs each year.

  5.9  NICE has not considered reduced benefit dependency and improved ability to work following effective drug treatment both for patients and their carers, despite this being a recommendation of the Health Select Committee 2002 inquiry. The Dementia UK report concluded that annually carers lose £690 million in income through having to give up employment or cut back their work hours. This lost employment means a loss of £123 million in taxes paid to the Exchequer.

  5.10  Nice has a duty to include the costs and benefits that most fair-minded people would deem appropriate.[29] In cases such as dementia where such a significant proportion of costs are met by individuals and their families, there is a strong case for going beyond costs to NHS and personal social services.

Capturing benefits of the drug treatments

  5.11  The survey carried out by the Society to inform our submission demonstrated that the benefits of the drug treatments extend well beyond outcomes commonly captured in clinical trials such as stabilisation of illness and improvements in function and cognition; and include other key benefits such as being more aware and more active, calmer, taking more interest in things, improved conversation, better quality of life and restored confidence.[30] However, it is difficult to incorporate these types of benefits reported by users and carers into the health economic analysis.

  5.12  NICE's processes are heavily weighted to outcomes measured in clinical trials to the exclusion of other, harder to statistically measure, benefits. This approach will inevitably disadvantage groups where benefits of drug treatments are heterogeneous and hard to capture within a clinical trial. User-defined outcomes reveal what patients and carers think about an intervention in terms that are meaningful for their own lives. This kind of evidence is vital if NICE is to come to proper decisions on the basis of a fully rounded view of new health technologies.

Additional problems in using QALYs in dementia include:

  5.13  The long-term nature of the condition. While people can live with dementia for up to 10 years most clinical trials last for only 6-12 months, meaning that the long-term effects of treatments have to be projected using modelling techniques. This increases the risk of introducing errors. Furthermore, oversimplified models should be avoided if the complexities of a disease and intervention experienced over a long period of time are to be captured. For the Alzheimer's appraisal, NICE developed a model with one cost-driver—moving into full time care. This model is particularly weak at assessing benefits to the subgroup of people with mild dementia because there will be such a time lapse before these individuals move into full time care.

  5.14  Many people with dementia have concurrent health conditions, mainly because they tend to be older people. This can mean that even if dementia was not present the person is less likely to achieve a high QALY score. The impact of this on the economic analyses of treatments should be considered.

  5.15  At the appeal hearing the appraisal committee chair argued that despite the problems in calculating a QALY in dementia `there was no plan B'. This is an inadequate response. The health and wellbeing of many thousands of people with long-term conditions such as dementia are suffering because NICE's model does not work for their condition. NICE have a duty to respond to this by appraising its methods and accepting the challenge of developing a new approach that works for all. We would be happy to work with NICE on developing such an approach.

  5.16  Until such an approach is developed, the Institute has a duty to consider what weight is given to QALY estimates when the robustness of the model is in doubt.

Appeal process

  5.17  Although changes were made to the NICE appeal process following the Health Select Committee inquiry of 2002, the process is still not independent given that it is made up primarily of non-executive directors of NICE. The Alzheimer's Society firmly believes that the Institute must establish a properly independent appeals process if it is to maintain the confidence of the public.

  5.18  In relation to the Alzheimer's appeal, we have concerns around the transparency of the appeal panel decisions. Little explanation was given as to how decisions were reached and why points raised by appellants were ignored.

RECOMMENDATIONS

  1.  Methods should be developed to incorporate patient evidence into the economic analysis. Consensus methodology such as Delphi (a technique which aims to find a reliable consensus opinion from a group of experts) is one way of doing this.

  2.  When cost per QALY estimates are uncertain, patient evidence must be given more weight. In our experience, the balance between the weight given to results of a much-criticised economic model and the evidence of people with dementia, carers and professionals has been wrong.

  3.  Representatives of patient groups should be able to act as non-speaking observers at appraisal committee meetings at which a relevant technology is discussed.

  4.  A full minute of the meeting should be available, with sufficient detail so that it is possible to understand how decisions were reached. We did request a record of the appraisal committee meeting through a freedom of information act request, but this was refused.

  5.  Fuller explanations should be provided as to how a decision was reached in FADs and ACDs. "Considered not appropriate" is not good enough.

  6.  The health and wellbeing of many thousands of people with long-term conditions such as dementia are suffering because NICE's model does not work for their condition. NICE have a duty to respond to this by appraising its methods and accepting the challenge of developing a new approach that works for all. We would be happy to work with NICE on developing such an approach.

  7.  Until such an approach is developed, the Institute has a duty to consider what weight is given to QALY estimates when the robustness of the model is in doubt.

  8.  The Alzheimer's Society firmly believes that the Institute must establish a properly independent appeals process if it is to maintain the confidence of the public.

Alzheimer's Society

March 2007





24   Knapp, M and Prince, M, 2007, Dementia UK (A report to the Alzheimer's Society on the prevalence and economic cost of dementia in the UK produced by King's College London and London School of Economics). London. Back

25   Birks J, 2007, cholinesterase inhibitors for Alzheimer's disease, The Cochrane Database of Systematic Reviews, Issue 1. Back

26   McShane R, Areosa Sastre A, Minakaran N, 2007, Memantine for dementia, The Cochrane Database of Systematic Reviews 2007 Issue 1. Back

27   National Institute for Health and Clinical Excellence, 2006, Donepezil, galantamine, rivastigmine (review) and memantine for treatment of Alzheimer's disease (final appraisal document). http://www.nice.org.uk/page.aspx?o=322952 Back

28   Coucill W, Bryan S, Bentham P, Buckley A, Laight A, 2001, EQ-5D in patients with dementia: an investigation of inter-rater agreement. Medical Care 39:760-771. Back

29   Nice, 2005, Guidance document for consultation, Social Value Judgements, www.nice.org.uk Back

30   Alzheimer's Society, 2004, Drugs for the treatment of Alzheimer's Disease, Alzheimer's Society, London. Back


 
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