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.
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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