Download Alzheimers consultee and commentator comments

ALZHEIMER’S SOCIETY REPORT
Alzheimer's Society response to Nice Appraisal
consultation document 2
February 2006
1. Introduction
The Alzheimer’s Society is relieved that the huge response from people with
dementia, carers and professionals to Nice’s first appraisal consultation
document (ACD) has resulted in Nice reconsidering a total withdrawal of all four
drugs. However, we believe that serious flaws remain in the revised draft
decision and the basis upon which it was made.
Dementia is a devastating condition for the person developing the illness and
for their families. It is a frightening disease and it can make people feel more
afraid and worthless as symptoms progress. The current draft decision
suggests that the experience and values of the person with dementia and their
families have been lost. While Nice must carry out a detailed assessment, it is
vital that the resulting figures are seen in the context of the goals of treatment
and what is important to the people experiencing the illness. It is clear from the
huge and overwhelmingly critical response from both the public and
professionals to the first ACD that both groups are united in believing that the
drug treatments should be available to all who may benefit.
Nice is charged with promoting excellence in clinical practice. The current draft
guidance goes against what is known to be best practice in dementia care (for
example, guidance from the British Association of Psychopharmacology due to
be published in the next few months) and would be extremely difficult to
implement in clinical practice. If this guidance is unchanged it will entail a huge
setback for dementia care, and will have a significant negative impact on the
lives of those in the early and late stages of Alzheimer’s disease.
This response details the Alzheimer’s Society’s comments on the second ACD.
The Society’s 18 recommendations for improving the 2001 Nice guidance on
drug treatments for Alzheimer’s disease are attached as Appendix 1. We
believe that these recommendations should be adopted to enable fair and
appropriate access to drug treatments.
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2. Anticholinesterase drug treatments
“If people could continue to get drugs in the early stages of their disease, the
early stages would simply be prolonged. This is better for everyone both
mentally, emotionally and physically. Trust me.”
Carer
2.1 Withdrawing anticholinesterase drugs from the mild stages is the
wrong decision
The Alzheimer's Society firmly believes that withdrawing access to the
anticholinesterase drug treatments for people with an MMSE of 21 and above is
the wrong decision and is not the most effective way to use the treatments. The
evidence clearly demonstrates that, as used in clinical practice, the drugs are
clinically and cost-effective in the mild and moderate stages of Alzheimer’s.
2.1.1 Stabilisation in the early stages of Alzheimer’s should be the goal of
treatment
The draft recommendation to withhold anticholinesterase treatments from
people in the mild stages of Alzheimer’s suggests a limited understanding of the
goals of dementia care.
We know from our membership that people with dementia and their carers
value stabilisation at the earliest point, as this enables the best possible quality
of life to be maintained for as long as possible. We also know that, based upon
the responder analysis, the anticholinesterase drugs are clinically effective in
the early stages of Alzheimer’s disease. The responder analysis best reflects
the way in which treatments are prescribed in clinical practice and is the
analysis method recommended by all the key professional stakeholder groups
and by the Department of Health. For this reason, it is staggering that Nice is
recommending that people should have to wait until their symptoms progress
before they have access to drugs to stabilise and possibly slow the
deterioration. The recommendation does not support what is accepted as best
practice in dementia care, is contrary to what people with dementia and their
carers want and contradicts the best available evidence.
Stabilisation and a delay in progression in the early stages gives people with
dementia longer in the period when symptoms are mild. At this stage people are
likely to be relatively independent, to be better able to plan together with their
family for the future, and to enjoy hobbies and interaction with others. They
usually experience a very good quality of life with the right support, care and
treatment. People with dementia and their carers talk about the value of this
borrowed time when their relationships are as similar to how they were before
the diagnosis as they will ever be. It would be incredibly frustrating and
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distressing to know that this stage could be preserved for longer, but that they
will have to wait for their symptoms to worsen before any treatment is available.
2.1.2 Clinicians would find it hard to implement the draft guidance
Withdrawing anticholinesterase drugs from those people in the mild stages of
Alzheimer’s disease would also be very difficult guidance for clinicians to
implement. Withholding a potentially effective treatment from a person who
could benefit, especially when this contradicts best practice guidelines, would
create a serious ethical dilemma for most doctors. This is clearly demonstrated
by a recent survey of consultants by the Royal College of Psychiatrists, which
indicated that two-thirds of specialist Old Age Psychiatrists felt unable to
withhold a trial of cholinesterase inhibitor treatment from someone with
Alzheimer’s disease who met the licensing requirements for these treatments.
2.1.3 People who begin drug treatment later never catch up
Importantly, research suggests that people who begin drug treatment at a later
stage never catch up with those who began earlier, strongly indicating that
earlier treatment leads to an improved long term prognosis. Open label
continuation trials support this conclusion. For example, Farlow et al reported
that patients who received placebo for the first 26 weeks and were then
commenced on rivastigmine (Exelon) for weeks 27-52 had a less favourable
outcome than people prescribed rivastigmine from the beginning of the trial (1.4
difference on the ADAS-cog).i An open label extension study of donepezil
(Aricept) supports this conclusion. Patients who received placebo in the original
26 week randomized controlled trial (RCT), and were then commenced on
donepezil declined by 13-18 points on the ADAS-cog over 12 months,
compared to a 10-12 point decline in the group that had received donepezil
from the beginning of the RCT.ii Similar findings were also evident in an open
label extension study of galantamine (Reminyl), where the group who had
received 24 mg/day of the active treatment from the beginning of the RCT were
more likely to maintain ADAS-cog scores near their baseline values than people
only prescribed galantamine in the open label extension phase.iii These studies
provide clear evidence that the drug treatments should be used from the
earliest possible point to maximise benefit. The aim of the Nice guidance should
be to achieve the best quality of life possible for the person with Alzheimer’s, for
as long as possible. A threshold of an MMSE score of 20 would not attain this
objective.
2.1.4 It is harder to demonstrate efficacy in the mild stages of Alzheimer’s
The natural progression of Alzheimer’s means that a drug treatment that slows
progression during the early stages will show a smaller effect size using an
assessment scale such as ADAS-cog. This is because progression of
symptoms is slower in the mild stages than in the moderate stages. Therefore a
drug treatment that delays progression for six months (for example) in the early
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stages will have a smaller magnitude of change than a drug that delays
progression for the same amount of time in the moderate stages. This will
clearly impact on the subgroup analysis and should be taken into consideration
by the committee.
2.1.5 Impact on early diagnosis
Restricting access to the anticholinesterase drugs to people with an MMSE
score of between 10 and 20 will discourage early diagnosis and counteract the
positive work that has gone on in recent years to encourage people to seek
help earlier.
The benefits of early diagnosis are well known. Early detection of dementia
allows individuals and carers quick access to appropriate agencies and support
networks, which can reduce the disabling psychological distress that carers can
experience.iv
Other benefits of early diagnosis include:
• Treatable causes of dementia can be spotted and dealt with.
• People may feel reassured to know their symptoms are the result of a
physical illness.
• It allows people to plan for the future and to access services and benefits.
• As many as one in five people with early Alzheimer’s disease experience
depression that could be identified and treated by a GP. Treatment of
depression improves cognitive function and self care. This is likely to
improve quality of life and probably reduce the level of required support and
hence the cost.
• Consulting GPs would also enable appropriate treatment of vascular risk
factors, which has a substantial stabilizing effect on the progression of
cognitive impairment and functional disabilities in people with vascular
dementia.v
The 2001 Nice guidance has made a huge difference to dementia care but
there is still more to do to promote early diagnosis. We know that people can
wait months or years after symptoms of dementia appear before seeking help.
The growing awareness that there are drug treatments available can only
encourage people to seek help and a diagnosis. In order to be consistent with
the work to support early diagnosis (for example the statement in the NSF for
older people) we believe people with dementia should be considered for
treatment with anticholinesterase drugs upon diagnosis (ie as early as
possible).
2.2 Nice should have used the results of the responder analysis
We were pleased that Nice responded to the Alzheimer's Society and other
consultees and asked for more data to carry out a responder analysis.
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Consultees, including the Alzheimer’s Society, the Royal College of
Psychiatrists and the Department of Health, felt that this was the most
appropriate analysis that best reflected how the treatments are used in clinical
practice.
The results of the responder analysis demonstrated that the cholinesterase
inhibitor drugs are both clinically effective and cost effective across the full
range of mild to moderate dementia.
We are therefore very disappointed that the appraisal committee decided to
disregard the results of this analysis. The ACD states that the committee had
been advised that the analysis was subject to bias and therefore any results
were unreliable. This is a very vague explanation of a decision with serious
implications and more detail must be provided to justify the decision, especially
as any other form of analysis grossly over-estimates the drug costs over the
treatment period.
A responder analysis is the best reflection of how the drug treatments are used
in clinical practice and therefore provide more realistic figures. We believe this
benefit far outweighs problems introduced by carrying out a retrospective
analysis. To ignore the results will mean that the problems identified by
consultees and acknowledged by Nice if non-responders are not removed from
the analysis remain. Any resulting cost-effectiveness figures will be unreliable.
2.3 Ongoing problems with the model
Nice have responded to the points raised by the Alzheimer’s Society and other
consultees about the reliability of the model. However, we do not believe many
of these responses adequately address the flaws raised. Nice have dismissed
some key points with inadequate explanation. We feel strongly that the model
remains flawed and any resulting estimates of cost-effectiveness are unreliable
and inaccurate.
Ongoing problems include:
2.3.1 Utility scores of people with dementia are unreliable
Although Nice report that more work is required to assess whether DEMQOL
could generate utility weightings,vi the findings from this research demonstrate
that quality of life in dementia is extremely complex and that modelling on the
current available data is highly speculative and not sufficiently robust to base a
decision on how the drugs should be used.
Although the modelling is only to inform the committee’s decision making, it is
vital that the most accurate available figures are used. We continue to argue
that if there is an attempt to derive a cost per QALY, it should use the best
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available evidence. The current scores used in the appraisal are based upon
Neumann et al in which carer proxies responded on behalf of people with
dementia using the Health Utilities Index 2 (HUI2).vii, viiiAs the authors point out,
this is a scale which has not been validated for use in Alzheimer’s disease and
certainly not for proxy use. Results should therefore be used with extreme
caution. In the response to the first ACD, we also noted that four of the six
subscales in the index do not change between mild and severe dementia, so it
is completely counter-intuitive to base a model for change between mild and
moderate dementia on these parameters.
Evidence suggests that self-care, but not cognition, is associated with quality of
life. ix Therefore, it would appear valid to use only scores from the self-care
subscale. This results in scores of 0.88 for mild dementia and 0.14 for severe
dementia rather than 0.60 and 0.34.
The Alzheimer's Society recommends that, if Nice continue to use the Neumann
study as the basis for the calculations, it should use these more accurate
figures.
2.3.2 Quality of life carers has not been considered
Improvements to carers’ quality of life continue to be barely acknowledged,
despite the huge response from carers to the original ACD. As reported in
Nice’s summary of the 7,748 comments received:
• Over a third of respondents pointed out that improvements brought about by
taking the drug treatments to patients’ cognitive functioning or quality of life
also brought benefits to carers.
• 20 per cent queried whether carers quality of life had been properly
considered.
This concern was also raised by the Department of Health, as well as other
consultees. It therefore seems incredible for the appraisal committee to be
satisfied that a 0.01 increment for carer utility is sufficient.
We have already highlighted that although Nice attempted to include carer
benefit in the model, the method used was flawed. Again, many of the
subscales (eg cognition) seem to have little relevance to carers’ quality of life
and the carers surveyed had no experience of the drug treatment.
It states on page 40 of the ACD2 that although at any point in time a carer may
have a higher utility if the person they cared for was benefiting from drug
treatment “the effect of the drug would be to delay progression of the condition,
in which case the carer would still be faced at some time in the future with the
same difficulties caused by disease progression.” This statement brings into
question the committee’s understanding of why carers feel so strongly about the
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drug treatments. Carers are all too aware that the drugs are not a cure and
Alzheimer’s is a progressive disease. However, it is the delay in symptom
progression that carers value and that allows them to enjoy more time with the
person they care for before symptoms are more advanced.
The Society acknowledges that data are not available, but as the guide to the
methods of technology appraisal points out, patient evidence can identify the
limitations in the published research literature. We believe this is the case with
carer quality of life and, based on reports of carers, greater weighting must be
given to improvements in carer quality of life.
2.3.3 Reduction in carer time ignored
Despite evidence being available to demonstrate that the drug treatment can
save an hour a day of carer time,x Nice have chosen not to include this benefit.
The guide to the methods of technology appraisal states “If the inclusion of a
wider set of costs or outcomes is expected to influence the results significantly,
such analyses should be presented in addition to the reference case analysis.”
(para 5.3.3.1) The Alzheimer's Society believes reduction in carer time is an
important outcome of the drugs that would influence the results of the costeffectiveness analysis considerably and therefore should be included.
2.3.4 The increased prescribing of neuroleptic drugs treatments is ignored
The model also fails to consider the cost of reduced prescription of neuroleptic
drug treatments with anticholinesterase drug use, demonstrated by a metaanalysis of US and European data from clinical trials (reduction in neuroleptic
use from 25 per cent to 9 per cent following anticholinesterase treatment).xi This
is a very important benefit that has been dismissed by Nice as inappropriate for
them to consider without any kind of justification.
Neuroleptic drugs are not licensed for use in Alzheimer's disease and have
certainly never had their clinical and cost effectiveness assessed. They are
known to have harmful side-effects, including worsening the symptoms of
dementia and increasing the risk of falls and of stroke. In addition, the additional
cost of prescribing a neuroleptic for one year is an estimated £750, which
should be costed in the model. The Alzheimer’s Society believes the model
must include the benefits of reduced neuroleptic prescription that follows
anticholinesterase drug treatment.
2.3.5 Inadequate costs of care used in model
Nice report that they have used a reasonable cost of care, but the Alzheimer’s
Society strongly challenges this. We have argued that £355 per week for full
time care is a serious underestimate that does not consider the full range of
care used by people with dementia. The two most expensive types of care,
specialist units for people with special needs and NHS continuing care, cost in
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excess of £1,000 per week. Full time care for younger people with dementia
can also cost in the region of £1,500 per week. Research tells us that over the
five-year period of the model the majority of people would be expected to move
to a more specialised level of care (figures from Ballard et al, 2002).xii In
addition, 10 per cent of the people moving care facilities require a period of time
in psychiatric in-patient facilities (a standard admission would be four to eight
weeks) to stabilise the situation before the transfer to a new care facility can be
achieved. This is just the “headline cost” of the care facility and does not
account for the considerable additional care and treatment received by these
individuals.
The Alzheimer's Society recommends that the average cost of care is increased
to a more realistic level and an estimated cost of 0.5 days per annum of
psychiatric in-patient care should be added to the per patient per annum cost.
2.4 Additional points
2.4.1 The MMSE is not suitable for identifying who will benefit from drug
treatment
The Society does not believe the MMSE is an appropriate tool to identify people
who may benefit from drug treatment. It is a screening tool, and has not been
validated as a mechanism for identifying the different stages of dementia. The
test is biased and relies heavily on language. Level of education and learning
disabilities will also impact on scores. If it was to be used to identify people with
an MMSE of above 20, people with good language skills and a high level of
education will be at a disadvantage. When it comes to assessing whether the
drug treatment should be stopped as an MMSE of 10 has been reached, this
group would be at a significant advantage. People with English not as their first
language, with dysphasia as part of illness and with lower levels of education
will be disadvantaged.
There is also a risk that people will try to deliberately score lower in order to
have access to the drugs and clinicians may want to score more harshly. This
has clear negative consequences for an effective clinician/patient relationship.
2.4.2 Restricting prescription of anti-dementia drugs may impact on
memory clinics
The creation of memory clinics as a result of the Nice 2001 guidance has been
discussed in the Society and others’ submissions to Nice and there is
considerable concern that funding will be withdrawn if prescription is further
restricted. Their role as a hub of services is important and they should play a
role in the new ‘community hospitals’ that the Government discuss in their
recent health and social care white paper.
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2.4.3 Clinicians should choose the most suitable drug for each individual
The ACD states that the anticholinesterase drug with the lowest acquisition cost
should be the first choice. The Alzheimer's Society challenges this. The drugs
have different methods of titration, with the cheapest drug requiring more visits
to the specialist clinic. This should clearly be taken into consideration. The
clinician should use their own judgement to decide which the most appropriate
drug is for each individual.
2.5 Conclusion
The Alzheimer’s Society condemns the draft decision to withdraw
anticholinesterase drugs from people in the mild stages of the illness. This
recommendation does not support what is accepted as best practice in
dementia care, is contrary to what people with dementia and their carers want
and contradicts the best available evidence. In order to maximise benefit, the
anticholinesterase drugs should be prescribed as early as possible. We
recommend that people with dementia should be considered for treatment with
anticholinesterase drugs upon diagnosis.
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3 Memantine
“Without any exaggeration, our lives changed almost overnight. Mum became
quieter and noticeably less violent within the first couple of weeks.,, wash times
and especially cleaning her teeth became much less dreaded – the heavily
physical attacks, accompanied with high pitched screaming, simply stopped.
Now she has started tapping you on the arm to look at birds flying past the
window… All generally making for a much more varied, interesting and happy
life for everybody.”
Carer of a person taking Ebixa
The Alzheimer’s Society is hugely disappointed that Nice have not reversed
their March 2005 decision that memantine (Ebixa) should not be prescribed to
people in the moderate to severe stages of Alzheimer’s disease. This is the only
effective drug treatment available for this stage of the disease and it is hugely
valued by people with dementia and their carers. We believe there is evidence
of both the clinical and cost effectiveness of memantine and it should be
available initially as a trial to everyone in the moderate to severe stages of
Alzheimer’s disease.
The benefits brought by the drug treatments to people with behavioural
symptoms are particularly important. The evidence that memantine is effective
at reducing these distressing symptoms is an important motivation to make the
drug available.
3.1 Clinical effectiveness
The Nice review confirmed that trials of memantine were of generally good
quality and showed benefits on a number of outcomes. A 2004 Cochrane
review of memantine also found that it had a beneficial effect.xiii This has been
confirmed by people with dementia and their carers. In the Alzheimer's Society
2004 survey, of the 66 people who had tried memantine (and had no
experience of an anticholinesterase drug) 69.7% felt it was beneficial. One
carer told us:
‘My husband has only been on memantine for one week and already the
change in his condition has been remarkable. Previously, he was unable to go
to the toilet unaided. Now he can. He is in a care home and he was not able to
walk by himself. Now he is up and about.’
The Alzheimer’s Society considers that Nice has not sufficiently acknowledged
the evidence of clinical efficacy and this has resulted in an unfair final
conclusion from the committee.
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We believe that the pooled analysis should use the results of both the two
memantine monotherapy RCTs and the memantine plus donepezil RCT.
Although donepezil is not licensed for the severe stages of Alzheimer’s, it is
licensed for the moderate stage and we know of a number of people with
dementia who have benefited from taking the two drug treatments. The
evidence suggests this may be the best treatment option. In addition, it is
harder to demonstrate benefit from memantine in patients who are already
stabilised on donepezil, so the positive results from this trial should be given
more weighting. A carer told us:
‘My husband has early onset Alzheimer's which was diagnosed over three
years ago and was prescribed Aricept with amazing results and then for the last
year has, in addition, been prescribed Ebixa which, until very recently, enabled
him to continue at work.’
As demonstrated by the quote above, for some people memantine brings a
considerably improvement. However, even the small changes it can bring for
others are very important in the later stages of Alzheimer’s. We highlighted
these in our original submission, but feel it is important to reiterate them to
ensure their importance is not lost:
• Memantine may help the person retain the ability to speak a few words. This
could mean that they are able to ask to go to the toilet or say when they are
hungry or thirsty, helping to avoid dehydration or malnutrition.
• Retaining some mobility may mean that hoists and the distress they cause
are avoided. It can also mean that the person is less likely to get pressure
sores.
• If the person with dementia is able to feed themselves, they are less likely to
suffer from dehydration or malnutrition. This is particularly likely when they
are in hospital or in a care home, where care staff may not be aware that
they are not eating or drinking adequate amounts.
An important benefit of memantine is enabling people to maintain key skills that
may delay moves to more specialised care or may enable them to remain at
home. The Alzheimer’s Society believes that a key consideration of clinicians
considering prescribing memantine should be whether it may enable a person
to maintain key skills therefore delaying a move from the home or to more
specialist care.
Treatment with memantine should continue if there are no severe adverse
effects or significant deterioration and a positive benefit is shown.
3.2 Memantine is particularly effective for behavioural symptoms
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“Before Ebixa was given 18 months ago, most people at the day care home,
including some residents, had felt Mary’s fist or hand. That could not have been
continued.”
As a result of evidence which suggests memantine is particularly effective for
those people with behavioural symptoms such as aggression and agitation Nice
asked for further data from the manufacturer to explore this subgroup. These
symptoms are extremely distressing for both the person with dementia and their
carer. Memantine’s impact on these symptoms is important for a number of
reasons.
•
These symptoms are often those that the carer finds most difficult.xiv They
are linked with carer depression.xv In addition, carer quality of life is
negatively correlated with agitation/aggression as well as total
neuropsychiatric inventory (NPI) score.xvi
•
Data from the final field test of the DEMQOL system confirms that quality of
life in dementia is statistically significantly correlated with higher levels of
behavioural and psychological disturbance (based on NPI total score and
agitation, depression, anxiety, disinhibition and irritability subscales).ix A
regression analysis shows that behavioural problems account for 52 per
cent of the variance in quality of life, patient age with 31 per cent and
cognition with only 16 per cent.
•
The only alternative drug treatments for these symptoms are neuroleptics,
which have undesirable side effects and are not licensed for use in
Alzheimer’s disease. (discussed in more detail on page 13)
•
Research from the US also shows that the presence of behavioural
problems adds to the costs of dementia, by 247-409 USD per year per NPI
point (depending on whether carer costs are included).xvii
For these reasons, we believe the impact of memantine on behavioural
symptoms must be given far greater weighting by Nice. It can improve the
quality of life of both the person with dementia and their carer. Furthermore, a
reduction in aggression and anxiety following treatment with memantine leads
to cost savings. The cost effectiveness analysis must accurately capture these
important benefits of memantine.
3.3 Behavioural subgroup should have a clinically relevant threshold
The evaluation for the sub-group of people with behavioural or psychiatric
symptoms included within the NICE draft appraisal document seems to indicate
adequate cost-effectiveness therefore indicating that the treatment should be
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made available for these individuals. The important point that is raised in the
report however is whether this constitutes a valid sub-group.
For four key reasons it is clear that people with Alzheimer’s disease with
behavioural or psychiatric symptoms do represent a meaningful sub-group of
patients.
•
A number of studies using cluster analysis or principle component analysis
techniques have shown distinct groups of individuals with
behavioural/psychiatric symptoms emerging as independent clusters.xviii
•
The course of Alzheimer’s disease is different for individuals with
behavioural or psychiatric symptoms, with more rapid decline evident in
individuals experiencing these symptoms; and demonstrating that this subgroup of people has a different prognosis.xix
•
Genetic studies have linked identified polymorphisms to key behavioural and
psychiatric symptoms and post-mortem studies have demonstrated different
profiles of neurochemical changes in theses individuals. This clearly
indicates important biological associations which strongly support the validity
of people with behavioural o psychiatric symptoms as a distinct sub-group.xx
•
Behavioural and psychiatric symptoms form a distinct and important clinical
treatment indication in people with Alzheimer’s disease, for which
pharmacological treatments are frequently prescribed.
We do however suggest two caveats to the analysis presented by Lundbeck.
•
Clinically significant agitation, for which pharmacotherapy may be
appropriate would usually be defined as an NPI score of 4 or above.
•
Based upon published data,xxi memantine is much more effective for the
treatment of the specific behavioural syndrome agitation, than for psychosis
or other behavioural syndromes.
We would therefore recommend that clinically significant agitation in people with
moderate to severe Alzheimer’s disease should be a key indicator for treatment
with memantine. Treating this more focussed group (about 20% of the trial
population) is likely to be particularly cost effective as these are the individuals
most likely to be moved to nursing home or more expensive care facility
accommodation and the individuals most likely to be prescribed other
psychotropic drugs.
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3.4 Neuroleptic use
Nice’s assessment of memantine does not consider the reduction in use of
neuroleptic drug treatments. These are the only alternative drug treatments for
symptoms such as aggression and agitation, which are often experienced in the
moderate to severe stages of illness.
Despite not being licensed for the treatment of Alzheimer’s neuroleptics are
frequently prescribed. One study found they were prescribed to up to 40 per
cent of people with dementia in care homes and 22 per cent of people with
dementia in their own homes.xxii
Neuroleptic drugs are known to have harmful side-effects including increasing
confusion as well as the risk of falls and stroke. A reduction in their use could
improve health-related quality of life as well as produce cost savings from a
reduction in resulting medical problems linked to falls and strokes. This is in
addition to the cost savings on the neuroleptic drugs, which are approximately
£750 per year. We believe it is vital that the model takes this into account.
The ACD states that the committee did not feel it was appropriate to include an
element of harm from increased use of neuroleptics in the assessment of
anticholinesterase and does not refer to neuroleptics in the discussion of
memantine. The Alzheimer’s Society believes this is a serious omission and
looks to see a correction before the next committee meeting. As previously
stated, Nice’s objective is to promote clinical excellence. Reduction in
neuroleptic use through prescription of memantine would help to achieve this
aim. This must be factored into the model.
3.5 Ongoing problems with the analysis
From the analyses presented memantine appears cost effective. However, in a
more sensitive cost model which addressed the following points and also
looked at concurrent medical costs resulting from loss of key skills (for example
due to increased risk of falls, dehydration, etc) it would appear more costeffective.
3.5.1 Carer quality of life
There seems to be no additional benefit given for the improvement in carer
quality of life following treatment with memantine. While there may be limited
data available, we know from our membership that carers do value the benefits
that memantine can bring.
‘Memantine is excellent and has made a huge difference to both of our lives;
the improvement was evident within a few weeks. We have really got our lives
back.’
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There is evidence that carer quality of life is linked to neuropsychiatric
symptoms, which memantine is effective in reducing.xvi This should be factored
into the cost-effectiveness model. In addition, in the absence of research
evidence on memantine’s impact on carer quality of life (beyond that related to
reduction in neuropsychiatric symptoms), we believe more weight should be
given to patient evidence. As previously noted, the guide to the methods of
technology appraisal points out patient evidence can identify the limitations in
the published research literature. We believe this is the case with carer quality
of life and, based on reports of carers, greater weighting must be given to
improvements in carer quality of life.
3.5.2 Costs
The costs Nice have used in the memantine model seem unrealistic, particularly
for people in the moderate to late stages of Alzheimer’s who would be using this
treatment. As for the anticholinesterase drug treatments, the costs used do not
take into account the full spectrum of care used by people with dementia, in
particular NHS continuing care, which can cost well over £1,000 a week. The
points raised on page 7 of this submission apply to memantine as well as the
anticholinesterase drug treatments and highlight why more appropriate costs
should be used.
3.6 Additional points
3.6.1 Removing memantine as a treatment option removes choice
Currently, people in the moderate stages of Alzheimer’s who do not respond to
the anticholinesterase drug treatments have the option of trying memantine.
The implications of Nice’s draft decision are that this group will have no choice
in treatment. The anticholinesterase drug treatments do not work for everybody
and some people are not suitable for them. We believe it is important that those
people have the option of trying memantine. To recommend that memantine is
not available through the NHS takes away any treatment options for those
people.
3.6.2 Corrected data should have been provided promptly
The incorrect table was printed in the MRC biostatistics unit report and this was
not corrected until the publication of the ACD. Nice have a duty to provide
complete and accurate information to consultees to allow them to take a full part
in the process. We believe this mistake should have been rectified, with the
correct information sent to consultees as soon as Nice were aware of it.
3.7 Conclusion
The Alzheimer's Society believes that people should be considered for
treatment with memantine when they are in the moderate severe stage of the
disease. Key considerations should be the presence of clinically significant
agitation and whether memantine may enable a person to maintain key skills
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therefore delaying a move to more specialist care. To monitor the efficacy of
memantine, clinicians, in consultation with carers, should determine which skills
are key for the individual with Alzheimer's disease. A successful outcome of
treatment with memantine would be retention of these skills and/or reduction in
agitation.
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4 Conclusion
While the Alzheimer’s Society was somewhat relieved that the original ACD
decision has been changed, we do not support the current ACD
recommendations. The clinical benefits of all four drug treatments and their
positive impact on dementia care as a whole is now established. It is vital that
they are used in way that gets the maximum benefit from them. In 2004 the
Society submitted evidence which contained 18 recommendations which we
believe would further improve the 2001 Nice guidance on anticholinesterase
drugs. This should be the goal of the revised recommendations. The Society
believes that the current draft guidance would have the reverse effect.
The Alzheimer's Society believes that all four drugs for Alzheimer's disease
should be available through the NHS, following clinical assessment, to all
individuals who might benefit from their use.
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