NICE proposes to withdraw Alzheimer's drugs from NHS
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7490.495-a (Published 03 March 2005) Cite this as: BMJ 2005;330:495
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Sir,
I must comment on the advocates of EBM with reference to this debate.
I like many others who oppose the draft guidelines on drugs for dementia
do not oppose evidence based medicine, rather oppose it being a bedfellow
of what appears to be a flawed economic analysis and a somewhat biased
selection of the evidence. EBM also must be placed in the context of
experienced and expert clinical opinion. It seems to be the case with this
guidance, very few if any, of the NICE committee members are experienced
dementia clinicians and this is evident in their lack of understanding of
the good effect of these drugs in clinical practice.
I have read this and recent NICE guidance on mental health technology
with interest. Some seem to be at best no more than what experienced
clinicians have been practicing for years, and at worse exhibit a clinical
naivety divorced from everyday clinical practice. It is time I believe
NICE was counter-balanced by a peer group selected expert consensus
committee perhaps appointed through the Royal College's with equal
resources and decision making powers. For me NICE guidance is now
synonymous with an onerous hurdle to pass for busy clinicians trying to do
best for patients, not a helpful resource and addition to our scientific
understanding of the use of new medical technology.
Competing interests:
I prescribe all four anti-dementia drugs and have received sponsorships and honorarium from Eisai/Pfizer, Novartis, Shire Pharmaceuticals and Lundbeck Ltd.
Competing interests: No competing interests
Dear Sir
It was odd to read Zosia Kmietowicz's report (BMJ 2005, 330,
495)about the proposed withdrawal of a non-existent class of drugs. Of
course cholinesterase inhibitors (also known as anticholinesterases) are
used to treat some patients with Alzheimer's disease. However the article
referred to "anti-cholinesterase inhibitors" , which while it might
describe the attitude of NICE rather well, does not refer to any class of
drugs in current use. Doesn't anyone at the BMJ proofread this stuff?
David Ames
dames@unimelb.edu.au
20/3/05
Competing interests:
Consultancies, research support, conference attendance supported by Pfizer, Janssen and Novartis
Competing interests: No competing interests
Over the past few weeks, patients, carers, physicians and politicians
have raised concerns about the preliminary guidance from NICE to withdraw
drugs for Alzheimer’s disease from the NHS [1,2]. There is still hope that
the Institute may reverse its decision. Regardless, several important
issues deserve mention as they will outlast the polemic surrounding the
Institute’s proposals.
NICE has justified this preliminary guidance on the basis of
insufficient demonstration of clinical and cost-effectiveness for the four
drugs in question. The draft guidance states that the clinical evidence is
imperfect – yet the only change since the time of previous guidance is a
single trial which has been highly criticised by expert psychiatrists [3].
The Health Technology Assessment report, which forms the basis for the
Appraisals Committee decisions, claims that it is too complicated to gauge
the true burden of this disease from existing economic data. Yet it fails
to take into account several recent studies that unanimously point to the
high cost burden posed by Alzheimer’s disease and the potential for the
drugs in question to alleviate some of this burden [4,5]. It also argues
that the economic models presented are based on ‘optimistic’ assumptions
and are methodologically flawed – yet it exempts its own set of
assumptions and modelling approach from such criticism. Finally, the
lynchpin in its decision is that the cost-effectiveness ratio for the
drugs in question is too high. However, the Institute has granted positive
guidance to technologies that had similarly high cost-effectiveness ratios
in the past.
In short, the decision to reverse the previous positive guidance is
based on a single clinical trial and rather speculative economic
modelling. For a disease as devastating and complex as Alzheimer’s
disease, this conclusion is both irresponsible and short-sighted.
It also misses – and, ironically, underscores -- a crucial point:
Alzheimer’s disease is much more than a clinical problem. It is a social
phenomenon as yet unprecedented, which poses a tremendous burden to
patients, their families and society in general. The draft guidance
dismisses the claim, reiterated by the Royal College of Psychiatrists [6],
that these drugs are the only treatment currently available to patients
with Alzheimer’s disease. In fact, that these drugs do anything to improve
the quality of life of patients with Alzheimer’s disease should be
considered significant.
In an early critique of NICE, it was suggested that there the values
espoused by the Institute do not concord with those of the clinicians
expected to apply NICE guidance in practice [7]. This is evident from the
concern raised by professionals in response to this draft guidance.
Alzheimer’s disease is the most significant public health problem
facing us in years to come. There is alarming evidence that our health
care systems, clinical skills, social services, and societies are ill-
equipped to address the scale of this problem [8]. In an audit of mental
health services for older people in England and Wales conducted in 2000,
two-fifths of GPs were reluctant to diagnose dementia early, most of them
did not use protocols for diagnosis, less than half of them felt they had
sufficient training and over a third felt they did not have easy access to
a suitable specialist for their patients. Three-quarters of carers felt
they lacked suitable written information about local services available
[9]. These problems persist to this day.
The social costs linked to Alzheimer’s disease are poorly estimated,
mainly because so much care is provided informally by families.
Decentralisation of social services means that inequities in the provision
of formal care exist throughout the country and that these are poorly
documented. Long-term care expenditure in the UK would need to rise by
about 315 percent in real terms between 2000 and 2051 to meet current
demographic pressures, including those posed by dementia [8].
One may also be informed from the experience of other countries. The
Canadian Coordinating Office for Health. Technology Assessment (CCOHTA),
which was one of the prototype agencies upon which NICE was modelled,
reviewed these same Alzheimer’s drugs in 2001 and recommended their use on
the basis of much of the same clinical and economic data that were
included in the current NICE appraisal. In France, the tragic death toll
amongst older patients during the 2003 summer heat wave prompted the
government to develop comprehensive policies to address the needs of its
older citizens. In 2004, France launched the ‘Plan Alzheimer’, a strategic
plan similar to our National Service Frameworks. In parallel, Social
Security added Alzheimer’s disease to the limited list of conditions for
which all treatment, including drugs, is reimbursed at 100%. The monthly
cost of a donepezil is €100.59; that of rivastigmine is €50.80 per month.
The cost of these drugs is dwarfed by that of paid home care, which is not
reimbursed by Social Security. French patients and their families may pay
€1524 for 8 hours of care per day, and €4573 per month for 24-hour care
[10].
Alzheimer's research is severely under-funded in the UK - only £11 is
spent on research annually per Alzheimer's patient, compared with £289 for
cancer. The care solutions we can offer patients are limited. Most costs
are borne by patients and their families.
The number of people with cognitive impairment is expected to rise by
66% between 1998-2031. 75% of these are patients with Alzheimer’s disease
[8]. 32% of people in nursing care are there because of dementia [11]. The
goals set out in the National Service Framework for Older Persons as well
as those of the NSF for Mental Health are still far from being achieved.
In light of this, one must question how one can even begin to justify
withdrawing four drugs from the NHS that offer relief to patients with
Alzheimer’s disease and cost all of £2.50 a day.
REFERENCES:
1. Minister intervenes in row over drugs to treat Alzheimer’s. The
Guardian 14 March 2005.
2. Iliffe S. A Pandora’s box of policy contraindications. BMJ 7 March
2005.; Livingston G. NICE evaluation of Alzheimer’s disease drugs is
fundamentally flawed. BMJ 10 March 2005.
3. Jolley DJ. NICE and treatments for Alzheimer’s disease. BMJ 12
March 2005.
4. Fillit H, Hill J. The economic benefits of acetylcholinesterase
inhibitors for patients with Alzheimer disease and associated dementias.
Alzheimer Dis Assoc Disord. 2004 Apr-Jun;18 Suppl 1:S24-9.
5. Sano M. Economic effect of cholinesterase inhibitor therapy:
implications for managed care. Managed Care Interface 2004 August; 17(8):
44-9.
6. Royal College of Psychiatrists response to the proposal of the
National Institute of Clinical Excellence (NICE) to withdraw treatment for
Alzheimer’s disease from the NHS – college strongly disagrees with
preliminary recommendation.
7. Dent THS, Sadler M. From guidance to practice: why NICE is not
enough. BMJ 2002; 324: 842-5.
8. Raphael Wittenberg R., Comas-Herrera A., Pickard L. and Hancock R.
Future demand for long-term care in the UK. A summary of projections of
long-term care finance for older people to 2051. Joseph Rowntree
Foundation 2004.
9. Forget me not: mental health services for older people. Audit
Commission 2000.
10.
http://www.doctissimo.fr/html/dossiers/alzheimer/sa_4575_cout_social.htm.
11. Clive Bowman. Continuing Care Conference, International Longevity
Centre-UK, February 2004.
Competing interests:
The International Longevity Centre-UK benefits from a research grant from Pfizer and the Pfizer Foundation for its work on the Alliance for Health and the Future. However, none of the monies received are explictly linked to research on Alzheimer's disease.
Competing interests: No competing interests
I could not agree more with Dr Rumbold, 'In God we trust - all others
bring data.'
Competing interests:
Long term advocate of EBM and member of a number of guideline develoment groups
Competing interests: No competing interests
Going back to expert consensus would surely be against the whole
ethos of NICE which is to institute EBM for the NHS. Experts are part of
the process but their recommendations have to based on good evidence
rather than just opinion.
Competing interests:
None declared
Competing interests: No competing interests
NICE's preliminary guidance (1) on cholinesterase inhibitors in
Alzheimer's disease have rightly pointed out their clinical effectiveness,
in keeping with the views already held by most mental health professionals
who prescribe these medications.
We are pleased that NICE is also using it's resources to assess the
cost-effectiveness of cholinesterase inhibitors. There are some issues
which will need to be taken into consideration before arriving at the
decision that cholinesterase inhibitors should not be used as they are not
cost-effective.
-The current guidance does not take into consideration the efficacy
and/or cost-effectiveness of other forms of treatment. Therefore there is
a risk of replacing an effective treatment modality with one which may be
cost-effective but not effective.
-The guidance does not take into consideration the wishes of an
individual patient and his/her carers,thus denying them a chance of
benefitting from a proven effective form of treatment.
-The calculations of cost effectiveness do not take into account the
cost of treating the overburdened carers, who will have to bear the major
brunt of these changes.
-Implementation of such guidance has a risk of increasing burden and
burnout rates in mental health professionals working with patients
suffering from Alzheimer's disease.
-The money projected to be saved by not prescribing cholinesterase
inhibitors may never reach Old Age Psychiatry services for development of
non-pharmacological treatment methods.
In view of all the above we hope and sincerely wish that this
preliminary guidance is reviewed. Another option to avoid such
controversial guidelines in future would be development of Expert
Consensus guidelines.
(1) Kmietowicz Z. NICE proposes to withdraw Alzheimer's drugs from
NHS. BMJ 2005; 330 :495.
Competing interests:
None declared
Competing interests: No competing interests
Although I do not fully agree with the proposition of the NICE, we
need to
debate if the money spent on acetylcholinesterase inhibitors and memantine
is the best investment for AD patients and their caregivers. In other
words, we
should recognize that 120m£ invested in academic research instead might
lead to the discovery of disease-modifying therapeutic alternatives. At
this
day, AD treatment is a realistic hope, but not a reality.
Competing interests:
Involved in research funded by
public money
Competing interests: No competing interests
We are writing with regard to the National Institute for Clinical
Excellence (NICE) draft guidance on the drugs for Alzheimer’s disease.
The guidance states that these should not be available for new patients on
the NHS because of a lack of evidence of cost effectiveness. Since the
drugs were first introduced in 1997, they have been prescribed to around
50,000 patients in the UK. Clinical experience has shown that response to
the drugs is generally good, with improvement in a number of symptoms,
including memory loss, activities of daily living, psychiatric symptoms
(such as hallucinations) and behavioural disturbances. The moderate yet
clinically significant improvements seen have to be set against the
backdrop of a deteriorating and devastating disease both for patients and
their carers, and the absence of any other specific intervention which
improves, as opposed to merely suppresses, symptoms.
NICE do not question the safety and efficacy of these drugs but, on a
model of cost effectiveness, they conclude that the drugs have failed to
meet the level which would justify their prescription on the NHS.
However, the model used is largely based on measures that do not have
validity in Alzheimer’s disease and did not take into account the effects
of the disease on carers nor the specific positive benefits of the
medications on psychiatric symptoms and behavioural disturbances. The
assessment of quality of life in Alzheimer’s disease and its economic
equivalent quality of life years (QALY’s) is not well developed, the model
does not do justice to the myriad aspects of the disease and insufficient
data are available to support the assumptions presented by NICE. They
have carried out a thorough review of the available literature, but what
is striking from this is the lack of evidence available on which to base
the cost models generated (rather than there being actual evidence of a
lack of clinical or cost effectiveness).
At a time when safety of other drugs used in mental health is being
questioned (e.g. antidepressants and atypical antipsychotics), removal of
the anti-dementia drugs will significantly impair our ability to care for
people with Alzheimer’s disease. Patients in England and Wales will be
disadvantaged compared to those in other countries, we will see a return
of ‘post code’ prescribing of these drugs on the NHS and will leave
private prescriptions the only recourse available to patients and their
families to obtain a licensed and proven treatment. This is not only
against the ethos of the NHS but leaves vulnerable patients open to the
vagaries of the market place.
As clinicians, we believe the conclusions of the draft guidance are
wrong and do not do justice to the complex nature of Alzheimer’s disease.
Alistair Burns
Professor of Old Age Psychiatry, University of Manchester
Rob Howard,
Professor of Old Age Psychiatry, Institute of Psychiatry, London
David Wilkinson
Consultant in Old Age Psychiatry, Southampton
Sube Banerjee
Professor of Old Age Psychiatry, Institute of Psychiatry London
On behalf of the following signatories:
George Alexopoulos, New York USA
Harry Allen, Manchester, UK
Osvaldo Almeida, Perth, Australia
David Ames, Melbourne, Australia
Robert Baldwin, Manchester, UK
JS Bamrah, Manchester, UK
Andrew Barker, Southampton, UK
Susan Benbow, Wolverhampton, UK
Dan Blazer, Stanford, California. USA
Francoise Boller, Paris, France
Henry Brodaty, Randwick, NSW, Australia
Richard Brown, London, UK
Roger Bullock, Swindon, UK
Jane Byrne, Manchester, UK
Pasquale Calabrese, Bocham, Germany
Ed Chiu, Kew, Victoria, Australis
Helen Chiu, Hong Kong
Peter deDeyn, Belgium
Tom Dening, Cambridge, UK
Rachelle Doody, Houston, USA
Engin Eker, Istanbul, Turkey
Thomas Erben, Munich, Germany
Howard Feldman, Vancouver, Canada
Forstl Hans, Munich, Germany
Firmino Horacio, Coimbr, Portugal
George Grossberg, St Louis, USA
Lars Gustafson, Lund, Sweden
Clive Holmes, Southampton, UK
Akira Homma, Tokyo, Japan
Ralf Ihl, Dusseldorf, Germany
Robin Jacoby, Oxford, UK
Dilip Jeste, San Diego, USA
David Jolley, Wolverhampton, UK
Roy Jones, Bath, UK
Salman Karim, Manchester, UK
Cornelius Katona, Kent, UK
Alexander Kurz, Munich, Germany
Brian Lawlor, Dublin, Ireland
Sean Lennon, Manchester, UK
Iracema Leroi, Manchester, UK
James Lindesay, Leicester, UK
Antonio Lobo, Zaragoza, Spain
Constantine Lyketsos, Baltimore, USA
Carlos Mendonca Lima, Prilly, Switzerland
Jacobo Mintzer, Charleston, USA
John O’Brien, Newcastle, UK
Marcel Olde-Rikkert, Nijmegen, The Netherlands
Martin Orrell, London, UK
Richard Oude Voshaar, Nijmegen, The Netherlands
Ross Overshott, Manchester, UK
Mike Philpot, London, UK
Anton Porsteinsson, Rochester, New York, USA
Nitin Purandare, Manchester, UK
Peter Rabins, Baltimore, USA
Joy Ratcliffe, Manchester, UK
Barry Reisberg, New York, USA
Phillipe Robert, Nice, France
Evelyn Russell, Manchester, UK
Philip Scheltens, Amsterdam, The Netherlands
Pierre Tariot, Rochester, New York, USA
Pippa Tyrrell, Manchester, UK
Bruno Vellas, Toulouse, France
Frans Verhey, Maastricht, The Netherlands
Martin Vernon, Manchester, UK
Gunhild Waldemar, Copenhagen, Denmark
Gordon Wilcock, Bristol, UK
Ken Wilson, Liverpool, UK
Bengt Winblad, Stockholm, Sweden
Michael Zaudig, Windach, Germany
The signatories are all specialists in the diagnosis and management
of people with Alzheimer’s disease.
Competing interests:
The authors have received support from the pharmaceutical industry for research and educational activities.
Competing interests: No competing interests
The rapid responses already published in response to this news item
make a number of important observations including the inappropriate use of
the QALY model by Nice and its failure to take account of benefit to
patients and carers in a broad sense. We should also be concerned that
this draft appraisal establishes an expectation that treatments should
result in cost savings or at least be cost neutral. The fact that this is
patently not the case in most other therapeutic areas serves only to
highlight the impression that we are looking at an example of double
standards if not intitutionalised ageism.
Richard Prettyman
Competing interests:
I am a consultant old age psychiatrist involved in the treatment of patients with Alzheimer's disease. I have received lecture fees and honoraria from time to time from pharmaceutical companies that manufacture antidementia drugs.
Competing interests: No competing interests
Can we do better in Alzheimers Disease?
There is a treatment for Alzheimers disease which delays
institutionalisation by an average of 10 months [1] and produces sustained
psychological benefit for carers [2]. It isn't a drug. Shouldn't we be
fighting harder for good supportive care?
1. Mittelman MS, Ferris SH, Shulman E, Steinberg G, Levin B.A family
intervention to delay nursing home placement of patients with Alzheimer
disease. A randomized controlled trial. JAMA. 1996;276(21):1725-31.
2. Mittelman MS, Roth DL, Coon DW, Haley WE. Sustained benefit of
supportive intervention for depressive symptoms in caregivers of patients
with Alzheimer's disease. Am J Psychiatry. 2004;161(5):850-6.
Competing interests:
None declared
Competing interests: No competing interests