Abacus International, Bicester
Institute of Psychiatry, London, UK
Correspondence: Juliet Warner, Abacus International, 34 Market Square, Bicester OX26 6AA, UK
Declaration of interest This project was sponsored by Novartis Pharmaceuticals UK Ltd.
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ABSTRACT |
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Aims To model the impact of increased clozapine prescribing on lives saved and resource utilisation.
Method A model was built to compare current levels of clozapine prescribing with a scenario in which all suitable patients with treatment-resistant schizophrenia received clozapine.
Results It was estimated that an average of 53 lives could be saved in the UK each year. If clozapine is cost-neutral, the cost per life-year saved is £5108. If clozapine achieves a 10% reduction in annual support costs, the net saving is £8.7 million per annum. An average of 167 acute beds would be freed each year.
Conclusions The use of clozapine in treatment-resistant schizophrenia saves lives, frees resources and is cost-effective.
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INTRODUCTION |
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Clozapine has been shown to be more effective than conventional neuroleptic drugs in reducing both the positive and negative symptoms of schizophrenia (Wahlbeck et al, 1999), being effective in around 60% of all patients with treatment-resistant disease (Meltzer et al, 1990). Studies in the UK and USA now show that clozapine may also reduce the risk of suicide (Meltzer & Okayli, 1995; Munro et al, 1999).
Although the average annual acquisition cost of clozapine is significantly greater than that of either typical or atypical drugs (£2920 and £1770 respectively), clozapine has been shown to significantly decrease in-patient stay and therefore total health service costs (National Institute for Clinical Excellence, 2002).
The aim of this study was to model the potential impact of increased clozapine prescribing on patient mortality and the resulting resource implications.
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METHOD |
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The model compared the impact of extending current levels of clozapine prescribing to all those with treatment-resistant schizophrenia who were willing to take the drug and were compliant with therapy. Although 30% of patients are reported to have treatment-resistant illness (Meltzer, 1997) and are therefore potentially suitable for clozapine therapy, a proportion will decline therapy or not comply. Accordingly we assumed that only 20% of patients would be treated with clozapine and that 60% of this group would experience sufficient clinical benefit to remain on treatment (Meltzer et al, 1990). The percentage of patients currently prescribed clozapine was derived from data provided by the Clozaril Patient Monitoring Service.
Modelling the rate of suicide
In each scenario, patients were divided into those receiving clozapine and
those receiving conventional neuroleptic therapy. No comparison was made with
other atypical neuroleptics, as clozapine remains the only medication licensed
for use in patients with treatment-resistant schizophrenia.
The annual incidence of suicide in people with schizophrenia was calculated from data presented in Safer Services: National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (Appleby, 1999). The reduction in risk experienced by patients on clozapine therapy was taken from Munro et al (1999). In this study of 12 760 patients, those treated with clozapine experienced a four-fold decrease in the expected risk of suicide compared with the general population with schizophrenia. The annual incidence of suicide in people with schizophrenia was combined with the findings of Munro et al in order to calculate suicide rates for patients prescribed cloza clozapine and those treated with other drugs. These incidence rates were then applied to the two patient groups, those on clozapine therapy and those on standard neuroleptic therapy. The resulting number of suicides was combined to give a total figure for each year.
Cost calculations
Costs were divided into patient support and suicide costs.
Cost of patient support
Annual support costs were calculated using a weighted average cost of
£5127 per patient per year. This was based on an incident patient cost
to the National Health Service (NHS) of £8740
(Guest & Cookson, 1999) and
a prevalent patient cost of £5038
(Knapp et al, 2002).
Using these figures, a weighted cost was calculated based on the proportion of
incident and prevalent patients (the incidence of
schizophrenia being 1/10 000 (Turner,
1997) or 2.4% of the population with schizophrenia).
Patients surviving each year were assumed to incur the total annual support cost, whereas those who committed suicide were assumed to incur only half this figure. This uses the concept of half-cycle correction and is based on the assumption that equal proportions of patients die in each month of the year. Some die in the first month, avoiding management costs for the whole year, whereas others die in the last month, having used 12 months of health care resources. Arithmetically, this is the same as assuming that all patients who die do so at month 6.
Clozapine therapy and the cost of patient support
Evidence suggests that treatment with clozapine is either cost-saving or
cost-neutral when compared with standard neuroleptic therapy
(Revicki, 1999; details of a
recent unpublished systematic review are available from the author upon
request). Guidance from the National Institute for Clinical Excellence
(2002) has estimated that
clozapine generates savings regardless of whether the patient has previously
been treated with a typical or an atypical antipsychotic drug, and that the
levels of savings are similar. In our analysis, costs were calculated for both
scenarios, one in which clozapine was assumed to be cost-neutral and a second
in which it was assumed to be cost-saving. In the cost-saving scenario,
support costs were reduced by 10% for all patients taking clozapine
(Aitchison & Kerwin, 1997). This is relatively conservative in relation to the recent estimates from the
National Institute for Clinical Excellence.
Cost of suicide
A cost of £187 was applied to suicides
(Netten & Dennett, 1996). This figure includes only general hospital costs and is
therefore narrow in its definition, excluding the considerable consequences
associated with distress and lost productivity.
Acute bed requirement calculations
Utilisation of acute bed days was calculated from hospital episode
statistics for schizophrenic psychosis
(Department of Health, 1996). These data suggest that 16.7% of people with schizophrenia use acute
in-patient services each year, with an average length of stay of 129.7 days.
The number of days hospitalised was reduced by 16.9% for people treated with
clozapine (Rosenheck et al,
1997). Other studies have reported reductions in
hospitalisation, but this figure is less easily applied to the
calculation of a reduction in bed days.
Life-years saved calculations
Life-years saved were calculated on the assumption that the life expectancy
of a person with schizophrenia at diagnosis is 37 years
(Davies & Drummond, 1993).
It was assumed that the average life expectancy of a patient at any one time
was half this figure.
Discounting
When estimating the cost-effectiveness of treatments that have an impact
over extended periods, it is common practice to discount both future costs and
benefits. This reflects the fact that people attach a lower value today to
benefits and costs that occur in future years. Outcomes were discounted at
1.5% and costs at 6% in accordance with recommendations. We have reported our
results both with and without discount rates applied.
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RESULTS |
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Cost-neutral scenario
In the cost-neutral scenario (Table
2) the additional cost associated with keeping patients alive was
approximately £3.8 million per year. A proportion of this cost was
offset by savings that result from a reduction in the number of suicides.
These savings totalled approximately £10 000 per year. Our analysis
indicates that current support costs are just over £1300 million per
year. An incremental £3.8 million therefore equates to a 0.3% increase
in the cost of patient support. The cost per life-year saved was
£5108.
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Cost-saving scenario
In the cost-saving scenario (Table
3), the additional cost associated with keeping patients alive was
more than offset by savings that accrue when patients are switched from
conventional neuroleptic therapy to clozapine. Based on a 10% reduction in the
cost of support for those receiving clozapine, the total cost of support fell
by more than £8.7 million per year. Taking into account the £10
000 saved as a result of fewer suicides each year, the net annual saving
totalled approximately £8 748 000.
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Acute beds
If more patients are kept alive, the impact on hospitalisation and
therefore acute bed requirements is very positive. Studies show a reduction in
hospitalisation among patients receiving clozapine therapy
(Meltzer et al, 1993;
Rosenheck et al,
1997). Modelling this effect led to a saving of 167 acute beds in
the UK per year.
Sensitivity analysis
A sensitivity analysis was carried out by varying the suicide risk
reduction experienced by patients on clozapine therapy . patients on
conventional neuroleptic therapy from 25%
(Meltzer et al, 1993) to 75% (Munro et al,
1999), the cost of patient support between £5038
(Knapp et al, 2002)
and £8740 (Guest & Cookson,
1999), and the reduction in the support cost of patients receiving
clozapine from a 0% cost saving (i.e. cost-neutral;
Revicki, 1999) to 50%
(Meltzer et al,
1993). Ten thousand random scenarios were generated using figures
ranging between the lowest and highest of these estimates. Suicides avoided,
life-years saved, cost per life-year saved and cost savings were recorded
based on the current UK population.
The mean number of suicides avoided was 35 per year (95% CI 34.9635.09), the average number of life-years saved at 20 years was 6833 (95% CI 6831.86834.3) and the average cost per life-years saved was £6864 (95% CI 6863.46864.7). Cost savings occurred in 94.4% of cases and averaged £29.8 million per year (95% CI 29.7929.82).
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DISCUSSION |
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Clozapine therapy
Schizophrenia is a major cause of suicide. Those most at risk are those
who, despite medication, experience persistent positive and negative symptoms,
depression and hopelessness, characteristics apparent in those resistant to
treatment. In such patients, clozapine has been shown to reduce suicidality in
a controlled trial setting. Real life data from over 12 000
patients prescribed clozapine have further supported this observation. In
terms of both the quality and quantity of evidence for the effectiveness of
any given mental health intervention in preventing or reducing suicide,
clozapine probably has the strongest supporting data. This study has shown
that, given expected levels of efficacy, clozapine could prevent approximately
53 suicides per year, thus meeting 5.3% of the Government's target.
Impact on NHS budgets
The impact on NHS budgets and resource use requires some consideration.
Prescribing clozapine keeps more patients alive. Although such cost
considerations would not be used to prevent the introduction of a treatment,
it is none the less important for health planners to be aware of the budgetary
impact of a new prescribing policy. This study sought to highlight the
economic impact of a clozapine-based strategy to reduce rates of suicide. The
majority of published health economic studies and reviews have suggested that
clozapine is cost-saving when used in treatment-resistant schizophrenia,
mainly owing to a reduction in hospitalisation. This analysis suggests that
the additional cost of keeping patients alive is more than offset by expected
savings.
However, this analysis takes no account of the resource and cost impact of attempted suicide. It is expected that an analysis of these data would strengthen the case put here, but would require more thorough modelling to address the issue.
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Clinical Implications and Limitations |
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LIMITATIONS
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Received for publication October 3, 2002. Revision received January 7, 2003. Accepted for publication January 7, 2003.
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