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Measuring the economic benefit of treatment with atypical antipsychotics
Eur Psychiatry 1998;13 (Suppl 1):37s45s 0 Elsevier, Paris
Measuring the economic benefit of treatment with atypical antipsychotics MRJ Knapp Personal Social Services Research Unit, London ,ichool of Economics and Political Science, Houghton Street, London WCZA 2AE Centre of the Economics of Mental Health, Institate of Psychiatry;, De Crespigny Park, Denmark Hill, London SE8, UK
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Summary - Schizophrenia has a major impact on the quality of life of sufferers, and its broader impact on families and on society are well known, although less thoroughly documented. The m;Ljority of sufferers require long-term treatment and support, and there are depressingly frequent media stories about violent incidents involviq: people with the illness. Consequently the costs of schizophrenia, broadly defined, loom large, not just from the perspective of health care decision-makers and governments, but also from that of sufferers and their families, to many other people with only indirect experience of the disease. schizophrenia
/ costs / society / atypical
antipsychot
.cs I economic
INTRODUCTION The enormous and persistent personal and I ocial consequences of schizophrenia have long been rl:cognised. The chronicity of the illness and its impact c n so many aspects of cognition, health, functioning, ant1 quality of life leave many sufferers and their families with devastated lives and facing many costs. In addit,on, health care and other agencies, in caring for people with schizophrenia in hospital or in community settings, in supporting their families, and in endeavouring .o treat the symptoms and the clinical and social sequclae of the illness, incur potentially considerable costs. The consequences of schizophrenia, therefore, tin be farreaching and expensive. As well as its obvious and many implications for patients and their families, the fact that schizophrenia has a large economic impact has generated interest in its cost dimension. Surprisingly, this interest is relatively new, although it is now quite perva:;ive in the sense that many modes of treatment are the subject of economic research, and most countries in the developed world have recognised the need for economic insights. What, then, are the costs of schizophrenia and how might they be reduced by better treatments while maintaining or improving effectiveness? BROAD COSTS OF IMPACT The costs of schizophrenia
fall widely: to the patient,
evaluation
to the patient’s family and other caregivers, to the health care system, and to the wider society. Each of these needs to be recognised. The fragmentation of care systems and the pressures of cost containment in many countries are, unfortunately, encouraging ‘cost shifting’: one agency or stakeholder has a greater opportunity and a greater incentive to reduce its own expenditure by limiting the volume or range of treatment, but in so doing it may - unwittingly or otherwise -- increase levels of expenditure by other parts of the care system or by patients and their families. Cost to the patient As we know, the consequences of schizophrenia to the patient can be far-reaching and long-term. Few people recover from an episode of schizophrenia to the extent that they return to a pre-illness level of functioning (Shepherd et al, 1989). The illness strikes at interpersonal relationships, making it more difficult for sufferers to initiate and maintain meaningful close friendships and other relationships. Self-care and related capabilities can also be damaged, making it difficult for sufferers to carry out or maintain the normal activities of daily living without help. In the labour market, people with schizophrenia find it harder to get paid jobs and to keep them, such is the competitive nature of employment now. This of course directly affects their income, even in countries with reasonably generous social security systems, and also limits the size of their
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social networks, thus lowering self-esteem and social status. Schizophrenia also damages other aspects of life, such as sexual functioning and performance. People with schizophrenia also have a higher risk of mortality (Alleback, 1989). Each of these negative consequences of the illness has a cost. Some costs are direct - such as the loss of employment - while others are more indirect and perhaps not intuitively expressed in monetary terms,
health services, and primary care. Within these services, some proportion of expenditure - usually a modest proportion - will be accounted for by medications and associated laboratory and diagnostic tests. How do these various health care costs stack up? The costs of treating schizophrenia expressed as a proportion of total health care expenditure appear to be fairly consistent across much of the developed world, usually between 1.5 and 2.5 per cent in European and North American countries.
Costs to caregivers Costs to the society In general, people with schizoph *enia in most northern European countries are less likely to be living with their families than is often the case in southern Europe or in most of the developing world. It is widely recognised, however, that the illness ofter results in families, friends, neighbours, or volunteer helpers offering substantial amounts of informal caregiver support. By their very nature, many of the costs of caregiver support are hidden from view, and certainly I hey are not easily reduced to monetary measures, even though they can be sizeable. For instance, Rice et al ‘1990) estimated that the time costs alone of caregiver support for people with schizophrenia in the USA amounted to $2.5 billion a year. The caregiver support provider1 to people with schizophrenia living outside hospital a nd specialist residential facilities can cause substantial psychological strain as well as personal risks to caregivers, although by no means all of the effects should be seen as negative (Szmukler, 1996). Direct costs may be incurred by the need to pay for some treatment or support services, but it is the indirect costs associated with the effects on family routine and relationships, work and leisure opportunities, mental and physical health, distress, stigma, and guilt which can be SC substantial (Schene et al, 1994). These broader and lor.ger-term impacts on caregiver quality of life and health help to explain why the UK reforms introduced in the I 990 National Health Service and Community Care Act placed such emphasis on supporting family caregivers. Costs to the health care system When the issue of the costs of schizophrenia is raised, most people tend to think first af health care costs. These are, after all, the most direct and most easily identified costs of treatment and support. The direct costs include expenditures on in patient hospitalisation, out-patient services, day treatment, accident and emergency services, the various community mental
Finally, there are the wider costs to society. Of course, ‘society’ in its broadest sense bears all of those costs mentioned above, plus certain other direct care costs falling outside the health care system, particularly those associated with social care (social welfare) services, special housing, criminal justice services, and social security or income support. With the rapid movement away from hospital-based treatment to care in community settings in many countries, these various agencies are playing an increasingly important part. The often significant indirect social costs would clearly include the wider impact on society of patients’ or carers’ lost employment and associated lost productivity. There may be further societal costs associated with fears that psychiatric patients living in the community might be a danger to themselves or to others. A series of violent incidents, some tragic, involving schizophrenia sufferers in the UK have, for example, generated some quite widespread concerns about personal safety (Audit Commission, 1994; Ritchie et al, 1994). Most of these indirect societal costs are particularly difficult to measure, but arguably no less important than the more readily computed direct costs when considering the broader social and economic impact of schizophrenia. TOTAL COSTS Pulling these patient, caregiver, health care, and social costs together reveals the enormity of the economic impact of schizophrenia. A common approach to demonstrating this impact is to offer cost-of-illness estimates. For the USA, for example, Rice et al (1990) estimated a total cost of illness of $38 billion. Of this total, direct health care treatments accounted for 53%, indirect costs of lost income/productivity and premature mortality 37%, and other costs (social welfare, criminal justice, and so on) 10%. There is no reliable equivalent figure for the UK, but
Economic tenefits of atypical
antipsychotic
Balance of public expenditure
Balance of care Living independently
- primary care
Living independently Specialized
supported Short-stay
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treatments
- specialist
accommodation hospltaliratlon
Long-stay hospitalization Special hospital (Broadmoor...) Homeless In prison
el. 14%
1%
10%
20%
I
I
30%
40%
1 50%
% patients with schizophrenia
Fig 1. Schizophrenia
10%
20%
30%
40%
50%
% patients with schizophrenia
- care and costs in England (from Kavanaugh et al, 1995).
if we use the National Health Service Execul ive (1996) programme budgets and the ‘bottom-up’ e:.timates of Kavanagh et al (1995), plus an estimate of indirect costs from Davies and Drummond (1994), we filld that the total national cost of schizophrenia inEnglard in 19921993 amounted to roughly $4.2 billion (Knapp, 1997). Cost-of-illness estimates are available for Eome other countries - for instance, $0.4 billion for Tie Netherlands in 1989 (Evers and Ament, 1995) and 1,O.l billion for Australia in 1975 (Andrews et al, 198:‘). Both of these latter amounts need inflation to current price levels to make them more meaningful. Such costs are currently being built up for a number of othel,countries. These sums are invariably enormous amounts of money, and they clearly point to the major economic and social consequences of what remains an incurable, debilitating disease. There are, however, serious methodological reservations about the relevanl:e of such cost-of-illness figures (Drummond, 1992). There are at least two ways to proceed frc m cost-ofillness estimates of this kind. The first is to work with the disaggregated data contained within tht: total estimates of the costs of a disease. One illustra ion of this is offered by our own research in England, where we constructed estimates of the treated prevalence of schizophrenia from various sources, and then calculated the direct costs of treatment and support for each of the main accommodation settings (Kavanagh ei al, 1995). A highly summarised picture of the resultz.nt balance and costs of care in England is given in figure 1. Interestingly, although more than half ofthe iden ified cases
lived independently, receiving their treatment from primary health care and/or specialist psychiatric clinicians, only 11% of total direct public expenditure is accounted for by these people. On the other hand, 5 1% of total public expenditure is allocated to the 14% of schizophrenia sufferers living in hospital settings. THE COST OF HOSPITALISATION It is obvious from the figures for England (fig 1) and equivalent data for other countries that one of the largest cost components in the treatment and support of people with schizophrenia is hospitalisation (in-patient care). The economic importance of hospitalisation stems not from the fact that a high proportion of people are living in hospital, but from the high per diem cost of an in-patient stay. In the UK, for example, the daily cost on an acute psychiatric ward is currently around &126, and it is higher in London (Netten and Dennett, 1996). In the more specialised settings, such as an intensive care psychiatric unit or a high-security unit, the cost can be as high as &321 per day (Hyde and Harrower-Wilson, 1995). Outside hospital, but still within the specialist accommodation sector, highly staffed residential facilities can cost much more than &400 per week, even without the need for secure provision, and not including the cost of all the non-residential services used (Chisholm et a1,1997). For patients whose florid symptoms of schizophrenia are many years behind them and who have been discharged from long-stay psychiatric hospitals to com-
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Table I. Restrictions on use of atypic;, antipsychotics. Results based on a postal questionnaire members of the Royal College of Psychiatrists in the UK during April-July, 1995 (n = 761).
Psychiatrists who Have Have Have Have Have Have Think Think
never prescribed this drug no patients on this drug currently five or more patients receiving this drug been challenged about the cost of this drug experienced formal rationing of n lmber of patients prescribed this drug experienced informal guidelines/ritioning drug cost inhibits its use drug cost Dossib[yinhibits its use
survey of ‘social/community
psychiatrist’
Clozapine %
Risperidone %
19 35 25 46 10 14 20 24
12 25 35 52 6 I1 17 23
Source:Hogman(1996).
munity accommodation settings, hospitalisation continues to figure large in their ‘c:re packages’, and the associated costs can be significant (Beecham et al, 1997). Those long-stay resident!; in psychiatric hospitals who need secure provision. but who must move from the old asylums as they are closed down, can easily impose weekly costs of over 6.1000 (Hallam, 1996). For people in the acute phases of their illness, in-patient admissions can be frequent and lengthy. Two further European examples illustr;,te how hospital care dominates costs. In an evaluation of the Maudsley Hospital’s Daily Living Programme [an alternative to hospitalisation for patients facing a crisis admission), 86% of the total care and treatment costs for the control group receiving standard care in the UK were accounted for by in-patient stays in the first four months after the randomisation which sil;nalled the start of the research period, and 69% over t le first 20 months. In the fourth year of the study, holipitalisation costs accounted for 10% of the total COSIs of care, and 54% of the health care costs (Knapp et al, 1994). The second illustration comc:s from Italy, which passed legislation nearly 20 years ago to close all psychiatric hospitals. Even in this r;.ther different service context, in-patient hospital stay!; (now in psychiatric beds in general hospitals) represtnted 40% of the total health care costs over a one year period (Amaddeo et al, in press). One third of the 1315people with schizophrenia and related disorders who were on the South Verona case register and who had at least one contact with psychiatric services during 1he year had an in-patient episode, the mean duration of which was 87 days. The high costs of hospitalisation are particularly pertinent in the context of the discussion of the atypical antipsychotic drugs because a large proportion of people with schizophrenia are readmitted to hospital after their first episode. This is one of the reasons why psychiatrists and health care budget holders are keen to
find affordable treatments which are more effective and/or which help to improve patient compliance or adherence (Weiden and Olfson, 1995). About a third of acute patients show little or no improvement with standard antipsychotics (Macmillan et al, 1986). This is one reason why there is such interest in the development of the new antipsychotics. THE ATYPICAL ANTIPSYCHOTICS The new antipsychotics have been labelled atypical because of their ‘efficacy in refractory patients and against negative symptoms, and reduced capacity to induce extrapyramidal side effects, tardive dyskinesia, and elevate prolactin’ (Lieberman and Fleischhacker, 1996). But the two new antipsychotics that have been marketed for longest - clozapine and risperidone could also be called atypical because of their high prices. The many other ‘atypicals’ now being launched onto world markets will be similar in having prices considerably higher than those that currently apply to standard treatment modes. Of course, the price of any new antipsychotic varies from country to country, but can range from between 50 times and 100 times the price of the conventional antipsychotic drugs (see, for example, Hogman, 1996). The higher price is leading to restrictions on the use of the atypical antipsychotics. This is shown by a very interesting study by Hogman (1996) on behalf of the National Schizophrenia Fellowship, based on a postal questionnaire survey of ‘social/community psychiatrist’ members of the Royal College of Psychiatrists in the UK during April-July 1995. A total of 761 completed questionnaires were returned (59% response rate). A summary of some of the key survey findings is given in table I, which reveals that surprisingly low proportions of psychiatrists were prescribing the two ‘atypicals’ available in the UK in 1995. The survey
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Economic benefits of atypical antipsychotic treatments
exposed what Hogman interprets as misundt:rstandings among community psychiatrists as to some key characteristics of clozapine and risperidone - fcr example, in relation to blood monitoring and side-effect profiles, 10% of psychiatrists felt that the need for b ood monitoring made risperidone unsuitable. Some of the most interesting findings, however, relate to actual and perceived costs and their mpacts on prescribing patterns, also summarised in ta >le I. Hogman interprets these findings as showing th’: small but significantformal impact of drug price. Although relatively large numbers of psychiatrists felt th;it cost was a factor that affected the use of atypical dlugs, especially clozapine, far fewer translated this into the actual practice of formal rationing. However, a small but significant number of psychiatrists are limited n their use of these two new antipsychotics, even though the level of prescribing seems comparatively low (Hogman, 1996). Clearly, there have been restrictions on the use of the new antipsychotics in the UK. More generally, there are budgetary and other restrictions now operating in a number of countries (Bloor and Freemantle, 1996). One consequence of restrictions of this kind, building on the often substantial differences in treatment preferences and practices between different heal] h care systems and different cultures of psychiatry, is that the percentage of patients with schizophrenia being prescribed the atypical antipsychotics will tiary from country to country, and probably markedly (‘Gerlach J, unpublished results 1996). Despite these in:emational differences, it is becoming increasingly common in all countries to hear pharmacy budget holders, clinical managers, political leaders, and others voice concern about the high prices of some of the new rr edications becoming available. These are valid concerns, and at one leve it is heartening to hear that cost consciousness is abroad within health care systems. However, although tota I spending on drugs can be a sizeable part of total health care expenditure (around 10% in England; Depitrtment of Health, 1994) and is growing (Freemantle md Bloor, 1996), it must not be forgotten that drug cDsts are in fact a much smaller proportion of the total health care and other costs of treating schizophrenia. F:ecent calculations from NHS programme budgets for England suggest a proportion of only 4% (Knapp, lS97), and it may be as small as 1% in some countries (Evers and Ament, 1995). Nor must it be forgotten that the newer drugs are showing greater effectiveness in relation to some symptoms, behaviours, and side effi:cts. Most worrying, perhaps, is that a wide-ranging in emational
by Bloor and Freemantle (1996) could find no ‘methodologically sound evaluations of incentive systems aimed at prescribers’. In other words, we do not yet know what the effects of budgetary or other restrictions are on those who prescribe drugs. review
HIGH PRICE...
LOW COST?
Two of the most pressing questions in the treatment of schizophrenia currently remain unanswered: Are the higher prices of the atypical antipsychotics outweighed by either improved symptoms or better quality of life for patients or their caregivers? Are the overall treatment and support costs reduced now or will they be in the future? Neither question is easy to answer, yet without answers it would be premature to support or to block the wider use of the new drugs on economic grounds. It would, of course, be irresponsible, because of the dangers to patient health or quality of life, to promote a new treatment without evidence on efficacy. Equally, there is a need for evidence on cost and cost effectiveness before decisions on policy and practice are taken that might later be regretted because of their financial implications, or because affordable opportunities to improve patient quality of life have been missed. A new treatment mode does not have to demonstrate that it is less costly than alternative modes in order to be cost effective, but it must demonstrate that any increase in costs (compared to its closest alternative) is at least matched by increased effectiveness or reductions in non-drug related costs. In forming a view of cost effectiveness, the evaluative perspective ought to be broad and long-term, for the network of potential associations and causal impacts are many and complex (fig 2). The narrowest direct costs of treating schizophrenia (see the left-hand side of figure 2) are the expenditures on drugs, psychosocial therapies, and other mental health care supports and services. These treatments hopefully have a direct impact on some or all of a number of dimensions of patient and caregiver health and quality of life: the positive and negative symptoms of schizophrenia, personal and family functioning, social interactions, subjective quality of life, satisfaction with services, caregiver burden, societal fear, and so on (Lehman et al, 1995). The atypical antipsychotics aim to be more effective than the ‘standard agents’ in achieving improvements along one or more of those dimensions. They also aim to be more effective via the indirect route of having fewer side effects and thereby possibly encouraging better compliance.
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Reatments and costs
Intermediate effects
Medications I+1
sid!ZTcts
Fig 2. Treatment,
W
Better compliance
t
I)
improved symptoms...
. ..less health care
I)
Better functioning...
. ..less supportneeded
I)
Better access to resources...
...more employment
I)
Improved quality of life...
. ..belier integration
I)
Reduced caregiver burden...
. ..more employment
W
Satisfaction with services...
...less disruption
*
Societal outcomes...
...fewer externalcosts
outcome, cost-offset.
Directly or indirectly, the consequence could be significant cost reductions in the longer term because of the need for less support from wealth care, less social services, better functioning, gre;lter participation in the labour-force, and reduced family burden. Although there is currently little reliable evidence on the longer term cost effectiveness of treatment with atypical antipsychotics, and certainly none ,.vhich is robust for the UK, community psychiatrists l.esponding to the National Schizophrenia Fellowship Survey questionnaire were of the opinion that long t:rm cost-effectiveness would be achieved (Hogman, 1!)96). ECONOMIC EVALUATIONS To address the core questions of relative costs and outcomes, it is clear that thorough economic evaluation is needed. There are four main types of evaluation, each with different data demands, aid each with different uses and possibilities. Evaluative
Cost reductions in longer term from:
/
Psychosocial therapies
treatment services and supports
Outcomes
criteria
Economic evaluations have tended to concentrate on the criteria of effectiveness, economy, efficiency, and equity (justice), either singly or in combination. Economy is the saving of resources, ;md its pursuit requires detailed data on costs, but no at ention need be paid to the impact of lower spending UKon patients or families (the outcomes of treatment). Economy is the criterion addressed in the simplest of cos evaluations (cost-off-
set and cost-minimisation analyses). Effectiveness is conventionally defined in terms of improvements to patient and family health and quality of life; costs are disregarded. There are whole batteries of instruments to measure effectiveness, scaling and scoring psychopathology (including specific measures related to specific aspects of the disorder), social functioning, family and peer group relations, and so on. Economic evaluations include effectiveness measures on such instruments, but a steadily increasing number are also including unidimensional ‘utility’ measures (see below). The criterion of efficiency combines the resource (cost) and effectiveness dimensions. The pursuit of efficiency could mean reducing the cost of achieving a given level of effectiveness, or improving the volume and quality of outcomes achieved from fixed budgets. Efficiency can seem to be a controversial objective, but properly understood and put in the appropriate context it ought to be widely acceptable. Efficiency is not a euphemism for ‘cutback’, for it can sometimes be promoted by spending more, not less. Efficiency is sometimes examined in combination with the fourth criterion of equity (or justice). Equity is not the same as equality. Targeting services on needs is one example of adopting an equity criterion, although even this has efficiency implications and interpretations. Modes of evaluation The three most useful and common modes of economic evaluation are cost-effectiveness analysis, cost-benefit
Economic benefits of atypical antipsychotic
analysis and cost-utility analysis. (See reviews in Drummond et al, 1997; Kavanagh and Stewart, 1995.) These modes have some common elements, particularly in relation to cost definition and measurement, but they differ in two main respects: they measure outcomes using different techniques, and consequently they address slightly different policy or practice questions. (Two other modes of evaluation - cost-offset and cost-minimisation analyses - do not measure outcomes. Cost-of-illness or burden-of-illness studies are not evaluations as such, although they are increasingly used as preludes to cost-effectiveness or other analyses. They calculate all direct and indirect costi resulting from an illness.) Cost-benefit analysis (CBA) is unique in that it addresses the extent to which a particular course of action, such as a new form of pharmacological or psychosocial therapy, is socially worthwhile. All costs and benefits are valued in the same units - usually in term of money - and can thus be directly compared. The simple comparison of ‘costs incurred’ with ‘costs save’d’ is not a CBA but a cost-offset analysis. Conducting; CBAs is particularly rare because of the difficulty of valuing benefits in monetary terms. Cost-effectiveness analysis (CEA) is cono:rned with ensuring that resources allocated to the treatment of schizophrenia, or to another activity, are used to maximum effect. CEA is usually used to help decision makers choose between alternative interventions available to or aimed at specific patient groups: 11’two treatments for acute schizophrenia cost equal amounts, which provides the greater benefits? Or if two treatments are equally beneficial in terms of their impact on patients or populations, which is the less costly? When CEAs have been conducted in the mental hl:alth field, generally batteries of functional and symptom-based outcome measures have been used, of the kind familiar to clinical evaluators from their own studie2.. Cost-utility analysis (CUA), the newest mode of economic evaluation, is similar to CEA w th the important exception that it measures and then values the impact of an intervention on a patient’s hes lth-related quality of life as well as the cost of achieving that improvement. The value of health improvement from a treatment is measured in conflated units of ‘utility’, in contrast to CBA, which uses monetary val les. CUAs avoid the potential ambiguities with multi-d mensional outcomes in CEAs, and can be applied to chc ices across a range of treatments or diagnoses: they can compare one clinical area to another distinct area. [f properly conducted, they could compare antipsychotic treatment of schizophrenia with kidney dialy:;is or che-
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motherapy or osteopathy for lower back pain. The most common value measure of health outcomes used in CUAs is the quality-adjusted life-year. Despite their inherent attractiveness, and their growing use across a wide span of health care contexts, CUAs have rarely been used in evaluations of schizophrenia. These different modes of evaluation have a common aim in their approach to cost measurement, which - if a broad (societal) perspective is adopted (which is usually the case), is to include all direct and indirect costs, estimated as long-run (marginal) opportunity costs. The modes obviously differ with respect to their measurement of outcomes. Informed decision-making in relation to the treatment of schizophrenia needs a range of economic evaluations, although few such prospective evaluations have yet been conducted on atypical antipsychotics. There is insufficient space in this paper to summarise the available evidence, some of which is of debatable quality (Knapp, 1997), but instead the paper now turns to some methodological inadequacies in completed studies. In concluding this paper, I shall advocate certain improvements in the conduct of economic evaluations in this field. METHODOLOGICAL DEVELOPMENTS The published economic evidence on the atypical antipsychotics (and on other therapies, whether pharmacological or psychosocial) is mostly conjectural, partial, or flawed. The most damaging flaws are summarised in the left hand column of table II, with recommendations for methodological improvements in the right hand column. It is unnecessary to go through each pairing of flaw and improvement in detail, as the difficulties posed by the former are well known and the opportunities afforded by the latter are widely appreciated. However, some points should be emphasised. Firstly, there is no adequate substitute for direct observational data, even though delphi panels and decision trees are helpful in cutting through complex conceptual issues and in making informed projections beyond the period covered by prospective trials. The arguments for and against decision modelling as an alternative to direct observation have been widely aired (Sheldon, 1996), and ultimately the choice comes down to the quality and generalisability of the findings in a particular context. Modelling is helpful in the absence of decent observational data, or to supplement it, but needs a good information base from real-world settings if it is to be more than idle (or indeed partisan) speculation. A more straightforward choice is represented by the
MRJ Knapp
44s Table II. Economic evidence: present imperfect... imperatives.
future
Present imperfections
Future imperatives
Delphi panels and decision trees Imported from abroad Retrospective Matched design Short-term Narrow inclusion criteria Limited comparators Adjunct therapies excluded Small sample Variations ignored Service impact - hospitahsation Costs - narrow range Cost distribution ignored Outcomes evidence not integrated
Dire:t observation Comext-specific research Pros 3ective Ram lomised design Long;-term Gemmlised patient group Wide: range of comparators Adjunct therapies included Larg : sample Vari;uions explored Serv ce impact - comprehensive Cost-comprehensive Cost distribution explored Outcomes integrated with costs
second line in table II. In the absence of country-specific data (from decision model!; or direct observation) it has been common to import findings from abroad, and sometimes offering assumpt ions as to the relevance of the methods or the context. It would be invidious to cite examples. Prospective data are usually to be preferred to retrospective data, particularly when a randomised controlled design is used. Matched ot case-control designs have their advantages for some purposes, but generalisability and robustness tend to be better with randomisation. Long-term studies are more helpful than shortterm studies. As with other peirings summarised in table II, the meaning of the fla\vs and the advantages of the improvements apply with 3s much force to economic evaluations as they do to clinical evaluations. It is more generally straightforward to conduct clinical trials for people with schizophrenia if the patient inclusion criteria are narrowly drawn (for example, to exclude comorbid alcohol or drug abuse problems), if the number of comparator treatments is kept small (typically to two), and ifadjunct Iherapies are ruled out. But high proportions of schizophrenia sufferers have comorbid problems and make use of combinations of pharmacological and non-pharmacological treatments. Decision-makers need to become skilled at generalising from the tidy, narrowly desig led trial data currently available to the untidy reality of everyday clinical work. Cost-effectiveness projections from available data to the context of the real vlorld are certainly far from straightforward. As studies become larger, including more patients and fcr longer periods, it becomes more feasible to include a wider range of patient circumstances (including: comorbidities) and treatment combinations. But it then becomes essential
to interrogate
the data thoroughly, particularly through the statistical analysis of inter-patient variations in outcomes, needs, and costs, both across and within samples, and even within randomised trials. Finally, there are perhaps four flaw-improvement pairings relating to the comprehensiveness of data. Studies which make inferences about the resource consequences of alternative treatments on the basis only of hospitalisation data risk missing a wide spectrum of other service impacts. Even though hospital admissions dominate costs, the increasing reliance on communitybased interventions makes it highly desirable that the picture that is painted is of a comprehensive service (and hence calculation of comprehensive costs). The distribution of the cost burden between different agencies - and between formal services, family caregivers, and patients themselves - warrants especially close attention in the increasingly fragmented care systems of many countries (such as the UK), because there are many cost-shifting incentives inherent in these systems. The last line in table II states an obvious desideratum to integrate evidence on costs with outcome findings, but one which has particular pertinence as mental health care systems become more complex, and as associated evaluation designs necessarily become more sophisticated. It is clearly important that new evaluations tell us not only the comprehensive costs associated with a new treatment, including the costs associated with all side effects and all indirect costs associated, for example, with lost employment, but also how those costs are linked with treatment outcomes. New economic evaluations should pull together cost data with outcome or effectiveness data to tell us which alternatives give the best cost and outcome combinations. A new drug might prove to be more expensive than the standard drug currently in use, or a new configuration of community services might be more expensive than the old arrangement, but the new drug or service configuration might also be more effective. Economic evaluations should be designed to tell us whether it is worth spending the additional amounts of money in order to reap these additional benefits. CONCLUSION As noted earlier, the costs of relapse in schizophrenia, stemming from lack of treatment efficacy and/or noncompliance, can be especially high and persistent. Consequently, health care decision-makers need to evaluate carefully any new treatments which promise to tackle one or both of these root problems. The atypical antipsychotic agents (both those currently available
Economic
lxmefits of atypical antipsychotic
and those soon to be launched) are clearly promising in both regards, but their take-up and use havt: not been appreciable. Kerwin (1996) poses several reasons for this in the UK: costs; the false perception of ,zew drugs as dangerous; for clozapine, too strict a d@inition of treatment resistance; for risperidone, reserving its use in a clinical decision tree after first line treatments have been tried; jinally, many psychiatrist:, are concerned about compliance andprefer depot medication. Some of the concerns about costs are na vely constructed and misinformed, but there is a genuine widespread desire to know whether the consideraaly higher prices of the new drugs generate compensittory payoffs in terms of better health, quality of life, and other outcomes, and/or lower downstream costs. The price of a new drug is usually a small proportion of I otal treatment cost, so that a key unanswered economi z question is whether the broader and longer-term costs are higher or lower, and whether the outcomes are such as to generate system-wide cost-effectiveness. The need for well-designed evaluations is paramount. With the advent of the atypical antipsychotics, that need has extended into new areas. But c ost-effectiveness questions cannot satisfactorily be ar swered in ‘after-thought studies’: they need to be planned carefully and integrated into evaluative designs from the outset. REFERENCES Alleback P. Schizophrenia: a life-shortening disease. Schiz Bull 1989;15:81-9 Amaddeo F, Beecham JK, Bonizzato P, Fenyo A, Knapa MRJ, Tansella M. The use of a case register for evaluating the costs of psychiatric care. Acta Psychiarr Stand, in press. Andrews G, Hall W, Goldstein G et al. The economic costs of schizophrenia: implications for public policy. Arch Ceil Psychiatry 1985;42:537-43 Audit Commission. Finding a Place. London: HMSO ; 1994 Beecham JK, Hallam A, Knapp MRJ, Baines B, Fenyo P., Asbury M. Costing care in the hospital and in the community. 11: Leff J, ed. Community Care: Illusion or Reality? Chichester: Fr’iley; 1997 Bloor K, Freemantle N. Lessons from international e tperience in controlling pharmaceutical expenditure 11: influencing doctors. Br Med J 1996;312:1525 Chisholm D, Knapp MRJ, Astin .I, Beecham J, Audini 13, Lelliott P. The costs of residential care for people with mental health problems in eight services. J M Health 1997 Davies LM, Drummond MF. Economics and schizophnnia: the real cost. BrJPqchiarry 1994;165 (suppl 25):18-21 Department of Health. Healthand Personal Social Servl.es Statistics for England. London: HMSO ; 1994 Drummond MF. Cost-of-illness studies: a maior headaclte? Phurma coeconomics 1992;2: l-4
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Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the Economic Evaluation ofHealth Care Programmes 2nd ed. Oxford: Oxford Medical Publications; 1997 Evers SMAA, Ament AJHA. Costs of schizophrenia in the Netherlands, Schizophr Bull 1995; 21:141-53 Freemantle N, Bloor K. Lessons from international experience in controllingpharmaceuticalexpenditure1: influencingpatients. Br Med J 1996;312:1469-71 Hallam A. Costs and outcomes for people with special psychiatric needs. Ment Health Res Rev 1996;3: 10 Hogman G. Is Cosi a Factor? London: National Schizophrenia Fellowship 1996 Hyde C, Harrower-Wilson C. Resource consumption in psychiatric intensive cam: the cost of aggression. Psychiatr Bull 1995; 19:73-6 Kavanagh SM Stewart A. Economic evaluations of mental health care: modes and methods. In: Knapp MRJ, ed. The Economic Evaluation of Mental Health Care. Aldershot: Arena, 1995 Kavanagh S, Opit L. Knapp MRJ, Beecham J. Schizophrenia: shifting the balance of care. Sot Psychiarr Epidemiol 1995;30:206- 12 Kerwin RW. An essay on the new antipsychotics. Pvchinrr Bull 1996;20:23-9 Knapp MRJ. Costs of schizophrenia. Br JPsychiarv 1997;171:50918 Knapp MRJ, Beecham JK, Koutsogeorgopoulou V, Hallam A, Fenyo A, Marks I et al. Service use and costs of home-based versus hospital-based care for people with serious mental illness. Br J Psychiany 1994;165: 195-203 Lehman AF, Thompson JW, Dixon LB, Scott JE. Schizophrenia: treatment outcomes research. Schizophr Bull 1995;21:561-6 Lieberman JA, Fleischhacker WW, eds. Current Issues in the Development of Atypical Antipsychotic Drugs. Br J Psychiatry 1996;168 (suppl29) Macmillan JF, Crow TJ, Johnson AL, Johnstone EC. The Northwick Park study of first episodes of schizophrenia. III Short term outcome in trial entrants and trial-eligible patient. Br J Psychiarry 1986; 148: 128-33 National Health Service Executive. Burden of disease. London: NHSE ; 1996 Netten A, Dennett J. Unit Costs of Health and Social Care 1996. Canterbury: Personal Social Services Research Unit, University of Kent at Canterbury ; 1996 Rice DP, Kehnan S, Miller LS et al. The Economic Cosrs ofAlcohol and Drug Abuse and Mental Illness: 1985. Rockville: National Institute of Mental Health DHSS Pub No (ADM) 90 -1694 ; 1990 Ritchie JH, Dick D. Lingham R. The Report of the Inquiry into the Care and Treatment of Christopher Clunis. London: HMSO ; 1994 Schene AH, Tessler RC Gamache GM. Instruments measuring family or caregiver burden in severe mental illness. Sot Psychiatp Psychiatr Epidemiol 1994;28: 11-6 Sheldon T. Problems of using modelling in the economic evaluation of health care. Health Econ 1996;5:1-12 Shepherd M, Watt D, Falloon I et al. The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenics. Psych Med 1989;15:1-44 Szmukler G. From family burden to caregiving. Psychiatr Bull 1996;20:449-51 Weiden PJ Olfson M. Cost of relapse in schizophrenia. Schizophr Bull 1995;21:419-29
Measuring the economic benefit of treatment with atypical antipsychotics MRJ Knapp Personal Social Services Research Unit, London ,ichool of Economics and Political Science, Houghton Street, London WCZA 2AE Centre of the Economics of Mental Health, Institate of Psychiatry;, De Crespigny Park, Denmark Hill, London SE8, UK
;
Summary - Schizophrenia has a major impact on the quality of life of sufferers, and its broader impact on families and on society are well known, although less thoroughly documented. The m;Ljority of sufferers require long-term treatment and support, and there are depressingly frequent media stories about violent incidents involviq: people with the illness. Consequently the costs of schizophrenia, broadly defined, loom large, not just from the perspective of health care decision-makers and governments, but also from that of sufferers and their families, to many other people with only indirect experience of the disease. schizophrenia
/ costs / society / atypical
antipsychot
.cs I economic
INTRODUCTION The enormous and persistent personal and I ocial consequences of schizophrenia have long been rl:cognised. The chronicity of the illness and its impact c n so many aspects of cognition, health, functioning, ant1 quality of life leave many sufferers and their families with devastated lives and facing many costs. In addit,on, health care and other agencies, in caring for people with schizophrenia in hospital or in community settings, in supporting their families, and in endeavouring .o treat the symptoms and the clinical and social sequclae of the illness, incur potentially considerable costs. The consequences of schizophrenia, therefore, tin be farreaching and expensive. As well as its obvious and many implications for patients and their families, the fact that schizophrenia has a large economic impact has generated interest in its cost dimension. Surprisingly, this interest is relatively new, although it is now quite perva:;ive in the sense that many modes of treatment are the subject of economic research, and most countries in the developed world have recognised the need for economic insights. What, then, are the costs of schizophrenia and how might they be reduced by better treatments while maintaining or improving effectiveness? BROAD COSTS OF IMPACT The costs of schizophrenia
fall widely: to the patient,
evaluation
to the patient’s family and other caregivers, to the health care system, and to the wider society. Each of these needs to be recognised. The fragmentation of care systems and the pressures of cost containment in many countries are, unfortunately, encouraging ‘cost shifting’: one agency or stakeholder has a greater opportunity and a greater incentive to reduce its own expenditure by limiting the volume or range of treatment, but in so doing it may - unwittingly or otherwise -- increase levels of expenditure by other parts of the care system or by patients and their families. Cost to the patient As we know, the consequences of schizophrenia to the patient can be far-reaching and long-term. Few people recover from an episode of schizophrenia to the extent that they return to a pre-illness level of functioning (Shepherd et al, 1989). The illness strikes at interpersonal relationships, making it more difficult for sufferers to initiate and maintain meaningful close friendships and other relationships. Self-care and related capabilities can also be damaged, making it difficult for sufferers to carry out or maintain the normal activities of daily living without help. In the labour market, people with schizophrenia find it harder to get paid jobs and to keep them, such is the competitive nature of employment now. This of course directly affects their income, even in countries with reasonably generous social security systems, and also limits the size of their
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social networks, thus lowering self-esteem and social status. Schizophrenia also damages other aspects of life, such as sexual functioning and performance. People with schizophrenia also have a higher risk of mortality (Alleback, 1989). Each of these negative consequences of the illness has a cost. Some costs are direct - such as the loss of employment - while others are more indirect and perhaps not intuitively expressed in monetary terms,
health services, and primary care. Within these services, some proportion of expenditure - usually a modest proportion - will be accounted for by medications and associated laboratory and diagnostic tests. How do these various health care costs stack up? The costs of treating schizophrenia expressed as a proportion of total health care expenditure appear to be fairly consistent across much of the developed world, usually between 1.5 and 2.5 per cent in European and North American countries.
Costs to caregivers Costs to the society In general, people with schizoph *enia in most northern European countries are less likely to be living with their families than is often the case in southern Europe or in most of the developing world. It is widely recognised, however, that the illness ofter results in families, friends, neighbours, or volunteer helpers offering substantial amounts of informal caregiver support. By their very nature, many of the costs of caregiver support are hidden from view, and certainly I hey are not easily reduced to monetary measures, even though they can be sizeable. For instance, Rice et al ‘1990) estimated that the time costs alone of caregiver support for people with schizophrenia in the USA amounted to $2.5 billion a year. The caregiver support provider1 to people with schizophrenia living outside hospital a nd specialist residential facilities can cause substantial psychological strain as well as personal risks to caregivers, although by no means all of the effects should be seen as negative (Szmukler, 1996). Direct costs may be incurred by the need to pay for some treatment or support services, but it is the indirect costs associated with the effects on family routine and relationships, work and leisure opportunities, mental and physical health, distress, stigma, and guilt which can be SC substantial (Schene et al, 1994). These broader and lor.ger-term impacts on caregiver quality of life and health help to explain why the UK reforms introduced in the I 990 National Health Service and Community Care Act placed such emphasis on supporting family caregivers. Costs to the health care system When the issue of the costs of schizophrenia is raised, most people tend to think first af health care costs. These are, after all, the most direct and most easily identified costs of treatment and support. The direct costs include expenditures on in patient hospitalisation, out-patient services, day treatment, accident and emergency services, the various community mental
Finally, there are the wider costs to society. Of course, ‘society’ in its broadest sense bears all of those costs mentioned above, plus certain other direct care costs falling outside the health care system, particularly those associated with social care (social welfare) services, special housing, criminal justice services, and social security or income support. With the rapid movement away from hospital-based treatment to care in community settings in many countries, these various agencies are playing an increasingly important part. The often significant indirect social costs would clearly include the wider impact on society of patients’ or carers’ lost employment and associated lost productivity. There may be further societal costs associated with fears that psychiatric patients living in the community might be a danger to themselves or to others. A series of violent incidents, some tragic, involving schizophrenia sufferers in the UK have, for example, generated some quite widespread concerns about personal safety (Audit Commission, 1994; Ritchie et al, 1994). Most of these indirect societal costs are particularly difficult to measure, but arguably no less important than the more readily computed direct costs when considering the broader social and economic impact of schizophrenia. TOTAL COSTS Pulling these patient, caregiver, health care, and social costs together reveals the enormity of the economic impact of schizophrenia. A common approach to demonstrating this impact is to offer cost-of-illness estimates. For the USA, for example, Rice et al (1990) estimated a total cost of illness of $38 billion. Of this total, direct health care treatments accounted for 53%, indirect costs of lost income/productivity and premature mortality 37%, and other costs (social welfare, criminal justice, and so on) 10%. There is no reliable equivalent figure for the UK, but
Economic tenefits of atypical
antipsychotic
Balance of public expenditure
Balance of care Living independently
- primary care
Living independently Specialized
supported Short-stay
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treatments
- specialist
accommodation hospltaliratlon
Long-stay hospitalization Special hospital (Broadmoor...) Homeless In prison
el. 14%
1%
10%
20%
I
I
30%
40%
1 50%
% patients with schizophrenia
Fig 1. Schizophrenia
10%
20%
30%
40%
50%
% patients with schizophrenia
- care and costs in England (from Kavanaugh et al, 1995).
if we use the National Health Service Execul ive (1996) programme budgets and the ‘bottom-up’ e:.timates of Kavanagh et al (1995), plus an estimate of indirect costs from Davies and Drummond (1994), we filld that the total national cost of schizophrenia inEnglard in 19921993 amounted to roughly $4.2 billion (Knapp, 1997). Cost-of-illness estimates are available for Eome other countries - for instance, $0.4 billion for Tie Netherlands in 1989 (Evers and Ament, 1995) and 1,O.l billion for Australia in 1975 (Andrews et al, 198:‘). Both of these latter amounts need inflation to current price levels to make them more meaningful. Such costs are currently being built up for a number of othel,countries. These sums are invariably enormous amounts of money, and they clearly point to the major economic and social consequences of what remains an incurable, debilitating disease. There are, however, serious methodological reservations about the relevanl:e of such cost-of-illness figures (Drummond, 1992). There are at least two ways to proceed frc m cost-ofillness estimates of this kind. The first is to work with the disaggregated data contained within tht: total estimates of the costs of a disease. One illustra ion of this is offered by our own research in England, where we constructed estimates of the treated prevalence of schizophrenia from various sources, and then calculated the direct costs of treatment and support for each of the main accommodation settings (Kavanagh ei al, 1995). A highly summarised picture of the resultz.nt balance and costs of care in England is given in figure 1. Interestingly, although more than half ofthe iden ified cases
lived independently, receiving their treatment from primary health care and/or specialist psychiatric clinicians, only 11% of total direct public expenditure is accounted for by these people. On the other hand, 5 1% of total public expenditure is allocated to the 14% of schizophrenia sufferers living in hospital settings. THE COST OF HOSPITALISATION It is obvious from the figures for England (fig 1) and equivalent data for other countries that one of the largest cost components in the treatment and support of people with schizophrenia is hospitalisation (in-patient care). The economic importance of hospitalisation stems not from the fact that a high proportion of people are living in hospital, but from the high per diem cost of an in-patient stay. In the UK, for example, the daily cost on an acute psychiatric ward is currently around &126, and it is higher in London (Netten and Dennett, 1996). In the more specialised settings, such as an intensive care psychiatric unit or a high-security unit, the cost can be as high as &321 per day (Hyde and Harrower-Wilson, 1995). Outside hospital, but still within the specialist accommodation sector, highly staffed residential facilities can cost much more than &400 per week, even without the need for secure provision, and not including the cost of all the non-residential services used (Chisholm et a1,1997). For patients whose florid symptoms of schizophrenia are many years behind them and who have been discharged from long-stay psychiatric hospitals to com-
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Table I. Restrictions on use of atypic;, antipsychotics. Results based on a postal questionnaire members of the Royal College of Psychiatrists in the UK during April-July, 1995 (n = 761).
Psychiatrists who Have Have Have Have Have Have Think Think
never prescribed this drug no patients on this drug currently five or more patients receiving this drug been challenged about the cost of this drug experienced formal rationing of n lmber of patients prescribed this drug experienced informal guidelines/ritioning drug cost inhibits its use drug cost Dossib[yinhibits its use
survey of ‘social/community
psychiatrist’
Clozapine %
Risperidone %
19 35 25 46 10 14 20 24
12 25 35 52 6 I1 17 23
Source:Hogman(1996).
munity accommodation settings, hospitalisation continues to figure large in their ‘c:re packages’, and the associated costs can be significant (Beecham et al, 1997). Those long-stay resident!; in psychiatric hospitals who need secure provision. but who must move from the old asylums as they are closed down, can easily impose weekly costs of over 6.1000 (Hallam, 1996). For people in the acute phases of their illness, in-patient admissions can be frequent and lengthy. Two further European examples illustr;,te how hospital care dominates costs. In an evaluation of the Maudsley Hospital’s Daily Living Programme [an alternative to hospitalisation for patients facing a crisis admission), 86% of the total care and treatment costs for the control group receiving standard care in the UK were accounted for by in-patient stays in the first four months after the randomisation which sil;nalled the start of the research period, and 69% over t le first 20 months. In the fourth year of the study, holipitalisation costs accounted for 10% of the total COSIs of care, and 54% of the health care costs (Knapp et al, 1994). The second illustration comc:s from Italy, which passed legislation nearly 20 years ago to close all psychiatric hospitals. Even in this r;.ther different service context, in-patient hospital stay!; (now in psychiatric beds in general hospitals) represtnted 40% of the total health care costs over a one year period (Amaddeo et al, in press). One third of the 1315people with schizophrenia and related disorders who were on the South Verona case register and who had at least one contact with psychiatric services during 1he year had an in-patient episode, the mean duration of which was 87 days. The high costs of hospitalisation are particularly pertinent in the context of the discussion of the atypical antipsychotic drugs because a large proportion of people with schizophrenia are readmitted to hospital after their first episode. This is one of the reasons why psychiatrists and health care budget holders are keen to
find affordable treatments which are more effective and/or which help to improve patient compliance or adherence (Weiden and Olfson, 1995). About a third of acute patients show little or no improvement with standard antipsychotics (Macmillan et al, 1986). This is one reason why there is such interest in the development of the new antipsychotics. THE ATYPICAL ANTIPSYCHOTICS The new antipsychotics have been labelled atypical because of their ‘efficacy in refractory patients and against negative symptoms, and reduced capacity to induce extrapyramidal side effects, tardive dyskinesia, and elevate prolactin’ (Lieberman and Fleischhacker, 1996). But the two new antipsychotics that have been marketed for longest - clozapine and risperidone could also be called atypical because of their high prices. The many other ‘atypicals’ now being launched onto world markets will be similar in having prices considerably higher than those that currently apply to standard treatment modes. Of course, the price of any new antipsychotic varies from country to country, but can range from between 50 times and 100 times the price of the conventional antipsychotic drugs (see, for example, Hogman, 1996). The higher price is leading to restrictions on the use of the atypical antipsychotics. This is shown by a very interesting study by Hogman (1996) on behalf of the National Schizophrenia Fellowship, based on a postal questionnaire survey of ‘social/community psychiatrist’ members of the Royal College of Psychiatrists in the UK during April-July 1995. A total of 761 completed questionnaires were returned (59% response rate). A summary of some of the key survey findings is given in table I, which reveals that surprisingly low proportions of psychiatrists were prescribing the two ‘atypicals’ available in the UK in 1995. The survey
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Economic benefits of atypical antipsychotic treatments
exposed what Hogman interprets as misundt:rstandings among community psychiatrists as to some key characteristics of clozapine and risperidone - fcr example, in relation to blood monitoring and side-effect profiles, 10% of psychiatrists felt that the need for b ood monitoring made risperidone unsuitable. Some of the most interesting findings, however, relate to actual and perceived costs and their mpacts on prescribing patterns, also summarised in ta >le I. Hogman interprets these findings as showing th’: small but significantformal impact of drug price. Although relatively large numbers of psychiatrists felt th;it cost was a factor that affected the use of atypical dlugs, especially clozapine, far fewer translated this into the actual practice of formal rationing. However, a small but significant number of psychiatrists are limited n their use of these two new antipsychotics, even though the level of prescribing seems comparatively low (Hogman, 1996). Clearly, there have been restrictions on the use of the new antipsychotics in the UK. More generally, there are budgetary and other restrictions now operating in a number of countries (Bloor and Freemantle, 1996). One consequence of restrictions of this kind, building on the often substantial differences in treatment preferences and practices between different heal] h care systems and different cultures of psychiatry, is that the percentage of patients with schizophrenia being prescribed the atypical antipsychotics will tiary from country to country, and probably markedly (‘Gerlach J, unpublished results 1996). Despite these in:emational differences, it is becoming increasingly common in all countries to hear pharmacy budget holders, clinical managers, political leaders, and others voice concern about the high prices of some of the new rr edications becoming available. These are valid concerns, and at one leve it is heartening to hear that cost consciousness is abroad within health care systems. However, although tota I spending on drugs can be a sizeable part of total health care expenditure (around 10% in England; Depitrtment of Health, 1994) and is growing (Freemantle md Bloor, 1996), it must not be forgotten that drug cDsts are in fact a much smaller proportion of the total health care and other costs of treating schizophrenia. F:ecent calculations from NHS programme budgets for England suggest a proportion of only 4% (Knapp, lS97), and it may be as small as 1% in some countries (Evers and Ament, 1995). Nor must it be forgotten that the newer drugs are showing greater effectiveness in relation to some symptoms, behaviours, and side effi:cts. Most worrying, perhaps, is that a wide-ranging in emational
by Bloor and Freemantle (1996) could find no ‘methodologically sound evaluations of incentive systems aimed at prescribers’. In other words, we do not yet know what the effects of budgetary or other restrictions are on those who prescribe drugs. review
HIGH PRICE...
LOW COST?
Two of the most pressing questions in the treatment of schizophrenia currently remain unanswered: Are the higher prices of the atypical antipsychotics outweighed by either improved symptoms or better quality of life for patients or their caregivers? Are the overall treatment and support costs reduced now or will they be in the future? Neither question is easy to answer, yet without answers it would be premature to support or to block the wider use of the new drugs on economic grounds. It would, of course, be irresponsible, because of the dangers to patient health or quality of life, to promote a new treatment without evidence on efficacy. Equally, there is a need for evidence on cost and cost effectiveness before decisions on policy and practice are taken that might later be regretted because of their financial implications, or because affordable opportunities to improve patient quality of life have been missed. A new treatment mode does not have to demonstrate that it is less costly than alternative modes in order to be cost effective, but it must demonstrate that any increase in costs (compared to its closest alternative) is at least matched by increased effectiveness or reductions in non-drug related costs. In forming a view of cost effectiveness, the evaluative perspective ought to be broad and long-term, for the network of potential associations and causal impacts are many and complex (fig 2). The narrowest direct costs of treating schizophrenia (see the left-hand side of figure 2) are the expenditures on drugs, psychosocial therapies, and other mental health care supports and services. These treatments hopefully have a direct impact on some or all of a number of dimensions of patient and caregiver health and quality of life: the positive and negative symptoms of schizophrenia, personal and family functioning, social interactions, subjective quality of life, satisfaction with services, caregiver burden, societal fear, and so on (Lehman et al, 1995). The atypical antipsychotics aim to be more effective than the ‘standard agents’ in achieving improvements along one or more of those dimensions. They also aim to be more effective via the indirect route of having fewer side effects and thereby possibly encouraging better compliance.
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MFCJ Knapp
Reatments and costs
Intermediate effects
Medications I+1
sid!ZTcts
Fig 2. Treatment,
W
Better compliance
t
I)
improved symptoms...
. ..less health care
I)
Better functioning...
. ..less supportneeded
I)
Better access to resources...
...more employment
I)
Improved quality of life...
. ..belier integration
I)
Reduced caregiver burden...
. ..more employment
W
Satisfaction with services...
...less disruption
*
Societal outcomes...
...fewer externalcosts
outcome, cost-offset.
Directly or indirectly, the consequence could be significant cost reductions in the longer term because of the need for less support from wealth care, less social services, better functioning, gre;lter participation in the labour-force, and reduced family burden. Although there is currently little reliable evidence on the longer term cost effectiveness of treatment with atypical antipsychotics, and certainly none ,.vhich is robust for the UK, community psychiatrists l.esponding to the National Schizophrenia Fellowship Survey questionnaire were of the opinion that long t:rm cost-effectiveness would be achieved (Hogman, 1!)96). ECONOMIC EVALUATIONS To address the core questions of relative costs and outcomes, it is clear that thorough economic evaluation is needed. There are four main types of evaluation, each with different data demands, aid each with different uses and possibilities. Evaluative
Cost reductions in longer term from:
/
Psychosocial therapies
treatment services and supports
Outcomes
criteria
Economic evaluations have tended to concentrate on the criteria of effectiveness, economy, efficiency, and equity (justice), either singly or in combination. Economy is the saving of resources, ;md its pursuit requires detailed data on costs, but no at ention need be paid to the impact of lower spending UKon patients or families (the outcomes of treatment). Economy is the criterion addressed in the simplest of cos evaluations (cost-off-
set and cost-minimisation analyses). Effectiveness is conventionally defined in terms of improvements to patient and family health and quality of life; costs are disregarded. There are whole batteries of instruments to measure effectiveness, scaling and scoring psychopathology (including specific measures related to specific aspects of the disorder), social functioning, family and peer group relations, and so on. Economic evaluations include effectiveness measures on such instruments, but a steadily increasing number are also including unidimensional ‘utility’ measures (see below). The criterion of efficiency combines the resource (cost) and effectiveness dimensions. The pursuit of efficiency could mean reducing the cost of achieving a given level of effectiveness, or improving the volume and quality of outcomes achieved from fixed budgets. Efficiency can seem to be a controversial objective, but properly understood and put in the appropriate context it ought to be widely acceptable. Efficiency is not a euphemism for ‘cutback’, for it can sometimes be promoted by spending more, not less. Efficiency is sometimes examined in combination with the fourth criterion of equity (or justice). Equity is not the same as equality. Targeting services on needs is one example of adopting an equity criterion, although even this has efficiency implications and interpretations. Modes of evaluation The three most useful and common modes of economic evaluation are cost-effectiveness analysis, cost-benefit
Economic benefits of atypical antipsychotic
analysis and cost-utility analysis. (See reviews in Drummond et al, 1997; Kavanagh and Stewart, 1995.) These modes have some common elements, particularly in relation to cost definition and measurement, but they differ in two main respects: they measure outcomes using different techniques, and consequently they address slightly different policy or practice questions. (Two other modes of evaluation - cost-offset and cost-minimisation analyses - do not measure outcomes. Cost-of-illness or burden-of-illness studies are not evaluations as such, although they are increasingly used as preludes to cost-effectiveness or other analyses. They calculate all direct and indirect costi resulting from an illness.) Cost-benefit analysis (CBA) is unique in that it addresses the extent to which a particular course of action, such as a new form of pharmacological or psychosocial therapy, is socially worthwhile. All costs and benefits are valued in the same units - usually in term of money - and can thus be directly compared. The simple comparison of ‘costs incurred’ with ‘costs save’d’ is not a CBA but a cost-offset analysis. Conducting; CBAs is particularly rare because of the difficulty of valuing benefits in monetary terms. Cost-effectiveness analysis (CEA) is cono:rned with ensuring that resources allocated to the treatment of schizophrenia, or to another activity, are used to maximum effect. CEA is usually used to help decision makers choose between alternative interventions available to or aimed at specific patient groups: 11’two treatments for acute schizophrenia cost equal amounts, which provides the greater benefits? Or if two treatments are equally beneficial in terms of their impact on patients or populations, which is the less costly? When CEAs have been conducted in the mental hl:alth field, generally batteries of functional and symptom-based outcome measures have been used, of the kind familiar to clinical evaluators from their own studie2.. Cost-utility analysis (CUA), the newest mode of economic evaluation, is similar to CEA w th the important exception that it measures and then values the impact of an intervention on a patient’s hes lth-related quality of life as well as the cost of achieving that improvement. The value of health improvement from a treatment is measured in conflated units of ‘utility’, in contrast to CBA, which uses monetary val les. CUAs avoid the potential ambiguities with multi-d mensional outcomes in CEAs, and can be applied to chc ices across a range of treatments or diagnoses: they can compare one clinical area to another distinct area. [f properly conducted, they could compare antipsychotic treatment of schizophrenia with kidney dialy:;is or che-
treatments
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motherapy or osteopathy for lower back pain. The most common value measure of health outcomes used in CUAs is the quality-adjusted life-year. Despite their inherent attractiveness, and their growing use across a wide span of health care contexts, CUAs have rarely been used in evaluations of schizophrenia. These different modes of evaluation have a common aim in their approach to cost measurement, which - if a broad (societal) perspective is adopted (which is usually the case), is to include all direct and indirect costs, estimated as long-run (marginal) opportunity costs. The modes obviously differ with respect to their measurement of outcomes. Informed decision-making in relation to the treatment of schizophrenia needs a range of economic evaluations, although few such prospective evaluations have yet been conducted on atypical antipsychotics. There is insufficient space in this paper to summarise the available evidence, some of which is of debatable quality (Knapp, 1997), but instead the paper now turns to some methodological inadequacies in completed studies. In concluding this paper, I shall advocate certain improvements in the conduct of economic evaluations in this field. METHODOLOGICAL DEVELOPMENTS The published economic evidence on the atypical antipsychotics (and on other therapies, whether pharmacological or psychosocial) is mostly conjectural, partial, or flawed. The most damaging flaws are summarised in the left hand column of table II, with recommendations for methodological improvements in the right hand column. It is unnecessary to go through each pairing of flaw and improvement in detail, as the difficulties posed by the former are well known and the opportunities afforded by the latter are widely appreciated. However, some points should be emphasised. Firstly, there is no adequate substitute for direct observational data, even though delphi panels and decision trees are helpful in cutting through complex conceptual issues and in making informed projections beyond the period covered by prospective trials. The arguments for and against decision modelling as an alternative to direct observation have been widely aired (Sheldon, 1996), and ultimately the choice comes down to the quality and generalisability of the findings in a particular context. Modelling is helpful in the absence of decent observational data, or to supplement it, but needs a good information base from real-world settings if it is to be more than idle (or indeed partisan) speculation. A more straightforward choice is represented by the
MRJ Knapp
44s Table II. Economic evidence: present imperfect... imperatives.
future
Present imperfections
Future imperatives
Delphi panels and decision trees Imported from abroad Retrospective Matched design Short-term Narrow inclusion criteria Limited comparators Adjunct therapies excluded Small sample Variations ignored Service impact - hospitahsation Costs - narrow range Cost distribution ignored Outcomes evidence not integrated
Dire:t observation Comext-specific research Pros 3ective Ram lomised design Long;-term Gemmlised patient group Wide: range of comparators Adjunct therapies included Larg : sample Vari;uions explored Serv ce impact - comprehensive Cost-comprehensive Cost distribution explored Outcomes integrated with costs
second line in table II. In the absence of country-specific data (from decision model!; or direct observation) it has been common to import findings from abroad, and sometimes offering assumpt ions as to the relevance of the methods or the context. It would be invidious to cite examples. Prospective data are usually to be preferred to retrospective data, particularly when a randomised controlled design is used. Matched ot case-control designs have their advantages for some purposes, but generalisability and robustness tend to be better with randomisation. Long-term studies are more helpful than shortterm studies. As with other peirings summarised in table II, the meaning of the fla\vs and the advantages of the improvements apply with 3s much force to economic evaluations as they do to clinical evaluations. It is more generally straightforward to conduct clinical trials for people with schizophrenia if the patient inclusion criteria are narrowly drawn (for example, to exclude comorbid alcohol or drug abuse problems), if the number of comparator treatments is kept small (typically to two), and ifadjunct Iherapies are ruled out. But high proportions of schizophrenia sufferers have comorbid problems and make use of combinations of pharmacological and non-pharmacological treatments. Decision-makers need to become skilled at generalising from the tidy, narrowly desig led trial data currently available to the untidy reality of everyday clinical work. Cost-effectiveness projections from available data to the context of the real vlorld are certainly far from straightforward. As studies become larger, including more patients and fcr longer periods, it becomes more feasible to include a wider range of patient circumstances (including: comorbidities) and treatment combinations. But it then becomes essential
to interrogate
the data thoroughly, particularly through the statistical analysis of inter-patient variations in outcomes, needs, and costs, both across and within samples, and even within randomised trials. Finally, there are perhaps four flaw-improvement pairings relating to the comprehensiveness of data. Studies which make inferences about the resource consequences of alternative treatments on the basis only of hospitalisation data risk missing a wide spectrum of other service impacts. Even though hospital admissions dominate costs, the increasing reliance on communitybased interventions makes it highly desirable that the picture that is painted is of a comprehensive service (and hence calculation of comprehensive costs). The distribution of the cost burden between different agencies - and between formal services, family caregivers, and patients themselves - warrants especially close attention in the increasingly fragmented care systems of many countries (such as the UK), because there are many cost-shifting incentives inherent in these systems. The last line in table II states an obvious desideratum to integrate evidence on costs with outcome findings, but one which has particular pertinence as mental health care systems become more complex, and as associated evaluation designs necessarily become more sophisticated. It is clearly important that new evaluations tell us not only the comprehensive costs associated with a new treatment, including the costs associated with all side effects and all indirect costs associated, for example, with lost employment, but also how those costs are linked with treatment outcomes. New economic evaluations should pull together cost data with outcome or effectiveness data to tell us which alternatives give the best cost and outcome combinations. A new drug might prove to be more expensive than the standard drug currently in use, or a new configuration of community services might be more expensive than the old arrangement, but the new drug or service configuration might also be more effective. Economic evaluations should be designed to tell us whether it is worth spending the additional amounts of money in order to reap these additional benefits. CONCLUSION As noted earlier, the costs of relapse in schizophrenia, stemming from lack of treatment efficacy and/or noncompliance, can be especially high and persistent. Consequently, health care decision-makers need to evaluate carefully any new treatments which promise to tackle one or both of these root problems. The atypical antipsychotic agents (both those currently available
Economic
lxmefits of atypical antipsychotic
and those soon to be launched) are clearly promising in both regards, but their take-up and use havt: not been appreciable. Kerwin (1996) poses several reasons for this in the UK: costs; the false perception of ,zew drugs as dangerous; for clozapine, too strict a d@inition of treatment resistance; for risperidone, reserving its use in a clinical decision tree after first line treatments have been tried; jinally, many psychiatrist:, are concerned about compliance andprefer depot medication. Some of the concerns about costs are na vely constructed and misinformed, but there is a genuine widespread desire to know whether the consideraaly higher prices of the new drugs generate compensittory payoffs in terms of better health, quality of life, and other outcomes, and/or lower downstream costs. The price of a new drug is usually a small proportion of I otal treatment cost, so that a key unanswered economi z question is whether the broader and longer-term costs are higher or lower, and whether the outcomes are such as to generate system-wide cost-effectiveness. The need for well-designed evaluations is paramount. With the advent of the atypical antipsychotics, that need has extended into new areas. But c ost-effectiveness questions cannot satisfactorily be ar swered in ‘after-thought studies’: they need to be planned carefully and integrated into evaluative designs from the outset. REFERENCES Alleback P. Schizophrenia: a life-shortening disease. Schiz Bull 1989;15:81-9 Amaddeo F, Beecham JK, Bonizzato P, Fenyo A, Knapa MRJ, Tansella M. The use of a case register for evaluating the costs of psychiatric care. Acta Psychiarr Stand, in press. Andrews G, Hall W, Goldstein G et al. The economic costs of schizophrenia: implications for public policy. Arch Ceil Psychiatry 1985;42:537-43 Audit Commission. Finding a Place. London: HMSO ; 1994 Beecham JK, Hallam A, Knapp MRJ, Baines B, Fenyo P., Asbury M. Costing care in the hospital and in the community. 11: Leff J, ed. Community Care: Illusion or Reality? Chichester: Fr’iley; 1997 Bloor K, Freemantle N. Lessons from international e tperience in controlling pharmaceutical expenditure 11: influencing doctors. Br Med J 1996;312:1525 Chisholm D, Knapp MRJ, Astin .I, Beecham J, Audini 13, Lelliott P. The costs of residential care for people with mental health problems in eight services. J M Health 1997 Davies LM, Drummond MF. Economics and schizophnnia: the real cost. BrJPqchiarry 1994;165 (suppl 25):18-21 Department of Health. Healthand Personal Social Servl.es Statistics for England. London: HMSO ; 1994 Drummond MF. Cost-of-illness studies: a maior headaclte? Phurma coeconomics 1992;2: l-4
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