REVIEWARTICLE CNSDrugs 1999 Jul; 12(1):49-641172 7o4.99joooT-oo491sos.oo/o

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Measuring the Effect of Treatmenton Quality of Life in Patientswith SchizophreniaFocus on Utility-Based Measures

Thomas L. Patterson, Robert M. Kaplan and Dilip V. Jeste

University of California, San Diego, and the Department of Veterans Affairs Medical Center, SanDiego, California, USA

Contents

Abstract ................................................... 49], Which Clinical TrialsHave Utilised Quality-of-Life Outcomes? ...................... 502, Why Are Outcome Measures Important? ................................. 523, Defining and Measuring Quality of Life .................................. 534, Measuring Health-Related Quality of Life ................................. 53

4.] Cost-Utility versus Cost-Benefit .................................... 544.2 IsMental Health Measurement a Special Case? .......................... 554.3 Utility-Based Measures of Health-Related Quality of Life ..................... 55

4,3,] Canadian Approach: Health Utility Index .......................... 564.3.2 Quality of Life and Health Questionnaire .......................... 564.3.3 Quality of Well-Being Scale .................................. 564.3.4 European Approach: The EuroQOL .............................. 574.3.5 Population Survey Methods .................................. 58

4.4 Overview ................................................. 585. Isthe Utility Model Applicable to Mental Health? ............................ 586. Resource Allocation Decisions ....................................... 607, Conclusions .................................................. 62

Abstract This paper reviews utility-based measures of health-related quality-of-life out-comes that might be used in clinical trials involving patients with schizophrenia.Utility-based quality-of-life data can facilitate decision-making regarding allo-cation of shrinking resources. Comprehensive measures can help evaluate treat-ments that may provide benefits in one dimension of quality of life, while

providing no benefit or having negative effects in other dimensions of quality oflife. This review suggests that the measurement of outcome in mental healthclinical trials should include utility-based measures (e.g. the Quality of Well-Being scale, EuroQOL) which integrate a variety of outcome dimensions and

combine them into a single preference weighted index.

50 Pattersonet al.

Schizophrenia, the prototypical chronic psycho- treatment and antipsychotic medications. Utility-sis, occurs in approximately 1% of the population, based measures use patient or community prefer-and has been estimated to cost approximately $US65 ences to place wellness on a continuum rangingbillion per year in direct treatment costs, loss of from 0 for death to 1.0 for optimum health. Theseproductivity and expenditures for public assistance utility weights are used to adjust survival time for

in the US alone. {11In the public mental health sys- health-related quality of life. We also provide a ra-tern, the cost of schizophrenia has been found to be tionale for the use of utility-based measures with2 to 4 times that of other psychiatric illnessesJ 21 examples from mental health.

Currently, the most effective treatment for schizo-phrenia is symptomatic, and involves the use of anti- 1. Which Clinical Trials Have Utilised

psychotic drugs. Although these drugs have reduced Quality-of-Life Outcomes?the morbidity associated with schizophrenia andother psychoses, they can also cause serious iatro- Despite the large number of clinical trials de-genie problems, including persistent tardive dyski- signed to test the efficacy of various medicationnesia, p] As new medications for the treatment of and psychosoeial treatments for symptoms of sch-

symptoms of psychosis become available for effi- izophrenia, relatively few studies have examinedcacy trials, the quantification of functional improve- changes in quality of life associated with these treat-ments becomes an area of foremost importance. In ments, and fewer still have utilised utility-based mea-

sures. To date, the majority of studies of quality ofaddition to issues surrounding quantification ofmeasures in drug trials, as the funding available for life among people with chronic psychiatric disor-healthcare is reduced there is increasing competi- ders have been cross-sectional in nature (e.g. Leh-

tion among providers for scarce resources. Thus we man et al. [4]and Simpson et al.{51),and have failedare witnessing a paradigm shift in the way medi- to consider therapeutic responses other than psycho-

pathology. [6,71Although there is mounting evidencecine is practiced, taught and evaluated, that treatments directed at enhancing psychosocial

Until recently, medicine in the US was little con-skills (e.g. social cognitive skills training, cognitive-

cerned with cost containment. New diagnostic pro- behavioural therapy) improve outcomes, includingcedures led to more medical and surgical proce- quality of life, in patients with schizophrenia,[ sd 11dures, and concomitantly increasing expense, and less emphasis has been placed on examining qual-it was assumed that patients would be the benefici- ity of life in trials of the effectiveness and efficacyaries of these advances. However, the uncontrolled of medication. A number of studies have shown that

costs of medical care and the poor documentation the combination of antipsychotic drugs and psychi-of patient benefit have ushered in a new era of cost attic rehabilitation is associated with decreased pos-consciousness. Now, there is a need to show that itive symptoms and improved social skills (e.g. An-medicine produces value for money. As a result, thony et al., [12]Goldstein et al., [131 Liberman et al. [141new methodologies such as cost-effectiveness an- and Hogarty{_SJ); however, fewer studies have at-alysis, cost-benefit analysis and cost-utility analy- tempted to determine if these changes are associ-sis have become commonplace in medical journals, ated with better quality of life (as perceived by theThis has created a need to revise medical education patient or others). In the following paragraphs weand postgraduate training in order to accommodate provide brief reviews of psychosocial treatment tri-new methodologies and new controversies, als and medication trials that have considered qual-

The purpose of this paper is to provide a brief ity of life as an outcome, and review studies thatreview of intervention research in patients with have examined costs in relation to treatments.

schizophrenia that used quality-of-life measures, A variety of psychosocial treatments have beenor utility-based measures of health-related quality utilised with patients with schizophrenia. Specificof life, in evaluating the efficacy of psychosocial skills training may not be necessary for gains in

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QualityofLifeIssuesinSchizophrenia 51

social functioning and quality of life to occur. At- reductions in negative symptoms and general psy-kinson et al.[t6]evaluated a 20-week education group chopathology were associated with improved qual-counselling programme which covered topics rang- ity of life in patients with schizophrenia treateding from problem solving and managing symptoms with clozapine; however, there was little associa-

to social skills and assertiveness, and found that tion between quality of life and changes in neuro-those who attended improved significantly in qual- psychological performance. Hamilton et a1.I231con-

ity of life, social functioning and social networks, ducted a double-blind study evaluating the impactbut showed no change in mental status or compli- of treatment with olanzapine compared with halo-ance with medication. Browne et al.u7] reported peridol and placebo among patients with schizo-that patients with schizophrenia who received a phrenia. They reported that after 24 weeks of ther-

16-week psychosocial and educative rehabilitation apy, patients who received olanzapine had fewerprogramme showed a 46% improvement in quality symptoms, particularly negative symptoms, corn-of life in the absence of any significant change in pared with patients in the other groups. Further-symptom severity. Barry and CrosbyUSl found that more, they observed improvements in quality ofpersons with long term psychiatric disorders who life (i.e. intrapsychic foundations, interpersonal re-

were discharged from the hospital after receiving lations, instrumental role and common objects andcomprehensive treatment showed improvements in activities) among olanzapine responders. Revickiliving conditions, higher levels of social contact et al. f241reported that patients with schizophreniaand increased leisure activities, treated with olanzapine had significantly greater

Although the effectiveness of various antipsy- improvements in their quality of life (measured withchotic drugs in reducing symptoms of schizophre- both the QOL I251and SF-36 ;z61)over 52 weeks of

nia has been demonstrated in many studies, their therapy compared with those treated with haloper-

effects on quality of life have not been widely ex- idol. In general, studies that have utilised quality-plored, particularly in trials utilising older conven- of-life measures have reported treatment-associatedtional antipsychotics. Jolley and colleagues [19]re- improvements.ported that, compared with patients who received Little intervention work has examined the effi-

continuous treatment with haloperidol, those who cacy of treatments using utility measures. A numberreceived periodic prophylactic treatment with hal- of studies have reported that although newer atypi-opcridol displayed lower scores for extrapyamidal cal antipsychotics, such as risperidone, have higheradverse effects, but there was no associated gain in acquisition costs they may not increase, or may even

social functioning.[ _91A direct comparison of out- reduce, the overall treatment costs of schizophreniapatients treated with conventional antipsychotics (e.g. Foster and Goa[27]). Aronson [2slargues withoutwith those treated with atypical antipsychotics re- empirical data that although risperidone is morevealed that treatment with atypical antipsychotics expensive, it is more cost effective because of re-

was associated with significantly higher quality of ductions in the number of hospital days, and thatlife (i.e. physical well-being, social life and every- by reducing the number of hospital days it increa-day life).[201 sesthepatient's qualityof life.Similarly,GlazerI291

Studies of atypical antipsychotics have utilised discussed cost saving associated with the introduc-

quality-of-life outcomes more frequently. For ex- tion of risperidone without providing data to sup-ample, Meltzer et al. _2_1reported that symptoms port this view. Williams and Dickson [3°j suggestand quality of life (i.e. intrapsychic foundations, that community-based care of patients with schizo-

interpersonal relations, instrumental role and corn- phrenia can be less costly than hospital-based pro-lnon objects and activities) of patients with chronic grammes and can improve patient quality of life. Thus,

schizophrenia significantly improved after 6 months the inclusion of utility-based measures has the po-of clozapine treatment. Galletly et al. [22Jfound that tential to move the field forward.

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52 Pattersonet al.

Given that health-related quality of life has been plethora of measures which make it difficult to com-shown to be a sensitive indicator of a number of pare findings from various trials. In this paper wetherapies, why does there continue to be a small num- argue that the evaluation of interventions shouldber of reports utilising these measures? Awad [311 include utility-based measures that are able to in-

and his colleagues 132jattribute this to a number of tegrate information on adverse effects and variousfactors: symptoms.Theuseof suchmeasureswillfacilitate

• the erroneous perception of investigators that decision-making regarding the efficacy of variousquality of life is largely undefinable and conse- treatments.

quently unmeasurable• a lack of psychometrically sound quality-of-life 2. Why Are Outcome

instruments sensitive enough to detect changes Measures Important?associated with clinical trials of antipsychotics

There are 2 major perspectives in the measure-. difficulties in choosing outcome criteria in ass-ment of outcomes that may be considered: societalessing quality of life of patients with schizo-and personal.phrenia who are taking medication

From a societal perspective there is a need for• concerns that self-reports of patients with schi-measures that allow clinicians and policy makerszophrenia are unreliableto determine the efficacy of various treatments. In• a lack of an integrative conceptual model of

quality of life for patients taking antipsychotics, order to make these decisions, it is necessary toconsider the financial costs associated with variousOther authors have discussed the added diffi-

treatments while taking into consideration poten-culty in measuring quality of life associated with

tial adverse effects that may result from treatments,heterogeneity in symptoms associated with schizo-

and the dimensions of outcome that may or may notphrenia (e.g. positive and negative symptoms, cog- be improved by the treatments. For example, pa-nitive dysfunction). [331Yet another potential prob- tients with schizophrenia may experience positivelem in the measurement of quality of life that has symptoms such as hallucinations that are assumed

often been neglected is the adverse effect profile to impair their ability to perform normal activities.associated with specific treatments. For example, Pharmacological treatments such as the use of anti-

Larsen and GerlachP4l found that 60% of patients psychotics may eliminate these positive symptoms,with chronic schizophrenia viewed depot antipsy- but have little effect on negative symptoms (e.g.chotic medications positively. Interestingly, only social withdrawal, blunted affect), and have the po-70% of the sample complained about adverse effects, tential to produce adverse effects such as tardive

even though objective measures indicated that 94% dyskinesia. The dilemma for the physician is deter-had them. Awad and Hogan p51 reported that pa- mining what value to place on each of these treat-tients with schizophrenia who had a negative view ment outcomes.

of antipsychotics were more likely to be noncom- From a personal perspective it is important to bepliant and had a less favourable therapeutic out- able to present the potential costs and benefits thatcome. In addition, Weiden et al. [361reported that may be associated with particular treatments to theover one-half of patients with schizophrenia be- patient. Benefits may include reductions in positivelieve that antipsychotics interfere with their quality symptoms. Costs may include the development ofof life, and those with increased akinesia reported tardive dyskinesia, while there may be little or nothe greatest impairments in the area of participation improvement in negative symptoms or psychoso-in their favourite physical activities, cial functioning. The complexity of these patterns,

Our review of the literature suggests that the and potential differences in values placed on eachcomplexity of measurement of outcome in schizo- of these outcomes, suggest that the measurementphrenia has led to the development and use of a of quality of life in ways that allow us to simulta-

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QualityofLifeIssuesinSchizophrenia 53

neously examine the costs and benefits of therapy medical conditions. An important considerationis pivotal in evaluation of treatments, in measuring outcome in patients with psychoses

is the validity of self-report. For example, patients

3. Defining and Measuring with schizophrenia may lack insight into their symp-Quality of Life toms. [421Although this has led to testing of perfor-

Quality of life is a multi-dimensional construct, mance-based measures (e.g. Direct Assessment ofwhich has been conceptualised differently by dif- Functional StatusI43]), results from our laboratory

ferent authors, p2] For example, Lawton [37,38]has suggest that outpatients with mild-to-moderate se-conceptualised 4 critical dimensions in the meas- verity of psychopathology were generally able tourement of quality of life. The first dimension is provide data that correlated with severity of psy-termed behavioural competence, and requires the chiatric symptoms, suggesting that self-report mayobjective evaluation of an individual's ability to be valid in outpatient groups. [44,45]function in terms of health, time-use and social in- Approaches to measurement of outcome includeteractions. The second dimension consists of the generic profile measures which yield dimension-

individual's subjective evaluation (i.e. perceived specific scores (e.g. Sickness Impact Profile [461orquality of life) of his/her ability to function in each Medical Outcomes Study health survey, which isarea of behavioural competence. The third dimen- sometimes referred to as the SF-36147]), or the usesion reflects environmental influences on the indi- of single indices (e.g. Karnofsky Performance Sta-

vidual's perceived quality of life, and the fourth tus and the Functional Living IndexI4S]). An alter-dimension weights the individual's behavioural corn- native approach to the measurement of outcomespetence based on psychological well-being, focuses on specific populations or diseases. One

It is clear that an individual's health affects his such instrument developed specifically for use with

or her quality of life, and it is a goal of healthcare patients with psychiatric disorders is a broad-basedto maintain optimal functioning and decrease dis- assessment of recent and current life experiences

abilities associated with chronic illnesses. [39]This in a variety of life areas that was developed byemphasis has led to a focus on health-related qual- Lehman et al.t 251Alternatively, investigators mayity of life. Broadly defined, health-related quality utilise customised batteries of individual measures

of life is a state of complete physical, mental and which attempt to capture specific dimensions of qual-

social well-being, and not merely the absence of ity of life thought to be important in particular dis-disease or infirmity. [4°] A number of domains of orders (e.g. Social Adjustment Scale I49,50]or Scaleshealth-related quality of life have been identified, for Assessment of Positive and Negative Sympt-

including physical health, emotional health, cogni- oms[511). Each of these approaches has limitations,tive functioning, sexual functioning, social role per- including difficulties comparing across dimensionsformance and work productivity, t411As decisions (i.e. weighting or nonweighting of specific dimen-are made regarding which treatments produce im- sions), and across populations and/or diseases.

provements in health-related quality of life, it is For the past decade, we [52-54]have argued thatimperative that careful consideration be given to mental and physical health should be assessed us-the measure(s) chosen to quantify changes in this ing a common measurement unit. In fact, compar-parameter, isons between any competitorsfor healthcarere-

sources require that outcomes be expressed using4. Measuring Health-Related some common denominator. Not all healthcare inter-

Quality of Life ventions are equally efficient in returning benefits

A number of approaches have been utilised in for the same expenditure. In cost-utility analysis,the measurement of health-related quality of life, the benefits of medical care, behavioural interven-both in schizophrenia and in other psychiatric and tions or preventive programmes are expressed in

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54 Pattersonetal.

terms of quality-adjusted life-years (QALYs) pro- ogies is that they do not allow for comparisons acrossduced. In section 4.1, we contrast different approa- very different treatment interventions. For example,ches to economic analysis in healthcare. Then we healthcare administrators often need to choose be-

examine specific methods for measuring outcomes, tween investments in different alternatives. Theymay need to decide between supporting clozapine

4. l Cost-Utility versus Cost-Benefit for a few patients versus behaviourally based reha-bilitation intervention for a large number of patients.

The terms cost-utility, cost-effectiveness and cost- For the same cost, treatments may achieve a largebenefit are used inconsistently in the medical liter- effect for a few people or a small effect for a largeature. I55]The key concepts are summarised in table I. number of people. The treatment-specific outcomes

Economists often favour cost-benefit analysis, used in cost-effectiveness studies do not permit suchwhich measures both programme costs and treat- comparisons.ment outcomesinmonetaryunits. For example, treat- Questions about the cost and effectiveness ofment outcomes for schizophrenia are sometimes medical care have created considerable attention

evaluated in relation to changes in use of medical for medical outcomes research. Investigators in both

services or the economic productivity of patients, the public and private sectors have struggled to findTreatments are cost beneficial if the economic re- appropriate methodologies to evaluate healthcareturn exceeds treatment costs. For example, patients technologies. In 1993, the US Department of Healthwith schizophrenia who are aggressively treated with and Human Services appointed a multidisciplinaryantipsychotics may use fewer emergency medical group of methodologists to recommend standard-services. The savings associated with decreased set- ised strategies for the evaluation of healthcare. The

vices might exceed treatment costs. Russell[561 has panel, which released its report in 1996, [571sug-argued that the requirement that healthcare treat-ments reduce costs might be unrealistic. Patients gested that standardised outcomes analyses be con-ducted to evaluate the cost effectiveness of medicaland their families are willing to pay for improve-

care. These analyses require preference-weightedments in health status just as they are willing to paymeasures of health-related quality of life. Althoughfor other desirable goods and services. We do not

treat chronic mental illness such as schizophrenia there has been considerable interest in measuringin order to save money alone; treatments are given the cost effectiveness of treatments for schizophre-in order to achieve better health outcomes, nia, little is known about the validity of general

Cost effectiveness is an alternative approach in outcome measures for these patients.which the unit of outcome is a reflection of treat- Cost-utility approaches use the expressed pref-

ment effect. In recent years, cost effectiveness has erence or utility of a treatment effect as the unit of

gained considerable attention. Some approaches em- outcome. As noted in World Health Organizationphasise simple, treatment-specific outcomes. The (WHO) documents, the goals of healthcare are tomajor difficulty with cost-effectiveness methodol- add years to life and to add life to years.[S81In other

words, healthcare is designed both to make peoplelive longer (increase life expectancy) and to haveTableI.Comparisonofcost-effectiveness,cost-utilityandcost-ben-

efitanalyses higher qualityof life in the years prior to death.

Typeofanalysis Compares With Cost-utility studies use outcome measures that com-Cost-effectivenessMonetaryvalueof Clinicaleffects bine mortality outcomes with quality-of-life meas-

resourcesused urements. The utilities are the expressed preferencesCost-utility Monetaryvalueof Quality oflife for observable states of function on a continuum

resources used producedCost-benefit Monetary valueof Monetary valueof ranging from 0 for death to 1.0 for optimum tune-

resourcesused resourcessavedor tion. [59]In recent years, cost-utility approaches have

created gained increasing acceptance as methods for com-

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Quality of Life Issues in Schizophrenia 55

paring many diverse options in healthcare. [57]For eral health status and that, moreover, considerable

example, some journals now require the consistent disadvantage can accrue from separate measure-use of these terms for all reports on cost-effective- ment and specification of mental function. Mentalness analyses.[6°1 health practitionersand evaluatorshave arguedthat

mental health outcomes are unique and cannot be4,2 IsMental Health Measurement a assessed using the metrics common to those usedSpecial Case? in other aspects of medicine. This partitioning of

outcome assessment has resulted in a separationIn its charter document, the WHO E4°ldefined between mental health and other aspects of health-

health as '...a state of complete physical, mental care, which may be disadvantageous. Briefly, weand social well-being and not merely the absence will present a generalised approach to the measure-of infirmity'. Most often, investigators use sepa- ment of health outcomes and then suggest that it berate methods for measuring the 3 components. The used for outcome studies in mental health. In sec-

separate category for mental health in the WHO tions 5 and 6 we will show how these general ap-definition prompted many investigators to develop preaches might influence decisions about resourceseparate measures of physical and mental health allocation in mental health.functioning. Perhaps the best known effort in this

area is the work by Ware and his associates.I261These 4.3 Utility-Based Measures of Health-Relatedinvestigators adapted Dupuy's [611General Well- Quality of LifeBeing Index and administered it to large numbers

of people as part of the Rand Health Insurance Ex- The literature on measurement of quality of lifeperiment. Ware f621argued that the correlation be- has been extensively reviewed elsewhere (see

tween psychological distress and physical function- Spilker_661). In addition, a number of authors (e.g.ing is only 0.25 and suggested that this confirmed Awad _311or Awad and Hogan f35]) have reviewed

that mental health was a separate dimension, In quality-of-life measurement in schizophrenia. Weaddition, WareL6al offered comparisons between cannot review this enormous volume of literaturethose with no physical limitations but with differ- in this brief paper. Instead, we will concentrate on

ences on items about psychological distress. For measures that can be used for economic analysis.this physically high-functioning group, those with These utility-based measures have been developedhigher scores on mental distress used 3 times as in several countries, including Canada, New Zea-many mental health services as those low in dis- land, the European Community and the US.tress. Inordertounderstandhealthoutcomes,it isne-

When the World Bank and the WHO [631used cessary to build a comprehensive theoretical modelgeneric measures to characterise world health prob- of health status. This model includes several compo-lems, they discovered that mental health problems, nents. The major aspects of the model include mor-such as unipolar depression and schizophrenia, were tality (death) and morbidity (health-related qualityamong the most serious health problems in the of life). Diseases and disabilities are important forworld. Earlier methods that emphasised mortality 2 reasons. First, illness may cause the life expec-missed the importance of mental health conditions, tancy to be shortened. Secondly, illness may makeOnly when physical and mental health conditions life less desirable at times prior to death (health-were measured in common units was the relative related quality of life). [53,591seriousness of mental illness made apparent.j64] Central to a generic model of health outcome is

The separate measurement of mental health a general conceptualisation of quality of life. Theremains a major issue in the conceptualisation of model separates aspects of health status and lifegeneral health status. [41,651We believe that mental quality into distinct components. These are life ex-health should be conceptualised as an aspect of gen- pectancy (mortality), functioning and symptoms

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56 Pattersonet al.

(morbidity), preference for observed functional igned to be useful in large-scale studies. This briefstates (utility) and duration of stay in health states 4-item questionnaire utilises generic terms (e.g. 'phy-(prognosis). There are several different methods for sical suffering' rather than 'pain'), and has empir-estimating these components. Our approach uses a ically derived preferences concerning outcomes. Workmeasurement methodology known as the Quality with a sample of over 600 individuals recruited thr-of Well-Being (QWB) scale. [54] Related approaches oughout the state of New Jersey in the US from ainclude the Health Utility Index t67]the EuroQOL, _6sl variety of settings, including support groups forthe HALex [571and the Quality of Life and Health patients with chronic illnesses, suggests an absenceQuestionnaire. [69,7°1In sections 4.3.1 to 4.3.5 we of differences in comparative preferences forconsider some of these methods and note the geo- health states across demographic or clinical states.graphical origin of each approach. This questionnaire has been validated in a cohort

of cancer patients, I7°1but no evaluations of psychi-4.3.I Canadian Approach: HealthUtilityIndexThe Health Utility Index (HUI) Mark [ [71] gen- atric populations have been reported.

erates scores that can be used to adjust survival 4.3.3Qualityof Well-BeingScaleduration by reduced quality of life. The HUI Mark Over the last 25 years our group at the Univer-I assesses 4 major concepts of health-related qual- sity of California, San Diego, US, has developed aity of life: physical function, which includes mob- general health policy model (GHPM). Using theseility and physical activity; role function, which in- methods, patients are classified according to objec-eludes self-care and role activity; social-emotional tire levels of functioning. These levels are repre-function, which includes well-being and social ac- sented by scales of mobility, physical activity andtivity; and health problems. The concepts and levels social activity. In addition to classification intoof function within the concepts comprise a health these observable levels of function, individuals are

status classification scheme. Individuals are cate- also classified by the symptom or problem that theygorised into one, and only one, level within each found to be most undesirable. On any particularconcept according to their functional status at the day, nearly 80% of the general population is opti-time the data are collected, really functional. However, less than half of the

The HUI group has developed 2 additional ver- population is symptom-free. Symptoms or prob-sions of the HUI. These are known as the HUI Mark lems may be severe, such as serious chest pain, orII and the HUI Mark III. The most recent version minor, such as taking medication or a prescribed(Mark III) contains 8 attributes: vision, hearing, diet for health reasons.

speech, ambulation, dexterity, emotion, cognition Human value studies have been conducted toand pain. [671Each of these attributes has 5 to 6 lev- place the observable states of health and function-els. Preference weights for members of the general ing onto a preference continuum for the desirabilitypublic are available. Preferences are measured us- of various conditions, giving a 'quality' rating be-ing a visual analogue scale and standard gamble tween 0 for death and 1.0 for completely well. Theinstruments. Questionnaires are available in 3 for-

well-life expectancy is the current life expectancymats: face-to-face interview, telephone interview adjusted for diminished quality of life associatedand self-administration. Overall, the HUI is a widely with dysfunctional states, and the duration of stayused and well validated measure. I6v,721However, in each state. It is possible to consider mortality,there have been few applications of the HUI in mental morbidity and the preference weights for the vari-health evaluations and, to our knowledge, it has not ous observable states of function. The model quan-been used in studies of patients with schizophrenia, tifies the health activity or treatment programme in

4.3.2 Quality of Lifeand Health Questionnaire terms of the QALYs that it produces or saves.Hadorn and Uebersax [691have developed the Qual- A mathematical model integrates components

ity of Life and Health Questionnaire, which is des- of the model to express outcomes in a common

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QualityofLifeIssuesinSchizophrenia 57

measurement unit. Using information on current The GHPM has been used in a wide variety offunctioning and duration, it is possible to express population studies. [731In addition, the methods havethe health outcomes in terms of equivalents of been used in clinical trials and studies to evaluate

well years of life or, as some have described them, therapeutic interventions in a wide range of medi-QALYs. A QALY is defined as the equivalent of a cal and surgical conditions/74! including cancer _52_completely well year of life, or a year of life free and Alzheimer's diseaseF 51Furthermore, the methodof any symptoms, problems or health-related dis- has been used for health resource allocation model-

abilities, lingand hasservedas thebasis for an innovativeThe model for point-in-time QWB is: experiment on rationing healthcare by the state of

Oregon in the US. [761

QWB ---1 - [(observed morbidity x morbidity weight) The major differences between the QWB and+ (observed physical activity x physical activity HUI relate to the scoring systems. Both measuresweight) + (observed social activity x social activity weight health states by human judgments. The QWBweight) + (observed symptom/problem xsymptom/problem weight)] uses standardised preferences obtained from the gen-

eral community, whereas the HUI uses both patient-

The net cost-utility ratio is defined as: generated and community-based preferences. Forresource allocation, it has been argued that com-

net cost/(net QWB x duration in years) munity preferences are appropriate because it iscommunity resources that will be consumed. Ad-

where 'net cost' = cost of treatment - cost of vocates for use of patient-level preferences suggestalternative and 'net QWB' = QWB2 - QWB_, where that the community cannot accurately represent theQWB2 and QWB j are measures of quality of well- preferences for people who occupy specific healthbeing taken after and before treatment, respective- states. This may not be a real issue since, althoughly. therearesomedifferencesbetweenpatientandcom-

Consider, for example, a person who is affected munity preference weights, the differences are typ-by schizophrenia and in an objective state of func- ically small and often nonsignificant._ 771

tioning (restricted to a hospital) that is rated by Another difference between the HUI and QWBcommunity peers as 0.50 on a 0 to 1.0 scale. If the is that the QWB uses rating scales to obtain pref-person remains in that state for 1 year, he or she erence data whereas the HUI uses time trade-offs

would have lost the equivalent of one-half of 1 year and standard gambles. These methods, particularlyof life (0.5 well years). However, a person who has the standard gamble, are consistent with the von

acute depression may also be rated as 0.50. In this Neumann and Morgenstern axioms because theycase, the symptoms might only last 3 days and the explicitly incorporate attitudes toward risk. Thus,total loss in well years would be 0.5 x (3/365) which they are more appropriately described as 'utilities'is equal to 0.004 well years. This may not appear rather than preferences. There is a significant de-significant as an outcome. But, suppose that 5000 bate about which of these 2 methodologies is appro-people in a community experience an episode of priate. Psychologists tend to prefer rating scalesacute depression. The QALYs lost would then be while economists argue in favour of trade-offs. This5000 x 0.004 which is equal to 20 years. Now sup- issue is addressed in section 4.1.pose that a treatment has become available andthat acute depression can be eliminated by treat- 4.3.4 European Approach: The EuroQOL

ing the 5000 people in the community. The cost of A collaborative group in the European commu-the treatment is $100 per person or $500 000. The nity has developed a standardised method for esti-cost-utility ratio of the programme would be: mating QALYs. For example, the EuroQOL is a

commonly used health outcome measure. However,

$500 000 (cost)/20 years (utility) = $25 000/well year there are few published data on the sensitivity of

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58 Pattersonet aL

the EuroQOL [781and to our knowledge it has not any attempt to measure them using a uniform meas-yet been used to evaluate outcomes in schizophre- urement strategy is like comparing apples to or-nia research, anges.We believethat while mental andphysical

health outcomes are distinct, and may call for mea-4.3.5PopulationSurveyMethodsThe National Center for Health Statistics has suring the effects of treatment using different units,

it is also important that a common measurementrecently developed a new measure, the Health Ac-tivity and Limitation Index (HALex), which is used strategy be used to ensure that the productivity of

mental health and physical health providers can beto build years of healthy life. This approach is at-tractive because it is linked to the US population directly compared. Since mental health providersvia the National Health Interview Survey. Is71How- compete with all other healthcare providers for the -ever, the measure is crude and it is unlikely to pick same resources, a common outcome metric can al-up minor variations in wellness. It has the advan- low for head-to-head comparisons of treatment ef-

rage of simplicity, but the sensitivity remains to be fectiveness.tS°ldemonstrated. We look forward to more research Several years ago, we Is31argued that there are

on each of these promising approaches, many similarities in mental health and physical healthoutcomes. In this section, we confine our comments

4.4 Overview to the QWBbecause it has been used more oftenthan other preference-based measures in studies of

The most popular measures of health-related patients with mental health problems. These corn-quality of life are psychometrically based profiles, ments may apply equally to other preference-based

The SF-36 is clearly the most widely used measure measures. The QWB system includes the basic di-in the field. The SF-36 has the advantage of linkage mensions of observable functioning, symptoms andto a wide variety of databases. The SF-36 also pro- duration. Mental health problems, like physicalvides a profile of outcomes. The major disadvan- health problems, can be represented by symptomsrage of the SF-36 is that it does not provide data and by disrupted role functioning.

that is easily used in cost-utility or cost-effectiveness Consider some examples. Suppose that a patientanalyses. A deficiency is that it is not scored by has the primary symptom of a headache. If the head-preference. Fryback et al. [79]have developed equa- ache does not disrupt role function, the QWB score

tions that can translate SF-36 scores into QWB and might show a small deviation from 1. If the head-HUI scales. However, these translation equations ache is more serious and keeps the person at home,leave much of the variance unaccounted for. The

the QWB score will be lower. If the headache ismajor criticism of the use of preference and utility very severe, it might limit the person to a hospitalmeasures is that they require subjective judgments, and may have serious disruptive effects upon roleThat issue will be explored in section 5. functioning and result in an even lower QWB score.

Headaches can be of different duration. A headache

5. Is the Utility Model Applicable to associated with the flu may have a serious impactMental Health?

on functioning that may last only a short period of

Despite widespread interest in the model among time. This would be indicated by a minor deviationpractitioners in many different specialties, the con- in well years. In contrast, a chronically recurringcept of a QALY has received very little attention in migraine headache would be associated with sig-the mental health area, due largely to the belief that nificant loss of QALY because duration is a majormental health and physical health outcomes are con- component of the calculation.

ceptually distinct. As noted earlier, Ware and Sher- Now consider the case of a patient with schizo-boumd 411have emphasised that since mental health phrenia, who reports experiencing hallucinations.and physical health constitute different constructs, Hallucinations may be a symptom reported by a

© Adis International Limited. All rights reserved, CNS Drugs 1999 Jul; 12 (1)

QualityofLifeIssuesinSchizophrenia 59

patients with schizophrenia, just as a headache is istered the QWB and the Hamilton Depressionreported by other patients. Hallucinations without Rating Scale to 285 men with HIV disease and 61disruption of role function would cause a minor male controls. The men with HIV infection werevariation of wellness. If the hallucinations caused divided into those with and without AIDS and the

the person to stay at home, the QWB score would presence of depression. The results indicated thatbe lower. Severe hallucinations might require the QWB scores were significantly related to depres-

person to be in a hospital or special facility and sion. HIV-positive patients with little or no depres-would result in a lower QWB score. Symptoms sion had higher QWB scores compared with those

such as hallucinations, like headaches, may have with mild or more serious depressive symptoms.different durations. Patients with schizophrenia with Further, we [861showed that improvement in depre-

hallucinations that are experienced over long peri- ssive symptoms over 1 year was associated withods would experience the loss of more QALYs than improved QWB scores, whereas those who devel-

would patients with hallucinations experienced for oped depressive symptoms showed reductions ina shorterduration. QWBscores.

Some evidence supports the validity of the QWB An important feature of the QWB is that it allowsin studies of mental health. One recent study by our the researcher to compare findings across popula-

group [44,451evaluated the validity of the QWB as an tions. Figure 1 illustrates how QWB scores of pa-outcome measure for older patients with schizoph- tients with schizophrenia compared with those of

renia. 72 patients with schizophrenia and 28 matched healthy controls and with patients with other psy-controls from the San Diego Veterans Affairs Med- chiatric and medical conditions. As can be seen,ical Center completed the QWB, the Structured Clin- older patients with schizophrenia have average QWBical Interview for the DSM-III-R Patient Version scores of 0.57, compared with 0.63 among patients

(SCID_PI811), Scales for the Assessment of Positive with ambulatory AIDS and 0.64 in patients withand Negative Symptoms (SAPS and SANS, resp- depression. Thus, on average, patients with schizo-

ectively), I511and the Global Severity Index (GSI) I821 phrenia lose 0.07 QALYs (0.64 - 0.57) each yearfrom the Brief Symptom Inventoryfi 31The QWB compared with patients with depression and 0.17correlated with the SANS -0.52 (p < 0.001), with QALYs (0.74 - 0.57) compared with healthy olderthe SAPS -0.57 (p < 0.001) and with the GS1-0.62 adults. Thus, for every 100 patients with schizo-

(p < 0.001). Patients and controls were significantly phrenia, each year 17 more QALYs [(0.74 - 0.57)different on the QWB and there was a linear rela- × 100] are lost compared with their healthy coun-

tionship between QWB and severity of illness (as terparts. Conversely, if treatment with antipsy-

classified by the SANS and the SAPS). In addition, chotics improved the QWB score of an older pa-component scores of the QWB (i.e. mobility, phys- tient with schizophrenia (i.e. 0.57) to the level ofical activity, social activity and worst symptom) a healthy older person (i.e. 0.74) for 1 year, 17

were significantly lower among patients as corn- QALYs would be generated for every 100 patientspared with controls, and declined systematically as treated successfully. Using information from thispsychiatric symptoms increased, t441 calculation, in combination with the estimated cost

The QWB is also sensitive to symptoms of other of treatment, it is relatively easy to determine the

psychiatric disorders and medical illnesses. For ex- cost-utility ratio (i.e cost per well year generated).ample, we [84]compared QWB scores between pa- Such data can then be used to make objective deci-tients with major depression and controls. Patients sions regarding the relative financial and medical

had significantly lower QWB scores compared with benefits of various treatment regimens for differentcontrols, _841and among the patient group QWB disorders.

scores systematically decreased as symptoms of de- Measuring mental health productivity in QALYpression increased, tgSJIn other work, we _s6_admin- units would allow the assessment of investments in

© Ad[s International Limited, All rights reserved, CNS Drugs 1999 Jul; 12 (1)

6(] Pattersonetal.

0.9 - 0.810.8- 0.74

o7 1064060.6- 0.57

0.51

8 0.5-

0.4-o 0.3-

0.20.1

0 i i i i i i

Fig. 1.MeanscoresontheQualityof Well-Being(QWB) scaleforyounger[83]andolder[451healthyindividuals,outpatientswithmajordepression,[ 83] ambulatory patients with AIDS, [86]older patients with schizophrenia 14s]and nonhospitalised patients with Alzheimer'sdisease.F 4]

mental health services to be compared directly with About 60% of the patients had the same rank order

those in other aspects of healthcare. The cost-utility using standard gamble and paired comparisons. Theratio is the ratio of the cost of a treatment divided results suggest that complex methods such as the

by the QALYs that the treatment produces. In most standard gamble method or paired comparisons

other areas of medicine, QALY production reports might be difficult for patients with schizophrenia.It is still unclear which method yields the mosthave become relatively common. However, we are

not aware that treatments for schizophrenia have valid and reliable results.been evaluated in terms of cost/QALY. In order to In summary, the general QWB measure has ev-

compete for resources, psychopharmacology reseat- idence for validity in different diseases. It has beenshown to be responsive to change and its applica-chers may benefit from this type of analysis.tion has been found to be feasible in a wide varietyA novel approach to utility assessment has beenof clinical populations. Recent evidence shows that

reported by Lenert and colleagues. [871These inves-the measure has validity for studies in mental

tigators used an interactive computer survey to ev- health as well as for studies of nonpsychiatric med-aluate preferences for adverse effects of antipsych- ical illnesses. It may be useful for demonstratingotic medication. The 3 adverse effects considered the cost-utility of drug treatment. Examples of ap-in the study were tardive dyskinesia, akathisia and plications of these measures in clinical studies andpseudo-parkinsonism. Utility assessments were ob- public policy making are described in section 6.tained from 41 healthy volunteers and 22 patients

who had been diagnosed with schizophrenia. Three 6. Resource Allocation Decisionsdifferent methods were used to evaluate preference:

visual analogue scales, paired comparison and the Mental health service providers must neces-standard gamble. The evaluation showed that there sarily compete with other healthcare providers forwas considerable disagreement in the rank order- limited resources. In order to compete successfully,ing of health states across methods. For example, it will be necessary to document that mental healthonly 44% of the patients with schizophrenia rank- services provide a benefit to the consumer. One of

ordered the cases in the same way using the visual the advantages of using QALY outcomes is that theanalogue scale and the paired comparison method, common metric allows for comparisons among very

f) Adis International Limited, All rights reserved, C NS Drugs 1999 Jul; 12 (1)

QualityofLifeIssuesinSchizophrenia 61

different types of services. All providers in the obsessive-compulsive disorders; 400 was episcler-

healthcare system have the common objectives of itis; 500 was surgical repair of ruptured Achilles

increasing length of life and improving quality of tendon; 600 was medical treatment of nonsexually

life. The general model allows evaluations of the transmitted urethritis; and 700 was laser surgery

relative value of investing in each of these special- for central serous retinopathy.ties in comparison to the resources that they use. The World Bank and the WHO have also rec-

Several different governments have proposed allo- ognised that traditional health indicators, such as

cating resources based on systematic data. [_s/For life expectancy and infant mortality, may be rela-

example, the Australian government now requires lively unaffected by many of the investments in

evidence of cost-effectiveness before granting for- public health for the developing world. They pro-

mulary listing and subsidisation for a new drug, as posed an index similar to the QALY, known as the

do a variety of European governments. Canada has Disability-Adjusted Life Year (DALY). [64]In order

officially proposed the QALYas a basis for making to calculate DALYs, they considered 109 diseasesdecisions about which drugs would be purchased that cause about 95% of all deaths in the world.

by the different provinces. [891This has also been Using the 1990 mortality data, they estimated the

considered in the UK. [901 distribution of these diseases by age, gender and

Formal models of resource allocation have been demographic region of the world. Next, they esti-

implemented by at least one state in the US. Oregon mated mortality from each of these diseases and

has attempted to prioritise the cost utility of dif- created life tables for each condition by each re-

ferent health services in an innovative experiment gion. The next step involved healthy life expec-

with their Medicaid Program. One of the landmark tancy estimates for these regions using experts to

features of the Oregon experiment was the attempt judge the distribution in disability levels by diag-

to prioritise mental health services and other health nostic category. Finally, expert judgment was usedservices on the same basis. Although funding cut- to create qualitative ratings for levels of disability.

offs were not actually instituted, the proposed cut- Using this methodology they evaluated world health

off was below roughly 600 on a rank order basis, problems and concluded that there was too much

At the top of the list were services such as treat- eftbrt being directed toward infectious diseases, suchlnent for rumination disorder of infancy, schizo- as the Ebola virus. In terms of DALYs lost, mental

phrenia, AIDS dementia and for a single episode illness is the leading threat to worldwide health.of major depression. In the middle of the list were

Noncommunicable problems such as smoking andservices such as psychotherapy for anxiety disor-

der and panic disorder and for schizophrenia, sim-

ple type. These services would clearly be funded Table U. Examples ot mental health items from the Oregonintegrated list of health service priorities 1911by the programme. However, at the bottom of the Rankorder Itemlist were services such as psychotherapy for anti- 88 Psychogenicruminationsocial personality disorder, psychotherapy for trans- 159 Schizophrenia

sexualism and psychotherapy for schizoid person- 169 AIDSdementia

ality disorder. Table II presents selected disorders 183 Majordepression,singleepisode

from the 1995 version of the list. To provide a fur- 213 TreatmentofAlzheimer'sdisease258 Alcoholicdelirium

ther perspective on these rankings: number 1 was 333 Panicdisordertreatment of severe or moderate head injury caus- 371 Anxietydisordering loss of consciousness; number 100 was repair 424 Schizophreniasimpletypeof total anomalous pulmonary venous connection; 678 Schizoidpersonalitydisorder

200 was antibiotic treatment of sexually transmit- 692 Transsexualism

ted gonococcal infections; 300 was treatment of 723 Antisocialpersonalitydisorder

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62 Patterson et al.

traffic accidents are second and third. The authors Acknowledgements

of the study noted that traditional indicators thatSupport for this work was provided, in part, by NIMH

consider only death tend to ignore some of the most Center grant P30 MH49671, NIMH grants MH43693 and

important health problems associated with psycho- MH45131, and by the Department of Veterans Affairs.

logical and psychiatric illnesses. However, using a

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