The study examined second-generation antipsychotic medication in the treatment of schizophrenia.  The comparator was the first-generation class of antipsychotic medication.

Treatment

The objective of the study was to evaluate the cost-effectiveness of second-generation antipsychotics in terms of reducing tardive dyskinesia.  The author did not state a study perspective.  The perspective adopted appears to have been that of the health care system. 

Cost-utility analysis

The study population comprised patients with schizophrenia who were being treated with second-generation antipsychotics.  No further details of the study population were given.

The setting was outpatient.  The author did not state which country the analysis was intended for.  However, the results were presented in US dollars and UK pounds sterling.

The effectiveness data were derived from studies published between 1994 and 2006.  No dates for resource use were explicitly reported.  The price year was not reported.

The clinical parameters associated with the study included incidence of tardive dyskinesia, severity of tardive dyskinesia, the Heinrichs-Carpenter Quality of Life Interview scores, and recovery. 

The clinical effectiveness data were derived from published studies.  The attributable risk of tardive dyskinesia complications with first-generation drugs was obtained from a literature review which included 4 randomised controlled trials (RCTs).  The severity of tardive dyskinesia was also derived from an RCT.

The author reported that a review of the literature was conducted, but the methods of the review were not reported in this paper.  Where possible, the clinical data were derived from papers used in the review, but some unpublished data that addressed the expected ranges of severity and duration of tardive dyskinesia and its relationship to functional capacity and quality of life were also used.

The measure of benefits used was the quality-adjusted life-years (QALYs).  Utility weights were obtained from the literature.  They were elicited from 620 members of the general public using the standard gamble method.

The author did not state the perspective of the study.  It appears that only the cost of antipsychotic medication was included in the analysis, although this was not clear from the paper.  The cost data used in this research were derived from a published study (Rosenheck et al. 2006, see 'Other Publications of Related Interest' below for bibliographic details).  US cost estimates were used.  No price year was stated.  No discounting was required as the base-case time horizon was 1 year.  No discounting was reported for the secondary 5-year analysis.

No productivity losses were included. 

UK pounds sterling (£) and US dollars ($).  The currency conversion ($ to £) was not reported. 

The costs were treated deterministically. 

Best- and worst-case scenarios were developed in order to examine different values of incidence and severity of dyskinesia, recovery and cost.  There was no other examination of uncertainty for the economic analysis. 

The QALY decrement per case of tardive dyskinesia and the difference were reported, but no summary measure of benefit. 

Three annualised estimates for the incremental cost of second-generation antipsychotics were considered: 

a lower bound estimate of £1,200 ($2,400) per year based on a stable drug difference of £100 ($200) per month between perphenazine and second-generation antipsychotics;

an intermediate cost of £1,700 ($3,500 per year), the annualised difference in monthly total health costs between perphenazine and olanzapine; and

an upper bound cost-difference of £3,100 ($6,200), representing the annualised total health cost-difference between perphenazine and quetiapine.

In the base-case analysis, using the best-case scenario for second-generation antipsychotics gave an incremental cost-effectiveness ratio of £26,000 ($52,000) per case of tardive dyskinesia avoided. This increased to £68,000 ($135,000) per case avoided with the higher cost estimates.  The author suggested that, in the base-case, one case avoided was assumed to represent one QALY gained.

In the second analysis, the QALYs gained for a case avoided were 0.143.  This produced a range of cost-effectiveness ratios from £186,335 to £482,609.  Assuming a QALY gain of 0.093, the range  of cost-effectiveness ratios was from $280,505 to £726,508.

It was also assumed that 15% of cases recovered and the estimated cost per QALY ranged from £330,000 ($660,000) to £855,000 ($1,700,000). 

When considering a 5-year time horizon and assuming that cost-differences remained the same over the 5 years, the cost per QALY ratios ranged from of £75,000 ($149,000) to £193,000 ($386,000).

The author concluded that second-generation antipsychotics for symptoms of extrapyramidal side-effects reduce the risk of tardive dyskinesia, but this does not appear likely to provide sufficient health benefit by itself to justify the predominant use of these agents in the treatment of schizophrenia.

The author compared one class of drugs with another.  Care must therefore be taken in applying the results to comparisons between two specific medications.  The comparator of first-generation antipsychotic drugs appeared to be the class of drugs most commonly used.

The sources of the clinical data were reported.  The author stated that all relevant studies were reviewed, but no systematic search for clinical data was reported.  Some of the data came from unpublished sources.  Generally, there was limited information about the primary sources, which means that an objective assessment of the validity of the clinical estimates is not possible. 

QALYs were an appropriate measure because they capture the impact of the intervention on quality of life and survival, which are the most relevant dimensions of health.  However, it was not clear whether all the relevant health outcomes were assessed.  The author stated that there was evidence of no difference in extrapyramidal symptoms between first- and second-generation medication.

The author did not explicitly state the perspective of the study.  It was not clear what costs were actually included.  If only drug costs were included this would have been inadequate.  It is not possible to judge the validity of the costs given the information reported in this paper, and the reader of this abstract is referred to Rosenheck et al. 2006 for further details.  The author acknowledged that it is not certain that US cost estimates would be generalisable to a UK setting.  As stated in the ‘Validity of estimate of measure of benefit’ field (above), it was not clear if all the relevant outcomes were costed.  In the secondary 5-year analysis, no discounting was reported even though it would have been appropriate.  

The author compared the findings with those of previous studies, and stated that this piece of research conformed to the previous trend of dyskinesia prevalence, severity and cost.  The author acknowledged that cost data favoured the new drugs because they incorporated the cost of transfer of patients from first- to second-generation antipsychotics.  The cost estimates did not apply to elderly people, in whom studies have shown greater risks of tardive dyskinesia.  The issue of the generalisability of the results was not addressed.  The author's conclusions adequately reflect the scope of the analysis.

The author stated that, even for the best-case scenario, second-generation antipsychotics do not seem likely to meet conventional standards for cost-effectiveness treatments, and that this could be an argument for lowering payments for these products to a level at which tardive dyskinesia benefits would be worth the price. 

Supported by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutica and Wyeth.

Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper.  Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.

Lenert L, Sturley AP, Rapaport MH,  et al.  Public preferences for health states with schizophrenia and a mapping function to estimate utilities from positive and negative syndrome scale scores.  Schizophr Res 2004;71:155-65.

Rosenheck RA, Leslie D, Sindelar J, et al.  Cost effectiveness of second generation antipsychotic and perphenazine in a randomized trial of treatment for chronic schizophrenia.  Am J Psychiatry 2006;163:2080-9.

Correl CU, Leucht S, Kane JM. Lower risk of tardive dyskinesia associated with second generation antipsychotics: a systematic review of 1-year studies.  Am J Psychiatry 2004;161:414-25.

This record was compiled by CRD commissioned reviewers according to a set of guidelines developed in collaboration with a group of leading health economists.