|Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany
|Laux G, Heeg B M S, van Hout B A, Mehnert A
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
The three treatment strategies investigated were first-line treatment with haloperidol depot, long-acting risperidone and oral olanzapine for patients with schizophrenia.
Economic study type
Cost-effectiveness analysis and cost-utility analysis.
The study population comprised patients with multiple schizophrenia relapses who experience total or partial recovery between episodes. In particular, it comprised patients aged 34.4 (standard deviation 11.0) years, with an average life expectancy, after correcting for suicide, of 61 years for men and 65 years for women.
The study setting was secondary care. The economic study was carried out in Germany.
Dates to which data relate
The effectiveness and resource use data were derived from studies published between 1994 and 2003. The price year was 2004.
Source of effectiveness data
The effectiveness data were derived from the literature and were supplemented by advice from a panel of five psychiatrists.
A discrete event simulation model was chosen to simulate individual patients and analyse relationships between events and expected costs and effects. In the model, treatment switches were made if relapse or side effects occurred, generating second- and third-line options within each strategy.
Outcomes assessed in the review
The outcomes assessed in the review were:
the probabilities of side effects;
the effectiveness of treatments in reducing the Positive and Negative Syndrome Scale (PANSS - a severity score used as the main indicator for the severity of a patient's condition);
compliance rates with the medication;
the disorganisation index, which measures the patient's ability to self care; and
Study designs and other criteria for inclusion in the review
Sources searched to identify primary studies
Criteria used to ensure the validity of primary studies
Methods used to judge relevance and validity, and for extracting data
Number of primary studies included
Approximately 10 studies were included in the review.
Methods of combining primary studies
Investigation of differences between primary studies
Results of the review
The authors reported very limited details of the review. In addition, many of the estimates used in the model were based on the results of the review and expert opinion.
Methods used to derive estimates of effectiveness
The effectiveness data derived from the literature were also supplemented by advice from a panel of five psychiatrists. Each expert was interviewed individually, guided by a questionnaire, and asked to evaluate the presented treatment alternatives, model structure, underlying assumptions and all estimates concerning transition probabilities.
Estimates of effectiveness and key assumptions
The authors assumed an 11% reduction in the PANSS score for patients receiving conventional drugs, and 17% for those receiving atypical antipsychotic agents.
Total recovery patients who were receiving treatment were estimated to have the following PANSS scores with atypical antipsychotic agent (conventional antipsychotic agent): 59 (63) for non severe, 84 (90) for medium severe and 99 (106) for very severe.
For the first relapse after model entry for the partial recovery groups, the mean PANSS scores with atypical antipsychotic agent (conventional antipsychotic agent) were 115 (123) for non severe, 120 (128) for medium severe and 125 (134) for very severe.
Between relapses, PANSS scores in these groups were estimated to decrease by 20 points for very severe, 30 for medium severe and 40 for non severe partial recovery.
Between relapses, the PANSS score of total recovery patients was estimated to be 50.
The authors assumed that compliance was higher with depot rather than oral medications, and that it would increase for all medications when administered in an environment that allowed closer supervision. For haloperidol, compliance was assumed to be 5% lower between relapses than during relapses.
Measure of benefits used in the economic analysis
The measure of benefits used was the quality-adjusted life-years (QALYs). These were derived by linking outcomes in terms of the PANSS with utility values according to the results of a study published in 1997. Other measures of benefits included the average number of relapses, the cumulative PANSS score (calculated as the sum of the annual average PANSS score over the 5 years) and time spent in psychosis.
The direct costs to the German health care system were included in the analysis. These were for drug costs, home treatment, psychiatrist visits, sheltered living, day care, hospitalisation and institutionalisation. Drug prices were obtained from the online version of the Rote List, and were checked for congruence with the German official price list. Other costs were derived from national references, tariffs and results from other studies. Since the costs were incurred over a 5-year period, all future costs were discounted at an annual rate of 5%, as recommended by German guidelines. The average costs were reported. The price year was 2004.
Statistical analysis of costs
The costs were reported as point estimates (i.e. the data were deterministic).
In line with the perspective adopted, indirect costs were not included.
A series of one-way sensitivity analyses was undertaken by varying the PANSS reduction achieved by atypical agents, the disorganisation index, the location costs, the symptom severity during relapse, the probability of switch caused by side effects, the effect of non-compliance, the time between relapse and the discount rate. The authors also undertook sensitivity analyses by treating oral risperidone as second-line treatment, and oral risperidone and oral olanzapine as second-line treatment.
Estimated benefits used in the economic analysis
Over the 5-year period, the long-acting risperidone strategy was estimated to avoid a mean number of undiscounted (discounted) relapses per patient of 0.23 (0.22) in comparison with haloperidol depot and 0.33 (0.32) in comparison with oral olanzapine.
Long-acting risperidone reduced the cumulative PANSS score (discounted) by 25 points (23) in comparison with haloperidol depot and by 33 points (31) in comparison with olanzapine.
The cumulative time in psychotic episodes (discounted) was 1.94 (1.72) years with haloperidol depot, 1.80 (1.59) with long-acting risperidone and 2.01 (1.78) with oral olanzapine.
The QALYs gained (discounted) were 1.95 (1.78) with haloperidol depot, 2.06 (1.87) with long-acting risperidone and 1.97 (1.79) with oral olanzapine.
The direct undiscounted (discounted) medical costs per patient after 5 years were EUR 97,336 (88,892) for haloperidol depot, EUR 95,316 (87,284) for long-acting risperidone and EUR 101,414 (92,706) for oral olanzapine.
Synthesis of costs and benefits
The costs and benefits were not combined as long-acting risperidone was found to be both more effective and less costly than oral olanzapine and haloperidol depot (i.e. long-acting risperidone was dominant).
The results of the sensitivity analysis confirmed that long-acting risperidone provided greater clinical effectiveness and lower costs under the vast majority of scenarios tested.
The results of the sub-group analysis showed that, among patients at high risk of non-compliance, long-acting risperidone was dominant. Further, it remained the most effective strategy in all severity sub-group analyses.
Long-acting risperidone, as a first-line strategy, was more effective than first-line haloperidol depot or first-line oral olanzapine strategies. It also reduced the costs.
CRD COMMENTARY - Selection of comparators
A justification was given for using haloperidol and olanzapine as the comparators. They represented a mainstay treatment for schizophrenia and were still an acceptable treatment strategy. You should decide if these two interventions represent current practice in your own setting.
Validity of estimate of measure of effectiveness
The authors did not report if a systematic review of the literature was undertaken to identify all relevant research and minimise biases. Further, they did not provide any details of the methods used in the review, and provided very limited results arising from the review. However, the authors did explain in more detail how the effectiveness estimates were derived from experts. Given these limitations, it is not possible to ascertain that the best available evidence has been used to populate the model.
Validity of estimate of measure of benefit
The estimates of measures of benefits were derived from the discrete event simulation model employed by the authors. This appears to have been appropriate for the study question. All benefits were appropriately discounted, with the authors reporting mean average results both discounted and undiscounted.
Validity of estimate of costs
All the categories of cost relevant to the health care system perspective adopted appear to have been included in the analysis. No major relevant costs appear to have been omitted from the analysis. The costs and the quantities were not reported separately, which will limit the generalisability of the results. However, the authors did report the total costs by resource use category, which will help to minimise this limitation. The costs were derived from published sources and expert opinion. Appropriate sensitivity analyses were conducted. Since the costs were incurred during a 5-year period, all future costs were appropriately discounted. The price year was reported, which will assist any future inflation exercises.
The authors reported that their results agreed with those of similar models undertaken in other health care systems such as Belgium, the Netherlands, Canada and Italy. The issue of generalisability to other settings was addressed in the sensitivity analysis. The authors do not appear to have presented their results selectively, although it would have been desirable for them to have presented the results of their review and the methods employed in a more explicit manner. The authors reported a number of further limitations to their model. These were the way in which compliance was defined, restrictions on when medication switching was allowed, and the exclusion of indirect costs.
Implications of the study
The authors reported that their findings have clear relevance for long-term treatment in clinical practice and formulary decisions.
Source of funding
Supported by Janssen Pharmaceutica N.V., Belgium and Janssen-Cilag GmbH, Germany.
Laux G, Heeg B M S, van Hout B A, Mehnert A. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany. PharmacoEconomics 2005; 23(Supplement 1): 49-61
Other publications of related interest
De Graeve D, Smet A, Mehnert A, Caleo S, Miadi-Fargier H, Mosqueda GJ, et al. Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis. Pharmacoeconomics 2005;23 Suppl 1:35-47.
Chue PS, Heeg B, Buskens E, van Hout BA. Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada. Pharmacoeconomics 2005;23 Suppl 1:62-74.
Heeg BM, van Aalst G, van den Arend JJ. A discrete events model of long-term outcomes and cost of treatment with long acting risperidone in schizophrenia. Value Health 2003;6:515-6.
Subject indexing assigned by NLM
Administration, Oral; Antipsychotic Agents /administration & Benzodiazepines /administration & Cost of Illness; Cost-Benefit Analysis; Delayed-Action Preparations /economics; Economics, Pharmaceutical; Germany; Haloperidol /administration & Humans; Models, Economic; Quality-Adjusted Life Years; Risperidone /administration & Schizophrenia /drug therapy /economics; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use
Date bibliographic record published
Date abstract record published