|
Methylphenidate in children with hyperactivity: review and cost-utility analysis |
Gilmore A, Milne R |
|
|
Record Status 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. Health technology The use of methylphenidate for the treatment of children with hyperkinetic disorders, as defined using the ICD-10 criteria.
Study population The study population comprised children aged 6 to 12 years of age, presenting with hyperkinetic disorders. The disease definition was based on the ICD-10 criteria. These stated that all three features (inattention, hyperactivity and impulsiveness) were required to establish a diagnosis and should be pervasive, that is, present in more than one situation (usually at home and school).
Setting The setting was a hospital. The economic study was conducted in the UK.
Dates to which data relate The effectiveness data were derived from studies published between 1985 and 1997. No dates for resource use were reported. The price year was 1997.
Source of effectiveness data The effectiveness evidence came from a review of published studies, augmented by the authors' assumptions.
Outcomes assessed in the review The main outcomes assessed in the review were the absolute response rate of methylphenidate, and the response rate in comparison with placebo. This outcome was reported in short-, medium- and long-term studies. The side effects of the treatment were also evaluated from published studies.
Study designs and other criteria for inclusion in the review The inclusion criteria for the review were:
studies using DSM Criteria for Pervasive ADHD/ADDH or Barkleys Research Criteria at study entry;
studies in children aged 6 to 12 years (or those including this age group), with a primary diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) or ADDH, who were otherwise normal;
studies should exclude or analyse results separately in children with co-morbid anxiety, but studies in children with conduct, oppositional defiant or learning disorders would be included;
randomised controlled trials or crossover trials comparing methylphenidate with placebo, a sample size larger than 15 and clear entry criteria;
studies assessing the effect of methylphenidate on inattention, impulsivity and hyperactivity, academic function and mother-child relationships.
The study designs of the primary studies were reported.
Sources searched to identify primary studies MEDLINE (1966 - 1997), EMBASE (1989 - 1997), the Social Sciences Citation Index (1981 - 1997), British Education Index (1976 - 1997), and Cochrane and PsycLIT (1974 - 1997) databases were searched for effectiveness evidence. Further evidence was retrieved from journals published around the time of the study. Unpublished evidence was sought by contacting the Portsmouth Hospitals' drug information service, the manufacturers of methylphenidate, the ADD/ADHD Family Support Group, and asking experts to identify other important studies or conference proceedings.
Criteria used to ensure the validity of primary studies The authors reported some quality criteria required for selection of the studies for the review. These included a blinded assessment of the outcomes, relevant outcome measures, use of confidence intervals, baseline comparability, equal treatment, basis of the clinical analysis, and management of confounding factors.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included Fifteen primary studies were included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The absolute response rate of methylphenidate was approximately 70%. The response rate in comparison with placebo appears to have ranged from 60 to 65%.
In terms of side effects of the treatment, insomnia, stomach ache and headache occurred in 15 to 37% (over and above the placebo rates) of patients on low-dose regimens, and in 10 to 40% (over and above the placebo rates) of patients on high-dose regimens.
In one specific study, approximately 8.6% (over and above the placebo rates) of patients terminated the treatment due to side effects over a 4-month period.
Methods used to derive estimates of effectiveness The authors made some assumptions in order to calculate the benefits used in the economic analysis.
Estimates of effectiveness and key assumptions It was assumed that benefits seen at 4 to 6 months would persist for a year, provided that medication continued;
6% of the patients would discontinue treatment due to side effects; and
the average response rate in those remaining was 70%.
Measure of benefits used in the economic analysis Quality-adjusted life-years (QALYs) were used as the benefit measure in the economic analysis. They were calculated using data from the literature review and the Index of Health Related Quality of Life (IHRQL). The benefits did not require discounting since the children were treated during a 1-year period.
Direct costs Discounting was not relevant since the time horizon of the study was one year. The unit costs were reported separately from the quantities of resources used. The health service costs included in the analysis were initial and follow-up outpatient visits and drug therapy. The cost/resource boundary adopted in the study was that of the NHS. The costs were estimated using actual data derived from Mimms for the drugs, and from four trusts in the South West region of England for child and adolescent psychiatry/child and family therapy outpatient clinics. The data on resource consumption were derived from contacts with a group of five child psychiatrists. Additional information on drug usage came from the literature. The price year was 1997.
Statistical analysis of costs The costs were treated deterministically in the base-case.
Indirect Costs The indirect costs were not included in the analysis.
Sensitivity analysis Sensitivity analyses were conducted to take into account the uncertainty in the effectiveness (quality of life improvements and response rate) and cost values used in the study. The type of analysis conducted was unclear. The impact of different scenarios on the cost-utility results was also assessed.
Estimated benefits used in the economic analysis The estimated QALYs per 100 children treated over one year were 94.06 with methylphenidate. Placebo led to 88.4 QALYs gained. Thus, the treatment gained an additional 5.66 QALYs per 100 children over one year.
Cost results The total cost of treating 100 children over a 1-year period was 51,930.
Synthesis of costs and benefits An incremental cost-utility analysis was carried out to combine the costs and benefits of the treatment in comparison with placebo. Under the most realistic scenario, the cost per QALY gained would be 9,177 (range: 5,965 - 14,233). The widest range for the cost per QALY ranged from 5,782 (most favourable scenario) to 29,049 (least favourable scenario). By using a higher level of disability for the study disease (due to the insensitivity of the IHRQL for the study disease), the cost per QALY ranged from 4,840 to 11,267.
Authors' conclusions The short-term treatment of hyperkinetic children with methylphenidate was highly effective in comparison with placebo. In addition, it offered a relatively low cost per quality-adjusted life-year (QALY) from the perspective of the National Health Service (NHS). Under the most likely scenario, the cost per QALY ranged from 7,446 to 9,177.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator was clear. Placebo was selected since the aim of the study was to assess the active value of the treatment. You should decide whether it represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence came from a review of published studies, although the authors stated that a systematic and comprehensive review of the literature was not undertaken and the issue of publication bias was not addressed. The methodology and conduct of the review were satisfactorily reported, and the inclusion criteria and sources searched were explicit. The designs and drawbacks of the primary studies were reported, as were the quality criteria required for including studies in the review. However, the method used to combine the results of the individual primary studies was not given. The authors made some assumptions to support the data used in the analysis. Some of these assumptions were made on the basis of published studies, and most were investigated in sensitivity analyses. The authors added that the closing time for the review was 1997 and more recent valid trials may have been published.
Validity of estimate of measure of benefit The benefit measure used in the economic analysis was QALYs, which appears to have been appropriate. The use of QALYs enables comparisons to be made with the benefits of other health care interventions. Only medium-term benefits were calculated, on account of the limited evidence from long-term studies. The QALYs were calculated using the IHRQL. The authors acknowledged that the IHRQL was quite insensitive to the actual degree of disability of the disease under study.
Validity of estimate of costs The perspective adopted in the study was reported. It appears that all the relevant additional costs of the treatment over placebo (extra visits and drug therapy) have been included in the analysis. The unit costs were, appropriately, reported separately from the quantities of resources used and the price year was stated. Thus it is possible to reproduce the study in other settings. The costs were treated deterministically in the base-case, but extensive sensitivity analyses were conducted. The source of the cost data was reported. Resource consumption was based on estimates from a group of experts.
Other issues The authors did not compare their findings with those from other published studies. They also did not address the issue of the generalisability of the study results to other settings. However, the external validity of the analysis was high because the methodology of the study was clearly reported and the analysis could be easily reproduced in other settings. The sensitivity analyses performed showed that the analysis was robust to wide variations and the assumptions made were quite conservative. Thus, the final benefits of the treatment may have been underestimated. The authors stated that, due to the lack of reliable published evidence, greater uncertainty was observed on the long-term effect of the treatment.
Implications of the study The study suggests that methylphenidate should be recommended for the treatment of children with hyperkinetic disorders since the study proved the cost-utility of the therapy from the perspective of the NHS. However, further valid evidence on the long-term effectiveness of the treatment is required.
Bibliographic details Gilmore A, Milne R. Methylphenidate in children with hyperactivity: review and cost-utility analysis. Pharmacoepidemiology and Drug Safety 2001; 10(2): 85-94 Other publications of related interest The Wessex Development and Evaluation Committee. Methylphenidate in Children with Hyperactivity (Report No 78). NHS Research and Development: 1998. Bristol. Milne R, Stein K (eds).
Indexing Status Subject indexing assigned by NLM MeSH Attention Deficit Disorder with Hyperactivity /drug therapy /economics; Child; Costs and Cost Analysis; Great Britain; Humans; Methylphenidate /economics /therapeutic use; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Sympathomimetics /economics /therapeutic use AccessionNumber 22001001358 Date bibliographic record published 31/08/2003 Date abstract record published 31/08/2003 |
|
|
|