Cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy vs. no treatment after an initial steroid course in patients with atopic dermatitis in Sweden--with model applications for Denmark, Norway and Finland.

BACKGROUND: Atopic dermatitis (AD) affects health and quality of life and it has great impact on both health-care costs and costs to the society. OBJECTIVES: The objective of this study was to develop a model to analyse the cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy compared with no treatment after initial treatment with betamethasone valerate in adult patients with AD in Sweden. A further aim was to apply a similar health-economic analysis for Denmark, Norway and Finland. METHODS: A Markov simulation model was developed including data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate AD treated with either a moisturizing cream or no treatment, (ii) resource utilization and quality of life data, and (iii) unit prices from official price lists. A societal perspective was used and the analysis was performed according to treatment practice in Sweden. The model simulation was also applied for Denmark, Norway and Finland with inclusion of country-specific unit costs. Sensitivity analyses were performed to test the robustness of the results. RESULTS: The results from the present analyses of treatment for patients with moderate AD indicate that maintenance treatment with a moisturizing cream during eczema-free periods could be cost-effective in a societal perspective. Similar results were obtained for Sweden, Denmark, Norway and Finland. CONCLUSIONS: According to the analysis, treatment with a moisturizing cream was found to be a cost-effective option compared with no treatment in eczema-free periods in adult patients with AD in the four Nordic countries.

The cost-effectiveness of etanercept and infliximab for the treatment of patients with psoriatic arthritis.

OBJECTIVE: Tumour necrosis factor (TNF) antagonists have been shown to improve the outcomes in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We assess the cost-effectiveness of two TNF antagonists and so-called 'palliative care' for the treatment of active PsA from the perspective of the UK National Health Service (NHS). METHODS: Bayesian statistical methods were used to synthesize evidence from three Phase III trials, identified through a systematic review, and estimate the relative efficacy of etanercept, infliximab and palliative care. A probabilistic decision analytic model was then used to compare these treatments after the failure of at least two conventional disease-modifying anti-rheumatic drugs (DMARDs), following the British Society for Rheumatology (BSR) guidelines for use. The primary outcome measure, quality-adjusted life years (QALYs), was derived from utility values estimated as a function of disability measured by the Health Assessment Questionnaire (HAQ). The deterioration experienced in HAQ at treatment withdrawal (rebound) was incorporated using alternative scenarios to represent best- and worst-case assumptions. The model was extended beyond the trial duration to a 10-yr and lifetime horizon, using available evidence and expert opinion-based assumptions on disease progression. Resource utilization was based on literature, national databases and expert opinion. Prices were obtained from routine NHS sources and published literature. RESULTS: At a 10-yr time horizon, the incremental cost-effectiveness ratio (ICER) for etanercept compared with palliative care was pound sterling26 361 per QALY gained for the best-case rebound scenario, which increased to pound sterling30 628 for the worst-case. The ICERs for infliximab compared with etanercept were pound sterling165 363 and pound sterling205 345 per QALY, respectively. These findings are mainly explained by the fact that infliximab has higher acquisition and administration costs without substantially superior effectiveness compared with etanercept. Results were sensitive to estimates of rebound assumptions at withdrawal and the time horizon. CONCLUSIONS: Only results for etanercept remained within the range of cost-effectiveness estimates considered to represent value for money in the NHS by the National Institute for Health and Clinical Excellence. Further research appears most valuable in relation to the short-term effectiveness, utility parameters and assumptions regarding the effect of rebound.

Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses.

OBJECTIVES: To determine the cost-effectiveness of prenatal strategies for preventing group B streptococci (GBS) and other serious bacterial infections in early infancy and to establish the expected value of further information. DATA SOURCES: Electronic databases were searched up to March 2006. Expert opinion was also sought. REVIEW METHODS: Twelve mutually exclusive maternal risk groups were defined at presentation in labour and the consequences considered of early-onset GBS and non-GBS bacterial infections and late onset GBS infection, measured in terms of lifetime NHS costs and quality-adjusted life-years (QALYs). These were for preterm delivery (<37 weeks): (1) planned Caesarean section, (2) previous baby with GBS disease, (3) positive urine or vaginal swab for GBS in current pregnancy, (4) fever >or=38 degrees C during labour, (5) membrane rupture >or=2 hours before labour onset, (6) membrane rupture <2 hours before labour onset. For term delivery (>or=37 weeks): (7) planned Caesarean section, (8) previous baby with GBS disease, (9) positive urine or vaginal swab for GBS in current pregnancy, (10) fever >or=38 degrees C during labour, (11) membrane rupture >or=18 hours, and (12) none of the above risk factors. Fourteen intervention strategies were applied to each maternal risk group. Data inputs were obtained from systematic reviews, primary data and expert opinion. The model parameters were simultaneously estimated from the data inputs using Bayesian evidence synthesis. The expected net benefit was calculated relative to no intervention for each intervention within each risk group for two scenarios, with and without vaccination. Interventions with more than a 1% probability of being cost-effective (i.e. maximising net benefit at a threshold of 25,000 pounds per QALY gained) in a specific risk group were combined to form strategies. To limit antibiotic exposure, women who were low risk at presentation could not be treated without a positive culture or polymerase chain reaction result. RESULTS: Current best practice, comprising intravenous treatment for pyrexia, previous GBS baby and previous GBS swab or urine culture, and oral treatment for preterm pre-labour membrane rupture (groups 2-5 and 8-10) was not cost-effective. All cost-effective options involved treatment of all preterm groups and high-risk term groups (groups 8-10). Testing high-risk women for maternal GBS colonisation would not be cost-effective, as even those with negative results would be better off treated to reduce the risk of early-onset non-GBS infection. In the absence of vaccination, culture-based testing of women in groups 11 and 12, combined with treatment for the rest, would be the most cost-effective strategy. If vaccination was available, vaccination for all and treatment for groups 1-10 would be marginally more cost-effective than treatment for groups 1-10 and culture for groups 11 and 12, but this is uncertain and is based on expert opinion on vaccine efficacy. The expected value of perfect information results suggest that moderate investment in research would be worthwhile. CONCLUSIONS: Based on our findings, immediate extension of current practice to treat all preterm and high-risk term groups would be beneficial. Further research aimed at the realisation of a GBS vaccine should be prioritized.

Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have inadequate response to standard treatment, including disease-modifying antirheumatic drug (DMARD) therapy. DATA SOURCES: Electronic databases were searched up to July 2004. REVIEW METHODS: A systematic review evaluated the clinical efficacy and adverse effects of etanercept and infliximab. The efficacy of DMARDs in the treatment of PsA was also reviewed and treatments were compared using Bayesian evidence synthesis methods. Following evaluation of existing economic evaluations of etanercept and infliximab in PsA, a new economic model was developed (the York Model). This utilised the results from the evidence synthesis and data from a range of other sources. RESULTS: Across the two trials, at 12 weeks, around 65% of patients treated with etanercept achieved an American College of Rheumatology (ACR) 20 {pooled relative risk (RR) 4.19 [95% confidence interval (CI) 2.74 to 6.42]}, demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. In addition, around 45% of patients treated with etanercept achieved an ACR 50 [pooled RR 10.84 (95% CI 4.47 to 26.28)] and around 12% achieved an ACR 70 [pooled RR 16.28 (95% CI 2.20 to 120.54)], demonstrating a good level of efficacy. The subgroup analyses conducted in one trial revealed that the effect of etanercept was not dependent upon patients' concomitant use of methotrexate. In addition, almost 85% of patients treated with etanercept achieved a Psoriatic Arthritis Response Criteria (PsARC) [pooled RR 2.60 (95% CI 1.96 to 3.45). The Psoriatic Area and Severity Index (PASI) results indicate some beneficial effect on psoriasis at 12 weeks; however, the data are sparse. The statistically significant reduction (improvement) in Health Assessment Questionnaire (HAQ) score with etanercept compared with placebo indicates a beneficial effect of etanercept on function. Similar results were seen at 24 weeks, except that the results for PASI 75 and PASI 50 now achieved statistical significance and data for Total Sharp Score annualised rate of progression were available; this was statistically significantly lower in etanercept-treated patients than in placebo-treated patients. Uncontrolled follow-up of patients indicates that treatment benefit may be maintained for at least 50 weeks. At 16 weeks, 65% of patients treated with infliximab achieved an ACR 20 [RR 6.80 (95% CI 2.89 to 16.01)], demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. This level of efficacy was not dependent upon patients' concomitant use of methotrexate. Almost half the patients treated with infliximab achieved an ACR 50 [RR 49.00 (95% CI 3.06 to 785.06)] and over one-quarter achieved an ACR 70 [RR 31.00 (95% CI 1.90 to 504.86)] compared with none of the placebo group, demonstrating a good level of efficacy. In addition, 75% of patients treated with infliximab achieved a PsARC [RR 3.55 (95% CI 2.05 to 6.13)]. The beneficial treatment effect on psoriasis was also statistically significant with a mean difference in percentage change from baseline in PASI of -5 (95% CI -6.8 to -3.3), as was the percentage improvement from baseline in HAQ score with infliximab compared with placebo [mean difference 51.4 (95% CI 48.08 to 54.72)], indicating a beneficial effect of infliximab on functional status. Uncontrolled data from all measures of joint disease, psoriasis and HAQ collected up to 50 weeks of follow-up reflect those at 16 weeks. There were no radiographic assessments, so nothing can be determined about the potential or otherwise of infliximab to delay the progression of joint disease. Using the York cost-effectiveness model, infliximab was consistently dominated by etanercept because of its higher acquisition and administration costs without superior effectiveness. The incremental cost per quality-adjusted life-year (QALY) gained of etanercept compared with palliative care ranged from 14,818 pounds (females, 40-year time horizon) to 49,374 pounds (males, 1-year time horizon) if it is assumed that, when patients eventually fail on biological therapy, their disability (in terms of HAQ score) deteriorates by the same amount as it improved when they initially respond to treatment (rebound equal to gain). Results for etanercept ranged from 25,443 pounds (females, 40-year time horizon) to 49,441 pounds (males, 1-year time horizon) per QALY gained under the assumption that, when patients fail on therapy, their disability level returns to what it would have been had they never responded (rebound equal to natural history). CONCLUSIONS: The limited data available indicated that etanercept and infliximab are efficacious in the treatment of PsA with beneficial effects on both joint and psoriasis symptoms and on functional status. Short-term data indicated that etanercept can delay joint disease progression, but long-term data are needed. There are no controlled data as yet to indicate that infliximab can delay joint disease progression. Treatment with both etanercept and infliximab for 12 weeks demonstrated a significant degree of efficacy, with no statistically significant difference between them. For both drugs, adverse events were common with mild injection/infusion reactions being the main treatment-related effect. The York model indicated that etanercept is more cost-effective than infliximab as it has a lower cost with little difference in outcomes. The cost-effectiveness of etanercept is also sensitive to assumptions made about the extent of disease progression when patients are responding to therapy. The number of years for which a patient can be safely on biologicals is uncertain so these results should be considered with caution. Further research should include long-term controlled trials to confirm benefits, review adverse events and to explore further the implications of biologic therapy.

A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.

OBJECTIVES: To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents (<18 years of age) diagnosed with attention deficit hyperactivity disorder (ADHD) (including hyperkinetic disorder). DATA SOURCES: Electronic databases covering 1999--July 2004 for MPH, 1997--July 2004 for DEX and 1981--July 2004 for ATX. REVIEW METHODS: Selected studies were assessed using modified criteria based on CRD Report No. 4. Clinical effectiveness data were reported separately for each drug and by the type of comparison. Data for MPH were also analysed separately based on whether it was administered as an immediate release (IR) or extended release (ER) formulation. For all drugs, the data were examined by dose. Data for the core outcomes of hyperactivity (using any scale), Clinical Global Impression [as a proxy of quality of life (QoL)] and adverse events were reported. For crossover studies, the mean and standard deviation (SD) for each outcome were data extracted for end of trial data (i.e. baseline data were not considered). For parallel studies, change scores were reported where given, otherwise means and SDs were presented for end of trial data. In addition, mean differences with 95% confidence intervals were calculated for each study. For adverse events, self-ratings were reported when used, otherwise, parent reports were utilised. Percentages of participants reporting adverse events were used to calculate numbers of events in each treatment arm. All the clinical effectiveness data and economic evaluations (including accompanying models) included in the company submissions were assessed. A new model was developed to assess the cost-effectiveness of the alternative treatments in terms of cost per quality-adjusted life-year. To achieve this, a mixed treatment comparison model was used to estimate the differential mean response rates. Monte Carlo simulation was used to reflect uncertainty in the cost-effectiveness results. RESULTS: In total, 65 papers met the inclusion criteria. The results suggest that MPH and DEX are effective at reducing hyperactivity and improving QoL (as determined by Clinical Global Impression) in children, although the reliability of the MPH study results is not known and there were only a small number of DEX studies. There was consistent evidence that ATX was superior to placebo for hyperactivity and Clinical Global Impression. Studies on ATX more often reported the study methodology well, and the results were likely to be reliable. Very few studies made direct head-to-head comparisons between the drugs or examined a non-drug intervention in combination with MPH, DEX or ATX. Adequate and informative data regarding the potential adverse effects of the drugs were also lacking. The results of the economic evaluation clearly identified an optimal treatment strategy of DEX first-line, followed by IR-MPH for treatment failures, followed by ATX for repeat treatment failures. Where DEX is unsuitable as a first-line therapy, the optimal strategy is IR-MPH first-line, followed by DEX and then ATX. For patients contraindicated to stimulants, ATX is preferred to no treatment. For patients in whom a midday dose of medication is unworkable, ER-MPH is preferred to ATX, and ER-MPH12 appears more cost-effective than ER-MPH8. As identified in the clinical effectiveness review, the reporting of studies was poor, therefore this should be borne in mind when interpreting the model results. CONCLUSIONS: Drug therapy seems to be superior to no drug therapy, no significant differences between the various drugs in terms of efficacy or side effects were found, mainly owing to lack of evidence, and the additional benefits from behavioural therapy (in combination with drug therapy) are uncertain. Given the lack of evidence for any differences in effectiveness between the drugs, the economic model tended to be driven by drug costs, which differed considerably. Future trials examining MPH, DEX and ATX should include the assessment of tolerability and safety as a priority. Longer term follow-up of individuals participating in trials could further inform policy makers and health professionals. Such data could potentially distinguish between these drugs in a clinically useful way. In addition, research examining whether somatic complaints are actually related to drug treatment or to the disorder itself would be informative.