An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

An introduction to the methods of decision-analytic modelling used in economic evaluations for Dermatologists.

Economic evaluations are used to identify which health treatments or preventions offer the most effective use of resources, or value for money. This is achieved by identifying, measuring and valuing the inputs and outcomes of alternative interventions. These evaluations are often conducted alongside clinical trials; however, these trials may end before the outcomes of economic interest have been observed and measured. An alternative to within trial economic evaluation is to use decision modelling, which can model the cost-effectiveness of interventions over an extended time period. This paper aims to provide an overview for clinicians of the different modelling techniques used within health economic evaluations and to introduce methods for critical appraisal. The most common modelling approaches, and their associated strengths and weaknesses, were discussed. Alongside this, practical examples specific to dermatology were given. These examples include studies where the model chosen or the methods used may not have been the most appropriate. Methods for critical appraisal were also highlighted. Common modelling approaches include Decision Trees, Markov Cohort, extensions to the Markov model (Monte Carlo Simulation) and Discrete Event Simulation models. Items of the Philips Checklist were discussed in the context of performing critical appraisal. Health economic decision models are multi-faceted and can often be complex. Full critical appraisal requires clinicians' unique knowledge, which is complementary to the knowledge of health economists.

Understanding economic evidence for the prevention and treatment of atopic eczema.

BACKGROUND: Atopic eczema is an inflammatory skin condition, with a similar impact on health-related quality of life as other chronic diseases. Increasing pressures on resources within the National Health Service increase the importance of having good economic evidence to inform their allocation. OBJECTIVES: To educate dermatologists about economic methods with reference to currently available economic evidence on eczema. METHODS: The role of different types of economic evidence is illustrated by evidence found in a systematic literature search conducted across 12 online databases up to 22 May 2017. Primary empirical studies either reporting the results of a cost-of-illness study or evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema were included. Two reviewers independently assessed studies for eligibility and performed data abstraction, with disagreements resolved by a third reviewer. Evidence tables of results were produced for narrative discussion. The reporting quality of economic evaluations was assessed. RESULTS: Seventy-eight studies (described in 80 papers) were deemed eligible. Thirty-three (42%) were judged to be economic evaluations, 12 (15%) cost analyses, six (8%) utility analyses, 26 (33%) cost-of-illness studies and one a feasibility study (1%). The calcineurin inhibitors tacrolimus and pimecrolimus, as well as barrier creams, had the most economic evidence available. Partially hydrolysed infant formula was the most commonly evaluated prevention. CONCLUSIONS: The current level of economic evidence for interventions aimed at preventing and treating eczema is limited compared with that available for clinical outcomes, suggesting that greater collaboration between clinicians and economists might be beneficial.

A cohort study of influences, health outcomes and costs of patients' health-seeking behaviour for minor ailments from primary and emergency care settings.

OBJECTIVES: To compare health-related and cost-related outcomes of consultations for symptoms suggestive of minor ailments in emergency departments (EDs), general practices and community pharmacies. DESIGN: Observational study; prospective cohort design. SETTING: EDs (n=2), general practices (n=6) and community pharmacies (n=10) in a mix of rural/urban and deprived/affluent areas across North East Scotland and East Anglia. Participants Adults (≥18 years) presenting between 09:00 and 18:00 (Monday-Friday) in general practices and 09:00-18:00 (Monday-Saturday) in pharmacies and EDs with ≥1 of the following: musculoskeletal pain; eye discomfort; gastrointestinal disturbance; or upper respiratory tract-related symptoms. INTERVENTIONS: Participants completed three questionnaires: baseline (prior to index consultation); satisfaction with index consultation and follow-up (2 weeks after index consultation). MAIN OUTCOME MEASURES: Symptom resolution, quality of life, costs, satisfaction and influences on care-seeking behaviour. RESULTS: 377 patients participated, recruited from EDs (81), general practices (162) and community pharmacies (134). The 2-week response rate was 70% (264/377). Symptom resolution was similar across all three settings: ED (37.3%), general practice (35.7%) and pharmacy (44.3%). Mean overall costs per consultation were significantly lower for pharmacy (£29.30 (95% CI £21.60 to £37.00)) compared with general practice (£82.34 (95% CI £63.10 to £101.58)) and ED (£147.09 (95% CI £125.32 to £168.85)). Satisfaction varied across settings and by measure used. Compared with pharmacy and general practice use, ED use was significantly (p<0.001) associated with first episode and short duration of symptom(s), as well as higher levels of perceived seriousness and urgency for seeking care. Convenience of location was the most common reason for choice of consultation setting. CONCLUSIONS: These results suggest similar health-related outcomes and substantially lower costs with pharmacy consultations for minor ailments. Effective strategies are now needed to shift demand for minor ailment management away from EDs and general practices to the community pharmacy setting.

A multicentre randomised controlled trial and economic evaluation of ion-exchange water softeners for the treatment of eczema in children: the Softened Water Eczema Trial (SWET).

OBJECTIVES: To determine whether installation of an ion-exchange water softener in the home could improve atopic eczema in children and, if so, to establish its likely cost and cost-effectiveness. DESIGN: An observer-blind, parallel-group randomised controlled trial of 12 weeks duration followed by a 4-week observational period. Eczema was assessed by research nurses blinded to intervention at baseline, 4 weeks, 12 weeks and 16 weeks. The primary outcome was analysed as intent-to-treat, using the randomised allocation rather than actual treatment received. A secondary per-protocol analysis excluded participants who failed to receive their allocated treatment and who were deemed to be protocol violators. SETTING: Secondary and primary care referral centres in England (UK) serving a variety of ethnic and social groups and including children living in both urban and periurban homes. PARTICIPANTS: Three hundred and thirty-six children (aged 6 months to 16 years) with moderate/severe atopic eczema, living in homes in England supplied by hard water (≥ 200 mg/l calcium carbonate). INTERVENTIONS: Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care (group A) for 12 weeks or usual eczema care alone (group B) for 12 weeks. This was followed by a 4-week observational period, during which water softeners were switched off/removed from group A homes and installed in group B homes. Standard procedure was to soften all water in the home, but to provide mains (hard) water at a faucet-style tap in the kitchen for drinking and cooking. Participants were therefore exposed to softened water for bathing and washing of clothes, but continued to drink mains (hard) water. Usual care was defined as any treatment that the child was currently using in order to control his or her eczema. New treatment regimens used during the trial period were documented. MAIN OUTCOME MEASURES: Primary outcome was the difference between group A and group B in mean change in disease severity at 12 weeks compared with baseline, as measured using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. This is an objective severity scale completed by blinded observers (research nurses) unaware of the allocated intervention. Secondary outcomes included use of topical medications, night-time movement, patient-reported eczema severity and a number of quality of life measures. A planned subgroup analysis was conducted, based on participants with at least one mutation in the gene encoding filaggrin (a protein in the skin thought to be important for normal skin barrier function). RESULTS: Target recruitment was achieved (n = 336). The analysed population included 323 children who had complete data. The mean change in primary outcome (SASSAD) at 12 weeks was -5.0 [standard deviation (SD) 8.8] for the water softener group (group A) and -5.7 (SD 9.8) for the usual care group (group B) [mean difference 0.66, 95% confidence interval (CI) -1.37 to 2.69, p = 0.53]. The per-protocol analysis supported the main analysis, and there was no evidence that the treatment effect varied between children with and without mutations in the filaggrin gene. No between-group differences were found in the three secondary outcomes that were assessed blindly (use of topical medications; night-time movement; proportion showing reasonable, good or excellent improvement). Small, but statistically significant, differences in favour of the water softener were found in three of the secondary outcomes that were assessed by participants [Patient-Oriented Eczema Measure (POEM); well-controlled weeks (WCWs); Dermatitis Family Index (DFI)]. The results of the economic evaluation, and the uncertainty surrounding them, suggest that ion-exchange water softeners are unlikely to be a cost-effective intervention for children with atopic eczema from an NHS perspective. CONCLUSIONS: Water softeners provided no additional benefit to usual care in this study population. Small, but statistically significant, differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias. Whether or not the wider benefits of installing a water softener in the home are sufficient to justify the purchase of a softener is something for individual householders to consider on a case-by-case basis. This trial demonstrated overwhelming demand for non-pharmacological interventions for the treatment of eczema, and this is something that should be considered when prioritising future research in the field. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 8. See the HTA programme website for further project information. Results of this trial are also published at www.plosmedicine.org.

Second-eye cataract surgery in elderly women: a cost-utility analysis conducted alongside a randomized controlled trial.

AIM: The aim of this study was to evaluate the cost-effectiveness of second-eye cataract surgery for older women with minimal visual dysfunction in the eye to be operated on from a Health and Personal Social Services perspective, compared to waiting list controls who had already undergone first-eye cataract surgery. METHODS: A cost-utility analysis was undertaken alongside a randomized controlled trial of second-eye cataract surgery in secondary care ophthalmology clinics. A total of 239 women over 70 years old with one unoperated cataract were randomized to cataract surgery (expedited, approximately 4 weeks) or control (routine surgery, 12 months wait). Outcomes were measured in terms of quality-adjusted life years (QALYs), with health-related quality of life estimated using the EuroQol EQ-5D. RESULTS: The operated group had costs which were, on average, pound646 more than the control group (95% confidence interval, pound16-1276, P<0.04) and had a mean QALY gain of 0.015 (95% confidence interval, -0.039 to 0.068, P=0.59) per patient over 1 year. Therefore, the incremental cost-utility ratio was pound44,263 over the 1-year trial period. In an analysis modelling costs and benefits over patients' expected lifetime, the incremental cost per QALY was pound17,299, under conservative assumptions. CONCLUSIONS: Second-eye cataract surgery is not likely to be cost-effective in the short term for those with mild visual dysfunction pre-operation. In the long term, second-eye cataract surgery appears to be cost-effective unless carer costs are included.

A multicentre randomized controlled trial of ion-exchange water softeners for the treatment of eczema in children: protocol for the Softened Water Eczema Trial (SWET) (ISRCTN: 71423189).

BACKGROUND: There is epidemiological evidence linking increased water hardness with increased eczema prevalence. A number of plausible mechanisms can be forwarded to suggest why hard water could exacerbate eczema. The most likely explanation is increased soap usage in hard water areas, the deposits of which can cause skin irritation in individuals with eczema. OBJECTIVES: To assess the cost and cost-effectiveness of ion-exchange water softeners for the treatment of eczema in children. PATIENTS/METHODS: Three hundred and ten children aged 6 months to 16 years, with moderate to severe eczema. The children must live in hard water areas (>or= 200 mg L(-1) of calcium carbonate) and have a home that is suitable for the installation of a water softener. This is a single-blind, parallel-group, randomized controlled trial of 12 weeks duration followed by a 4-week cross-over period. RESULTS/ANALYSIS PLAN: PRIMARY OUTCOME: difference in the mean change in disease severity (Six Area, Six Sign Atopic Dermatitis score) at 12 weeks compared with baseline. SECONDARY OUTCOMES: (i) proportion of time spent moving during the night; (ii) self-reported global changes in eczema severity; (iii) amount of topical treatment used; (iv) Patient Oriented Eczema Measure; (v) number of totally controlled and well controlled weeks; (vi) impact on health-related quality of life for the child (EQ-5D) and the family (Dermatitis Family Impact questionnaire); and (vii) cost-effectiveness. It is planned that recruitment will be completed by the end of 2008 and results will be available towards the end of 2009.

The relationship between body mass index and health-related quality of life: comparing the EQ-5D, EuroQol VAS and SF-6D.

BACKGROUND: No other studies have compared the relationship between body mass index (BMI) and health-related quality of life (HRQL) on more than one utility measure. Estimating the HRQL effects of obesity on a (common) utility scale enables the relative cost-effectiveness of interventions designed to alleviate obesity to be estimated. OBJECTIVE: To examine the relationship between BMI and HRQL according to the EQ-5D, EuroQol visual analogue scale (EQ-VAS) and SF-6D. METHODS: Patients aged >/=45 years at one UK general practice were asked to complete the EQ-5D, EQ-VAS, SF-36 questionnaire (used to derive the SF-6D), and information on their characteristics and co-morbidity. Body mass index was categorized according to the World Health Organization (WHO) recommendations. Regression analysis was used to compare the HRQL of normal BMI patients to the HRQL of patients in other BMI categories, while controlling for patient characteristics and co-morbidity. RESULTS: A total of 1865 patients responded (67%), mean BMI 26.0 kg/m(2), 16% obese (BMI>/=30). Patients with back pain, hip pain, knee pain, asthma, diabetes or osteoarthritis were also significantly more likely to be obese. After controlling for other factors, compared to normal BMI patients, obese patients had a lower HRQL according to the EQ-5D (P<0.01), EQ-VAS (P<0.001) and SF-6D (P<0.001). Pre-obese patients were not estimated to have a significantly lower HRQL, and underweight patients were only estimated to have a significantly lower HRQL according to the SF-6D. These results arose because, on the EQ-5D, obese patients were found to have significantly more problems with mobility and pain, compared to physical functioning, social functioning and role limitations on the SF-6D. Whereas, according to the SF-6D, underweight patients had significantly more problems on the dimension of role limitation. CONCLUSION: The EQ-5D, EQ-VAS and SF-6D were in agreement that, relative to a normal BMI, obesity is associated with a lower HRQL, even after controlling for patient characteristics and co-morbidity. These three measures are thereby sensitive to the HRQL effects of obesity and can be used to estimate the cost-effectiveness of interventions designed to alleviate obesity.

Estimating time and out-of-pocket costs incurred by families attending a pediatric cochlear implant programme.

OBJECTIVES: The objectives of this study are to estimate time and out-of-pocket costs incurred by families attending a pediatric cochlear implant programme. In addition, qualitative data examine the intangible costs faced by families. METHODS: Data was collected during semi-structured face-to-face interviews with parents of children with a cochlear implant attending a clinic visit at Nottingham Cochlear Implantation Programme (NPCIP), UK. Information supplied included socio-demographic characteristics, mode of travel, out-of-pocket expenses, time foregone, and details of companions. Quantitative data was stored and analysed in SPSS version 11.5. RESULTS: Two hundred and sixteen face-to-face interviews were conducted with parents of children implanted for between 1 month and 13 years. Time and out-of-pocket costs were significantly higher for those in the first 2 years of the programme, mean UK pound 3090 per annum compared to UK pound 2159 per annum for those in years >2-5 and UK pound 1815 per annum for those in years >5 (P<0.001). The biggest component of this was time costs, although the sensitivity analysis revealed that these were also most variable depending on the methods used to estimate them. The largest out-of-pocket cost incurred by families was travel costs which accounted for 44%, although 16% of families received some financial help with travel costs. The qualitative findings are consistent with these findings, also showing that over time the financial and intangible costs incurred as a result of cochlear implantation decline. CONCLUSIONS: This study is the first to obtain primary data on the time and out-of-pocket costs incurred by families attending a pediatric cochlear implant programme in the UK. It finds that these costs are greatest for those families in the first 2 years of the programme and/or who live furthest from the programme.

Innovation and funding specialist services. Cochlear implantation.

This paper traces the innovative development of the Nottingham Cochlear Implant Programmes. The paediatric programme was the first to be established in the UK in 1989 and remains the largest programme in the UK today, whilst the adult programme developed later, in 1994. The first section of the paper describes trends in service development whilst the second section makes detailed reference to the history of funding arrangements which enabled the programme to become established. The third part of the paper examines the (de)merits of locality purchasing versus centralised purchasing for specialist services, using cochlear implantation as way of illustration. The paper aims to provide an informative history of the development of the service in Nottingham and from this background create debate as to the most appropriate future funding mechanism for cochlear implantation in particular and specialist services in general.

Willingness-to-pay for pediatric cochlear implantation.

OBJECTIVE: This paper presents the results of the first willingness-to-pay (WTP) study to be undertaken on cochlear implantation. It aims to measure the values parents place on the UK having a pediatric cochlear implantation (PCI) programme. METHODS: Face-to-face semi-structured interviews were conducted with parents of children from the Nottingham Pediatric Cochlear Implant programme, whom had been implanted for a period ranging from 1 month to 13 years. Parents willingness-to-pay for the UK to have a pediatric cochlear implantation programme were elicited using a bidding process question format and via a discrete choice question. To see if income was a significant determinant of willingness-to-pay an analysis of variance (ANOVA) was undertaken in the statistical package SPSS version 10. RESULTS: Two hundred and sixteen parents were interviewed over the period July 2001-August 2002, representing over 130h of interviewing. The mean and median willingness-to-pay values elicited were UK pound 127 and 50 per month, respectively (UK pound 2001/2002). Willingness-to-pay was positively related to income (P<0.020). When the income constraint was removed, 99% of parents choose the implant over having the money the implant would cost to spend in some other way to benefit their child. CONCLUSIONS: Parents of implanted children were willing to pay substantial monthly amounts for pediatric cochlear implantation. Most parents saw no alternative to pediatric cochlear implantation that could improve their child's quality of life to the same extent. Willingness-to-pay was sensitive to income as expected suggesting that the values elicited are both valid and influenced by a respondent's budget constraint.