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.

NHS health checks: a cross- sectional observational study on equity of uptake and outcomes.

BACKGROUND: The National Health Checks programme aims to reduce the incidence of cardiovascular diseases and health inequalities in England. We assessed equity of uptake and outcomes from NHS Health Checks in general practices in Bristol, UK. METHODS: A cross-sectional study using patient-level data, from 38 general practices. We descriptively analysed the socioeconomic status (SES) of patients invited and the SES and ethnicity of those attending. Logistic regression was used to test associations between invitation and attendance, with population characteristics. RESULTS: Between June 2010 to October 2014, 31,881 patients were invited, and 13,733 NHS Health Checks completed. 47% of patients invited from the three least and 39% from the two most-deprived index of multiple deprivation quintiles, completed a Check. Proportions of invited patients, by ethnicity were 64% non-black and Asian and 31% black and Asian. Men were less likely to attend than women (OR 0.73, 95% confidence interval 0.67 to 0.80), as were patients ≤ 49 compared to ≥ 70 years (OR 0.40, 95% confidence interval 0.65 to 0.83). After controlling for SES and population characteristics, compared to patients with low CVD risk, high risk patients were more likely to be prescribed cardiovascular drugs (OR 6.2, 95% confidence interval 4.51 to 8.40). Compared to men, women (OR 01.18, 95% confidence interval 1.03 to 1.35) were more likely to be prescribed cardiovascular drugs, as were those ≤ 49 years (50-59 years, OR 1.42, 95% confidence intervals 1.13-1.79, 60-69 years, OR 1.60, 95% confidence intervals, 1.22-2.10, ≥ 70 years, OR 1.64, 95% confidence intervals, 1.14 to 2.35). Controlling for population characteristics, the following groups were most likely to be referred to lifestyle services: younger women (OR 2.22, 95% CI 1.69 to 2.94), those in the most deprived IMD quintile (OR 3.22, 95% CI 1.63 to 6.36) and those at highest risk of CVD (OR, 2.77, 95% CI 1.91 to 4.02). CONCLUSIONS: We found no statistically significant evidence of inequity in attendance for an NHS Health Check by SES. Being older or a woman were associated with better attendance. Targeting men, younger patients and ethnic minority groups may improve equity in uptake for NHS Health Checks.

Instrumental delivery and ultrasound : a multicentre randomised controlled trial of ultrasound assessment of the fetal head position versus standard care as an approach to prevent morbidity at instrumental delivery.

OBJECTIVE: To determine whether the use of ultrasound can reduce the incidence of incorrect diagnosis of the fetal head position at instrumental delivery and subsequent morbidity. DESIGN: Two-arm, parallel, randomised trial, conducted from June 2011 to December 2012. SETTING: Two maternity hospitals in the Republic of Ireland. SAMPLE: A cohort of 514 nulliparous women at term (≥37 weeks of gestation) with singleton cephalic pregnancies, aiming to deliver vaginally, were recruited prior to an induction of labour or in early labour. METHODS: If instrumental delivery was required, women who had provided written consent were randomised to receive clinical assessment (standard care) or ultrasound scan and clinical assessment (ultrasound). [Correction added on 17 April 2014, after first online publication: Sentence was amended.] MAIN OUTCOME MEASURE: Incorrect diagnosis of the fetal head position. RESULTS: The incidence of incorrect diagnosis was significantly lower in the ultrasound group than the standard care group (4/257, 1.6%, versus 52/257, 20.2%; odds ratio 0.06; 95% confidence interval 0.02-0.19; P < 0.001). The decision to delivery interval was similar in both groups (ultrasound mean 13.8 minutes, SD 8.7 minutes, versus standard care mean 14.6 minutes, SD 10.1 minutes, P = 0.35). The incidence of maternal and neonatal complications, failed instrumental delivery, and caesarean section was not significantly different between the two groups. CONCLUSIONS: An ultrasound assessment prior to instrumental delivery reduced the incidence of incorrect diagnosis of the fetal head position without delaying delivery, but did not prevent morbidity. A more integrated clinical skills-based approach is likely to be required to prevent adverse outcomes at instrumental delivery.

A cluster randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of classroom-based cognitive-behavioural therapy (CBT) in reducing symptoms of depression in high-risk adolescents.

BACKGROUND: Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Although this is a major problem, relatively few adolescents with, or at risk of developing, depression are identified and referred for treatment. This suggests the need to investigate alternative approaches whereby preventative interventions are made widely available in schools. OBJECTIVE: To investigate the clinical effectiveness and cost-effectiveness of classroom-based cognitive-behavioural therapy (CBT) in reducing symptoms of depression in high-risk adolescents. DESIGN: Cluster randomised controlled trial. Year groups ( n = 28) randomly allocated on a 1 : 1 : 1 basis to one of three trial arms once all schools were recruited and balanced for number of classes, number of students, Personal, Social and Health Education (PSHE) lesson frequency, and scheduling of PSHE. SETTING: Year groups 8 to 11 (ages 12-16 years) in mixed-sex secondary schools in the UK. Data were collected between 2009 and 2011. PARTICIPANTS: Young people who attended PSHE at participating schools were eligible ( n = 5503). Of the 5030 who agreed to participate, 1064 (21.2%) were classified as 'high risk': 392 in the classroom-based CBT arm, 374 in the attention control PSHE arm and 298 in the usual PSHE arm. Primary outcome data on the high-risk group at 12 months were available for classroom-based CBT ( n = 296), attention control PSHE ( n = 308) and usual PSHE ( n = 242). INTERVENTIONS: The Resourceful Adolescent Programme (RAP) is a focused CBT-based intervention adapted for the UK (RAP-UK) and delivered by two facilitators external to the school. Control groups were usual PSHE (usual school curriculum delivered by teachers) and attention control (usual school PSHE with additional support from two facilitators). Interventions were delivered universally to whole classes. PRIMARY OUTCOMES: Clinical effectiveness: symptoms of depression [Short Mood and Feelings Questionnaire (SMFQ)] in adolescents at high risk of depression 12 months from baseline. Cost-effectiveness: incremental cost-effectiveness ratios (ICERs) based on SMFQ score and quality-adjusted life-years (from European Quality of Life-5 Dimensions scores) between baseline and 12 months. Process evaluation: reach, attrition and qualitative feedback from service recipients and providers. RESULTS: SMFQ scores had decreased for high-risk adolescents in all trial arms at 12 months, but there was no difference between arms [classroom-based CBT vs. usual PSHE adjusted difference in means 0.97, 95% confidence interval (CI) -0.34 to 2.28; classroom-based CBT vs. attention control PSHE -0.63, 95% CI -1.99 to 0.73]. Costs of interventions per child were estimated at £41.96 for classroom-based CBT and £34.45 for attention control PSHE. Fieller's method was used to obtain a parametric estimate of the 95% CI for the ICERs and construct the cost-effectiveness acceptability curve, confirming that classroom-based CBT was not cost-effective relative to the controls. Reach of classroom-based CBT was good and attrition was low (median 80% attending ≥ 60% of sessions), but feedback indicated some difficulties with acceptability and sustainability. CONCLUSIONS: Classroom-based CBT, attention control PSHE and usual PSHE produced similar outcomes. Classroom-based CBT may result in increased self-awareness and reporting of depressive symptoms. Classroom-based CBT was not shown to be cost-effective. While schools are a convenient way of reaching a wide range of young people, implementing classroom-based CBT within schools is challenging, particularly with regard to fitting programmes into a busy timetable, the lack of value placed on PSHE, and difficulties engaging with teachers and young people. Wider use of classroom-based depression prevention programmes should not be undertaken without further research. If universal preventative approaches are to be pursued, their clinical effectiveness and cost-effectiveness with younger children (aged 10-11 years), before the incidence of depression increases, should be investigated. Alternatively, the clinical effectiveness of indicated school-based programmes targeting those already displaying symptoms of depression should be investigated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19083628. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 47. See the HTA programme website for further project information.

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of 'PhysioDirect' telephone assessment and advice services for physiotherapy.

BACKGROUND: As a result of long delays for physiotherapy for musculoskeletal problems, several areas in the UK have introduced PhysioDirect services in which patients telephone a physiotherapist for initial assessment and treatment advice. However, there is no robust evidence about the effectiveness, cost-effectiveness or acceptability to patients of PhysioDirect. OBJECTIVE: To investigate whether or not PhysioDirect is equally as clinically effective as and more cost-effective than usual care for patients with musculoskeletal (MSK) problems in primary care. DESIGN: Pragmatic randomised controlled trial to assess equivalence, incorporating economic evaluation and nested qualitative research. Patients were randomised in 2 : 1 ratio to PhysioDirect or usual care using a remote automated allocation system at the level of the individual, stratifying by physiotherapy site and minimising by sex, age group and site of MSK problem. For the economic analysis, cost consequences included NHS and patient costs, and the cost of lost production. Cost-effectiveness analysis was carried out from the perspective of the NHS. Interviews were conducted with patients, physiotherapists and their managers. SETTING: Four community physiotherapy services in England. PARTICIPANTS: Adults referred by general practitioners or self-referred for physiotherapy for a MSK problem. INTERVENTIONS: Patients allocated to PhysioDirect were invited to telephone a senior physiotherapist for initial assessment and advice using a computerised template, followed by face-to-face care when necessary. Patients allocated to usual care were put on to a waiting list for face-to-face care. MAIN OUTCOME MEASURES: Primary outcome was the Short Form questionnaire-36 items, version 2 (SF-36v2) Physical Component Score (PCS) at 6 months after randomisation. Secondary outcomes included other measures of health outcome [Measure Yourself Medical Outcomes Profile, European Quality of Life-5 Dimensions (EuroQol health utility measure, EQ-5D), global improvement, response to treatment], wait for treatment, time lost from work and usual activities, patient satisfaction. Data were collected by postal questionnaires at baseline, 6 weeks and 6 months, and from routine records by researchers blind to allocation. RESULTS: A total of 1506 patients were allocated to PhysioDirect and 743 to usual care. Patients allocated to PhysioDirect had a shorter wait for treatment than those allocated to usual care [median 7 days vs 34 days; arm-time ratio 0.32, 95% confidence interval (CI) 0.29 to 0.35] and had fewer non-attended face-to-face appointments [incidence rate ratio 0.55 (95% CI 0.41 to 0.73)]. The primary outcome at 6 months' follow-up was equivalent between PhysioDirect and usual care [mean PCS 43.50 vs 44.18, adjusted difference in means -0.01 (95% CI -0.80 to 0.79)]. The secondary measures of health outcome all demonstrated equivalence at 6 months, with slightly greater improvement in the PhysioDirect arm at 6 weeks' follow-up. Patients were equally satisfied with access to care but slightly less satisfied overall with PhysioDirect compared with usual care. NHS costs (physiotherapy plus other relevant NHS costs) per patient were similar in the two arms [PhysioDirect £ 198.98 vs usual care £ 179.68, difference in means £ 19.30 (95% CI -£ 37.60 to £ 76.19)], while QALYs gained were also similar [difference in means 0.007 (95% CI -0.003 to 0.016)]. Incremental cost per QALY gained was £ 2889. The probability that PhysioDirect was cost-effective at a £ 20,000 willingness-to-pay threshold was 88%. These conclusions about cost-effectiveness were robust to sensitivity analyses. There was no evidence of difference between trial arms in cost to patients or value of lost production. No adverse events were detected. CONCLUSIONS: Providing physiotherapy via PhysioDirect is equally clinically effective compared with usual waiting list-based care, provides faster access to treatment, appears to be safe, and is broadly acceptable to patients. PhysioDirect is probably cost-effective compared with usual care.

A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial.

OBJECTIVE: The TREAting Depression with physical activity (TREAD) study investigated the cost-effectiveness of a physical activity intervention, in addition to usual general practitioner care, as a treatment for people with depression. DESIGN: An individually randomised, pragmatic, multicentre randomised controlled trial with follow-up at 4, 8 and 12 months. A subset of participants took part in a qualitative study that investigated the acceptability and perceived benefits of the intervention. SETTING: General practices in the Bristol and Exeter areas. PARTICIPANTS: Aged 18-69 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) diagnosis of depression and scoring ≥ 14 on the Beck Depression Inventory (BDI). Those who were unable to complete self-administered questionnaires in English, with medical contraindications to physical activity or with psychosis, bipolar disorder or serious drug abuse were excluded. INTERVENTIONS: We devised an intervention designed to encourage choice and autonomy in the adoption of physical activity. It consisted of up to three face-to-face and ten telephone contacts delivered by a trained physical activity facilitator over an 8-month period. MAIN OUTCOME MEASURES: The primary outcome was the BDI score measured at 4 months. Secondary outcomes included depressive symptoms over the 12 months and quality of life, antidepressant use and level of physical activity. RESULTS: The study recruited 361 patients, with 182 randomised to the intervention arm and 179 to the usual care arm; there was 80% retention at the 4-month follow-up. The intervention group had a slightly lower BDI score at 4 months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no evidence that the intervention improved outcome for depression. Neither was there any evidence to suggest a difference in the prescription of or self-reported use of antidepressants. However, the amount of physical activity undertaken by those who had received the intervention was increased (odds ratio 2.3, 95% CI 1.3 to 3.9) and was sustained beyond the end of the intervention. From a health-care perspective, the intervention group was more costly than the usual care group, with the cost of the intervention £220 per person on average. It is therefore extremely unlikely that the intervention is cost-effective as a treatment for depression using current willingness-to-pay thresholds. CONCLUSIONS: This physical activity intervention is very unlikely to lead to any clinical benefit in terms of depressive symptoms or to be a cost-effective treatment for depression. Previous research has reported some benefit and there are three possible reasons for this discrepancy: first, even though the intervention increased self-reported physical activity, the increase in activity was not sufficiently large to lead to a measurable influence; second, only more vigorous activity might be of benefit; and third, previous studies had recruited individuals with a pre-existing commitment to physical activity. Future research is needed to identify and explain the mechanisms by which depression might be effectively treated, including, in particular, specific guidance on the optimum type, intensity and duration of physical activity required to produce a therapeutic effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 10. See the HTA programme website for further project information.

Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

OBJECTIVES: To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever, and the relief of fever-associated discomfort in young children who can be managed at home. DESIGN: The trial design was a single-centre (multisite), individually randomised, blinded, three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately. SETTING: There were three recruitment settings, as follows: 'local' where research nurses were recruited from NHS primary care sites; 'remote' where NHS sites notified the study of potentially eligible children; and 'community' where parents contacted the study in response to local media advertisements. PARTICIPANTS: Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home. INTERVENTIONS: The intervention was the provision of, and advice to give, the medicines for up to 48 hours: paracetamol every 4-6 hours (maximum of four doses in 24 hours) and ibuprofen every 6-8 hours (maximum of three doses in 24 hours). Every parent received two bottles, with at least one containing an active medicine. Parents, research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines. The dose of medicine was determined by the child's weight: paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose. RESULTS: For additional time without fever in the first 4 hours, use of both medicines was superior to use of paracetamol alone [adjusted difference 55 minutes, 95% confidence interval (CI) 33 to 77 minutes; p < 0.001] and may have been as good as ibuprofen (adjusted difference 16 minutes, 95% CI -6 to 39 minutes; p = 0.2). Both medicines together cleared the fever 23 minutes (95% CI 2-45 minutes; p = 0.015) faster than paracetamol alone, but no faster than ibuprofen alone (adjusted difference -3 minutes, 95% CI 24-18 minutes; p = 0.8). For additional time without fever in the first 24 hours, both medicines were superior to paracetamol (adjusted difference 4.4 hours, 95% CI 2.4-6.3 hours; p < 0.001) or ibuprofen (adjusted difference 2.5 hours, 95% CI 0.6-4.5 hours; p = 0.008) alone. No reduction in discomfort or other fever-associated symptoms was found, although power was low for these outcomes. An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures. No difference in adverse effects was observed between treatment groups. The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8% and 11% of children respectively. Over the 5-day study period, paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [standard deviation (SD) 23 pounds] versus 20 pounds (SD 38 pounds) for paracetamol and 18 pounds (SD 40 pounds) for ibuprofen. Both medicines were also cheapest for parents because the lower use of health care services resulted in personal saving on travel costs and less time off work: 24 pounds (SD 46 pounds) versus 26 pounds (SD 63 pounds) for paracetamol and 30 pounds (SD 91 pounds) for ibuprofen. This more than compensated for the extra cost of medication. However, statistical evidence for these differences was weak due to lack of power. Overall, a quarter of children were 'back to normal' by 48 hours and one-third by day 5. Five (3%) children were admitted to hospital, two with pneumonia, two with bronchiolitis and one with a severe, but unidentified 'viral illness'. CONCLUSIONS: Young children who are unwell with fever should be treated with ibuprofen first, but the relative risks (inadvertently exceeding the maximum recommended dose) and benefits (extra 2.5 hours without fever) of using paracetamol plus ibuprofen over 24 hours should be considered. However, if two medicines are used, it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose. Manufacturers should consider supplying blank charts for this purpose. Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS. Parents and clinicians should be aware that fever is a relatively short-lived symptom, but may have more serious prognostic implications than the other common symptom presentations of childhood.

Effects of patients' preferences on the treatment of atrial fibrillation: observational study of patient-based decision analysis.

OBJECTIVE: To investigate the effect of patients' preferences in the treatment of atrial fibrillation by using individualized decision analysis in which probability and utility assessments are combined into a decision tree. DESIGN: Observational study based on interviews with patients. SETTING: 8 general practices in Avon, England. PARTICIPANTS: 260 randomly selected patients aged 70 to 85 years with atrial fibrillation. MAIN OUTCOME MEASURES: Patients' treatment preferences regarding anticoagulation treatment (warfarin sodium) after individualized decision analysis; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription. RESULTS: Of 195 eligible patients, 97 participated in decision making using decision analysis. Among these 97, the decision analysis indicated that 59 (61%; 95% confidence interval, 50%-71%) would prefer anticoagulation treatment, considerably fewer than those who would be recommended treatment according to guidelines. There was marked disagreement between the decision analysis and guideline recommendations (kappa> or =0.25). Of 38 patients whose decision analysis indicated a preference for anticoagulation, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin, although the results of their decision analysis suggested they wanted to be. CONCLUSIONS: In the context of shared decision making, individualized decision analysis is valuable in a sizable proportion of elderly patients with atrial fibrillation. Taking account of patients' preferences would lead to fewer prescriptions for warfarin than under published recommendations. Decision analysis as a shared decision-making tool should be evaluated in a randomized controlled trial.

The impact of patients' preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis.

OBJECTIVE: To investigate the impact of patients' preferences for the treatment of atrial fibrillation, by using individualised decision analysis combining probability and utility assessments into a decision tree. DESIGN: Observational study based on interviews with patients. SETTING: Eight general practices in Avon. PARTICIPANTS: 260 randomly selected patients aged 70-85 years with atrial fibrillation. MAIN OUTCOME MEASURES: Patients' treatment preferences regarding anticoagulation treatment (warfarin) after individualised decision analysis; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription. RESULTS: Of 195 eligible patients, 97 participated in decision making using decision analysis. Among these 97, the decision analysis indicated that 59 (61%; 95% confidence interval 50% to 71%) would prefer anticoagulation treatment-considerably fewer than those who would be recommended treatment according to guidelines. There was marked disagreement between the decision analysis and guideline recommendations (kappa=0.25 or less). Of 38 patients whose decision analysis indicated a preference for anticoagulation, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be. CONCLUSIONS: In the context of shared decision making, individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation. Taking account of patients' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations. Decision analysis as a shared decision making tool should be evaluated in a randomised controlled trial.