Seow Tien Yeo

Long-term effectiveness of a parenting intervention for children at risk of developing conduct disorder

BACKGROUND The typical pattern for intervention outcome studies for conduct problems has been for effect sizes to dissipate over time with decreasing effects across subsequent follow-ups. AIMS To establish whether the short-term positive effects of a parenting programme are sustained longer term. To observe trends, and costs, in health and social service use after intervention. METHOD Parents with children aged 36-59 months at risk of developing conduct disorder (n = 104) received intervention between baseline and first follow-up (6 months after baseline n = 86) in 11 Sure Start areas in North Wales. Follow-ups two (n = 82) and three (n = 79) occurred 12 and 18 months after baseline. Child problem behaviour and parenting skills were assessed via parent self-report and direct observation in the home. RESULTS The significant parent-reported improvements in primary measures of child behaviour, parent behaviour, parental stress and depression gained at follow-up one were maintained to follow-up three, as were improved observed child and parent behaviours. Overall, 63% of children made a minimum significant change (0.3 standard deviations) on the Eyberg Child Behavior Inventory problem scale between baseline and follow-up (using intention-to-treat data), 54% made a large change (0.8 standard deviations) and 39% made a very large change (1.5 standard deviations). Child contact with health and social services had reduced at follow-up three. CONCLUSIONS Early parent-based intervention reduced child antisocial behaviour and benefits were maintained, with reduced reliance on health and social service provision, over time.

Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial

BACKGROUND Proliferative diabetic retinopathy is the most common cause of severe sight impairment in people with diabetes. Proliferative diabetic retinopathy has been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We report the 1 year safety and efficacy of intravitreal aflibercept. METHODS In this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged ≥18 years) with type 1 or 2 diabetes and previously untreated or post-laser treated active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic centres. Patients were randomly assigned (1:1) to repeated intravitreal aflibercept (2 mg/0·05 mL at baseline, 4 weeks, and 8 weeks, and from week 12 patients were reviewed every 4 weeks and aflibercept injections were given as needed) or PRP standard care (single spot or mutlispot laser at baseline, fractionated fortnightly thereafter, and from week 12 patients were assessed every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by minimisation with a web-based computer generated system. Primary outcome assessors were masked optometrists. The treating ophthalmologists and participants were not masked. The primary outcome was defined as a change in best-corrected visual acuity at 52 weeks with a linear mixed-effect model that estimated adjusted treatment effects at both 12 weeks and 52 weeks, having excluded fluctuations in best corrected visual acuity owing to vitreous haemorrhage. This modified intention-to-treat analysis was reapplied to the per protocol participants. The non-inferiority margin was prespecified as -5 Early Treatment Diabetic Retinopathy Study letters. Safety was assessed in all participants. This trial is registered with ISRCTN registry, number 32207582. FINDINGS We recruited 232 participants (116 per group) between Aug 22, 2014 and Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group) contributed to the modified intention-to-treat model, and 210 participants (104 in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was non-inferior and superior to PRP in both the modified intention-to-treat population (mean best corrected visual acuity difference 3·9 letters [95% CI 2·3-5·6], p<0·0001) and the per-protocol population (4·0 letters [2·4-5·7], p<0·0001). There were no safety concerns. The 95% CI adjusted difference between groups was more than the prespecified acceptable margin of -5 letters at both 12 weeks and 52 weeks. INTERPRETATION Patients with proliferative diabetic retinopathy who were treated with intravitreal aflibercept had an improved outcome at 1 year compared with those treated with PRP standard care. FUNDING The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Preferences of people with diabetes for diabetic retinopathy screening: a discrete choice experiment

Diabet. Med. 29, 869–877 (2012)

Conducting Economic Evaluations Alongside Randomised Trials: Current Methodological Issues and Novel Approaches

Trial-based economic evaluations are an important aspect of health technology assessment. The availability of patient-level data coupled with unbiased estimates of clinical outcomes means that randomised controlled trials are effective vehicles for the generation of economic data. However there are methodological challenges to trial-based evaluations, including the collection of reliable data on resource use and cost, choice of health outcome measure, calculating minimally important differences, dealing with missing data, extrapolating outcomes and costs over time and the analysis of multinational trials. This review focuses on the state of the art of selective elements regarding the design, conduct, analysis and reporting of trial-based economic evaluations. The limitations of existing approaches are detailed and novel methods introduced. The review is internationally relevant but with a focus towards practice in the UK.

Diabetic retinopathy screening: perspectives of people with diabetes, screening intervals and costs of attending screening

Diabet. Med. 29, 878–885 (2012)

Cost-effectiveness of steroid (methylprednisolone) injections versus anaesthetic alone for the treatment of Morton’s neuroma: economic evaluation alongside a randomised controlled trial (MortISE trial)

BackgroundMorton’s neuroma is a common foot condition affecting health-related quality of life. Though its management frequently includes steroid injections, evidence of cost-effectiveness is sparse. So, we aimed to evaluate whether steroid injection is cost-effective in treating Morton’s neuroma compared with anaesthetic injection alone.MethodsWe undertook incremental cost-effectiveness and cost-utility analyses from the perspective of the National Health Service, alongside a patient-blinded pragmatic randomised trial in hospital-based orthopaedic outpatient clinics in Edinburgh, UK. Of the original randomised sample of 131 participants with Morton’s neuroma (including 67 controls), economic analysis focused on 109 (including 55 controls). Both groups received injections guided by ultrasound. We estimated the incremental cost per point improvement in the area under the curve of the Foot Health Thermometer (FHT-AUC) until three months after injection. We also conducted cost-utility analyses using European Quality of life-5 Dimensions–3 Levels (EQ-5D-3L), enhanced by the Foot Health Thermometer (FHT), to estimate utility and thus quality-adjusted life years (QALYs).ResultsThe unit cost of an ultrasound-guided steroid injection was £149. Over the three months of follow-up, the mean cost of National Health Service resources was £280 for intervention participants and £202 for control participants – a difference of £79 [bootstrapped 95% confidence interval (CI): £18 to £152]. The corresponding estimated incremental cost-effectiveness ratio was £32 per point improvement in the FHT-AUC (bootstrapped 95% CI: £7 to £100). If decision makers value improvement of one point at £100 (the upper limit of this CI), there is 97.5% probability that steroid injection is cost-effective. As EQ-5D-3L seems unresponsive to changes in foot health, we based secondary cost-utility analysis on the FHT-enhanced EQ-5D. This estimated the corresponding incremental cost-effectiveness ratio as £6,400 per QALY. Over the recommended UK threshold, ranging from £20,000 to £30,000 per QALY, there is 80%-85% probability that steroid injection is cost-effective.ConclusionsSteroid injections are effective and cost-effective in relieving foot pain measured by the FHT for three months. However, cost-utility analysis was initially inconclusive because the EQ-5D-3L is less responsive than the FHT to changes in foot health. By using the FHT to enhance the EQ-5D, we inferred that injections yield good value in cost per QALY.Trial registrationCurrent Controlled Trials ISRCTN13668166

Randomised feasibility study to compare the use of Therabite® with wooden spatulas to relieve and prevent trismus in patients with cancer of the head and neck

Our aim was to compare the efficacy of the Therabite® jaw motion rehabilitation system (Atos Medical) with that of wooden spatulas to relieve and prevent trismus in patients who have had radiotherapy for stage three and four oral and oropharyngeal cancer. Secondary aims were to assess the feasibility and the impact of exercise on health-related quality of life (QoL), and the use of health services after treatment. We designed a randomised, open-label, controlled, three-centre feasibility study to compare the effectiveness and cost of the Therabite® and wooden spatulas. We studied compliance with exercises and health-related QoL, assessed cost using three health economics measures, and conducted semistructured interviews with patients. Patients were randomised into two groups: the Therabite® group (n = 37) and the wooden spatula group (n = 34). All patients had some sense of jaw tightening before the study started. Mean mouth opening after six months increased in both groups, but the difference between the groups was not significant (p = 0.39). Completion rates for the three economic measures were good. There was no significant difference between the two groups in frequency of contact with care services or in QoL. Exercises during and after radiotherapy can ameliorate trismus in patients with stage three and four oral and oropharygeal cancers, but differences between groups in efficacy, compliance, QoL, or use of hospital or community health services, were not significant.

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: Randomised controlled feasibility trial

Background:Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation.Methods:We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care.Results:The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer.Conclusions:We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care.

Patient understanding and acceptability of an early lung cancer diagnosis trial: a qualitative study.

BackgroundThe ELCID (Early Lung Cancer Investigation and Diagnosis) trial was a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of lowering the threshold for referral for urgent chest x-ray for smokers and recent ex-smokers, aged over 60 years with new chest symptoms. The qualitative component aimed to explore the feasibility of individually randomising patients to an urgent chest x-ray or not and to investigate any barriers to patient recruitment and participation. We integrated this within the feasibility trial to inform the design of any future definitive trial, particularly in view of the lack of research exploring symptomatic patients’ experiences of participating in diagnostic trials for possible/suspected lung cancer. Although previous studies contributed valuable information concerning screening for lung cancer and patient participation in trials, this paper is the first to explore issues relating to this specific patient group.MethodsQualitative interviews were conducted with 21 patients, comprising 9 who had been randomised to receive an immediate chest x-ray, 10 who were randomised to receive the standard treatment according to the National Institute for Health and Care Excellence guidelines, and 2 who chose not to participate in the trial. Interviews were analysed using a framework approach.ResultsThe findings of this analysis showed that altruism, personal benefit and the reassurance of not having lung cancer were important factors in patient participation. However, patients largely believed that being in the intervention arm was more beneficial, highlighting a lack of understanding of clinical equipoise. Disincentives to participation in the trial included the stigmatisation of patients who smoked (given the inclusion criteria). Although the majority of patients reported that they were happy with the trial design, there was evidence of poor understanding. Last, for several patients, placing trust in health professionals was preferred to understanding the trial processes.ConclusionsThe integration of a qualitative study focusing on participant experience as a secondary outcome of a feasibility trial enabled exploration of patient response to participation and recruitment. The study demonstrated that although it is feasible to recruit patients to the ELCID trial, more work needs to be done to ensure an understanding of study principles and also of smoking stigmatisation.Trial registrationClinicalTrials.gov, NCT01344005. Registered on 27 April 2011.

Development of an intervention to expedite cancer diagnosis through primary care: a protocol

Background GPs can play an important role in achieving earlier cancer diagnosis to improve patient outcomes, for example through prompt use of the urgent suspected cancer referral pathway. Barriers to early diagnosis include individual practitioner variation in knowledge, attitudes, beliefs, professional expectations, and norms. Aim This programme of work (Wales Interventions and Cancer Knowledge about Early Diagnosis [WICKED]) will develop a behaviour change intervention to expedite diagnosis through primary care and contribute to improved cancer outcomes. Design & setting Non-experimental mixed-method study with GPs and primary care practice teams from Wales. Method Four work packages will inform the development of the behaviour change intervention. Work package 1 will identify relevant evidence-based interventions (systematic review of reviews) and will determine why interventions do or do not work, for whom, and in what circumstances (realist review). Work package 2 will assess cancer knowledge, attitudes, and behaviour of GPs, as well as primary care teams’ perspectives on cancer referral and investigation (GP survey, discrete choice experiment [DCE], interviews, and focus groups). Work package 3 will synthesise findings from earlier work packages using the behaviour change wheel as an overarching theoretical framework to guide intervention development. Work package 4 will test the feasibility and acceptability of the intervention, and determine methods for measuring costs and effects of subsequent behaviour change in a randomised feasibility trial. Results The findings will inform the design of a future effectiveness trial, with concurrent economic evaluation, aimed at earlier diagnosis. Conclusion This comprehensive, evidence-based programme will develop a complex GP behaviour change intervention to expedite the diagnosis of symptomatic cancer, and may be applicable to countries with similar healthcare systems.