The feasibility of using the EQ-5D-3L with adults with mild to moderate learning disabilities within a randomized control trial: a qualitative evaluation.

BACKGROUND: In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to  moderate learning disability and type 2 diabetes. METHODS: Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. RESULTS: Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as 'unreliable witnesses' by both researchers and supporters. CONCLUSIONS: It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41897033 [registered 21 January 2013].

Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.

Costs of cancer care for use in economic evaluation: a UK analysis of patient-level routine health system data.

BACKGROUND: The rising financial burden of cancer on health-care systems worldwide has led to the increased demand for evidence-based research on which to base reimbursement decisions. Economic evaluations are an integral component of this necessary research. Ascertainment of reliable health-care cost and quality-of-life estimates to inform such studies has historically been challenging, but recent advances in informatics in the United Kingdom provide new opportunities. METHODS: The costs of hospital care for breast, colorectal and prostate cancer disease-free survivors were calculated over 15 months from initial diagnosis of cancer using routinely collected data within a UK National Health Service (NHS) Hospital Trust. Costs were linked at patient level to patient-reported outcomes and registry-derived sociodemographic factors. Predictors of cost and the relationship between costs and patient-reported utility were examined. RESULTS: The study population included 223 breast cancer patients, 145 colorectal and 104 prostate cancer patients. The mean 15-month cumulative health-care costs were £12 595 (95% CI £11 517-£13 722), £12 643 (£11 282-£14 102) and £3722 (£3263-£4208), per-patient respectively. The majority of costs occurred within the first 6 months from diagnosis. Clinical stage was the most important predictor of costs for all cancer types. EQ-5D score was predictive of costs in colorectal cancer but not in breast or prostate cancer. CONCLUSION: It is now possible to evaluate health-care cost using routine NHS data sets. Such methods can be utilised in future retrospective and prospective studies to efficiently collect economic data.

The cost-effectiveness of primary care referral to a UK commercial weight loss programme.

Primary care referral to commercial weight loss programmes that follow best practice is included in current UK guidance on the management of adult obesity. This study investigated whether such a programme was cost-effective compared with usual care. A decision-analytical Markov model was developed to estimate the lifetime costs and benefits of the referral programme compared with usual care and enable a cost-utility analysis. The model cohort transited between body mass index classifications and type 2 diabetes, stroke and myocardial infarction (MI) with risk, cost and effect parameter values taken from published literature. The cost per incremental quality-adjusted life year (QALY) was calculated. Extensive deterministic and scenario sensitivity analyses and probabilistic sensitivity analyses (PSA) were conducted. At 12 months, the incremental cost-effectiveness ratio was £6906, indicating that programme referral was cost-effective. Over a lifetime, referral to the commercial programme was dominant as it led to a cost saving of £924 and conferred incremental benefit (0.22 QALY) over usual care. Model simulations estimated lower lifetime rates of type 2 diabetes, stroke and MI as a result of the weight loss achieved. The results were robust to extensive sensitivity analyses. The PSA indicated that programme referral had a 68% chance of being cost-effective at a willingness to pay per incremental QALY threshold of £20,000. Referral to the programme dominated usual care, being both cheaper and more effective. These results compare favourably with economic evaluations of other obesity interventions and add to a growing evidence base on the cost-effectiveness of commercial weight loss providers and practices.

Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care patients and lacks effective treatments. A previous randomised controlled Phase II trial suggested that an intravenous (i.v.) infusion of salbutamol may be beneficial, as it reduced extravascular lung water and plateau airway pressure. The Beta-Agonist Lung injury TrIal-2 (BALTI-2) was initiated to evaluate the effects of this intervention on mortality in patients with ARDS. OBJECTIVES: To evaluate whether or not, in patients with ARDS, an i.v. infusion of salbutamol given at 15 µg/kg ideal body weight (IBW)/hour for up to 7 days, compared with a placebo (0.9% sodium chloride) infusion, reduces 28-day all-cause mortality and other clinical outcomes. To evaluate salbutamol's clinical effectiveness and its cost-effectiveness in subgroups of patients. DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Forty-six intensive care units (ICUs) in the UK. PARTICIPANTS: Patients were eligible if they (1) were intubated and mechanically ventilated patients in participating ICUs; (2) were within 72 hours of onset of ARDS; (3) fulfilled American-European Consensus Conference definition for ARDS {acute-onset, severe hypoxaemic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen ≤ 26.7 kPa (200 mmHg)] and bilateral infiltrates on the chest radiograph in the absence of clinical evidence of left atrial hypertension}; and (4) were aged ≥ 16 years. INTERVENTIONS: Intravenous infusion of salbutamol (15 µg/kg IBW/hour) or placebo (0.9% saline) for up to 7 days. MAIN OUTCOME MEASURES: All-cause mortality 28 days after randomisation, mortality at (first) discharge from ICU, mortality at (first) discharge from hospital, number of ventilator-free days, number of organ failure-free days, mortality at 12 months post randomisation, side effects (tachycardia/new arrhythmia/lactic acidosis) sufficient to stop treatment with trial drug, health-related quality of life (European Quality of Life-5 Dimensions and Short Form questionnaire-12 items at 6 and 12 months after randomisation), length of stay in critical care unit and length of stay in hospital. RESULTS: Forty-six ICUs recruited patients to the trial. A total of 326 patients were randomised; 162 were allocated to salbutamol and 164 to placebo. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality: 55 (34%) of 161 patients died in the salbutamol group compared with 38 (23%) of 163 in the placebo group (risk ratio 1.47, 95% confidence interval 1.03 to 2.08). CONCLUSIONS: Treatment with i.v. salbutamol early in the course of ARDS was poorly tolerated, is unlikely to be beneficial and could worsen outcomes. Further trials of ß-agonists in patients with ARDS are unlikely to be conducted. Some questions remain, such as whether or not there may be benefit at a different dose or in specific populations, but any studies investigating these would require a very strong rationale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38366450. FUNDING: The National Institute for Health Research Health Technology Assessment programme.