Belen Corbacho

Valuing QALYs at the end of life

The possibility of weighting QALYs differently for different groups of patients has been a source of debate. Most recently, this debate has been extended to the relative value of QALYs at the end of life (EoL). The objective of this study is to provide evidence of societal preferences in relation to this topic. Three cross-sectional surveys were conducted amongst Spanish general population (n = 813). Survey 1 compared increases in life expectancy for EoL patients with health gains from temporary health problems. Survey 2 compared health gains for temporary health problems with quality of life gains at the EoL (palliative care). Survey 3 compared increases in life expectancy with quality of life gains, both for EoL patients. Preferences were elicited using Person Trade-Off (PTO) and Willingness to pay (WTP) techniques presenting two different durations of health benefit (6 and 18 months). Health benefits, measured in QALYs, were held constant in all comparisons. In survey 1 mean WTP was higher for life extending treatments than for temporary health problems and the majority of respondents prioritised life extension over temporary health problems in response to the PTO questions. In survey 2 mean WTP was higher for palliative care than for temporary health problems and 83% prioritized palliative care (for both durations) in the PTO questions. In survey 3 WTP values were higher for palliative care than for life extending treatments and more than 60% prioritized palliative care in the PTO questions. Our results suggest that QALYs gained from EoL treatments have a higher social value than QALYs gained from treatments for temporary health problems. Further, we found that people attach greater weight to improvements in quality of life than to life extension at the end of life.

Relative Effectiveness Assessment of Pharmaceuticals: Similarities and Differences in 29 Jurisdictions

OBJECTIVEnAssessment of the effectiveness compared with alternative treatment(s) plays an important role in many jurisdictions in determining the reimbursement status of pharmaceuticals. This type of assessment is often referred to as a relative effectiveness assessment (REA) and is carried out by many jurisdictions. Increased sharing of information across jurisdictions may save costs and reduce duplication. The objective of this study was to explore the main similarities and differences in the major methodological aspects of REA in multiple jurisdictions.nnnMETHODSnData were gathered with a standardized data extraction form by searching publicly available information and by eliciting information from representatives at relevant organizations.nnnRESULTSnOf the initially included 35 jurisdictions, data were gathered for 29 jurisdictions. There seem to be substantial similarities on the choice of the comparator, the role of indirect comparisons, and preferred end points in REAs (except for the use of health state utilities). Jurisdictions, however, differ in whether effectiveness (usual circumstances of health care practice) is estimated in case no (comparative) effectiveness data are available and how this is done.nnnCONCLUSIONnSome important methodological aspects for REA are approached in a similar way in many jurisdictions, indicating that collaboration on assessments may be feasible. Enhanced collaboration in the development of methods and best practices for REA between jurisdictions will be a necessary first step. Important topics for developing best practice are indirect comparisons and how to handle the gap between efficacy and effectiveness data in case good quality comparative effectiveness data are not yet available at the time of reimbursement decisions.

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial)

BACKGROUNDnDespite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks.nnnOBJECTIVEnTo evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management.nnnDESIGNnFive-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs).nnnSETTINGnFollow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals.nnnPARTICIPANTSnQuestionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%.nnnINTERVENTIONSnThree hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication.nnnMAIN OUTCOME MEASURESnPrimary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications.nnnRESULTSnThe randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses.nnnCONCLUSIONSnAfter 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective.nnnTRIAL REGISTRATIONnCurrent Controlled Trials ISRCTN15517081.nnnFUNDINGnThis project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

Cost-effectiveness of laparoscopic fundoplication versus continued medical management for the treatment of gastro-oesophageal reflux disease based on long-term follow-up of the REFLUX trial

Laparoscopic fundoplication surgery has been shown to be a cost‐effective alternative to continued medical management over 1u2009year for patients with gastro‐oesophageal reflux disease (GORD). The longer‐term cost‐effectiveness is, however, uncertain. This study evaluated the long‐term health benefits, costs and cost‐effectiveness of laparoscopic fundoplication compared with continued medical management in patients with GORD.

Can patient involvement improve patient safety? A cluster randomised control trial of the Patient Reporting and Action for a Safe Environment (PRASE) intervention

Objective To evaluate the efficacy of the Patient Reporting and Action for a Safe Environment intervention. Design A multicentre cluster randomised controlled trial. Setting Clusters were 33 hospital wards within five hospitals in the UK. Participants All patients able to give informed consent were eligible to take part. Wards were allocated to the intervention or control condition. Intervention The ward-level intervention comprised two tools: (1) a questionnaire that asked patients about factors contributing to safety (patient measure of safety (PMOS)) and (2) a proforma for patients to report both safety concerns and positive experiences (patient incident reporting tool). Feedback was considered in multidisciplinary action planning meetings. Measurements Primary outcomes were routinely collected ward-level harm-free care (HFC) scores and patient-level feedback on safety (PMOS). Results Intervention uptake and retention of wards was 100% and patient participation was high (86%). We found no significant effect of the intervention on any outcomes at 6 or 12u2005months. However, for new harms (ie, those for which the wards were directly accountable) intervention wards did show greater, though non-significant, improvement compared with control wards. Analyses also indicated that improvements were largest for wards that showed the greatest compliance with the intervention. Limitations Adherence to the intervention, particularly the implementation of action plans, was poor. Patient safety outcomes may represent too blunt a measure. Conclusions Patients are willing to provide feedback about the safety of their care. However, we were unable to demonstrate any overall effect of this intervention on either measure of patient safety and therefore cannot recommend this intervention for wider uptake. Findings indicate promise for increasing HFC where wards implement ≥75% of the intervention components. Trial registration number ISRCTN07689702; pre-results.

The ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial - a pragmatic multicentre randomised controlled trial evaluating the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment for proximal fracture of the humerus in adults.

BACKGROUNDnProximal humeral fractures account for 5-6% of all fractures in adults. There is considerable variation in whether or not surgery is used in the management of displaced fractures involving the surgical neck.nnnOBJECTIVEnTo evaluate the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment of the majority of displaced fractures of the proximal humerus involving the surgical neck in adults.nnnDESIGNnA pragmatic parallel-group multicentre randomised controlled trial with an economic evaluation. Follow-up was for 2 years.nnnSETTINGnRecruitment was undertaken in the orthopaedic departments of 33 acute NHS hospitals in the UK. Patient care pathways included outpatient and community-based rehabilitation.nnnPARTICIPANTSnAdults (aged ≥u200916 years) presenting within 3 weeks of their injury with a displaced fracture of the proximal humerus involving the surgical neck.nnnINTERVENTIONSnThe choice of surgical intervention was left to the treating surgeons, who used techniques with which they were experienced. Non-surgical treatment was initial sling immobilisation followed by active rehabilitation. Provision of rehabilitation was comparable in both groups.nnnMAIN OUTCOME MEASURESnThe primary outcome was the Oxford Shoulder Score (OSS) assessed at 6, 12 and 24 months. Secondary outcomes were the 12-item Short Form health survey, surgical and other shoulder fracture-related complications, secondary surgery to the shoulder or increased/new shoulder-related therapy, medical complications during inpatient stay and mortality. European Quality of Life-5 Dimensions data and treatment costs were also collected.nnnRESULTSnThe mean age of the 250 trial participants was 66 years and 192 (77%) were female. Independent assessment using the Neer classification identified 18 one-part fractures, 128 two-part fractures and 104 three- or four-part fractures. OSS data were available for 215 participants at 2 years. We found no statistically or clinically significant differences in OSS scores between the two treatment groups (scale 0-48, with a higher score indicating a better outcome) over the 2-year period [difference of 0.75 points in favour of the surgery group, 95% confidence interval (CI) -1.33 to 2.84; pu2009=u20090.479; data from 114 surgery and 117 non-surgery participants] or at individual time points. We found no statistically significant differences between surgical and non-surgical group participants in SF-12 physical or mental component summary scores; surgical or shoulder fracture-related complications (30 vs. 23 respectively); those undergoing further shoulder-related therapy, either surgery (11 vs. 11 respectively) or other therapy (seven vs. four respectively); or mortality (nine vs. five respectively). The base-case economic analysis showed that, at 2 years, the cost of surgical intervention was, on average, £1780.73 more per patient (95% CI £1152.71 to £2408.75) than the cost of non-surgical intervention. It was also slightly less beneficial in terms of utilities, although this difference was not statistically significant. The net monetary benefit associated with surgery is negative. There was only a 5% probability of surgery achieving the criterion of costing <u2009£20,000 to gain a quality-adjusted life-year, which was confirmed by extensive sensitivity analyses.nnnCONCLUSIONSnCurrent surgical practice does not result in a better outcome for most patients with displaced fractures of the proximal humerus involving the surgical neck and is not cost-effective in the UK setting. Two areas for future work are the setting up of a national database of these fractures, including the collection of patient-reported outcomes, and research on the best ways of informing patients with these and other upper limb fractures about initial self-care.nnnTRIAL REGISTRATIONnCurrent Controlled Trials ISRCTN50850043.nnnFUNDINGnThis project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 24. See the NIHR Journals Library website for further project information.

Dabigatran for the Prevention of Stroke and Systemic Embolism in Atrial Fibrillation: A NICE Single Technology Appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer’s submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80xa0years are treated with dabigatran 150xa0mg twice daily (DBG150) and patients 80xa0years and over are given dabigatran 110xa0mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80xa0years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80xa0years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a ‘minded no’ decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83–85xa0% of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

Health economic decision-making: a comparison between UK and Spain

OBJECTIVEnThis review examines the impact of economic evaluation in informing national or local policies within both jurisdictions. We focus on the factors that have made the economic evaluation evolves differently in both settings.nnnAREAS OF AGREEMENTnEconomic evaluation facilitates decision-making regarding the efficiency of interventions. The existence of national or local bodies regulating the process has contributed to increasing its use in decision-making and the development of its methods.nnnAREAS OF CONTROVERSYnCost-effectiveness approach is based on the assumption of health maximization subject to a budget constraint. Decision-makers are not only interested in health maximization alone. This may result in policy-makers failing to consider economic evaluations into their allocation decisions. AREAS TO DEVELOP RESEARCH: Methods that incorporate wider decision-makers goals (mainly local) and research to study the real impact of economic evaluation in terms of improved efficiency and equity are particularly required.

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

Background Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. Design Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. Results In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. Conclusion There was a small reduction in falls. The intervention may be cost-effective. Trial Registration ISRCTN ISRCTN68240461

Cost effectiveness of surgical versus non-surgical treatment of adults with displaced fractures of the proximal humerus: economic evaluation alongside the PROFHER trial.

AIMSnA pragmatic multicentre randomised controlled trial (PROFHER) was conducted in United Kingdom National Health Service (NHS) hospitals to evaluate the clinical effectiveness and cost effectiveness of surgery compared with non-surgical treatment for displaced fractures of the proximal humerus involving the surgical neck in adults.nnnMETHODSnA cost utility analysis from the NHS perspective was performed. Differences between surgical and non-surgical treatment groups in costs and quality adjusted life years (QALYs) at two years were used to derive an estimate of the cost effectiveness of surgery using regression methods.nnnRESULTSnPatients randomised to receive surgical intervention accumulated mean greater costs and marginally lower QALYs than patients randomised to non-surgery. The surgical intervention cost a mean of £1758 more per patient (95% confidence intervals (CI) £1126 to £2389). Total QALYs for the surgical group were smaller than those for non-surgery -0.0101 (95% CI -0.13 to 0.11). The probability of surgery being cost effective was less than 10% given the current NICE willingness to pay at a threshold of £20 000 for an additional QALY. The results were robust to sensitivity analyses.nnnDISCUSSIONnThe results suggest that current surgical treatment is not cost effective for the majority of displaced fractures of the proximal humerus involving the surgical neck in the United Kingdoms NHS.nnnTAKE HOME MESSAGEnThe results of this trial do not support the trend of increased surgical treatment for patients with displaced fractures of the proximal humerus involving the surgical neck within the United Kingdom NHS.