Ceri Phillips

Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme

BACKGROUND Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care. METHODS Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated. RESULTS Each rehabilitation programme for up to 20 patients cost £12 120. The mean incremental cost of adding rehabilitation to standard care was £ –152 (95% CI –881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below £0 was 0.64. CONCLUSIONS This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.

Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (κ=0.81, s.e.=0.05; κW=0.83), compared with very poor agreements of 65% for DRE (κ=0.08, s.e.=0.068, κW=0.16) and 69% for EUS (κ=0.17, s.e.=0.065, κW=0.17). The resource benefits resulting from the use of MRI rather than DRE was £67164 and £92244 when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.

The Costs and Consequences of Adequately Managed Chronic Non-Cancer Pain and Chronic Neuropathic Pain

Chronic pain is distressing for patients and a burden on healthcare systems and society. Recent research demonstrates different aspects of the negative impact of chronic pain and the positive impact of successful treatment, making an overview of the costs and consequences of chronic pain appropriate.

Fibromyalgia: Moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain

&NA; Chronic pain is associated with a range of other problems, including disturbed sleep, depression, anxiety, fatigue, reduced quality of life, and an inability to work or socialise. We investigated whether good symptom control of pain (using definitions of moderate and substantial benefit) is associated with improvement in other symptoms. Individual patient data from four randomised trials in fibromyalgia (2575 patients) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient (1858), divided into one of five groups according to pain reduction, irrespective of treatment: substantial benefit – ≥50% pain reduction; moderate – 30% to <50%; minimal – 15% to <30%; marginal – 0% to <15%; worse – <0% (increased pain intensity). We then calculated change from baseline to end of trial for measures of fatigue, function, sleep, depression, anxiety, ability to work, general health status, and quality‐adjusted life year (QALY) gain over a 12‐month period. Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures, with values by trial end at or approaching normative values. Substantial pain intensity reduction resulted in 0.11 QALYs gained, and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period. Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief. Pain intensity reduction is a simple and effective predictor of which patients should continue treatment, and which should discontinue and try an alternative therapy.

Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses.

a Pain Research and Nuffield Division of Anaesthetics, Department of Clinical Neurosciences, University of Oxford, The Churchill Hospital, Oxford, UK b Department of Occupational, Social and Environmental Medicine, University Medical Center Göttingen, Göttingen, Germany c Centre for Pain Research, The University of Bath, Bath, UK d The UK Cochrane Centre, NHS R&D Programme, Summertown Pavilion, Middle Way, Oxford, UK e Pain Clinic/Regional Centre of Excellence in Palliative Care, Haukeland University Hospital, Bergen, Norway f Pain Clinic, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Meilahti Hospital, Helsinki, Finland g College of Human and Health Sciences, Swansea University, Swansea, Wales, UK

Endoscopic ablation of dysplastic Barrett's oesophagus comparing argon plasma coagulation and photodynamic therapy: a randomized prospective trial assessing efficacy and cost-effectiveness.

Objective Endoscopic mucosal ablation is a promising technique that is used to treat dysplastic Barretts oesophagus. The purpose of this study was to investigate the efficacy and cost-effectiveness of two promising techniques, argon plasma coagulation (APC) and photodynamic therapy (PDT), in the ablation of dysplastic Barretts oesophagus. Material and methods Twenty-six patients with dysplastic Barretts oesophagus (21 M, median age 60 years, median length 4 cm, 23 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD)) were randomized to APC: 13 patients, PDT: 13 patients. APC was performed at a power setting of 65 W and argon gas flow at 1.8 l/min in 1–6 sessions (mean 5). PDT was performed 48 h after intravenous injection of Photofrin 2 mg/kg with a 630 nm red laser light, 200 J/cm through a PDT balloon in one session. All patients received treatment with high-dose proton pump inhibitors. Cost analysis was undertaken and the results were assessed by endoscopy and biopsies at 4 months and 12 months after therapy. Results All patients in both groups showed a reduction in the length of Barretts oesophagus. The median length of Barretts oesophagus eradicated at the 4-month follow-up: APC 65%, PDT 57% and at the 12-month follow-up: APC 56%, PDT 60%. Dysplasia eradication at 4 months: APC 62%, PDT 77%, p=0.03 (95% CI 0.66–0.96) and at 12 months APC 67%, PDT 77%. Buried columnar glands with intestinal metaplasia were seen in both groups, with one patient in the PDT arm developing adenocarcioma under the neo-squamous epithelium. Severe adverse events included APC 2/13 (15%) stricture, 1/13 (8%) odynophagia, chest pain and fever; PDT 2/13 (15%) photosensitivity, 2/13 (15%) stricture. PDT would cost an additional £266 for every percentage reduction in Barretts length and £146 per percentage reduction in dysplasia compared with APC treatment. Conclusions APC and PDT are equally effective in eradicating Barretts mucosa, with PDT being the more expensive treatment. However, PDT is more effective in eradicating dysplasia and the extra benefits of PDT are generated at an extra cost. The occurrence of buried columnar glands and carcinoma warrants caution. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium to justify these interventions.

Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice

BackgroundGastrointestinal harm, known to occur with NSAIDs, is thought to be lower with NSAID and gastroprotective agent, and with inhibitors selective to cyclooxygenase-2 (coxibs) at usual plasma concentrations. We examine competing strategies for available evidence of reduced gastrointestinal bleeding in clinical trials and combine this evidence with evidence from clinical practice on whether the strategies work in the real world, whether guidance on appropriate prescribing is followed, and whether patients adhere to the strategies.MethodsWe used a series of systematic literature searches to find full publications of relevant studies for evidence about the efficacy of these different gastroprotection strategies in clinical trials, and for evidence that they worked and were adhered to in clinical practice – whether they were effective. We chose to use good quality systematic reviews and meta-analyses when they were available.ResultsEvidence of efficacy of coxibs compared to NSAIDs for upper gastrointestinal bleeding was strong, with consistent reductions in events of about 50% in large randomised trials (34,460 patients), meta-analyses of randomised trials (52,474 patients), and large observational studies in clinical practice (3,093 bleeding events). Evidence on the efficacy of NSAID plus gastroprotection with acid suppressants (proton pump inhibitors, PPIs, and histamine antagonists, H2As) was based mainly on the surrogate measure of endoscopic ulcers. The limited information on damage to the bowel suggested that NSAID plus PPI was more damaging than coxibs.Eleven observational studies studied 1.6 million patients, of whom 911,000 were NSAID users, and showed that 76% (range 65% to 90%) of patients with at least one gastrointestinal risk factor received no prescription for gastroprotective agent with an NSAID. The exception was a cohort of US veterans with previous gastrointestinal bleeding, where 75% had gastroprotection with an NSAID. When gastroprotection was prescribed, it was often described as inadequate. A single study suggested that patient adherence to prescribed gastroprotection was low.ConclusionEvidence for efficacy of gastroprotection strategies with NSAIDs is limited. In clinical practice few patients who need gastroprotection get it, and those who get it may not take it. For coxibs, gastroprotection is inherent, although probably not complete.

Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes.

OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products, N-A, Inadine and Aquacel, for patients with diabetic foot ulcers, as well as the feasibility and consequences of less frequent dressing changes by health-care professionals. DESIGN A multicentre, prospective, observer-blinded, parallel group, randomised controlled trial, with three arms. SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK. PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic (present for at least 6 weeks) full-thickness foot ulcer (on or below the malleoli) not penetrating to tendon, periosteum or bone, and with a cross-sectional area between 25 and 2500 mm(2). INTERVENTIONS Participants were randomised 1:1:1 to treatment with one of N-A (a non-adherent, knitted, viscose filament gauze), Inadine (an iodine-impregnated dressing), both traditional dressings, or Aquacel, a newer product. MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24. Secondary measures included time to healing, new ulcerations, major and minor amputations, and episodes of secondary infection. RESULTS A total of 317 patients were randomised. After 88 withdrawals, 229 remained evaluable. A greater proportion of smaller (25-100 mm(2) ulcers healed within the specified time (48.3% versus 37.3%; p = 0.048). There was, however, no difference between the three dressings in terms of percentage healed by 24 weeks, or in the mean time to healing, whether analysed on the basis of intention to treat (Inadine 44.4%, N-A 38.7%, Aquacel 44.7%; not significant) or per protocol (Inadine 55.2%, N-A 59.4%, Aquacel 63.0%; not significant). There was no difference in the quality of healing, as reflected in the incidence of recurrence within 12 weeks. Likewise, there was no difference in the incidence of adverse events, although a greater proportion of those randomised to the non-adherent dressings were withdrawn from the study (34.9% versus 29.1% Aquacel and 19.4% Inadine; p = 0.038). The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings (mean cost per patient: N-A 14.85 pounds, Inadine 17.48 pounds, Aquacel 43.60 pounds). The higher cost of Aquacel was not offset by the fewer dressings required. There was no difference in measures of either generic or condition-specific measures of quality of life. However, there was a significant difference in the change in pain associated with dressing changes between the first and second visits, with least pain reported by those receiving non-adherent dressings (p = 0.012). There was no difference in the costs of professional time, and this may relate to the number of dressing changes undertaken by non-professionals. Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer, although this ranged from 22% to 82% between the different centres. CONCLUSIONS As there was no difference in effectiveness, there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service, thus generating potentially substantial savings. The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs. TRIAL REGISTRATION Current Controlled Trials ISRCTN78366977.

The costs of traumatic brain injury: a literature review

Objective The purpose of this study was to review the literature relating to the psychosocial costs associated with traumatic brain injury (TBI). Methods Nine online journal databases, including MEDLINE, CINAHL, PsychINFO, and PUBMED, were queried for studies between July 2010 and May 2012 pertaining to the economic burden of head injuries. Additional studies were identified through searching bibliographies of related publications and using Google internet search engine. Results One hundred and eight potentially relevant abstracts were identified from the journal databases. Ten papers were chosen for discussion in this review. All but two of the chosen papers were US studies. The studies included a cost-benefit analysis of the implementation of treatment guidelines from the US brain trauma foundation and a cost-effectiveness analysis of post-acute traumatic brain injury rehabilitation. Conclusion Very little research has been published on the economic burden that mild and moderate traumatic brain injury patients pose to their families, careers, and society as a whole. Further research is needed to estimate the economic burden of these patients on healthcare providers and social services and how this can impact current health policies and practices.

Cost of NSAID adverse effects to the UK National Health Service

SummaryNon-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal problems, notably dyspepsia and bleeding. These adverse effects are costly both in terms of acute hospital admissions and in co-prescribing of gastroprotective agents. The costs of these interventions has been estimated for the National Health Service (NHS) in the UK on the basis of a typical Primary Care Group (PCG) of 100,000 people, the whole population, and for the average patient prescribed an NSAID. The annual burden of NSAID-related gastrointestinal adverse effects to the NHS is large. The middle estimate for an average PCG was £435,000 (range £290,000 to £633,000). The middle estimate for the UK was £251 million (range £166 million to £367 million). The middle cost per patient prescribed an NSAID was £48 (range £32 to £70). As much as half of all acid-suppressing prescribing in the UK may be for NSAID-related gastrointestinal effects.