A model-based cost-utility analysis of an automated notification system for deteriorating patients on general wards.

BACKGROUND: Delayed response to clinical deterioration of hospital inpatients is common. Deployment of an electronic automated advisory vital signs monitoring and notification system to signal clinical deterioration is associated with significant improvements in clinical outcomes but there is no evidence on the cost-effectiveness compared with routine monitoring, in the National Health Service (NHS) in the United Kingdom (UK). METHODS: A decision analytic model was developed to estimate the cost-effectiveness of an electronic automated advisory notification system versus standard care, in adults admitted to a district general hospital. Analyses considered: (1) the cost-effectiveness of the technology based on secondary analysis of patient level data of 3787 inpatients in a before-and-after study; and (2) the cost-utility (cost per quality-adjusted life-year (QALY)) over a lifetime horizon, extrapolated using published data. Analysis was conducted from the perspective of the NHS. Uncertainty in the model was assessed using a range of sensitivity analyses. RESULTS: The study population had a mean age of 68 years, 48% male, with a median inpatient stay of 6 days. Expected life expectancy at discharge was assumed to be 17.74 years. (1) Cost-effectiveness analysis: The automated notification system was more effective (-0.027 reduction in mean events per patient) and provided a cost saving of -£12.17 (-182.07 to 154.80) per patient admission. (2) Cost-utility analysis: Over a lifetime horizon the automated notification system was dominant, demonstrating a positive incremental QALY gain (0.0287 QALYs, equivalent to ~10 days of perfect health) and a cost saving of £55.35. At a threshold of £20,000 per QALY, the probability of automated monitoring being cost-effective in the NHS was 81%. Increased use of cableless sensors may reduce cost-savings, however, the intervention remains cost-effective at 100% usage (ICER: £3,107/QALY). Stratified cost-effectiveness analysis by age, National Early Warning Score (NEWS) on admission, and primary diagnosis indicated the automated notification system was cost-effective for most strategies and that use representative of the patient population studied was the most cost-saving strategy. CONCLUSION: Automated notification system for adult patients admitted to general wards appears to be a cost-effective use in the NHS; adopting this technology could be good use of scarce resources with significance for patient safety.

A systematic review of economic evaluations of advanced therapy medicinal products.

AIMS: Advanced therapy medicinal products (ATMPs) represent a new category of medicinal products with a potential for transformative improvements in health outcomes but at exceptionally high prices. Routine adoption of ATMPs requires robust evidence of their cost-effectiveness. METHODS: A systematic literature review of economic evaluations of ATMPs, including gene therapies, somatic cell therapies and tissue-engineered products, was conducted. Literature was searched using MedLine, Embase, PubMed, Cochrane Register, the NHS Economic Evaluation Database and the grey literature of health technology assessment organisations with search terms relating to ATMPs and economic evaluations. Titles were screened independently by 2 reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts reviewed. Study findings were appraised critically. RESULTS: 4514 articles were identified, of which 23 met the inclusion criteria. There was some evidence supporting the cost-effectiveness of: chimeric antigen receptor T-cell therapy axicabtagene-ciloleucel (Yescarta), embryonic neural stem cells, tumour infiltrating lymphocytes, in vitro expanded myoblast, autologous chondrocyte implantation, ex vivo gene therapy (Strimvelis) and voretigene neparvovec (Luxturna). However, estimates of cost-effectiveness were associated with significant uncertainty and high likelihood of bias, resulting from largely unknown long-term outcomes, a paucity of evidence on health state utilities and extensive modelling assumptions. CONCLUSION: There are critical limitations to the economic evidence for ATMPs, most notably in relation to evidence on the durability of treatment effect, and the reliability of opinion-based assumptions necessary when evidence is absent.

PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer.

BACKGROUND: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. DESIGN: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. PARTICIPANTS: Patients with suspected pancreatic malignancy. INTERVENTIONS: All patients to undergo PET/CT following standard diagnostic work-up. MAIN OUTCOME MEASURES: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. RESULTS: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. CONCLUSION: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. STUDY REGISTRATION: Current Controlled Trials ISRCTN73852054 and UKCRN 8166. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Goal Setting for Cognitive Rehabilitation in Mild to Moderate Parkinson's Disease Dementia and Dementia with Lewy Bodies.

Alongside the physical symptoms associated with Parkinson's disease dementia and dementia with Lewy bodies, health services must also address the cognitive impairments that accompany these conditions. There is growing interest in the use of nonpharmacological approaches to managing the consequences of cognitive disorder. Cognitive rehabilitation is a goal-orientated behavioural intervention which aims to enhance functional independence through the use of strategies specific to the individual's needs and abilities. Fundamental to this therapy is a person's capacity to set goals for rehabilitation. To date, no studies have assessed goal setting in early-stage Parkinson's disease dementia or dementia with Lewy bodies. Semistructured interviews were carried out with 29 participants from an ongoing trial of cognitive rehabilitation for people with these conditions. Here, we examined the goal statements provided by these participants using qualitative content analysis, exploring the types and nature of the goals set. Participants' goals reflected their motivations to learn new skills or improve performance in areas such as technology-use, self-management and orientation, medication management, and social and leisure activities. These results suggest that goal setting is achievable for these participants, provide insight into the everyday cognitive difficulties that they experience, and highlight possible domains as targets for intervention. The trial is registered with ISRCTN16584442 (DOI 10.1186/ISRCTN16584442 13/04/2015).

Cognitive rehabilitation for Parkinson's disease dementia: a study protocol for a pilot randomised controlled trial.

BACKGROUND: There is growing interest in developing non-pharmacological treatments to address the cognitive deficits apparent in Parkinson's disease dementia and dementia with Lewy bodies. Cognitive rehabilitation is a goal-oriented behavioural intervention which focuses on improving everyday functioning through management of cognitive difficulties; it has been shown to be effective in Alzheimer's disease. To date, no studies have assessed its potential efficacy for addressing the impact of cognitive impairment in people with Parkinson's disease or dementia with Lewy bodies. METHODS/DESIGN: Participants (n = 45) will be recruited from movement disorders, care for the elderly and memory clinics. Inclusion criteria include: a diagnosis of Parkinson's disease, Parkinson's disease dementia or dementia with Lewy bodies according to consensus criteria and an Addenbrooke's Cognitive Examination - III score of ≤ 82. Exclusion criteria include: a diagnosis of any other significant neurological condition; major psychiatric disorder, including depression, which is not related to the patient's Parkinson's disease and unstable medication use for their physical or cognitive symptoms. A single-blind pilot randomised controlled trial, with concurrent economic evaluation, will compare the relative efficacy of cognitive rehabilitation with that of two control conditions. Following a goal-setting interview, the participants will be randomised to one of the three study arms: cognitive rehabilitation (eight weekly sessions), relaxation therapy (eight weekly sessions) or treatment as usual. Randomisation and treatment group allocation will be carried out by a clinical trials unit using a dynamic adaptive sequential randomisation algorithm. The primary outcomes are patients' perceived goal attainment at a 2-months post-intervention assessment and a 6-months follow-up. Secondary outcomes include patients' objective cognitive performance (on tests of memory and executive function) and satisfaction with goal attainment, carers' perception of patients' goal attainment and patients' and carers' health status and psychosocial well-being, measured at the same time points. Cost-effectiveness will be examined to explore the design of a larger cost-effectiveness analysis alongside a full trial. DISCUSSION: This pilot study will evaluate the application of cognitive rehabilitation for the management of cognitive difficulties associated with Parkinson's disease dementia and dementia with Lewy bodies. The results of the study will inform the design of a fully powered randomised controlled trial. TRIAL REGISTRATION: ISRCTN16584442 DOI 10.1186/ISRCTN16584442 13 April 2015.

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.

Public health economics: a systematic review of guidance for the economic evaluation of public health interventions and discussion of key methodological issues.

BACKGROUND: If Public Health is the science and art of how society collectively aims to improve health, and reduce inequalities in health, then Public Health Economics is the science and art of supporting decision making as to how society can use its available resources to best meet these objectives and minimise opportunity cost. A systematic review of published guidance for the economic evaluation of public health interventions within this broad public policy paradigm was conducted. METHODS: Electronic databases and organisation websites were searched using a 22 year time horizon (1990-2012). References of papers were hand searched for additional papers for inclusion. Government reports or peer-reviewed published papers were included if they; referred to the methods of economic evaluation of public health interventions, identified key challenges of conducting economic evaluations of public health interventions or made recommendations for conducting economic evaluations of public health interventions. Guidance was divided into three categories UK guidance, international guidance and observations or guidance provided by individual commentators in the field of public health economics. An assessment of the theoretical frameworks underpinning the guidance was made and served as a rationale for categorising the papers. RESULTS: We identified 5 international guidance documents, 7 UK guidance documents and 4 documents by individual commentators. The papers reviewed identify the main methodological challenges that face analysts when conducting such evaluations. There is a consensus within the guidance that wider social and environmental costs and benefits should be looked at due to the complex nature of public health. This was reflected in the theoretical underpinning as the majority of guidance was categorised as extra-welfarist. CONCLUSIONS: In this novel review we argue that health economics may have come full circle from its roots in broad public policy economics. We may find it useful to think in this broader paradigm with respect to public health economics. We offer a 12 point checklist to support government, NHS commissioners and individual health economists in their consideration of economic evaluation methodology with respect to the additional challenges of applying health economics to public health.