The Challenges of Outcomes-Based Contract Implementation for Medicines in Europe.

OBJECTIVES: The aim was to outline the challenges of implementing outcomes-based contracts (OBCs) in Europe. METHODS: A scoping review was conducted, building on the searches of a previous systematic review and updating them for December 2017 until May 2021. The combined results were screened, based on inclusion and exclusion criteria. All identified studies published in the English language that described specific OBC schemes for medicines in European countries were included. Insights into the challenges of OBCs were extracted and analysed to develop a conceptual framework. RESULTS: Ten articles from the previous systematic review matched our inclusion criteria, along with 14 articles from electronic searches. Analysis of these 24 articles and classification of the challenges revealed that there are multiple barriers that must be overcome if OBCs that benefit all stakeholders are going to be adopted widely across Europe. These challenges were grouped according to five key themes: negotiation framework; outcomes; data; administration and implementation; and laws and regulation. CONCLUSIONS: If the promise of OBCs is to be fully realised in Europe, there remain major challenges that need to be overcome by all stakeholders working in partnership. The overlapping and interconnected nature of these challenges highlights the complexity of OBC arrangements.

Economic value of insertable cardiac monitors in unexplained syncope in the United States.

INTRODUCTION: Early use of insertable cardiac monitor (ICM) is recommended for patients with unexplained syncope following initial clinical workup, due to its superior ability to establish symptom-rhythm correlation compared with conventional testing (CONV). However, ICMs incur higher upfront costs, and the impact of additional diagnoses and resulting treatment on downstream costs and outcomes is unclear. We aimed to evaluate the cost-effectiveness of ICM compared with CONV for the diagnosis of arrhythmia in patients with unexplained syncope, from a US payer perspective. METHODS: A Markov model was developed to estimate lifetime costs and benefits of arrhythmia diagnosis with ICM versus CONV, considering all related diagnostic and arrhythmia-related treatment costs and consequences. Cohort characteristics and costs were informed by original claims database analyses. Risks of mortality, syncopal recurrence, injury due to syncope and quality of life consequences from syncopal events were identified from the literature. RESULTS: ICM was less costly and more effective than CONV. Most of the observed US$4532 cost savings were attributed to reduced downstream diagnostic testing. For every 1000 patients, ICM was projected to yield an additional 253 arrhythmia diagnoses and lead to treatment in an additional 168 patients. The ICM strategy resulted in overall improved outcomes (0.30 quality-adjusted life years gained), due to a reduction in syncope recurrence and injury resulting from arrhythmia treatment. The results were robust to changes in the base case parameters but sensitive to the model time horizon, underlying probability of syncope recurrence and prevalence of arrhythmias. CONCLUSIONS: Our model projected that early ICM for the diagnosis of unexplained syncope reduced long-term costs, and led to an improvement in overall clinical outcomes by shortening time to arrhythmia treatment. The cost of ICM was outweighed by savings arising from fewer downstream diagnostic episodes, and the increased cost of treatment was counterbalanced by fewer syncope-related event costs.

Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.

BACKGROUND: Seven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty. OBJECTIVE: The aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence. METHODS: We developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit. RESULTS: In the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses. CONCLUSIONS: Peg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations.

Care in the Home for the Management of Chronic Heart Failure: Systematic Review and Cost-Effectiveness Analysis.

BACKGROUND: The objective of this study was to determine the effect of care in the home (CHM) compared with usual care (UC) in patients with chronic heart failure (CHF) on clinical outcomes and healthcare use including a cost-effectiveness analysis. METHODS: A systematic literature search on MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, as well as Centre for Reviews and Dissemination was conducted to identify randomized controlled trials comparing CHM with UC in CHF. The randomized controlled trials meeting inclusion criteria were meta-analyzed by outcome, and the quality of evidence for each outcome was evaluated using Grading of Recommendations Assessment, Development, and Evaluation system. A cost-effectiveness model was developed to estimate costs and quality-adjusted life years. RESULTS: Six randomized controlled trials were identified from 1277 citations. Care in the home was predominately provided by a single health professional consisting of nurse-led education of varying duration and frequency. One study included pharmacist-led CHM. Care in the home showed a decreased risk for all-cause mortality and hospitalizations combined (risk ratio, 0.88; 95% confidence interval [CI], 0.80-0.97), but not all-cause mortality alone (risk ratio, 0.92; 95% CI, 0.81-1.04). Care in the home resulted in fewer hospitalizations (mean difference, -1.03; 95% CI, -1.53 to -0.53) and fewer emergency department visits (mean difference, -1.32; 95% CI, -1.87 to -0.77). Quality of life also improved with CHM delivered by nurses. Critical appraisal of the quality of evidence suggests uncertainty in the estimates for a number of outcomes. Care in the home resulted in a savings of $10,665 and a gain of 0.11 quality-adjusted life years compared with UC. CONCLUSIONS: In conclusion, the beneficial effect of CHM in CHF is by reducing mortality and hospitalizations combined. Care in the home in CHF seems to be more effective and less costly compared with UC.

Intermittent self catheterisation with hydrophilic, gel reservoir, and non-coated catheters: a systematic review and cost effectiveness analysis.

OBJECTIVE: To determine the most effective and cost effective type of catheter for patients performing intermittent self catheterisation in the community. DESIGN: Systematic review and meta-analysis. Results were incorporated into a probabilistic Markov model to compare lifetime costs and quality adjusted life years (QALYs). DATA SOURCES: We searched Medline, Embase, and Cochrane and Cinahl databases from 2002 to 18 April 2011 to identify studies comparing hydrophilic, gel reservoir, and non-coated intermittent catheters. Earlier guidelines were used to identify papers published before 2002. To capture studies comparing clean and sterile non-coated intermittent self catheterisation, each database was searched from its date of inception to 18 April 2011. MAIN OUTCOME MEASURES: Clinical outcomes included symptomatic urinary tract infection (UTI), bacteraemia, mortality, patient preference or comfort, and number of catheters used. The economic model included downstream complications of UTI and cost effectiveness was calculated as incremental cost per QALY gained. RESULTS: Eight studies were included in the systematic review. Most were conducted in patients with spinal cord injuries, and most of the included patients were men. People using gel reservoir and hydrophilic catheters were significantly less likely to report one or more UTIs compared with sterile non-coated catheters (absolute effect for gel reservoir = 149 fewer per 1000 (95% confidence interval -7 to 198), P=0.04; absolute effect for hydrophilic = 153 fewer per 1000 (-8 to 268), P=0.04). However, there was no difference between hydrophilic and sterile non-coated catheters when outcomes were measured as mean monthly UTIs (mean difference = 0.01 (-0.11 to 0.09), P=0.84) or total UTIs at 1 year (mean difference = 0.18 (-0.50 to 0.86), P=0.60). There was little difference in the incidence of one or more UTIs for people using clean versus sterile non-coated catheters (absolute effect = 12 fewer per 1000 (-134 to 146), P=0.86). Although the most effective, gel reservoir catheters cost >£54,350 per QALY gained and are therefore not cost effective compared with clean non-coated self catheterisation. CONCLUSION: The type of catheter used for intermittent self catheterisation seems to make little difference to the risk of symptomatic UTI. Given large differences in resource use, clean non-coated catheters are most cost effective. However, because of limitations and gaps in the evidence base and the designation of non-coated catheters as single use devices, we recommend a precautionary principle should be adopted and that patients should be offered a choice between hydrophilic and gel reservoir catheters.

Systematic review of the impact of urinary tract infections on health-related quality of life.

What's known on the subject? and What does the study add? Values for equivalent health states can vary substantially depending on the measure used and method of valuation; this has a direct impact on the results of economic analyses. To date, the majority of existing economic evaluations that include UTI as a health state refer to an analysis in which the Index of Well Being was used to estimate the quality of life experienced by young women with UTIs. Currently, there are no validated methods or filters for systematically searching for the type of generic quality of life data required for decision analytic models. This study is the only systematic review of quality of life in people with UTI in the literature. Twelve studies were identified which report quality of life using a variety of generic methods; the results of these papers were summarized in a way that is useful for a health researcher seeking to populate a decision model, design a clinical study or assess the effect of UTI on quality of life relative to other conditions. One research group provided previously unpublished data from a large cohort study; these scores were mapped to EuroQol 5-Dimension values using published algorithms and probabilistic simulations. The aim of this review was to identify studies that have evaluated the impact of symptomatic urinary tract infection (UTI) and UTI-associated bacteraemia on quality of life, and to summarize these data in a way that is useful for a health researcher seeking to populate a cost-utility model, design a clinical study or assess the effect of UTIs on quality of life relative to other conditions. We conducted a systematic search of the literature using MEDLINE, EMBASE, the NHS Economic Evaluations database, Health Technology Assessment database, Health Economics Evaluations database, Cost-Effectiveness Analysis Registry and EuroQol website. Studies that reported utility values for symptomatic UTI or UTI-associated bacteraemia derived from a generic QoL measurement tool or expert opinion were included. Studies using disease-specific instruments were excluded. Twelve studies were identified that included a generic measure of health-related quality of life for patients with UTIs. These measures included: the short-form (SF)-36 and SF-12 questionnaires; the Health Utilities Index Mark 2; Quality of Well Being; the Index of Well Being, standard gamble; the Health and Activity Limitation Index; and expert opinion. The authors of studies using either of the SF questionnaires were contacted for additional data. One research group provided previously unpublished data from a large cohort study; these scores were mapped to EuroQol 5-Dimension (EQ-5D) values using published algorithms and probabilistic simulations. The present review provides health researchers with several sources from which to select utility values to populate cost-utility models. It also shows that very few studies have measured quality of life in patients with UTI using generic preference-based measures of health and none have evaluated the impact of this health state on quality of life in children. Future studies ought to consider the inclusion of commonly used preference-based measures of health, such as the EQ-5D, in all patient populations experiencing symptomatic UTI or UTI-related complications.

The nerve of osteoarthritis pain.

OBJECTIVE: Cumulative data suggest that central sensitization may contribute to pain in osteoarthritis (OA) and present with symptoms typically associated with neuropathic pain (NP). We evaluated the responses from focus group participants on the knee OA pain experience for pain descriptions that suggest NP. METHODS: Focus group transcripts were analyzed by 2 independent assessors for unprompted use of pain descriptors that suggested NP. Items from validated NP symptom-based questionnaires were used to guide the analysis. Data on sociodemographic factors, duration of knee OA, and OA disease and pain severity (using the Western Ontario and McMaster Universities Osteoarthritis Index and a numerical rating scale) were obtained from questionnaires administered after focus group completion. These factors were compared among participants who did and did not use descriptors that suggested NP. RESULTS: Transcripts from 80 knee OA participants were analyzed. A range of NP descriptors was used to characterize their knee symptoms, including burning, tingling, numbness, and pins and needles. The proportion of participants who used NP descriptors was 0.34 (95% confidence interval 0.24-0.45). Those who used NP descriptors were younger (P = 0.003) and, although not statistically different, more likely to be women, with higher pain intensity and OA severity and longer OA duration, than those who did not use NP descriptors. CONCLUSION: During focus groups, a subset of adults with chronic, symptomatic knee OA used pain quality descriptors that were suggestive of NP. Elicitation of NP descriptors in people with OA may help identify those who could benefit from further evaluation and perhaps treatment for NP.

The cost of somatisation among the working-age population in England for the year 2008-2009.

Medically unexplained symptoms are one of the most commonly encountered symptoms across all healthcare settings. They are also responsible for a large proportion of disability in the workforce and decreased quality of life. These patients represent an important clinical phenomenon with considerable direct and indirect economic consequences.This study aims to calculate the economic burden of somatisation among English adults in 2008-2009.Using existing literature, estimates of prevalence, healthcare use and disability were combined in order to calculate the annual cost of healthcare use and productivity loss associated with these patients in excess of non-somatising patients.Based on the results of our analysis, the incremental health care cost incurred by somatising patients is estimated to be £3 billion. This represents approximately 10% of total NHS expenditure on these services for the working-age population in 2008-2009. The cost of sickness absence and decreased quality of life associated with these patients amounts to over £14 billion.By highlighting the magnitude of this phenomenon at each level of the health system and the considerable impact of non-healthcare costs, this study serves to draw attention to a group of patients who are frequently unrecognised or misdiagnosed by physicians who tend to repeatedly pursue organic possibilities through multiple tests, procedures and operations. As economic perspectives play an increasing role in healthcare planning, the reduction of health care use and improvement of functioning among this group of patients should be a major goal. In order to realise these goals, changed pathways and behaviour in primary and secondary care are needed, along with improved access to psychological therapy services.