To assess the health economic evidence of chronic heart failure (CHF) treatments through a targeted literature review.

To estimate the cost-effectiveness of vagus nerve stimulation (VNS) as an adjunctive therapy to anti-seizure medication (ASMs) when compared with a strategy of ASMs alone for the management of drug resistant epilepsy (DRE). A five health state cohort transition model was developed, with a 10-year time horizon, a 3-month cycle length and an English National Health Service perspective. Health states were defined by a percentage reduction in seizure frequency and aligned with randomised trial data informing the first cycle transition probabilities. Thereafter, non-VNS patients remained in state, while a systematic literature review informed further VNS patient transitions up to year 2, after which they remained in state (subject to death or device discontinuation). Extrapolation of registered VNS implant Kaplan-Meier data informed explantation and replacement probabilities. Health state utilities were age and gender adjusted. Published estimates, combined with trial data regarding mean seizure frequency, informed health state resource use. In addition to the base case analysis, scenarios, one-way deterministic and probabilistic sensitivity analyses were undertaken. Adjunctive VNS has an incremental cost-effectiveness ratio of £17,711 per quality-adjusted life year (QALY) when compared to a strategy of ASMs alone. Results were most sensitive to unit costs of inpatient care, with VNS expected to be dominant if the cost of a non-elective care admission exceeded £2,225. Using the UK National Institute of Health and Care Excellence threshold of £20,000 to £30,000 per QALY, VNS was cost-effective in the majority of scenarios evaluated, inclusive of varying the costs of device implantation, replacement and explantation by 15 percent. Management of DRE with VNS is a cost-effective option in comparison to ASM therapy alone. This finding is driven by a reduced seizure frequency with VNS, which is consequently expected to improve a patient's health-related quality of life and reduce downstream medical costs.

Treatment-resistant depression (TRD) is a debilitating condition with a significant impact on patients and carers, and health care spending. Treatment resistance occurs in approximately 30% of individuals affected by Major Depressive Disorder. This analysis explored the potential cost-effectiveness of introducing vagus nerve stimulation (VNS) adjunctive to treatment as usual (TAU) for patients with TRD who have failed on ≥4 adequate anti-depressant treatments in England and Wales. A Markov model simulated patient transitions between health states defined by type of treatment, battery status and disease severity, as defined by Montgomery–Åsberg Depression Rating Scale score. Effectiveness was based on individual patient data from the D-21 dosing trial and the D-23 observational study assessing the effectiveness of VNS plus TAU compared to TAU alone. Hypothetical patients included those with moderate and severe depression at baseline, reflecting the population that would be eligible for VNS. The model had a 10-year time horizon and took a UK NHS perspective. Longer time horizons were also explored, as was a societal perspective. Costs and benefits were discounted at a rate of 3.5%. One-way deterministic, probabilistic and scenario analyses were undertaken to test various model inputs. When considering direct costs, the total cost of the VNS strategy was £42,589 compared to £29,928 for TAU. VNS generated 0.42 incremental quality-adjusted life-years (QALYs) compared to TAU, giving an incremental cost-effectiveness ratio (ICER) of £29,995 per QALY gained. When societal costs were considered, the VNS strategy dominated. In the probabilistic sensitivity analysis, VNS had a 50% probability of being cost-effective at a willingness-to-pay threshold of £30,000 per QALY. Extending the time horizon of the analysis to 20 years resulted in an ICER of £25,764. This analysis shows that VNS in addition to TAU could represent a cost-effective option for patients with TRD in the UK.

Under right conditions Real-World-Data can support Real-World-Evidence by constituting valid scientific indication for regulatory decision-making. A literature review was conducted to determine the RWD and RWE state of art. Medline/PubMed database was investigated to include hints reporting the words RWD or RWE. Search string, released on 9th January 2018, was defined to include articles published up to 2017. All retrieved articles were assessed and selected based on information included in the title/abstract. There were no restrictions on language, year of publications, and type of reference. Data were collected following an extraction plan which included: ID, first author, year, journal, affiliation, type, topic, and type of RWD source. Data on 395 abstracts, published from 1991 to 2017, were collected and cleaned. Data on 381 abstracts were analyzed; 14 references using RWD/RWE as biologic or genetic term have been excluded. 38.5% articles where published in the 2017 (median 2016; interquartile range 2015-2017). First author affiliations were: 189 (49.6%) European (United Kingdom 13.1%, Italy 8.9%, Germany 6.3%), 106 (27.8%) Americans, 61 (16%) Asiatic and 6 (1.6%) Australian. Most of articles concerned drugs (clinical study 32.8%, review article 15.7%, comments/reply/editorial 10.2%) whereas 5 (1.3%) were about device. Topics of major interest were oncology (17.6%), cardiovascular (15.5%), endocrinology (9.4%). Articles were published by school/university (29.9%), sponsors (24.7%), hospital/care institute (20.5%). Information on data source is reported in 137 (63%) (electronic records 20.2%, registries 8.4%, claim data 4.2%); of these 6.6% specified more than one source database (range 1-5). The usage of RWD has grown exponentially in the last 30 years thanks to the evolution of technological tools that has made this information more accessible. European researchers are the most interested. Oncology and cardiovascular drugs are the principal fields of application. Electronic medical/health records remain the main type of source used.

To analyze the role of real world evidence in Value Based Health Care of medical devices. A literature search (research string released on 2nd April, 2018) was performed on PubMed including the following as main keywords: medical devices, real-world data and value-based healthcare. No restrictions on language, year of publications, and type of reference were imputed. Fifty-eight papers were identified and scrutinized. 2 additional references were identified through other sources. 27 were included. The records were published between 2004 and 2018. Once plotted against the year of publication, an upward trend was visible starting from 1 (4%) publications in 2004 up to 4 (15%) in 2016 and 5 (19%) in 2018. 81% of the records reported evidence in cardiology and cardiac surgery area; 7% in neurology. Most data came from registries (63%) and administrative databases (33%). The sponsors were healthcare industry (4%), academia (93%), health authorities (4%). Value based healthcare has become a hot topic both for policy makers and for the medical devices industry. The constantly increasing production of real world evidence and analyses based on observational data, registry and administrative databases confirms the increasing interest in this research area. The clinical practice may substantially differ from controlled trials; the use of real world data not only completes the body of evidence on a specific therapy, but also may drive the updates of clinical guidelines. Both the technological progress and the production of real world evidence have become so fast that an adequate way to timely develop guidelines should be sought. Alongside, the use of real world evidence may play a relevant role when policy makers need to measure the value of a medical technology.

Health tourism is a reality. However, clinical excellence is not the only reason for patients wishing to travel for therapy: some reimbursement policies may affect the way patients seek treatment. This study is a first attempt at interpreting patient migration with respect to Vagus Nerve Stimulation (VNS) Therapy for Drug-Resistant Epilepsy in Italy. Based on patient anonymous information obtained from 2017 implantation cards an extraction protocol was created to: (i) map the region of origin of VNS Therapy patients (i.e. the prescribing physician's region of practice) and the region of implantation and (ii) correlate region of origin and presence/absence of VNS DRE-specific reimbursement. Desk research identified regional policies to provide the information on the availability of medical device reimbursement. VNS Therapy has been growing rapidly at a rate of 15% per year since 2013. Information from implantation cards was available for 2017. Of the 21 Italian Regional Health Care Authorities, 15 provide at least one implantation center for VNS Therapy (median 2; interquartile range 1-3.5). Seven regions provide VNS DRE-specific reimbursement for VNS Therapy. All procedures on patients treated outside their residence region have a VNS DRE-specific reimbursement. Approximately 66% of all procedures were performed with VNS DRE-specific reimbursement. 20% of the procedures in regions without a VNS DRE-specific reimbursement concerned non-resident patients. Most regions are equipped with at least one implanting center, therefore it may not be necessary for patients to travel. VNS DRE-specific reimbursement is available in 7 regions; the national policy ensures the VNS DRE-specific reimbursement for all patients treated outside their residence region. Most of the implanting activity takes place where the circumstances allow for a VNS DRE-specific reimbursement; reimbursement policies may influence the patient flow.

Treatment-resistant depression (TRD) is a debilitating condition with a significant impact on patients and carers, and a substantial burden on health care budgets. The objective of this analysis was to evaluate the budget impact of introducing vagus nerve stimulation (VNS) for TRD in England. The analysis was based on population estimates from a Clinical Commissioning Group (CCG) in England (N=366,000). Patient records from 5 GP practices were analysed based on ICD10 codes, age, history of depression and referrals, to determine a group of patients eligible for VNS. Estimates of the burden of TRD on the NHS regarding hospital admissions and psychiatrist visits were derived from an analysis of Hospital Episode Statistics (HES). Unit costs were obtained from the NHS reference costs. Several sales forecast scenarios were explored. The cost of VNS to the NHS, including the device, implantation procedure, programming, monitoring, and battery replacement, was estimated at under £15,000 per patient. The hospital length of stay for the average TRD patient was estimated at 40 days per completed episode (range: 6 – 68 days); reduced to 27 days after implantation. The average annual number of booked outpatient appointments was 11 (4 – 18); reduced to 5 appointments with VNS. Using forecasts that reflected an exponential growth in the adoption of VNS, the net budget impact was estimated at a total of £1.5 million over the years 2019 to 2023. This estimate corresponded to just over £2000 for each patient implanted with VNS. If past UK adoption rates of VNS and deep brain stimulation for other indications were used to forecast instead, the introduction of VNS would produce total savings in 2023. When considering all relevant costs and resource use, the introduction of VNS in NHS England can be a long-term cost-saving option for patients suffering with TRD.