Disinvestment in healthcare: An overview of HTA agencies and organizations activities at European level

Background: In an era of a growing economic pressure for all health systems, the interest for "disinvestment" in healthcare increased. In this context, evidence based approaches such as Health Technology Assessment (HTA) are needed both to invest and to disinvest in health technologies. In order to investigate the extent of application of HTA in this field, methodological projects/frameworks, case studies, dissemination initiatives on disinvestment released by HTA agencies and organizations located in Europe were searched. Methods: In July 2015, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and the International Network of Agencies for HTA (INAHTA) were accessed and searched through the use of the term "disinvestment". Retrieved deliverables were considered eligible if they reported methodological projects/frameworks, case studies and dissemination initiatives focused on disinvestment in healthcare. Results: 62 HTA agencies/organizations were accessed and eight methodological projects/frameworks, one case study and one dissemination initiative were found starting from 2007. With respect to methodological projects/frameworks, two were delivered in Austria, one in Italy, two in Spain and three in U.K. As for the case study and the dissemination initiative, both came from U.K. The majority of deliverables were aimed at making an overview of existing disinvestment approaches and at identifying challenges in their introduction. Conclusions: Today, in a healthcare context characterized by resource scarcity and increasing service demand, "disinvestment" from low-value services and reinvestment in high-value ones is a key strategy that may be supported by HTA. The lack of evaluation of technologies in use, in particular at the end of their lifecycle, may be due to the scant availability of frameworks and guidelines for identification and assessment of obsolete technologies that was shown by our work. Although several projects were carried out in different countries, most remain constrained to the field of research. Disinvestment is a relatively new concept in HTA that could pose challenges also from a methodological point of view. To tackle these challenges, it is necessary to construct experiences at international level with the aim to develop new methodological approaches to produce and grow evidence on disinvestment policies and practices

Additive energy forward curves in a Heath-Jarrow-Morton framework

One of the peculiarities of power and gas markets is the delivery mechanism of forward contracts. The seller of a futures contract commits to deliver, say, power, over a certain period, while the classical forward is a financial agreement settled on a maturity date. Our purpose is to design a Heath-Jarrow-Morton framework for an additive, mean-reverting, multicommodity market consisting of forward contracts of any delivery period. The main assumption is that forward prices can be represented as affine functions of a universal source of randomness. This allows us to completely characterize the models which prevent arbitrage opportunities: this boils down to finding a density between a risk-neutral measure $\mathbb{Q}$, such that the prices of traded assets like forward contracts are true $\mathbb{Q}$-martingales, and the real world probability measure $\mathbb{P}$, under which forward prices are mean-reverting. The Girsanov kernel for such a transformation turns out to be stochastic and unbounded in the diffusion part, while in the jump part the Girsanov kernel must be deterministic and bounded: thus, in this respect, we prove two results on the martingale property of stochastic exponentials. The first allows to validate measure changes made of two components: an Esscher-type density and a Girsanov transform with stochastic and unbounded kernel. The second uses a different approach and works for the case of continuous density. We apply this framework to two models: a generalized Lucia-Schwartz model and a cross-commodity cointegrated market.Comment: 28 page

Age- and risk-related appropriateness of the use of available influenza vaccines in the Italian elderly population is advantageous: Results from a budget impact analysis

Introduction. Nowadays, four different types of influenza vaccines are available in Italy: trivalent (TIV), quadrivalent (QIV), MF59-adjuvanted (aTIV) and intradermal TIV (idTIV) inactivated vaccines. Recently, a concept of the appropriateness (i.e. according to the age and risk factors) of the use of different vaccines has been established in Italy. We conducted a budget impact analysis of switching to a policy, in which the Italian elderly (who carry the major disease burden) received the available vaccines according to their age and risk profile. Methods. A novel budget impact model was constructed with a time horizon of one influenza season. In the reference scenario the cohort of Italian elderly individuals could receive either available vaccine according to 2017/18 season market share. The alternative scenario envisaged the administration of TIV/QIV to people aged 65-74 years and at low risk of developing influenza-related complications, while aTIV/idTIV were allocated to high-risk 65-74-year-olds and all subjects aged \ue2\u89\ua5 75 years. Results. Switching to the alternative scenario would result in both significant health benefits and net budget savings. Particularly, it would be possible to prevent an additional 8201 cases of laboratory-confirmed influenza, 988 complications, 355 hospitalizations and 14 deaths. Despite the alternative strategy being associated with slightly higher vaccination costs, the total savings derived from fewer influenza events completely resets this increase with net budget savings of \ue2\u82\uac 0.13 million. Conclusions. An immunization policy in which influenza vaccines are administered according to the age and risk profile of Italian elderly individuals is advisable

Mapping host-related correlates of influenza vaccine-induced immune response: An umbrella review of the available systematic reviews and meta-analyses

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus-and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed

23-valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal diseases (IPDs) in the elderly: is it really effective?

Introduction. Incidence of invasive pneumococcal diseases (IPDs) in Italy is constantly increasing and that is particularly true among the elderly. 23-valent polysaccharide pneumococcal vac- cine (PPV23) is recommended to this age group and offered in all Italian regions. However, efficacy of PPV23 on preventing IPDs is debated. We therefore performed a review of the most recent avail- able meta-analyses in order to assess the efficacy of PPVs. Methods. The literature search was conducted using PubMed and Scopus search engines. We used the following keywords: ?pneu- mococcal?, ?polysaccharide?, ?vaccine?, ?efficacy?, ?elderly?, ?meta analysis?. Only meta-analyses published in the last 7 years were selected. We examined the results of the selected meta-anal- yses and assessed their quality according to the PRISMA recom- mendations. Results. The search returned 16 results in PubMed and 12 in Scopus: among them we selected 3 meta-analyses. According to our quality assessment, all meta-analyses showed generally posi- tive results and almost all items of the PRISMA checklist were respected. However, the research protocol and the registration number were absent in all the 3 revisions and the flow-chart was not shown in Moberley?s and Melegaro?s works. In the study by Huss et al. the relative risk of developing IPDs among vaccinated subjects was 0.90 (95%CI: 0.46-1.77, I2 4.9%), indicating a very slight benefit after vaccination. This contrasts with the results of the Cochrane Review by Moberley et al., in which the PPVs showed a protective efficacy in reducing the risk of IPDs of 74% (OR 0.26, 95%CI: 0.15-0.46) with no statistical heterogeneity (I2 0%). Melegaro et al. found a reduction not statistically signifi- cant of the incidence of IPD of 65% (OR 0.35; 95%CI 0.08-1.49) among healthy elderly, while the global estimate of vaccine efficacy among high risk elderly was minimal (OR 0.80; 95%CI 0.22-2.88). Conclusions. Most of the studies suggest that the PPVs confer low protection against IPDs. Anyhow, their methodological het- erogeneity does not allow definitive conclusions. While waiting to see the results of new trials about the efficacy of PPVs, in particular of PPV23, and the extension of the use of conjugate vaccine among the population over 65, stakeholders should be aware of the results of the meta-analyses discussed in this paper during the implementation of the vaccination programs for the elderly in Public Health. The full article is free available on www.jpmh.or

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis

This is the final version of the article. Available from the publisher via the DOI in this record.The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.The study was financed by the Italian Ministry of University and Research (MIUR, project PRIN 2009; Grant number: 2009ZPM4×4)

The use of nonrandomized evidence to estimate treatment effects in health technology assessment

Health technology assessment (HTA) is increasingly informed by non-randomised studies but there is limited guidance from HTA bodies on expectations around evidence quality and study conduct. We developed recommendations to support the appropriate use of such evidence based on a pragmatic literature review and a workshop involving 16 experts from 8 countries as part of the European Union’s Horizon-2020 IMPACT-HTA programme (work package 6). To ensure HTA processes remain rigorous and robust, HTA bodies should demand clear, extensive, and structured reporting of non-randomised studies, including an in-depth assessment of the risk of bias. In recognition of the additional uncertainty imparted by non-randomised designs in estimates of treatment effects, HTA bodies should strengthen early scientific advice and engage in collaborative efforts to improve use of real-world data

Mapping host-related correlates of influenza vaccine-induced immune response: An umbrella review of the available systematic reviews and meta-analyses

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus-and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed

Invasive fungal infections in patients with acute myeloid leucemia and in those submitted to allogeneic hemopoieticstem cell transplant: who is at highest risk ?

Invasive fungal infections (IFIs) are a growing cause of morbidity and mortality in patients with acute myeloid leukemia (AMLs) and in recipients of allogeneic hemopoietic stem cell transplantation (allo-HSCTs) (1–6). It is widely debated if either allo-HSCTs or AMLs are to be considered at higher risk, but no data comparing the two categories of patients have been reported in literature so far. This cohort study has been conducted from January 1999 to December 2003 in hematology wards located throughout Italy. The study was aimed at evaluating the incidence and mortality for IFIs in adult AMLs and in patients submitted to all types of allo-HSCT procedures; a comparison between the two categories of patients was carried out