Long-term modeling on HPV vaccination: do we really need any more?

The human papillomavirus (HPV) is closely related to cervical cancer. In 2007, the EMA approved two vaccines, a bivalent and a quadrivalent one, launched at three-dose schedules and very high prices worldwide. We describe what happened in the EU and what might change in the near future from an economic perspective. HPV vaccination is now established in most EU countries. The main target group of the programs is girls aged 10-14 years. Many western countries used competitive tendering to purchase the two vaccines, achieving considerable savings. The extension to males has been a hotly debated issue. The sex limitation implies that this vaccination cannot by definition achieve a 'herd immunity' effect. EMA recently approved a two-dose schedule for both vaccines that should lead to savings, although it is hard to predict how the forthcoming nonavalent vaccine will affect the market situation. Several economic evaluations based on long-term models have been published on the HPV vaccination in the recent years, using official list prices as a baseline. Most of these models can be considered mere exercises in long-term forecasting. Recently, further long-term models have been published with two- and three-dose schedules as alternatives, and the nonavalent vaccine. We wonder what added value they give for public policy purposes.

Cost-effectiveness of trastuzumab in metastatic breast cancer: mainly a matter of price in the EU?

Trastuzumab (TR), a monoclonal antibody approved by EMA in 2000 and one of the first examples of "targeted therapy", is indicated to treat human epidermal growth factor receptor 2 (HER2) positive breast cancer. TR, whose patent will expire in 2015 in Europe, has been judged positively for reimbursement by most public authorities in the EU. Here we critically review the existing evidence on TR in metastatic breast cancer (MBC), in line with the multidisciplinary health technology assessment (HTA) approach, to assess whether the existing evidence supports TR positive reimbursement decisions taken in MBC by EU health authorities. We did a literature search for the main HTA topics (efficacy, quality of life and ethics) on the PubMed international database (2000-2013). Then, we did a specific literature search to select the full economic evaluations (FEEs) conducted in EU countries focused on TR as first-line innovative therapy in MBC. We retrieved scant evidence in the literature to support TR reimbursement in MBC. We found only two clinical trials and their results were unclear because of the large proportion of patients who crossed over. Moreover, the quality of methods was poor in all four European FEEs selected. This example of HTA exercise on a mature monoclonal antibody in a specific indication casts doubts on how often the reimbursement decisions taken by EU health authorities in emotional pathologies like cancer are rational. These decisions should at least be reconsidered periodically on the basis of the latest evidence.

Regional tenders on biosimilars in Italy: an empirical analysis of awarded prices.

OBJECTIVE: The goal of the present study is to assess the awarded prices and thus the real level of competition the regional tenders referring to biosimilars in Italy achieved. METHODS: We conducted a web-based analysis to collect detailed information on regional biosimilar tenders, up to December 2012. We identified 191 lots referring to the three off-patent biologicals (somatropin, epoetin and filgrastim) mentioned in the 24 tenders that took place during the study period (2008-2012). A multiple linear regression analysis was conducted to assess the relationship between prices awarded (dependent variable) and potentially explanatory variables (base quantities, bioagent, number of competitors, purchasing region and time). RESULTS: While the price of somatropin stayed steady, those of filgrastim and epoetin dropped steeply. The mean number of competitors was lowest for somatropin and highest for filgrastim. One additional competitor was associated with about a 10% reduction in the price on average. The benefits of having many competitors did not fade with increasing numbers of companies. DISCUSSION: Our analysis confirms the theory that worthwhile savings can be generated in tenders, once the bid is designed in such a way that competition can produce its effects, i.e. allowing more than one manufacturer to tender. However, most of the Italian regional tenders on off-patent bioagents do not seem to exploit potential competition to the full.

Vaccination planning and vaccine prices in a decentralizing country - Italy.

This paper gives an overview, in the era of regionalization, of vaccination planning and vaccine price management in the Italian National Health Service. In particular, we analyse the current National Vaccination Plan (NVP) and end with two "case studies" of the latest entries in the Italian vaccination calendar, comparing HPV and PCV vaccines, the most expensive ones in Italy at present. The present NVP put an end to the long period without official documents for vaccination planning, mainly reflecting the controversial relationships between the national and regional tiers. However, this document is not really useful for planning from the health professionals' point of view, lacking epidemiological information. Thorough systematic assessment of the new, expensive vaccines is becoming a real priority in the light of current financial difficulties. In this perspective, the two examples discussed have given different results so far, starting from a heterogeneous situation of potential market competition.

A critical systematic review of budget impact analyses on drugs in the EU countries.

BACKGROUND: Budget impact analysis (BIA) is a relatively recent technique that is supposed to be complementary to more established economic evaluations (EEs). OBJECTIVE: We reviewed the BIAs published on drugs in the EU since December 2008, to assess whether these studies have improved in quality in the last few years. METHODS: We conducted a literature search on the international databases PubMed and EMBASE. The selected articles were screened using a two-step approach to assess (1) their main methodological characteristics and (2) the level of adherence to the latest BIA definition. The assessment was made by two independent reviewers and any disagreement was resolved through discussion. RESULTS: Eventually, 17 articles were reviewed. Thirteen referred to a stand-alone BIA not accompanying a full EE, only nine focussed on a new treatment, 15 were sponsored by the manufacturer of the drug of reference, all but one claiming savings for healthcare budgets. The quality of methods was poor in many of the studies, and only a few of them attempted to estimate real local costs in a credible way. Therefore, the crucial items that in theory make a BIA different from other types of EEs were often the major points of weakness of the studies reviewed. CONCLUSIONS: Our review confirmed that the BIA is not yet a well-established technique in the literature and many published studies still fail to reach an acceptable quality. In particular, BIAs funded by pharmaceutical companies appear to be tailored to show short-term savings induced by new, highly priced products.

Cost effectiveness of the new pneumococcal vaccines: a systematic review of European studies.

INTRODUCTION: Diseases caused by Streptococcus pneumoniae (pneumococcus) are a major global public health problem. Despite their importance, information on the burden of the different pneumococcal diseases is limited and estimates vary widely. OBJECTIVE AND METHODS: We critically reviewed the full economic evaluations (FEEs) on the new pneumococcal conjugate vaccines (PCVs) conducted in the European Union (EU) to assess their potential contribution to public decision making. We selected the FEEs focussed on PCV-10 and PCV-13 and published in English from January 2007 until June 2013. We screened the selected articles to assess their main methodological features using a common checklist composed of epidemiological, clinical and economic items. RESULTS: All the ten studies selected were based on modelling and the time horizon was always long term. Two studies focused on adults, the remaining eight on infants. Only one study based herd immunity on national data, eight used foreign data or modelling and the last did not consider it. National prices and tariffs were claimed to be sources for unit costs in all studies; however, half of them assumed price parity when one vaccine was not yet marketed, and the figures varied within the countries where more than one study was conducted. Conclusions supported the economic utility of pneumococcal vaccination in all studies, raising some concern only in (i) the independent study, which found that PCV-13 was borderline cost effective, and (ii) the study sponsored by both manufacturers, which estimated an incremental ratio slightly above the national threshold for both PCV-10 and PCV-13. CONCLUSION: The European studies we analysed are mostly based on weak sources of data. Because of the limited information on vaccine effectiveness and lack of epidemiological and economic data, the need for extensive recourse to assumptions leads to great within- and between-study variability generated by authors' choices.

Ethics for end-of-life treatments: metastatic colorectal cancer is one example.

The number of biological agents (BAs) registered with an indication related to cancer treatment is flourishing and the cost of these treatments is rising dramatically, making the situation potentially unsustainable for healthcare systems. Here we focus on the examples of bevacizumab (BV) and cetuximab (CX), two BAs approved for metastatic colorectal cancer (mCRC). The first clinical trials show an increase in median overall survival of a few months, though these results could not always be repeated in subsequent studies. We reviewed full economic evaluations (FEEs) on BV or CX and despite frequently arguable estimates based on indirect efficacy, only one estimated the addition of CX was cost-effective in a virtual subgroup of patients, albeit with flawed methods. Most Western European countries reimburse BV and CX for mCRC, though clinical evidence seems weak and economic evidence even absent. The underlying question is whether national health authorities are prepared to spend an increasing share of healthcare budgets on very expensive end-of-life treatments, their impact on life expectancy (a few additional months at best) and QoL (enhanced mainly by patients' hopes) being doubtful and their cost-effectiveness hardly ever proved. Further research is needed to explore how ethics could be included and thus assessed under these circumstances.