Developing a methodology to balance benefit-sharing : application in the context of biodiversity beyond national jurisdiction

The effectiveness and success of benefit-sharing measures to date, particularly in contributing towards the conservation and sustainable use of biodiversity, has been questionable. This is likely related to the degree of beneficial impacts versus burden on the users and regulatory authorities in terms of administrative complexities. It is, therefore, timely to reconsider which forms of benefit-sharing may most favourably balance the associated beneficial and burdensome aspects. The aim of this paper is to develop and demonstrate a benefit-sharing balance methodology which can be used as a tool to help decision-makers to select options in an objective and transparent manner. Application in the biodiversity beyond national jurisdiction context provides a useful example of how this tool can be used. Results suggest that sharing of genetic sequence data and research results provide the most favourable balance in terms of non-monetary benefit sharing, whilst the most favourable monetary benefit-sharing options were associated with research funding and salaries. The benefit-sharing balance methodology presented here provides a useful tool and starting point, which can be built upon in the future, to include more detailed information gathered from expert groups to consolidate the perceived balance of beneficial impacts versus burden. In addition, the equation can be tailored according to different policy settings where different benefit-sharing factors may be more appropriate. Ultimately, use of this tool could help to enhance implementation of benefit-sharing policies/legislation with greater potential to balance beneficial impacts with associated burden, thereby enhancing workability of the access and benefit-sharing system as a whole

The entry of adalimumab biosimilars in Europe : an overview of price evolution and country responses

Background: From October 2018, adalimumab biosimilars could enter the European market. However, some countries, such as the Netherlands, report high discounts for the originator product that influence biosimilar entry. Consequently, we researched European (list) prices and reimbursement status of originator adalimumab, before and after the entry of biosimilars, and discuss relevant policy measures. Methods: Survey distributed via email to national experts consisting of three parts: i) general financing/co-payment of medicines, ii) reimbursement status and prices of originator adalimumab and availability of biosimilars, and iii) policy measures related to the use of adalimumab. Results: In the 27 surveyed countries, originator adalimumab is reimbursed (fully or only partial, and sometimes with restrictions in use), except for Kosovo, where it is not marketed. Following adalimumab biosimilars, a few countries have made changes to the reimbursement status/level or setting where adalimumab is available. Overall, a decrease in list prices of originator adalimumab was seen after loss of exclusivity rights. Some countries (Bulgaria, Germany, Greece, Italy, Latvia, the Netherlands and Romania) reported that list prices have not changed up to May 2019, although confidential discounts may exist. Adalimumab biosimilars were available in 23 of the 27 surveyed countries. Countries adopted various approaches to leverage competition from the use of (biosimilar) adalimumab. In some countries, a strategy was implemented even before patent expiry (Scotland), while others did not report specific measures. Conclusion: This study documented how European countries responded differently to patent expiry of originator adalimumab and biosimilar market entry, with implications for pricing and reimbursement

Classifiers in de Vlaamse Gebarentaal: case study van handvormen voor auto, mens en vogel: onderzoeksrapport 2014

In dit rapport wordt het onderzoek naar classifiers in de Vlaamse Gebarentaal (VGT) voor drie referenten – auto, mens en vogel1 - toegelicht. Eerst worden de definities voor classifier constructies en classifiers besproken die in de literatuur over gebarentalen aan bod komen. Vervolgens wordt chronologisch beschreven welke categorieën internationale gebarentaalonderzoekers hanteren. Verder wordt er een overzicht geschetst van wat al gekend was over classifier constructies en classifiers in de VGT, waarna het volgende hoofdstuk de gehanteerde methodologie van dit onderzoek behandelt. De resultaten van de diepteanalyse voor de gehanteerde classifiers voor de referenten concepten auto, mens en vogel worden nadien uitvoerig besproken. Aansluitend wordt een aantal specifieke aspecten van de onderzochte handvormen belicht. Ten slotte worden de meest opvallende bevindingen met betrekking tot classifiers in VGT voor auto, mens en vogel overzichtelijk samengevat in het besluit van dit rapport. Er wordt ook aangegeven in welke zin deze studie aanleiding kan geven tot verder onderzoek. In bijlage vindt u de diepteanalyse van alle classifiers die in de data werden gebruikt voor de referenten auto, mens en vogel. Deze kan een handig instrument zijn bij dit onderzoek

Biosimilars in Belgium: a proposal for a more competitive market

More than ten years after the first biosimilars were authorized for use in the European Union, Belgium still experiences limited competition from biosimilars, as exemplified by low market shares. Achieving high biosimilar market shares is not necessarily a goal in itself, as cost savings are also realized by mandatory price reductions on originator medicines in Belgium. However, we believe that biosimilars play a role in ensuring the long-term sustainability of the off-patent biologicals market. It is therefore crucial to list what has been done and what is needed to support the Belgian government in establishing a policy framework for a competitive off-patent biologicals market. We provide a comprehensive overview of the Belgian biosimilar market, including existing hurdles for biosimilar use in Belgium. Based on these hurdles and supplemented with learnings from other European countries, we propose practical recommendations that can be implemented to overcome them. Several Belgian stakeholders had the opportunity to comment on these recommendations. Specifically, we suggest to evolve towards a long-term consistent, integrated policy framework via i) the creation of a proactive and transparent climate supporting a level playing field for both biosimilar and reference product, including public dissemination of how savings at the level of the Belgian healthcare system are used, ii) investment in educational activities, including raising awareness of societal responsibility, iii) enforcement of the practical implementation of public procurement law, and iv) the development of incentives for physicians, who are key stakeholders in the Belgian off-patent biologicals market

An overview of patents on therapeutic monoclonal antibodies in Europe: are they a hurdle to biosimilar market entry?

As patents on many high-selling biological medicines are expiring, non-innovator versions, such as biosimilars, may enter this multi-billion dollar market. This study aims to map patents and patent applications for innovator as well as biosimilar monoclonal antibodies in Europe, and investigates legal challenges associated with patenting the innovator product and alleged infringing activities, focusing on consequences for biosimilar developers. Via an exploratory literature review in PubMed and a database analysis in Darts-ip, Derwent Innovation, and Espacenet, an overview of basic patents and exclusivity rights for some of the best-selling biologicals is given, supplemented with a detailed analysis of patents taken during the medicine’s life cycle via three specific case studies (trastuzumab, bevacizumab, cetuximab). Case law was used to determine which patents were viewed by biosimilar developers as blocking market entry. For the selected monoclonal antibodies, the key protection instruments appeared to be the basic patent and the additional protection provided by a supplementary protection certificate. We observed that additional patents filed after the basic patent are hard to obtain and often insufficient in blocking market entry of biosimilars, but can in some cases be a substantial hurdle for biosimilar developers to overcome in patent litigation cases or to invent around, creating uncertainty on the launch date of a biosimilar on the market. These hurdles, however, seem to be surmountable, given that many cases were won by biosimilar developers. Also, biosimilars can be protected by filing new patents and these mainly pertain to new formulations

The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium:a nationwide interrupted time series analysis

Background: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake. Methods: An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses. Results: In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI −61.61 to −14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI −880.113 to −19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648–3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797–2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI −203.128 to −100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536–1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant. Conclusions: The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other pa

Adoption of biosimilar infliximab for rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel diseases in the EU5: A budget impact analysis using a Delphi panel

Introduction: Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. Methods: An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy. Epidemiological parameters were derived from published literature reviewed in July 2015. Current market shares of biologics were derived from Therapy Watch (2012/2013 data). Respondents in a Delphi panel, conducted in 2015 and consisting of several leading rheumatologists and gastroenterologists from different nationalities, were asked to forecast uptake of biosimilar infliximab and estimate the proportion of patients eligible for a particular type of biological treatment, including biosimilar infliximab. Scenario analyses assessed the influence of various factors, including price reductions, on the budget. Results: Uptake of biosimilar infliximab was particularly expected for naïve patients; switching patients that already received other biologics was not expected much. Market shares after 5 years of biosimilar infliximab were ~2% in rheumatology in all five countries and in gastroenterology ranged from 4% in France to over 30% in Italy. Except for France, budgets were expected to decrease for rheumatologic diseases. For gastroenterology, budgets were expected to decrease in Spain and Italy. Budgets were expected to increase substantially in the UK and Germany, due to the introduction of vedolizumab in the studied period. In France, budget was expected to slightly increase for ankylosing spondylitis, Crohn's Disease, and ulcerative collitis. Savings in budget were expected in all countries, for all diseases, when larger price discounts on biosimilar infliximab were used. Discussion and Conclusion: This study has shown that only when price reductions are large en

Inclusive innovation : Enhancing global participation in and benefit sharing linked to the utilization of marine genetic resources from areas beyond national jurisdiction

Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement ID: GA 721421 H2020-MSCA-ITN-2016. Declaration of competing interest MJ is founder of, has shares in, and consultant to GyreOx Ltd, a company that uses marine genetic resources from areas within national jurisdiction to develop potential drug molecules. Acknowledgements Many thanks to Arianna Broggiato and Abbe Brown for helpful discussions and comments on the manuscript. Thanks also to the Marie Curie H2020 fund for supporting this research.Peer reviewedPublisher PD