Access Agreements Research Articles

Judicial review of Common Foreign and Security Policy by the ECtHR and the (re)negotiation on the accession of the EU to the ECHR

The article addresses the issue of judicial control of the implementation of Common Foreign and Security Policy at international regional level within the framework of the relaunching of the negotiation in view of the accession of the EU to the ECHR. Considering the extent of jurisdiction of the CJEU in respect of Common Foreign and Security Policy field in the light of its case law (sections 1 and 2), it analyses the question of judicial review of Common Foreign and Security Policy within international regional justice by the ECtHR in the light of the ongoing negotiations (section 3), in the perspective of the relationship between non-national courts (section 3.A), having as background the (2013) Draft Agreement of accession (section 3.B.1). After addressing the relaunching of the negotiation procedure (section 3.B.2) and the issue of CFSP control by the ECtHR according to the recent (re)negotiation meetings (section 3.B.3), some concrete proposals, including for the redrafting of the accession agreement, will be put forward (section 3.B.4), as well as a conclusion (section 4).

“Free” open access agreements

“Free” open access agreements

Open access agreements for European and UK authors

Open access agreements for European and UK authors

Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England

BackgroundWe present baseline characteristics and follow-up data of a Managed Access Agreement (MAA), including patients with mucopolysaccharidosis IVA (MPS IVA) receiving elosulfase alfa enzyme replacement therapy (ERT) in England on a conditional basis. Patients enrolled in the MAA programme are reviewed on an annual basis. Therapy can be continued if patients are compliant, able to tolerate infusions, and meet four out of five pre-defined clinical and patient-reported outcomes (PRO) criteria. Baseline and follow-up clinical and PRO data are presented for all participants who completed ≥ 1 year of assessments in the MAA.ResultsThe analysis included data from 55 patients, including 26 patients previously enrolled in clinical trials and 29 who started ERT after enrolling in the MAA. In patients with both baseline and follow-up data, mean 6-min walk test distance increased from 217 m at baseline to 244 m after a mean follow-up of 4.9 years. Improvement or stabilisation was seen regardless of age at treatment initiation or duration of treatment. Mean forced vital capacity and forced expiratory volume in 1 s were 0.87 L and 0.78 L, respectively at baseline and 1.05 L and 0.88 L after a mean follow-up of 5.5 years. PRO data showed overall improvements over time in Mobility, Self-care, and Caregiver assistance scores of the MPS-Health Assessment Questionnaire, relatively stable quality of life, and some improvements in pain scores.ConclusionsThe MAA data confirm the effects of elosulfase alfa on clinical and PRO results observed in the clinical trials and provide real-world evidence for long-term stabilisation in these measures, suggesting a positive impact on the natural history of MPS IVA.

After the dust settles: Community resilience legacies of unconventional gas development

This paper explores the socio-economic legacy created by an extractive industry as it developed, or sought to develop, in nine different communities or regions across Australia, Canada, the United States, and Wales – drawing on mixed-method research collected between 2011 and 2018. By the early 2010s, a number of unconventional fossil fuel companies were securing land access agreements for seismic and drilling exploration in the Western Downs region of South-East Queensland, the Northern Rivers region of North-Eastern New South Wales, the states of New York and Pennsylvania, the Province of New Brunswick, and southern Wales. Stark cultural, social and environmental contrasts between communities within each nation shaped community responses to potential industry development – levels of social license for developments, community responses and subsequent unconventional fossil fuel development varied widely. This article explores the impact of the industry on community resilience. A resilient community is likely to have high social capital, including strong social networks, feelings of safety and trust, sense of belonging, diversity, citizen power and participation. These social responses to the industry, combined with the existing local contexts and the differing regulatory frameworks of each community/region, can be argued to have led to divergent effects on overall community social and economic resilience across our case studies. Power, industrial impacts, relationships, resources, social action, timing of the debates, equity concerns, and strategic decision making (or lack thereof) shaped the degree of resilience with which each community/region responded. In four of our cases, resilience declined (e.g., due to increased economic homogenisation, decreasing social connectivity and citizen power); in five cases resilience increased (e.g., the legacy created by the emergence of social movements substantially increased social connectivity, sense of belonging and citizen power).

The Dayton Agreement and social reform: Omne principium difficile est

The Dayton Agreement rests on the principle of establishing a self-sustaining system that respects the multinational and multiconfessional structure of the population of Bosnia and Herzegovina, composed of entities with independent constitutive, legislative, executive and judicial functions. The organisation and functioning of the constitutionally-determined institutions of power in BiH is based on the constituent nature of the nations, enclosed in amendments to the entity constitutions made after the 2000 Decision of the Constitutional Court on the Constituency of Peoples, which regulate representation and the manner of the protection of the interests of the peoples. This article proceeds from the point that vital discussion on constitutional regulation is leading to a marginalisation of the discussion on harmonising domestic legislation with the EU acquis, conditio sine qua non in terms of fulfilling the requirements of the Stabilisation and Accession Agreement, not least in the area of labour law, and gaining admission to the EU. Above all, society is only changed through reform in which - panta rei - everything flows.

Dynamic Management of Security Policies in PrivOrBAC

This article is a continuation of our previous work on identifying and developing tools and concepts to provide automatic management and derivation of security and privacy policies. In this document we are interested in the extension of the PrivOrBAC model in order to ensure a dynamic management of privacy-aware security policies. Our approach, based on smart contracts (SC) and the WS-Agreement Specification, allows automatic agents representing data providers and access requesters to enter into an access agreement that takes into consideration not only service level clauses but also security rules to protect the privacy of individuals. Our solution can be deployed in such a way that no human intervention is required to reach this type of agreement. This work shows how to use the WS-Agreement Specification to set up a process for negotiating, creating and monitoring Service Level Agreements (SLAs) in accordance with a predefined access control policy. This article concludes with a case study accompanied by a representative implementation of our solution.

ACTUAL ISSUES OF LEGAL RELATIONS DEVELOPMENT OF INTELLECTUAL PROPERTY LICENSING

The article considers the main trends in the development of legal relations in the field of granting the right to use (licensing) intellectual property. It has been established that the content of classic license agreements, which is exclusively patent, ie based only on the transfer of rights to inventions protected by patents, is currently losing relevance. Licensing agreements mostly regulate the relationship between several intellectual property objects with different legal regimes (complex agreement) and include elements of different legal relations (mixed agreement). A modern license agreement is an agreement that consists not only in granting permission to use intellectual property, but in general the set of obligations of the licensor to provide the licensee with technical secrets, special knowledge, specific experience and a range of assistance services (consulting, debugging, training) on their use (technical assistance) and application (supply of equipment, materials, components, raw materials, etc.). The content of the negative agreement, based on the owner's non-denial of the rights to use the patented invention, becomes a positive obligation, which is to create a practical opportunity for the licensee to use intellectual property to achieve a certain technical result. The general trends in the development of licensing relations are the desire to facilitate the turnover of objects by simplifying the procedure for concluding agreements, easing the requirements for the form of agreements, the transition from licensing to compensatory, and strengthening the role of electronic agreements and accession agreements. It is established that the legislative regulation requires the definition of the technology transfer agreement, set out in the current legislation and the procedure for concluding license agreements with the use of electronic digital signature. Ukraine's ratification of the "Singapore Trademark Agreement" requires amendments to bylaws to simplify the procedure for registering license agreements.

NICE agrees a managed access agreement for Tecartus

NICE agrees a managed access agreement for Tecartus

Editorial

i Editorial Last year’s volume of Proceedings of the Royal Irish Academy was a special issue on the theme of ‘Climate and society in Ireland: from prehistory to the present’. It was initially published in the journal’s usual format and then, in summer 2021, as a separate title. Though too early to judge its impact, the initial response to the volume has been very encouraging. Currently, its key findings are being communicated to a wider audience through a series of blogs and podcasts available on the Academy’s website. The editors and board of the journal sincerely hope that the volume and related content will make a meaningful contribution to wider discourse and debate, in Ireland and beyond, on the complex relationships between climate and societies in the longue durée and how knowledge of climate history might usefully inform our approach to the current climate crisis. Though more disparate in the themes they address, the papers collected in the current volume maintain the high standards that readers expect from Proceedings . There is a wide chronological span from early prehistory to the early twentieth century. Given the journal’s long record of publishing prehistoric research , it is gratifying to see two substantial contributions in this area, following on from the very considerable prehistoric component in last year’s thematic volume. The flow of high-quality submissions in this area remains strong, so prehistory is also likely to feature prominently in next year’s volume, while the online supplement and open access agreements mentioned below should further raise the profile of the journal among prehistorians. In the present volume, Dowd and colleagues present a reassessment of the 1902 excavation of Alice and Gwendoline Cave, Co. Clare, informed by a recent re-excavation, which, like the original, was funded by the Academy. The second paper, by Kearney and O’Brien, presents a palynological study spanning much of the Holocene undertaken at the excavated later Bronze Age copper mine at Derrycarhoon in West Cork. The continuing legacy of prehistoric hillforts in the early medieval landscape is considered in O’Driscoll and Gleeson’s paper on Baltinglass, County Wicklow. There follows three papers on complementary aspects of the medieval archaeology and history of major ecclesiastical sites: Manning on the buildings and layout of Monasterboice; Murray on two crosiers associated with Clonmacnoise; and Bhreathnach and Dowling’s interdisciplinary study of Ferns, Co. Wexford. From a historical perspective, Grace’s paper on bloodletting, spanning the medieval to modern periods, is followed by O’Neill on the role and experience of women during the Nine Years War, while Barnard takes the study of material culture into a new arena with his exploration Proceedings of the Royal Irish Academy Vol. 121C, i–iv © 2021 Royal Irish Academy https://doi.org/10.3318/PRIAC.2021.121.11 Editorial ii of the circulation of English ceramics in Ireland in the eighteenth and nineteenth centuries. Finally, Coghlan and colleagues present new evidence about the life and work of Percy Ludgate, ‘Ireland’s first computer designer’. The concept of themed special issues, inaugurated a decade ago, is but one of the ways Proceedings has evolved and adapted in recent years. A complementary new initiative is the recent decision by the editorial board to approve the production next year of an online supplement on Mesolithic Ireland . With an introductory essay by Prof. Graeme Warren, a member of the board, the supplement will bring together the most important papers about the Mesolithic period published in the journal over the past century or so. Its appearance will coincide with UCD’s hosting of the thirteenth Conference on Hunting and Gathering Societies (CHAGS) in June 2022, the first time this major international meeting will take place in Ireland. There are precedents for such online supplements among the Academy’s journals,1 and in the case of Proceedings further opportunities may arise in the years ahead to employ this format to showcase the journal’s unique and enduring contribution to the study of Ireland’s past. Another welcome development is the recent Read and Publish agreement between the Academy and IReL, the Irish e-resources licensing consortium for leading higher education institutions in Ireland, which...

Types of Contractual Obligations with the Participation of the State of Ukraine

It is established that the state of Ukraine can be a party to civil agreements. It is determined that agreements with the participation of the state of Ukraine are mostly bilateral, paid, can be both real and consensual, and are concluded in writing. At the same time, the state of Ukraine cannot be a party to public contracts, and therefore is not a party to the contract of retail sale, rental agreement, household contract, bank deposit, etc. In the vast majority of cases, agreements with the participation of the state of Ukraine are mixed, as they contain elements of different types of agreements. The legal framework on the types of agreements in which the state of Ukraine may be a party is analyzed, and the methods underlying the division are identified. Thus, according to the method of concluding agreements with the participation of the state of Ukraine are divided into: concluded at the auction and accession agreements. According to the obligation to conclude agreements with the participation of the state of Ukraine, they are obligatory and voluntary. According to the method of fixing the terms of the contract they are standard and model contracts. By main areas of application the agreements can be fuel and energy; defensive (military); banking, etc. By territory of action the agreements are divided into domestic and foreign. The article provides a general description of each type of agreement with the participation of the state of Ukraine. In particular, the following subject classification of agreements with the participation of the state of Ukraine was introduced: agreements on transfer of property to ownership; agreements on the transfer of property for temporary possession and use; agreements for the performance of works and provision of services. Thus, agreements with the participation of the state of Ukraine on the transfer of property to ownership are a contract of sale and gift. In this case, contracts of sale may be concluded in the form of contracts for the purchase, redemption, supply, contracting of agricultural products. A lease agreement and a loan are included to the agreements with the participation of the state of Ukraine on the transfer of property into temporary possession and use. Agreements with the participation of the state of Ukraine on the performance of works and provision of services include a concession agreement, production sharing agreements, joint venture agreement, storage agreements, commission instructions, property management, as well as credit, loan. It is investigated that the state of Ukraine cannot be a party to the contract of supply of electric or other resources through the connected network, rent, lifetime maintenance, some lease agreements, insurance contract, agreements on disposition of intellectual property rights, etc.

Increasing Use of Compassionate Use/Managed Access Channels to Obtain Medicines for Use in COVID-19.

The COVID-19 pandemic has triggered an extensive need for new therapeutics and there has been widespread use of unapproved/repurposed medicines. Several countries have regulations for access to unapproved medicines, known as compassionate use, managed/expanded access or emergency use. The Novartis Managed Access activity for COVID-19 delivered unapproved/repurposed medicines to nearly 6,000 patients over a 6-month period. With the rapid growth of such access mechanisms to address COVID-19, a better understanding of these channels is required.

PCN241 Complex Innovative Design Trials: Too Complex for Market Access?

Complex innovative design (CID) trials aim to address multiple clinical questions, including efficacy in biomarker-selected patients, specific cancer cohorts or combination regimens. While CID trials could speed up the traditional route to European Medicines Agency marketing authorisation, they can be more challenging to evaluate through Health Technology Assessments (HTA) versus conventional randomized controlled trials. This research explores whether CID oncology trials can accelerate time to regulatory approval and patient access while maintaining optimised pricing and market access outcomes. Thirty-minute, qualitative, in-depth interviews were conducted with payer advisors from France, Germany and the UK to understand perspectives on HTA outcomes for larotrectinib and expectations for entrectinib, histology-independent cancer drugs studied in CID trials and targeting neurotrophic tyrosine receptor kinase (NTRK) solid tumours. In England, following the submission of a revised price, larotrectinib was recommended for inclusion in the Cancer Drugs Fund (CDF). This allows for data collection to address clinical uncertainties, stemming from the pooled analysis of single-arm trials with limited patient numbers, while providing access. In contrast, larotrectinib has broad access in Germany though its price may have been negatively impacted by its ‘no additional benefit’ rating based on clinical uncertainties. In France, early access to larotrectinib was provided via a cohort Temporary Use Authorisation (ATU), however payers expect less favourable HTA outcomes given uncertainties in the clinical benefit due to the trial design. Payers expect entrectinib will face similar hurdles to larotrectinib which, coupled with reduced unmet needs, will negatively impact pricing and market access opportunity. CID trials create significant uncertainty on the benefit of oncology drugs assessed using existing HTA frameworks, risking negative reimbursement outcomes. The availability of managed/early access agreements can be leveraged by manufacturers for timely access. Additionally, upcoming changes to the NICE methods review may help address uncertainties for histology-independent oncology products to optimise access.

PNS141 Deal or No Deal: Twenty Years of Pricing and Access Agreements in Products Assessed by NICE

Since their introduction, access arrangements such as patient access schemes (PAS) have become increasingly common in the UK. The objective of this analysis is to describe trends in uptake of commercial arrangements over time and to compare arrangements that have been implemented for National Institute for Health and Care Excellence (NICE) recommended medicines. A complete list of appraisals undertaken by NICE up to 30 June 2020 was extracted and analysed against published details of commercial arrangements. Products receiving negative recommendations were excluded from analysis. Decisions from multiple technology appraisals assessing >1 product or indication were counted as discrete outcomes. The proportion of appraisals utilising a commercial arrangement was calculated each year using the number of positive recommendations as the denominator. A total of 956 decisions were reviewed, of which 739 (77%) were positive. The proportion of approved products with any commercial arrangement generally increased from 2007 to 2020, with a peak of 91% (50 of 55 recommended products) in 2018. Over the last 5 years, approximately two thirds of positive recommendations were supported by a commercial arrangement of some form. The most common type of arrangement was the simple PAS, accounting for an average of 61% of all commercial arrangements from 2007 onwards. We identified a shift away from use of the complex PAS, towards more frequent use of commercial access agreements (CAA, with or without associated PAS) over the last 5 years (from 14% to 36%). There has been an increasing trend towards confidential agreements (such as simple PAS and CAA) since 2007. In part this is likely to reflect the challenges of achieving UK access in a wider context of global markets and price referencing. With the increasing prevalence of high cost therapies, this is a trend that is set to continue.

PCN236 A Review of the Access Status of CDF-approved Drugs in Scotland: What can we learn?

The primary objective of this research was to assess outcomes in Scotland for CDF-approved drugs and to investigate whether there is differential access to oncology medicines in Scotland due to the absence of a CDF type fund. The secondary objective was to assess the reasons for entry into the CDF and reasons for negative or restricted use recommendations by the SMC. 34 drugs were identified via the NICE website as being in the CDF and eligible for analysis. The Managed Entry Access agreements were identified for each drug in the CDF and data collection requirements were tabulated. The reasons for uncertainty were quantified into 7 different categories. As a next step, the 34 drugs were identified on the SMC website and their assessment outcome recorded. For the drugs which were restricted or rejected, the submission paperwork was reviewed and categorised using the same 7 categories as the CDF drugs for comparison. Out of 34 drugs that are currently in the CDF, 55% (19/34) were approved, 29% (10/34) were approved for restricted use and 14% (5/34) were not approved by the SMC. The primary reasons for the SMC to restrict or reject the use of a drug were the survival analysis and the comparator presented by companies. Of the five not approved drugs, three were rejected due to a non-submission by the company and two of the drugs were rejected due to a single-arm trial design. In conclusion, the majority of CDF-approved drugs were approved without restriction in Scotland. However, a small proportion were not approved by the SMC and a larger proportion were approved with restrictions. There may be scope for further policy changes (such as, but not limited to, an interim funding mechanism such as the CDF) to support access for these drugs.

PPM6 Cost-Effectiveness and Reimbursement of CELL and GENE Therapies: A Review

Cell and gene therapy products offer potential curative effects to chronic but are imbedded with data uncertainty and high-costs. New reimbursement models are emerging, that serve as a catalyst for adoption of cell and gene therapies in the future. This research aims to review the cost-effectiveness evidence for ex vivo gene therapy Strimvelis, and CAR T-cell therapies Kymriah (Tisagenlecleucel), Yescarta (Axicabtagene Ciloleucel) and explore the emerging reimbursement models. Pubmed, MEDLINE and Cochrane Library database were searched to December 2019 for (i) ex vivo gene therapy for adenosine deaminase deficiency severe combined immunodeficiency (Strimvelis) and CAR T-cell therapies (ii) tisagenlecleucel (Kymriah) and (iii) axicabtagene ciloleucel (Yescarta) and (iv) reimbursement models for cell and gene therapies. A total of 13 articles were identified as relevant for full-text screening: 8 (66%) analysed cost-effectiveness of Strimvelis, Kymriah and Yescarta in a NHS healthcare setting. The cost per quality adjusted life year (QALY) estimates were highly variable due to uncertainty in the data. New reimbursement models are set to accommodate future high-cost of cell and gene therapy with data uncertainty. Proposed managed access agreements (MMA) encourage collaboration between NHS England and the manufacturer to manage the risks.

PNS80 Early Access and Targeted Supply Considerations in Emerging Markets

The aim was to evaluate the existing frameworks in place for managed access agreements in emerging markets and identify factors that influence access to innovative therapies. In-depth secondary research identified provisions of managed access within a selection of emerging market countries including, Argentina, Brazil, Colombia, Turkey, Russia, China, South Korea. The likely pathway for managed access was assessed to summarize temporary access mechanisms, stakeholders, budget impact barriers, and access timelines for launching innovative therapies. Consideration was also given to impact of local infrastructure, regulatory framework, and political climate. Provisions of access mechanisms manifest differently in each of selected markets. The infrastructure and political environment within geographical region are not equivalent. The environment for access programs is continually evolving. Most countries have an early access program (EAP) but there is variation in the acceptance level and the capacity of the country to implement. Some countries also have post approval entry agreements. The mechanism of managed access (post approval) programs range from being contingent on disease severity and unmet need (Brazil, Colombia), to being managed by different stakeholders (Turkey) or is in its infancy (China). Time to achieve an early access or managed access agreement is not quick and can take 12-18 months depending on country. Managed access agreements are a useful tool in introducing innovative therapies in emerging markets, and it is important to plan ahead at an early stage, as well as understand the differences between country frameworks. There are opportunities and challenges in utilizing managed entry patient access programs in the emerging markets, it is not applicable to all innovations and the decision to include in the planning will depend on local context.

PNS145 Access to Medicines in the United Kingdom: A Review of HTA Decisions for New Medicines

To examine Health Technology Assessment (HTA) decisions for new innovative medicines in the UK (England, Scotland, Wales, Northern Ireland). The study examined HTA decisions made between 2017 and 2020 across UK countries for innovative medicines licensed by European Medicines Agency (EMA) in 2017. The analysis was done using published documents. The decisions were classified as “recommend without restrictions,” “recommend with restrictions,” or “not recommended”. EMA approved licenses for 56 new innovative medicines in 2017. From the date of licensing the medicines in 2017 until January 2020, the National Institute for Health and Care Excellence (NICE) in England had completed the appraisal of 28 out of the 56 medicines. Out of these 28, 12 were “recommended without restrictions” 14 were “recommended with restrictions” and 2 were “not recommended”. Majority of the NICE recommendations (i.e. 21 of 26 or 81%) were done through managed access agreements. The Scottish Medicines Consortium (SMC) has assessed 31 out of the 56 medicines licensed in 2017. Out of these 31, 8 were, “recommended without any restriction”, 22 were “recommended with restriction” and 1 was “not recommended”. AWMSG in Wales follows NICE guidance and does not review a medicine if NICE is considering assessing it in the next 12 months. Northern Ireland follows HTA guidance issued by NICE or SMC and adopts a decision shortly after either has made its decision. In Northern Ireland, 37 recommendations were adopted from either NICE or SMC. These 37 include: 10 without restrictions, 21 with restrictions and 6 not recommended decisions. Adoption of HTA recommendations is low and it varies across UK countries. The number of HTA assessments resulting in “not recommended” decision was found consistently low across all UK countries. However, the number of “recommendation with restriction” is relatively high compared to the “recommendation without restrictions”.

PNS181 Exploring the Use of VALUE of Information Analysis in HTA Decision Making at Nice

Value of information analysis (VOI) is a quantitative method to estimate the expected value of additional research to reduce uncertainty in decision making. As part of the NICE methods review, we aimed to develop a VOI framework that could potentially help inform decision makers when considering the value of further evidence to reduce uncertainty in health technology assessment (HTA), and to explore barriers to implementing such a framework. A 2016 Decision Support Unit report considered the use of VOI when developing managed access agreements. Expanding on its principles, we developed a decision-making framework based on the expected value of perfect information (EVPI) and expected net benefit (NB) of approving a technology with current uncertainty, outlining scenarios where additional evidence to reduce uncertainty may add value. We evaluated the potential limitations of the framework and the practical implications of implementing it in a NICE setting. The outcomes of the framework depend on whether a technology is expected to be cost effective based on current evidence. If it is, further research may still be worthwhile if EVPI is higher than NB. Where a technology is expected to be cost ineffective, further research may be worthwhile if EVPI is higher than the expected NB loss of approval, otherwise a price reduction may be required. However, EVPI is an upper limit on the value of reducing parameter uncertainty. Less idealistic approaches are likely to estimate VOI more accurately but are more complex and require additional information (e.g. research design). Other considerations include the relevant time horizon, beneficiary population size and importance of uncertainties captured by VOI. A formal VOI framework may help HTA decision makers consider the suitability of recommending further research. Implementing the framework in a real-world HTA setting has methodological and practical challenges.

PNS83 Analysis of Market Access Agreements in Turkey

PNS83 Analysis of Market Access Agreements in Turkey