'Linkage' pharmaceutical evergreening in Canada and Australia

'Evergreening' is not a formal concept of patent law. It is best understood as a social idea used to refer to the myriad ways in which pharmaceutical patent owners utilise the law and related regulatory processes to extend their high rent-earning intellectual monopoly privileges, particularly over highly profitable (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while the courts are an instrument frequently used by pharmaceutical brand name manufacturers to prolong their patent royalties, 'evergreening' is rarely mentioned explicitly by judges in patent protection cases. The term usually refers to threats made to competitors about a brand-name manufacturer's tactical use of pharmaceutical patents (including over uses, delivery systems and even packaging), not to extension of any particular patent over an active product ingredient. This article focuses in particular on the 'evergreening' potential of so-called 'linkage' provisions, imposed on the regulatory (safety, quality and efficacy) approval systems for generic pharmaceuticals of Canada and Australia, by specific articles in trade agreements with the US. These 'linkage' provisions have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They require such drug regulators to facilitate notification of, or even prevent, any potential patent infringement by a generic pharmaceutical manufacturer. This article explores the regulatory lessons to be learnt from Canada's and Australia's shared experience in terms of minimizing potential adverse impacts of such 'linkage evergreening' provisions on drug costs and thereby potentially on citizen's access to affordable, essential medicines

Invited Commentary: Treatment Drop-in-Making the Case for Causal Prediction.

Clinical prediction models (CPMs) are often used to guide treatment initiation, with individuals at high risk offered treatment. This implicitly assumes that the probability quoted from a CPM represents the risk to an individual of an adverse outcome in absence of treatment. However, for a CPM to correctly target this estimand requires careful causal thinking. One problem that needs to be overcome is treatment drop-in: where individuals in the development data commence treatment after the time of prediction but before the outcome occurs. In this issue of the Journal, Xu et al. (Am J Epidemiol. 2021;190(10):2000-2014) use causal estimates from external data sources, such as clinical trials, to adjust CPMs for treatment drop-in. This represents a pragmatic and promising approach to address this issue, and it illustrates the value of utilizing causal inference in prediction. Building causality into the prediction pipeline can also bring other benefits. These include the ability to make and compare hypothetical predictions under different interventions, to make CPMs more explainable and transparent, and to improve model generalizability. Enriching CPMs with causal inference therefore has the potential to add considerable value to the role of prediction in healthcare

Alcohol dependence in public policy: towards its (re)inclusion

Public policy on alcohol in the UK relies on health promotion campaigns that encourage individuals who misuse alcohol to make healthier choices about their drinking. Individuals with alcohol-dependence syndrome have an impaired capacity to choose health. As a result, individuals with the worst alcohol misuse problems lie largely outside the reach of choice-based policy. However, such policy has been widely criticized and efforts to reform it are underway. This paper argues that the British Medical Association’s recent attempt to improve policy on alcohol in the UK by introducing strategies which have been shown to control drinking within populations still gives insufficient attention to alcohol dependence. This is because it fails accurately and consistently to characterize alcohol dependence and gives insufficient attention to the social challenges it presents

A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people

Background: Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.Method: We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.Results: Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [ pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54-2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51-4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97-5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).Conclusion: LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people

National Scientific Project: State Plane Coordinate Reference System - Republic of North Macedonia

The National Scientific Project: State Plane Coordinate Reference System – Republic of North Macedonia represents a strategic and scientifically driven initiative to establish a unified national plane coordinate reference system (CRS). The creation of such a system is not only a technical undertaking but also a fundamental prerequisite for ensuring precision, interoperability, and sustainability in the management of geospatial data across the Republic of North Macedonia. The project responds to the increasing demands for reliable spatial data that serve a wide range of disciplines, including geodesy, cartography, topography, civil engineering, environmental monitoring, land management, and cadastral administration. The overall objective of the project is to design and propose a state-level CRS that is scientifically rigorous, technically reliable, legally harmonized, and fully aligned with European and international geospatial standards. Such a system is envisioned to overcome the limitations of current practices, which are characterized by fragmentation, outdated methodologies, and insufficient adaptability to the growing needs of modern geospatial applications. The establishment of a new CRS is expected to enhance the accuracy of geospatial measurements, streamline institutional workflows, and provide a standardized framework for both public administration and private sector stakeholders. To achieve these goals, the project has been structured into a series of interrelated work packages, each addressing a specific dimension of CRS development. Work Package 1 (WP1) examines the history and current conditions of coordinate reference systems in North Macedonia, providing a baseline for subsequent research. Work Package 2 (WP2) undertakes a systematic literature review, drawing upon scientific sources, technical guidelines, and international reports to ensure that the project builds upon a solid theoretical and methodological foundation. Work Package 3 (WP3) investigates the legal and institutional frameworks, emphasizing the necessity of harmonization with European directives and international conventions. Work Package 4 (WP4) expands the analysis by examining comparative models from other countries, thereby identifying best practices and adaptable strategies. Building on this groundwork, Work Package 5 (WP5) develops and evaluates alternative technical and methodological options for a future CRS, with a focus on accuracy, usability, legal conformity, and compatibility with global standards. Finally, Work Package 6 (WP6) outlines the roadmap toward implementation, including technical evaluations, stakeholder consultations, and preparation for institutional adoption. An essential milestone in the life cycle of the project will be the International Scientific Conference, scheduled to take place in Skopje on September/October 2025 in a hybrid format (in-person and online). This event will provide a platform for the dissemination of project results, the exchange of knowledge with international experts, and the discussion of future directions for CRS implementation. By bringing together scholars, practitioners, policymakers, and institutional representatives, the conference will highlight both the scientific contributions and the practical implications of the project. In a broader perspective, the project embodies an interdisciplinary and collaborative approach that integrates geodetic science, cartographic methodology, legal analysis, and institutional capacity-building. Its outcomes are expected to significantly advance the modernization of North Macedonia’s spatial data infrastructure, ensuring that the country’s geospatial systems are fully compatible with those of the European Union and the wider international community. Moreover, by documenting methodologies, challenges, and lessons learned, the project will contribute to the global geospatial discourse and provide a model for similar initiatives in other countries. Ultimately, the project aspires to establish a modern, reliable, and sustainable national plane coordinate reference system that not only addresses the current geospatial challenges of North Macedonia but also anticipates future needs in the era of digital transformation, smart governance, and integrated spatial data ecosystems