Phase IV Drug Trials With a Canadian Site: A Comparison of Industry and Non-Industry-Funded Trials.

Recent regulatory reforms have favored expedited drug marketing and increased reliance on Phase IV clinical trials for safety and efficacy assurance. This study, utilizing ClinicalTrials.gov, assesses the characteristics of Phase IV trials, with at least one site in Canada, examing those funded by industry sponsors and those lacking industry funding. Additionally, it compares the publication status of industry-funded and non-industry-funded trials through a manual review of the medical literature. Between 2000 and 2022, 864 Phase IV trials were completed, with 480 (55.6%) receiving industry funding and 384 (44.4%) funded solely by non-industry sources. Industry-funded clinical trials were larger (mean 204 enrollees versus 70), more likely to be international (57.7% versus 9.6%) and reported results more promptly (1.21 years after completion versus 1.85 years), yet both types shared similar design, outcomes, and completion time. Publication rates were 81.8% for industry-funded and 65.8% for non-industry-funded trials. The ClinicalTrials.gov registry displayed 48 inaccuracies in publication associations, raising concerns about its accuracy. Our findings underscore the existing institutional limitations in ensuring comprehensive reporting and publication of Phase IV trial results funded by both industry and non-industry sources.

Correction: Whose shoulders is health research standing on? Determining the key actors and contents of the prevailing biomedical research agenda.

[This corrects the article DOI: 10.1371/journal.pone.0249661.].

Prevalence and nature of manufacturer-sponsored patient support programs for prescription drugs in Canada: a cross-sectional study.

BACKGROUND: Globally, pharmaceutical companies offer patient support programs in tandem with their products, which aim to enhance medication adherence and patient experience through education, training, support and financial assistance. We sought to identify the proportion and characteristics of such patient support programs in Canada and to describe the nature of supports provided. METHODS: We conducted a crosssectional study to identify and characterize all marketed prescription drugs available in Canada as of Aug. 23, 2022, using the Health Canada Drug Product and CompuScript databases. To describe the nature of supports provided, we conducted a content analysis of publicly available patient support program websites and Web-based documents. Using logistic regression, we identified characteristics of drugs associated with having a patient support program including brand-name or branded generic (generic medications with a proprietary name), orphan (medications for rare diseases) or biologic drug status; estimated total cost of prescriptions dispensed at retail pharmacies; and price per unit. RESULTS: Of the 2556 prescription drugs marketed by 89 companies in the study period, 256 (10.0%) had a patient support program in Canada. Many of the 89 drug manufacturers (n = 55, 61.8%) offered at least 1 patient support program, frequently relying on third-party administrators for delivery. Brandname and branded generic medications, biologic agents and drugs with orphan status were more likely to have a patient support program than generic drugs. Compared with drugs priced $1.01-$10.00 per unit, drugs priced $10.01-$100.00 per unit were nearly 8 times more likely to have a patient support program (adjusted odds ratio 7.54, 95% confidence interval 4.07- 14.64). Most sampled patient support programs included reimbursement navigation (n = 231, 90.2%) and clinical case management (n = 223, 87.1%). INTERPRETATION: About 1 in 10 drugs marketed in Canada has a manufacturersponsored patient support program, but these are concentrated around brand-name, branded generic, biologic and high-cost drugs, often for rare diseases. To understand the impact of patient support programs on health outcomes and sustainable access to cost-effective medicines, greater transparency and independent evaluation of patient support programs is necessary.

Commentary: Reconsidering Pharmaceutical Research and Development Investments.

Following Lee and colleagues' (2023) article explaining how Canadians are being shortchanged by drug companies when it comes to investments in research and development (R&D), this rejoinder adds context and appends two other very problematic elements in the debate between wishful narratives over the industry's contribution in R&D and actual numbers. First, even the current stricter definition of R&D investment might simply be too large considering that elements such as seeding trials - a well-known marketing device - can be accounted for as R&D expenditures. Second, this rejoinder identifies how Statistics Canada acted in concert with Innovative Medicines Canada to reinforce the industry's preferred narratives around R&D expenditures. This situation puts into question the trustworthiness of Canada's statistical agency.

Poisoning Regulation, Research, Health, and the Environment: The Glyphosate-Based Herbicides Case in Canada.

Despite discourse advocating pesticide reduction, there has been an exponential increase in pesticide use worldwide in the agricultural sector over the last 30 years. Glyphosate-Based Herbicides (GBHs) are the most widely used pesticides on the planet as well as in Canada, where a total of almost 470 million kilograms of declared "active" ingredient glyphosate was sold between 2007 and 2018. GBHs accounted for 58% of pesticides used in the agriculture sector in Canada in 2017. While the independent scientific literature on the harmful health and environmental impacts of pesticides such as GBHs is overwhelming, Canada has only banned 32 "active" pesticide ingredients out of 531 banned in 168 countries, and reapproved GBHs in 2017 until 2032. This article, based on interdisciplinary and intersectoral research, will analyze how as a result of the scientific and regulatory captures of relevant Canadian agencies by the pesticide industry, the Canadian regulation and scientific assessment of pesticides are deficient and lagging behind other countries, using the GBH case as a basis for analysis. It will show how, by embracing industry narratives and biased evidence, by being receptive to industry demands, and by opaque decision making and lack of transparency, Health Canada's Pest Management Regulatory Agency (PMRA) promotes commercial interests over the imperatives of public health and environmental protection.

Academic dependency: the influence of the prevailing international biomedical research agenda on Argentina's CONICET.

Background: The prevailing health and biomedical sciences (HBMS) research agenda, not only determined by leading academic institutions but also by large pharmaceutical companies, has been shown to prioritize the exploration of novel pharmacological interventions over the study of the socio-environmental factors influencing illness onset and progression. The aim of this investigation is to quantitatively explore whether and to what extent the prevailing international HBMS research agenda and the key actors setting this agenda influence research in non-core countries. Methods: We used the Web of Science database and the CorText platform to proxy the HBMS research agenda of a prestigious research institution from Latin America: Argentina's National Research Council (CONICET). We conducted a bibliometric and lexical analysis of 16,309 HBMS academic articles whereby CONICET was among the authors' affiliations. The content of CONICET's agenda was represented through co-occurrence network maps of the most frequent concatenation of terms found in titles, keywords, and abstracts. We compared our findings with previous reports on the international HBMS research agenda. Results: In line with the results previously reported for the prevailing international agenda, we found that terms linked to molecular biology and cancer research hegemonize CONICET's HBMS research agenda, whereas terms connecting HBMS research with socio-environmental cues are marginal. However, we also found differences with the international agenda: CONICET's HBMS agenda shows a marginal presence of terms linked to translational medicine, while terms associated with categories such as pathogens, plant research, agrobiotechnology, and food industry are more represented than in the prevailing agenda. Conclusions: CONICET's HBMS research agenda shares topics, priorities, and methodologies with the prevailing HBMS international research agenda. However, CONICET's HBMS research agenda is internally heterogeneous, appearing to be mostly driven by a combination of elements that not only reflect academic dependency (the adoption of the prevailing research agenda by non-core research institutions) but also local economic determinants associated with Argentina's place in the international division of labor as an exporter of primary goods.

Correction: Whose shoulders is health research standing on? Determining the key actors and contents of the prevailing biomedical research agenda.

[This corrects the article DOI: 10.1371/journal.pone.0249661.].

Whose shoulders is health research standing on? Determining the key actors and contents of the prevailing biomedical research agenda.

BACKGROUND: Conflicts of interest in biomedical research can influence research results and drive research agendas away from public health priorities. Previous agenda-setting studies share two shortfalls: they only account for direct connections between academic institutions and firms, as well as potential bias based on researchers' personal beliefs. This paper's goal is to determine the key actors and contents of the prevailing health and biomedical sciences (HBMS) research agenda, overcoming these shortfalls. METHODS: We performed a bibliometric and lexical analysis of 95,415 scientific articles published between 1999 and 2018 in the highest impact factor journals within HBMS, using the Web of Science database and the CorText platform. HBMS's prevailing knowledge network of institutions was proxied with network maps where nodes represent affiliations and edges the most frequent co-authorships. The content of the prevailing HBMS research agenda was depicted through network maps of prevalent multi-terms found in titles, keywords, and abstracts. RESULTS: The HBMS research agendas of large private firms and leading academic institutions are intertwined. The prevailing HBMS agenda is mostly based on molecular biology (40% of the most frequent multi-terms), with an inclination towards cancer and cardiovascular research (15 and 8% of the most frequent multi-terms, respectively). Studies on pathogens and biological vectors related to recent epidemics are marginal (1% of the most frequent multi-terms). Content of the prevailing HBMS research agenda prioritizes research on pharmacological intervention over research on socio-environmental factors influencing disease onset or progression and overlooks, among others, the study of infectious diseases. CONCLUSIONS: Pharmaceutical corporations contribute to set HBMS's prevailing research agenda, which is mainly focused on a few diseases and research topics. A more balanced research agenda, together with epistemological approaches that consider socio-environmental factors associated with disease spreading, could contribute to being better prepared to prevent and treat more diverse pathologies and to improve overall health outcomes.

Understanding the Battle for Universal Pharmacare in Canada Comment on "Universal Pharmacare in Canada".

Drug coverage in Canada is a patchwork; an inequitable inefficient and unsustainable patchwork with no coherence or purpose. Some people think that we can solve the problem by adding more patches, but the core of the problem is that it is a patchwork. For the working population, access to medicines is still organized as privileges offered by employers to their employees. Universal pharmacare would not only provide better access to needed prescription drugs, but also eliminate waste, ensure value-for-money and help improve drug safety and appropriate prescribing. Opponents fear that a universal pharmacare plan would ration drugs, and impede drug access for some patients. However, these claims misunderstand the reality of drug coverage, pricing and access. Opponents propose, instead, to "fill the gap" of current drug coverage by implementing catastrophic coverage, which would serve commercial interests without maximizing health outcomes for the Canadian population. In spite of overwhelming evidence and consensus in the academic community in favour of universal pharmacare, the battle is far from over.

Analyzing the impact of trade and investment agreements on pharmaceutical policy: provisions, pathways and potential impacts.

BACKGROUND: Trade and investment agreements negotiated after the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have included increasingly elevated protection of intellectual property rights along with an expanding array of rules impacting many aspects of pharmaceutical policy. Despite the large body of literature on intellectual property and access to affordable medicines, the ways in which other provisions in trade agreements can affect pharmaceutical policy and, in turn, access to medicines have been little studied. There is a need for an analytical framework covering the full range of provisions, pathways, and potential impacts, on which to base future health and human rights impact assessment and research. A framework exploring the ways in which trade and investment agreements may affect pharmaceutical policy was developed, based on an analysis of four recently negotiated regional trade agreements. First a set of core pharmaceutical policy objectives based on international consensus was identified. A systematic comparative analysis of the publicly available legal texts of the four agreements was undertaken, and the potential impacts of the provisions in these agreements on the core pharmaceutical policy objectives were traced through an analysis of possible pathways. RESULTS: An analytical framework is presented, linking ten types of provisions in the four trade agreements to potential impacts on four core pharmaceutical policy objectives (access and affordability; safety, efficacy, and quality; rational use of medicines; and local production capacity and health security) via various pathways. CONCLUSIONS: The analytical framework highlights provisions in trade and investment agreements that need to be examined, pathways that should be explored, and potential impacts that should be taken into consideration with respect to pharmaceutical policy. This may serve as a useful checklist or template for health and human rights impact assessments and research on the implications of trade agreements for pharmaceuticals.

Surviving niche busters: Main strategies employed by Canadian private insurers facing the arrival of high cost specialty drugs.

The Canadian patchwork system of prescription drug coverage and the employer sponsored private health benefits group plans appear vulnerable to cost growth due to insufficient balance of power between fragmented public and private buyers, and pharmaceutical manufacturers. The emergence of "bad" insurance risks caused by new and very expensive treatments featuring high cost specialty medicines - also known as niche buster drugs - exposes this vulnerability. This study fills a gap in knowledge by seeking to better understanding how Canadian private insurers face the arrival of specialty pharmaceuticals. It completes an overview of a body of grey literature composed of publicly available online articles from the employment benefits and group insurance consulting and administration industry; online documents from group benefits sector conferences; and online or on demand materials from Canadian life and health insurers. Claims for high cost specialty drugs generate new bad insurance risks that Canadian health insurers attempt to mitigate through isolated corporate initiatives, industry-wide strategies and calls for universal, public catastrophic coverage. The outcomes of these strategies are limited cost-control measures as well as risk and cost transfers onto plan sponsors, patients and provincial public programs.

Combating corruption in the pharmaceutical arena.

Corruption in healthcare generally and specifically in the pharmaceutical arena has recently been highlighted in reports by Transparency International. This article focuses on four areas of corruption: legislative/regulatory, financial, ideological/ethical, and communications. The problems identified and the solutions considered focus on structural considerations affecting how pharmaceuticals are discovered, developed, distributed, and ultimately used in clinical settings. These include recourse to user fees in the regulatory sphere, application of intellectual property rights to medical contexts (patents and access to research data), commercial sponsorship of ghost writing and guest authors, linkage/delinkage of the funding of research and overall health objectives to/from drug pricing and sales, transparency of payments to healthcare professionals and institutions, and credible regulatory sanctions. In general, financial and other incentives for all actors in the system should be structured to align with desired social outcomes - and to minimise conflicts of interest among researchers and clinicians.

Merger mania: mergers and acquisitions in the generic drug sector from 1995 to 2016.

BACKGROUND: Drug shortages and increasing generic drug prices are associated with low levels of competition. Mergers and acquisitions impact the level of competition. Record merger and acquisition activity was reported for the pharmaceutical sector in 2014/15, yet information on mergers and acquisitions in the generic drug sector are absent from the literature. This information is necessary to understand if and how such mergers and acquisitions can be a factor in drug shortages and increasing prices. METHODS: Data on completed merger and acquisition deals that had a generic drug company being taken over (i.e. 'target') were extracted from Bloomberg Finance L.P. The number and announced value of deals are presented globally, for the United States, and globally excluding the United States annually from 1995 to 2016 in United States dollars. RESULTS: Generic drug companies comprised 9.3% of the value of all deals with pharmaceutical targets occurring from 1995 to 2016. Globally, in 1995 there were no deals, in 2014 there were 22 deals worth $1.86 billion, in 2015 there were 34 deals totalling $33.56 billion, and in 2016 there were 42 deals worth in excess of $44 billion. This substantial increase was partially attributed to Teva's 2016 acquisition of Allergan's generic drug business. The surge in mergers and acquisitions for 2015/16 was driven by deals in the United States, where they represented 89.7% of the dollar value of deals in those years. CONCLUSIONS: The recent blitz in mergers and acquisitions signals that the generic drug industry is undergoing a transformation, especially in the United States. This restructuring can negatively affect the level of competition that might impact prices and shortages for some products, emphasizing the importance of updating regulations and procurement policies.