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Background: Per capita spending on drugs in the United States is double that of Canada. One commonly debated point when comparing the 2 countries is whether this additional spending allows residents of the United States access to valuable therapies not available in Canada., Objective: To characterize the therapeutic value of prescription drugs used in the United States that are not marketed in Canada., Methods: This cross-sectional study used IQVIA Multinational Integrated Data Analysis System data to identify drugs purchased in the United States but not in Canada from 2017 to 2021. Drug listing and regulatory review statuses were obtained. We categorized the drugs into 8 mutually exclusive groups: listing status in Canada ("cancelled post-market" or "dormant; approved but not marketed; cancelled pre-market"), other alternatives available ("formulation unavailable," "existing drug class," or "therapeutically similar"), "pre-approval," "atypical access available," or "unavailable without alternatives marketed" in Canada. Therapeutic value assessments of drugs in the last category were obtained from 3 international organizations., Results: 2,084 products were purchased in the United States but not in Canada from 2017 to 2021; 1,685 were excluded because they were not prescription drugs, were combinations in which each active pharmaceutical ingredient was already available in the United States as a separate drug, had been discontinued in the United States by August 30, 2023, or were marketed in Canada by August 30, 2023. After exclusions, there were 399 drugs; 120 (30%) were "cancelled post-market," 38 (10%) were "dormant; approved but not marketed; cancelled pre-market," 49 (12%) were "formulation unavailable," 130 (33%) were "existing drug class," 35 (9%) were "therapeutically similar," 3 (1%) were "preapproval," 15 (4%) were "atypical access available," and 9 (2%) were "unavailable" in Canada. 6 of the 9 drugs had been evaluated by 1 or more independent organizations, and all 6 were rated as offering minor to no additional therapeutic value compared with existing drugs., Conclusions: There was similar access to important prescription drug therapies in the United States and Canada. Overall, the additional spending in the United States may not have necessarily translated into access to important therapeutic innovations.

Competing Interests: Competing interests: David Menkes is a paid member of the Mental Health Advisory Committee, PHARMAC, New Zealand Government. He was paid by Atai Life Sciences for sessional supervision of a Phase One trial of dimethyltryptamine, a psychedelic drug, in healthy volunteers (2022). He is a coinvestigator in two clinical trials, neither of which is industry funded, both commencing in 2023: MDMA-assisted psychotherapy in terminal illness (charity funded); Low dose LSD in adult major depression (Health Research Council funded). Barbara Mintzes has acted as a paid expert witness for Health Canada in a legal case involving marketing of an unapproved drug product. Between 2019 and 2023, Joel Lexchin received payments for a writing brief on the role of promotion in generating prescriptions for a legal firm. He is a member of the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. He is participating in research funded by the Canadian Institutes of Health Research.

Background: Medical school deans wield considerable influence over research, clinical and educational missions at their institutions. This study investigates conflict of interest (COI) of Canadian medical school deans., Method: The websites of all 17 Canadian medical schools were searched for any mention of relationships between deans and pharmaceutical or medical device companies., Results: No COIs were discovered for 11 of the deans. Six had COIs, including participating in research funded by pharmaceutical companies and received consulting and speaker fees., Discussion: A minority of deans had COIs with healthcare industry companies. Whether deans' COIs affect policies at the medical schools they lead should be the subject of further investigation., (Copyright © 2024 Longwoods Publishing.)

The number of expensive drugs for rare diseases (EDRDs) approved by Health Canada and their contribution to healthcare costs have been rapidly increasing. The federal government has announced a three-year funding commitment of $1.4 billion for EDRDs, but principles need to be developed for how that funding will be allocated, especially in cases where insufficient data are available to guide decision making. Here, we review the role of evidence quality in making choices and draw on the experience from other countries to put forward five principles about how the money should be spent., (Copyright © 2024 Longwoods Publishing.)

Introduction: The independent French drug bulletin Prescrire International rates the therapeutic innovation of new drug-indications approved for marketing in France using an ordinal scale with the lowest rating being "not acceptable". This study investigates whether these drugs were approved by Health Canada., Methods: A list of "not acceptable" drug-indications was generated by handsearching all issues of Prescrire International between January 2013 and December 2022. The generic names, indications and reasons why Prescrire labeled them not acceptable were recorded. The approval date was determined by consulting the website of the European Medicines Agency (EMA). The status of these drug-indications in Canada was determined by searching multiple Health Canada websites. Therapeutic Evaluations for new drug-indications done by the Patented Medicine Prices Review Board (PMPRB) were recorded., Results: Prescrire rated 57 new drug-indications and 42 new indications for existing drugs as not acceptable. Seventy of these drug-indications were available in Canada- 42 new drug-indications and 28 new indications for existing drugs. Twenty (90.9%) of the 22 new drugs evaluated by the PMPRB were rated as slight/no therapeutic improvement and 2 as moderate therapeutic improvement. The median difference, in days, between approval times by the EMA/ANSM and Health Canada was 129 (interquartile range -102, 341) in favour of the former., Discussion: The majority of the not acceptable drug-indications were approved by Health Canada. The difference between when Prescrire and Health Canada examined the evidence for these drug-indications is unlikely to explain the difference in their evaluations. A change in regulatory standards at Health Canada may be one factor behind the presence of these drugs. To what degree those drugs led to more harms than benefits for patients who are taking them needs to be urgently investigated. Finally, the reasoning behind Health Canada's approval of these drugs should be interrogated., Competing Interests: Between 2020-2024, Joel Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for a legal firm, for being on a panel about pharmacare and for co-writing an article for a peer-reviewed medical journal. He is a member of the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. He is participating in research funded by the Canadian Institutes of Health Research. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Joel Lexchin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cambodia has experienced exponential economic growth in recent years and is expected to graduate from least developed country (LDC) status within the next decade. Membership of the World Trade Organization (WTO) will require Cambodia to grant product and process patents for pharmaceuticals upon LDC graduation. This study aims to measure the impact of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) on the price of HIV and hepatitis C medicine in Cambodia once it graduates from LDC status and is obliged to make patents available for pharmaceutical products and processes. Using scenarios based on likely outcomes of accession to the TRIPS Agreement, it measures the impact on the price of the HIV treatment program and compares that impact with the hepatitis C treatment program. Graduation from LDC status would be expected to result in a modest increase in the cost of the antiretroviral (ARV) treatment program and very large increases in the cost of the direct acting antivirals (DAA) treatment program. If annual treatment budgets remain constant, patent protection could see 1,515 fewer people living with HIV able to access ARV treatment and 2,577 fewer people able to access DAA treatment (a drop in treatment coverage of 93%)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so., Methods: This study uses two scenarios to cost the impact the CPTPP would have had on Thailand's 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated., Results: Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%., Conclusions: Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand's hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs., (© 2024. The Author(s).)

Studies based on the United States Open Payment database have demonstrated an association between the promotion and prescribing of opioids. An equivalent database does not exist in Canada; therefore, I undertook a narrative review of the literature. In 2015, Purdue spent over CAN$4 million promoting a single product and generated over 160 pages of journal advertising. In the current review, I describe each of the six different forms of promotion that companies used to try and influence prescribing behaviour: messages from sales representatives, journal advertisements, company involvement in undergraduate medical education, key opinion leaders, clinical practice guidelines, and the funding of patient groups. Recent regulatory changes have decreased the volume of opioid promotion, but it would be incorrect to assume that it does not continue to influence the prescribing of this class of drugs.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: DM is a paid member of the Mental Health Advisory Committee, PHARMAC, New Zealand Government. He was paid by Atai Life Sciences for sessional supervision of a phase 1 trial of dimethyltryptamine, a psychedelic drug, in healthy volunteers. BM has acted as a paid expert witness for Health Canada in a legal case involving marketing of an unapproved drug product. Between 2019 and 2023, JL received payments for writing on the role of promotion in generating prescriptions for a legal firm. He is a member of the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer and Co for books he has written. He is participating in research funded by the Canadian Institutes of Health Research.

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, examining 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 designs, outcomes, and completion times. 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., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The pharmaceutical industry has a long history of prioritizing the research and sale of medicines that will yield the largest amount of revenue and placing the health of people second. This gap is especially prevalent in countries of the Global South. This article first explores the dichotomy in research between the Global North and the Global South and then looks at examples of how access to key medicines used in diseases such as HIV, oncology and hepatitis C is limited in the latter group of countries. The role of pharmaceutical companies during the COVID-19 pandemic prompted negotiations for a pandemic accord that would ensure more equity in both research and access when the next pandemic comes. However, efforts by a combination of the pharmaceutical industry and some high-income countries (HICs) are creating serious obstacles to achieving the goal of an accord that would place health over profits., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: This study examined multiple aspects about the approval of new drugs: the characteristics of the drugs, the quality and quantity of information that Health Canada discloses about the demographics of patients enrolled in clinical trials, the characteristics of the trial, and the type of review that it uses. It examines whether there have been changes in these measures between 1 September 2012 and 31 March 2022., Methods: A list of all new drugs approved, type of review used, and drug characteristics was generated from Health Canada annual reports. Therapeutic categories were identified from the World Health Organization Collaborating Center for Drugs Statistics Methodology. The Summary Basis of Decision documents of Health Canada were used to identify patient demographics in clinical trials and clinical trial characteristics., Results: Health Canada approved 326 new drugs for 407 indications. The percent of orphan drugs approved increased from 35.6 to 51.3%. The number of indications per drug decreased ( p  = 0.0817) as did the number of pivotal trials per drug ( p  = 0.0091). The percent of Phase 3 trials dropped from 76.3% in 2012-2015 to 64.8% in 2019-2022 ( p  = 0.005). There was also a statistically significant decrease in the percent of trials that were randomized, controlled, and blinded. The clinical trial characteristics of orphan drugs and the type of review used were both significantly different compared with non-orphan drugs. The percent of trials which had information about the number of patients enrolled, the percent of trials that provided the age of the patients, and the sex breakdown all significantly increased., Conclusion: The results show that there has been a change in regulatory standards that may be due to them becoming less rigorous, because of an adaptation to the number of orphan drugs being submitted or a combination of both reasons. At the same time, there has been some improvement in the transparency of data. Health Canada has recently embarked on a series of reforms in drug regulation and clinical trial management. These changes need to be closely evaluated to be sure that they enhance the efficacy and safety of new drugs., Competing Interests: Between 2019–2023, JL received payments for writing briefs on the role of promotion in generating prescriptions for two legal firms. JL is a member of the Board of Canadian Doctors for Medicare. JL receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. JL is participating in research funded by the Canadian Institutes of Health Research., (Copyright © 2023 Lexchin.)

Semaglutide (▼Ozempic solution for injection, ▼Rybelsus tablets-Novo Nordisk) was initially granted market authorisation for the treatment of type 2 diabetes as an adjunct to diet and exercise. In 2021 and 2022, regulatory agencies in the USA and Europe licensed semaglutide (▼Wegovy solution for injection-Novo Nordisk) for the treatment of individuals who are obese, or overweight and who have at least one weight-related comorbidity. Manufacturer-sponsored randomised controlled trials have shown a loss of almost 12% of body weight over a 68-week period, however, once the medication is stopped people regain most of their pretreatment weight. Gastrointestinal adverse events occur commonly with semaglutide, and pancreatitis, diabetic retinopathy and severe allergic reactions have also been reported. Extensive hype in social and general media has resulted in increased demand for semaglutide leading to supply problems across the various licensed products including those used for treatment of diabetes. In the UK, the National Institute for Health and Care Excellence has recommended semaglutide as an option for weight management for a maximum treatment duration of 2 years. Further studies are underway to assess the effect of semaglutide on longer-term health benefits., Competing Interests: Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: Joel Lexchin received payments for writing briefs on the role of promotion in generating prescriptions for 2 legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Marc-André Gagnon reports research funding from the Social Sciences and Humanities Research Council, Canadian Institutes of Health Research (CIHR) and the Faculty of Public Affairs at Carleton University. Mina Tadrous reports research funding from the Ontario Ministry of Health and CIHR, as well as consulting fees from the Canadian Agency for Drugs and Technologies in Health, Health Canada and Green Shield Canada. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Although regulation of pharmaceutical promotion in Canada is covered under the Food & Drugs Act and Regulations, in practice it is regulated by two codes, one a code administered by the Pharmaceutical Advertising Advisory Board and a second one controlled by Innovative Medicines Canada, the lobby organization for the large majority of the Canadian and foreign-owned pharmaceutical companies operating in Canada. This study examines complaints about code violations between 2012 and 2021 and puts those complaints and their outcomes into the context of the stringency of the codes, their governance, monitoring, penalties for violations, and compliance by companies. It combines the findings from this analysis with international experience with industry-run codes and concludes that overall, the Canadian codes are ineffective in controlling promotion. Finally, it offers recommendations for how regulation can be improved and how doctors' reliance on information from pharmaceutical companies can be reduced., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine whether there has been a change in the number of therapeutically important new medicines not being introduced into the Canadian market in light of the December 2017 announcement of regulatory changes to lower Canadian prices., Methods: A list was compiled of medicines approved by the Food and Drug Administration (FDA) between 2014-2021 but not submitted to Health Canada. The therapeutic value of these medicines was assessed based on evaluations by two independent sources. If no evaluation was available, potential therapeutic value was determined based on the presence of one or more of three medicine characteristics. Interrupted time series was used to determine if there were changes in overall new medicine introductions and therapeutically important new medicines., Results: The FDA approved 364 new medicines of which 116 (31.9%) were not submitted to Health Canada. There was a decrease in overall annual number of submissions but that was not related to the announcement at the end of 2017. There was no change in the introduction of therapeutically important new medicines as a percent of all medicines not marketed in Canada but there was a decrease in the absolute number., Conclusions: The number of therapeutically important medicines not being introduced into Canada is increasing but that is not related to the proposed price reforms., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic showed the close relationship between the Canadian government and the pharmaceutical industry when it came to both domestic and international issues. Domestically, the government chose to prioritize advice about vaccine acquisition from a panel of heavily conflicted people; it signed contracts worth billions of dollars with companies for vaccines but the contents of contracts were largely kept secret. The government also committed over CAD$1 billion in funding for research on COVID-19 but without any requirement that any forthcoming intellectual property or diagnostic and therapeutic products had to be accessible and affordable in low- and middle-income countries (LMICs). On the international stage, Canada did not support the COVID-19 Technology Access Pool that aimed to provide a one-stop shop for scientific knowledge, data, and intellectual property to be shared equitably by the global community. It delayed donating vaccines to LMICs and bought vaccines from a facility designed mainly to provide vaccines to that group of countries. The government did not dismantle roadblocks that prevented a Canadian company from sending vaccines to Bolivia. Finally, it was ambiguous about whether it supported a patent waiver for COVID-19 technologies at the World Trade Organization.

Background: To help promote the effective delivery of drug donations, the World Health Organization (WHO) developed the Guidelines for Medicine Donations. The need for revisions is timely given the large-scale influx of medicine donations since the start of the COVID-19 pandemic. This study analyses current policies of donors and recipients that are commensurate with the recommendations in the Guidelines and examines current practices, challenges, and revision suggestions., Results: A search for medicine donation policies of donors and recipients was conducted in May/June 2022 and repeated in January 2023. Potential donor countries were identified from the high-income countries on the United Nation's (UN) List of G20 Countries. Potential pharmaceutical company donors were selected from those with 2021 revenue of $30 billion or greater. Potential non-government organization donors came from the WHO list of non-governmental organizations (NGOs) and two other sources. Potential recipient countries were those on the UN List of Least Developed Countries. These four lists were supplemented with actual donors and recipients identified from the literature. All policies retrieved were screened to identify which of the 12 recommendations from the WHO Guidelines were incorporated. We identified 38 policies from 1 donor country, 6 brand-name multinational pharmaceutical companies, 6 NGOs and 25 recipient countries. Most policies incorporated all 12 recommendations. Twenty-five of the 38 policies were developed in 2010 or later. The majority of actual donors and recipients did not have policies that were publicly available. A rapid literature review for publications from 2010 onwards identified challenges in implementing the WHO Guidelines and suggested for revisions. Challenges included: (1) information management; (2) medication presentation; (3) influence from the pharmaceutical industry; (4) donation sustainability; and (5) the belief that donations are inherently good., Conclusions: Our findings suggest that both donors and recipients could further align their policies with the existing Guidelines and both groups should be consulted on any revisions to ensure that their experiences are reflected and their needs are addressed. While the current WHO Guidelines for Medicine Donations are a solid base for medical humanitarian efforts, evidence points to the need for an update to meet current challenges., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Privatisation through the expansion of private payment and investor-owned corporate healthcare delivery in Canada raises potential conflicts with equity principles on which Medicare (Canadian public health insurance) is founded. Some cases of privatisation are widely recognised, while others are evolving and more hidden, and their extent differs across provinces and territories likely due in part to variability in policies governing private payment (out-of-pocket payments and private insurance) and delivery., Methods and Analysis: This pan-Canadian knowledge mobilisation project will collect, classify, analyse and interpret data about investor-owned privatisation of healthcare financing and delivery systems in Canada. Learnings from the project will be used to develop, test and refine a new conceptual framework that will describe public-private interfaces operating within Canada's healthcare system. In Phase I, we will conduct an environmental scan to: (1) document core policies that underpin public-private interfaces; and (2) describe new or emerging forms of investor-owned privatisation ('cases'). We will analyse data from the scan and use inductive content analysis with a pragmatic approach. In Phase II, we will convene a virtual policy workshop with subject matter experts to refine the findings from the environmental scan and, using an adapted James Lind Alliance Delphi process, prioritise health system sectors and/or services in need of in-depth research on the impacts of private financing and investor-owned delivery., Ethics and Dissemination: We have obtained approval from the research ethics boards at Simon Fraser University, University of British Columbia and University of Victoria through Research Ethics British Columbia (H23-00612). Participants will provide written informed consent. In addition to traditional academic publications, study results will be summarised in a policy report and a series of targeted policy briefs distributed to workshop participants and decision/policymaking organisations across Canada. The prioritised list of cases will form the basis for future research projects that will investigate the impacts of investor-owned privatisation., Competing Interests: Competing interests: Between 2019 and 2022, JL received payments for writing briefs on the role of promotion in generating prescriptions for two legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since 2019, the Chinese central government has taken significant steps to centralize national purchasing power and has implemented a pooled procurement system. In this paper, we provide an in-depth analysis of China's National Volume-Based Procurement (NVBP) policy, which represents a unique approach to pooled procurement within the pharmaceutical sector. The primary objectives of the NVBP are to reduce drug prices, enhance access to affordable medications, and improve the overall functioning of the pharmaceutical industry in China. Our analysis delves into the key features of the NVBP, including its centralized procurement system, volume-based procurement approach, and the guaranteed procurement volumes allocated to winning bidders. We also address the challenges and implications associated with the NVBP, such as its impact on the pharmaceutical industry, the sustainability of price reductions, and the importance of striking a balance between price reduction and industry sustainability. Through a comparative analysis, we shed light on the distinct characteristics of China's approach to pooled procurement and its potential ramifications for healthcare policies and practices. By examining the NVBP within the broader context of China's evolving healthcare landscape, we aim to contribute to a deeper understanding of the implications and effectiveness of this unique policy initiative., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The pharmaceutical industry's promotion of opioids in North America has been well-documented. Yet despite the clear consequences of improperly classifying pharmaceutical company messaging and frequently permissive approaches that allow the pharmaceutical industry to self-regulate its own advertising, there has been scarce investigation to date of how pharmaceutical industry stakeholders interpret definitions of "advertising." This study explores how variations of "marketing" and "advertising" are strategically framed by the different actors involved in the manufacturing and distribution of pharmaceutical opioids. We employed a framing analysis of industry responses to Health Canada's letter to Canadian manufacturers and distributors of opioids requesting their commitment to voluntarily cease all marketing and advertising of opioids to health care professionals. Our findings highlight companies' continuing efforts to frame their messaging as "information" and "education" rather than "advertising" in ways that serve their interests. This study also calls attention to the industry's continual efforts to promote self-regulation and internal codes of conduct within a highly permissive federal regulatory framework with little concern for violations or serious consequences. While this framing often occurring out of public sight, this study highlights the subtle means through which the industry attempts to frame their promotion strategies away from "marketing". These framing strategies have significant consequences for the pharmaceutical industry's capacity to influence healthcare professionals, patients, and the general public., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Eisenkraft Klein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Health Canada posts the outcomes of all New Drug Submissions. In some cases, companies have withdrawn submissions or submissions have been rejected by Health Canada for new active substances (NAS). This study explores the reasons for those decisions and compares them with decisions made by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA)., Methods: This is a cross-sectional analysis. Submissions for NAS between December 2015 and December 2022 were identified along with the original indications for the NAS, the information that Health Canada had available and the reasons for its decisions. Similar information was sourced from the FDA and the EMA. Their decisions were compared to those made by Health Canada. The time between decisions by Health Canada, the FDA and the EMA were calculated in months., Results: Health Canada considered 272 NAS and approved 257. Sponsors withdrew 14 submissions for 13 NAS and Health Canada rejected submissions for 2 NAS. The FDA approved 7 of these NAS and the EMA approved 6, rejected 2 and submissions were withdrawn by 2 companies. Health Canada and the FDA considered similar information in 4 of 7 cases. Indications were the same except in one case. The FDA made decisions a mean of 15.5 months (interquartile range 11.4, 68.2) before companies withdrew their submissions from Health Canada. There were 5 cases where Health Canada and the EMA considered the same information and in 2 of those the outcome was different. Health Canada and EMA decisions were generally made within 1-2 months of each other. Indications were the same in all cases., Conclusions: Differences in decision making by regulators are due to more than the data which with they are presented, the timing of the presentations and the indications for the drugs. Regulatory culture may have influenced decision making., Competing Interests: In 2019-2022, Joel Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for two legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written., (Copyright: © 2023 Joel Lexchin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To examine whether a combination of three characteristics of new drugs - review type, outcome of premarket trials (surrogate or clinical) and first-in-class is associated with significant therapeutic value., Design: Cross-sectional analysis of new drugs approved by Health Canada from January 1, 2011 to December 31, 2020., Setting: Canada., Participants: New drugs approved by Health Canada for which therapeutic evaluations, trial outcomes and first-in-class status was available., Main Outcome Measures: Distribution of therapeutic value (major, moderate, little to no) depending on how many of the three characteristics were present for each drug., Results: Health Canada approved 340 drugs of which 243 had data available for analysis. If all three characteristics were present 10 out of the 20 drugs had a major therapeutic rating. Conversely if none were present only 2 drugs out of 37 had a major therapeutic rating., Conclusion: This study introduces a new evaluation method for determining whether new drugs will have major therapeutic value that appears to be more successful than relying only on the type of review that drugs receive., Competing Interests: Declarations, (© 2023 The Author(s).)

Objective To examine the potential therapeutic value of new medicines approved in the US and both approved and not approved in Australia. Methods A list of new medicines approved by the US Food and Drug Administration (FDA) between 1 January 2015 and 31 December 2020 was assembled and it was determined which of these medicines were also approved in Australia. Three metrics - first in class, priority review and therapeutic rating by two independent organisations - were used to determine the potential therapeutic value of the medicines. The percent of medicines with and without potential significant therapeutic value was compared using each of the three metrics. Results A total of 273 drugs were approved by the FDA, of which 147 (53.8%) were approved by the Therapeutic Goods Administration, the Australian regulator. For each of these three metrics, the percent of medicines with and without potential significant therapeutic value approved in Australia was the same: first in class (yes vs no: Chi-squared P  = 0.8562), priority review (yes vs no: Chi-squared P  = 0.4593), therapeutic rating (major/moderate vs little/no: Chi-squared P  = 0.9006). Some of the 126 drugs not approved may be therapeutically important. Conclusions New medicines approved in the US between 2015 and 2020 without potential significant therapeutic value are as likely to be introduced into Australia as drugs with potential significant therapeutic value. Some potentially valuable drugs may not have been submitted for approval in Australia by the companies making them.

In 1987, the government passed legislation to protect brand-name pharmaceutical firms against competition from generic drug brands in exchange for economic investment in Canadian pharmaceutical research and development (R&D). Since 2002, brand-name pharmaceutical companies' R&D investments have fallen short of their commitment, while Canadians now pay the fourth highest drug prices of all the Organisation for Economic Co-operation and Development member countries. In this article, we examine the degree to which brand-name pharmaceutical companies have fallen short of their promises, discuss whether a patent policy is the best strategy to secure Canadian pharmaceutical R&D funding and propose practical alternatives to this arrangement., (Copyright © 2022 Longwoods Publishing.)

This issue of Healthcare Papers on expensive drugs for rare diseases (EDRDs) is very timely. According to the recently released Patented Medicine Prices Review Board's 2021 annual report, EDRDs have gone from 1.7% of pharmaceutical expenditures in 2012 to 12.2% in 2021, with a compound annual growth rate between 2012 and 2021 of 31.7% compared to 6.0% for all prescription medicines (PMPRB 2022)., (Copyright © 2023 Longwoods Publishing.)

Background: Information about the timing involved in various stages of making new drugs available to Canadians is important for understanding how a national pharmacare plan will affect timely access to new drugs. I explored the timing of the various steps between receiving a Notice of Compliance and a decision by the pan-Canadian Pharmaceutical Alliance (pCPA)., Methods: I gathered data from various databases (Canadian and other) about new drugs approved between 2011 and 2020, including generic names, date of application for approval (New Drug Submission [NDS]), date of Notice of Compliance, date of marketing, dates when a submission was made to the Canadian Agency for Drugs and Technologies in Health (CADTH) and the pCPA, and when these agencies made a decision., Results: Marketing dates were available for 301 of the 337 new drugs approved. The median time from NDS to marketing was less than the time to a positive pCPA decision for all years between 2011 and 2020. There was no significant change in the difference between the 2 periods over time ( p = 0.2). Additional therapeutic value did not make a difference in the delay ( p = 0.3) and companies did not take full advantage of the opportunity to file early submissions with CADTH., Interpretation: The delay between when drugs could be listed on private compared with public formularies was at least 1 year. If a national pharmacare plan is instituted, one of the priorities should be to concentrate on consolidating and working to shorten the CADTH and pCPA processes., Competing Interests: Competing interests: Joel Lexchin received payments for writing a brief in an action for side effects of a drug for Michael F. Smith, lawyer, and a second brief on the role of promotion in generating prescriptions for Goodmans LLP, in 2018–2021. He is a member of the Foundation Board of Health Action International. He receives royalties from the University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. He has received payments from the Canadian Institutes of Health Research for presenting at a workshop on conflict of interest in clinical practice guidelines., (© 2022 CMA Impact Inc. or its licensors.)

Background: Health Canada conditionally approves new drugs using its Notice of Compliance with conditions (NOC/c) policy. Under this policy Qualifying Notices (QNs) list confirmatory studies that need to be conducted to confirm the drug's efficacy. This study examines the depth of information about methodology and patient demographics in the confirmatory studies. It also compares the outcomes (surrogate or clinical) used to approve the drugs with the outcomes proposed in the confirmatory studies., Methods: A list of drugs approved under the NOC/c policy and their QNs were sourced from two previous publications as well as Health Canada's NOC/c website. Patient demographics and study methodology in the confirmatory studies listed in the QNs was recorded and counted. The primary outcome used to approve new drugs was recorded from Health Canada's Summary Basis of Decision website and compared to the type of outcome for studies mentioned in the QNs., Results: Seventy-eight drugs were approved using a NOC/c from the time the first drug was approved under the program in July 1998 until May 18, 2022. QNs were missing or all information was redacted for 3 drugs, the remaining 75 QNs listed 154 studies (median of 2 studies per QN, interquartile range 1,3). The outcome, randomization and blinding could not be determined for any study in 43 (57.3%), 36 (48.0%) and 42 (56.0%) QNs, respectively. No study gave the distribution of men and women and the number of patients was given in 23 (14.9%) studies. The expected time of completion of the studies was available for 36 (23.4%) out of 154 and information to identify studies was present for 77 (50.0%), absent for 23 (14.9%) and unclear for 26 (16.9%). Surrogate outcomes were used to approve 54 (84.4%) of 64 drugs. Eight (14.8%) confirmatory studies for these 54 drugs used clinical outcomes, 15 (27.8%) used surrogate outcomes and outcomes were unknown for 31 (57.4%). Specifically for oncology drugs, 44 were approved with surrogate outcomes and one with a clinical outcome. Eight (18.2%) of the 44 oncology drugs approved with surrogate outcomes had confirmatory studies that used clinical outcomes, 14 (31.8%) used surrogate outcomes and the outcome could not be determined for 22 (50.0%). The sole oncology drug approved with a clinical outcome had a confirmatory study with a surrogate outcome., Discussion: QNs contain little information about the methodology or patient demographics of confirmatory studies. Confirmatory studies with surrogate outcomes were used almost one-third of the time to validate efficacy in drugs initially approved using surrogate outcomes. Health Canada needs to develop a template about what information regarding confirmatory studies should be contained in a QN and rethink its use of confirmatory studies using surrogate outcomes. All the data were gathered by a single individual possibly introducing unintended biases., Competing Interests: In 2019-2021, Joel Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for Goodmans LLP and from the Canadian Institutes of Health Research for presenting at a workshop on conflict-of-interest in clinical practice guidelines. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. This does not alter my adherence to PLOS ONE policies on sharing data and materials.

Given the increasing role of patient groups in pharmaceutical policy-making in Canada, this observational study was undertaken to determine whether companies that are members of Innovative Medicines Canada (IMC) list, on their publicly available websites, the names of patient groups that they make donations to and reciprocally, whether patient groups publicly list the names of the companies that they receive donations from. Websites of IMC members were searched for the names of the patient groups receiving donations, value of the donations and year the donations were made. The website of each patient group that was listed as receiving a donation was then searched for information about the name of companies making donations along with the value of the donations, year the donations were made and percent of the patient groups' income represented by the donation. For donations over $50 000, an attempt was made to match donations that companies made to donations that patient groups received. Eleven of 44 IMC members reported making 165 donations to 114 different patient groups. Seventy-nine of these 114 groups reported receiving 373 donations from IMC members. Information about the value of donations, the year that they were given and received and the percent of patient groups' income that they represented was limited. Donations made and received could not be matched because of the absence of information about the donations. Reporting on websites about donations by both companies and patient groups in Canada is haphazard, inconsistent and incomplete. Reforms are need to both the way that companies and patient groups report donations., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Innovative Medicines Canada has said that companies are delaying the introduction of new drugs into Canada in anticipation of changes in how the Patented Medicine Prices Review Board determines prices for patented medicine. This study investigates whether this claim is accurate., Methods: Delays in seeking approval for and marketing of new drugs were examined using linear regression analysis and comparing the time between approvals by Health Canada and approvals of the same drugs by the United States (US) Food and Drug Administration (FDA). Linear regression was also used to examine changes in the percent of drugs approved by the FDA and also approved by Health Canada and whether fewer drugs approved by Health Canada were being marketed. Approvals in Australia served as a control., Results: There was no change in the difference in approval times between Health Canada and the FDA (p = 0.7073). Time between approval of new drugs and when they were marketed increased (p = 0.0002). Health Canada approved a smaller percent of drugs approved by the FDA (p = 0.0019) but the same trend was found in Australia. Fewer drugs approved in Canada were marketed (p = 0.0288)., Conclusion: There is mixed evidence about whether drug companies are delaying or simply not introducing new drugs into Canada., Competing Interests: Declaration of Competing Interest In 2019-2021, Joel Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for Goodmans LLP and from the Canadian Institutes of Health Research for presenting at a workshop on conflict-of-interest in clinical practice guidelines. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: Sukhy Mahl reports receiving organizational support from the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by a Canadian Institutes of Health Research (CIHR) Team Grant (CTP 87518) and the Ontario Ministry of Health. Joel Lexchin reports receiving royalties from the University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. Dr. Lexchin has also received payments from the CIHR and payment for expert testimony from Goodmans LLP. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. Brian Rowe’s research is supported by a Scientific Directors Operating Grant (SOP 168483) from CIHR. Dr. Rowe is the Scientific Director of the Institute of Circulatory and Respiratory Health, CIHR, and Professor and Director at the Emergency Medicine Research Group, Department of Emergency Medicine, Faculty of Medicine and Dentistry, College of Health Sciences. Shoo Lee reports receiving grant support for the MiCare team from CIHR. Dr. Lee is also the president of the Canadian Neonatal Foundation (a charity).

Objectives: To examine sponsorship of Australian and New Zealand medical societies by healthcare companies and whether societies have policies to deal with conflicts of interest., Design: Cross-sectional study conducted in March 2022., Setting: Australia and New Zealand., Participants: Medical societies in both countries., Main Outcome Measures: The percent of medical societies that list sponsorship from healthcare companies on either their home webpages or the webpages of their annual meetings and/or that issue prospectuses to potential sponsors. The percent of societies with sponsorship that also have policies about their interactions with their sponsors. Whether societies feature their sponsors' logos on their webpages and have hyperlinks to sponsors' webpages and what percent of societies' annual revenue comes from sponsorships., Results: Ninety-two medical societies were identified. Sixty-two had healthcare company sponsorship and 10 of the societies with sponsorship had policies to deal with interactions with their sponsors. Fifty-four societies displayed the logos of their sponsors on their home webpages and/or the webpages of their annual meetings. Only 6 societies provided enough information to calculate what percent of their revenue comes from sponsorships. For 5 of the 6 the percent was well below 50%., Conclusions: The acceptance of sponsorships from healthcare companies by Australian and New Zealand societies is common and few societies have policies to deal with these relationships. In general, societies appear to get only a small percent of their annual revenue from sponsorships., (© 2022 The Author(s).)

In March 2022, the New Democratic Party (NDP), Canada's social democratic party, and the centrist Liberal government signed a supply and confidence agreement. In return for the NDP agreeing to vote with the government on all crucial issues until June 2025, the Liberals pledged to bring in both pharmacare and dental care programs. Pharmacare, universal public insurance coverage for prescription drugs, had been promised for more than 50 years but never implemented, while public dental care was an almost completely neglected issue. This article explains the long genesis of pharmacare, the need for public dental care, and the political circumstances that led to the agreement. However, at this point, details about both plans are largely absent. As a result, how well those plans will serve the needs of Canadians is yet to be determined.

Objective Examine the use of priority and provisional approval pathways by the Australian Therapeutic Goods Administration (TGA) for evaluating new medicines. Methods This observational study assessed all new medicines approved by the TGA between 1 January 2018 and 18 October 2021. It examined how frequently priority and provisional approval pathways are being used, the conditions which the medicines are being approved to treat, how long medicines are spending in the approval pathways, the additional therapeutic value of the medicines being approved through these pathways and how the use of the pathways compares with similar regulatory pathways used by Health Canada. Results The TGA approved 138 new medicines in the time period under study, of which 33 were approved through either the priority or provisional approval pathways. Sixteen were approved to treat cancer. It took the TGA a mean of 130 (95% CI 118, 143) and 144 (95% 101, 188) working days for priority and provisional pathways, respectively. Therapeutic evaluations were available for 16 of these medicines and 11 offered little to no therapeutic gain over existing medicines. There was moderate agreement between the TGA and Health Canada in their use of these pathways (Kappa = 0.5458, 95% CI 0.3900, 0.7016). Conclusions The priority and provisional approval pathways are now being used by the TGA for about one-third of all new medicine approvals. Although the medicines approved in these ways are moving through the review process more quickly than those approved through the standard approval pathway, the majority of these medicines, for which an evaluation of therapeutic value is available, do not offer any substantial additional therapeutic value over existing medicines.

Introduction: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories., Methods: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013-March 2016) as well as in a BC advisory cohort (June 2014-May 2017)., Results: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66-0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors., Conclusion: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP., (© 2022. The Author(s).)

Objectives: This study investigates the information and policies that Canadian patient groups post on their publicly available websites about their relationships with pharmaceutical companies., Design: Cross-sectional study., Setting: Canadian national patient groups., Participants: Ninety-seven patient groups with publicly available websites., Interventions: Each patient group was contacted by email. Information from patient groups' websites was collected about: total annual revenue for the latest fiscal year, year revenue was reported, revenue from pharmaceutical company donors, purpose of the donation, presence of donors' logos on the website and hyperlinks to donors' websites, previous and current employment information about board members and staff, external audits about the group's finances and whether the group endorses products made by donors. Analysis of publicly available policies looking at: board and/or advisory board, acceptance of donations and revenue generation, independence of decision-making, endorsements, assistance to and/or interactions between patient members from a donor or another company/person acting on behalf of a donor and audits/monitoring/compliance., Primary and Secondary Outcome Measures: Number of patient groups posting information on their websites about their relationships with pharmaceutical companies; the presence and contents of patient group policies covering different topics about relationships with pharmaceutical companies., Results: Fifty-three (54.6%) of 97 groups reported donations from pharmaceutical companies. Forty-one (42.3%) groups showed the logos of pharmaceutical companies on their websites and 22 (53.7%) had hyperlinks to pharmaceutical company websites. Twenty-five (25.8%) of these groups endorsed pharmaceutical products produced by brand-name companies that had donated to the groups. Twenty-six (26.8%) groups had policies that dealt with relationships with pharmaceutical companies., Conclusions: Pharmaceutical industry funding of the included patient groups was common. Despite this, relatively little information was provided on patient group websites about their relationships with pharmaceutical companies. Only 26 out of 97 groups had publicly available policies that directly dealt with their relationships with pharmaceutical companies., Competing Interests: Competing interests: In 2017–2020, JL received payments for being on a panel at the American Diabetes Association, for talks at the Toronto Reference Library, for writing a brief in an action for side effects of a drug for Michael F Smith, lawyer and a second brief on the role of promotion in generating prescriptions for Goodmans and from the Canadian Institutes of Health Research for presenting at a workshop on conflict of interest in clinical practice guidelines. He is currently a member of research groups that are receiving money from the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co for books he has written. SB has received payment for commissioned briefs related to patient advocacy and industry funding from the Canadian Federation of Nurses Unions and the Canadian Health Coalition. In 2018, she received royalties from UBC Press for a book on industry funding of patient groups. She is a member of the executive of the Nova Scotia Health Coalition and a member of Independent Voices for Safe and Effective Drugs. AS and DG report no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation., Design: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories., Study Population: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months., Main Outcome Measures: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population., Results: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice., Conclusions: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest., Competing Interests: Competing interests: MLDB declares PhD grants from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO Pharma to the Copenhagen Centre for Regulatory Science; CH declares grants or contracts from Novo Nordisk A/S and H. Lundbeck A/S paid to her institution; BM is acting as an expert witness for Health Canada on a legal case and anticipates future payment for doing so; S-AP declares the Centre for Big Data Research in Health received funding for postmarket surveillance research, unrelated to the current study; LP has received a Michael Smith Foundation for Health Research Reach Grant; AS declares grants or contracts from Arnold Ventures and the FDA paid to his institution, consulting fees from West Health and payment for expert testimony from the ACLU; IS has received a CIHR Canadian Network for Observational Drug Effect Studies grant and a Drug Evaluation Alliance of Nova Scotia grant, and payment for serving as a member of the Patented Medicine Prices Review Board., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Starting in 2017, retroactive to 2016, Innovative Medicines Canada (IMC) - the lobby group representing most of the large research-based pharmaceutical companies operating in Canada - initiated a voluntary system for companies to annually report on payments that they make to healthcare providers and organizations. Over the five years that the system has been in operation, 10 companies reported spending almost $345 million. The largest payments were to healthcare providers. Four companies spent more than $10 million in one or more years. The names of people and organizations receiving the payments and their purpose are not disclosed. Even if IMC makes disclosures mandatory for all its members, those reforms will not be enough to ensure transparency of company payments., (Copyright © 2022 Longwoods Publishing.)

Early in the COVID-19 pandemic, the federal government established a COVID-19 Vaccine Task Force to provide it with recommendations on a wide variety of issues related to vaccines. This article explores how the conflicts of interest of the Task Force members are declared and managed and what the implications are for the advice that they offer to the government. The Canadian government needs to go beyond just managing conflicts and work toward eliminating them on the Task Force., (Copyright © 2022 Longwoods Publishing.)

Background: Oncology drugs are frequently approved on the basis of surrogate outcomes that require further trials to confirm the benefits, but at times these trials fail and regulators need to decide whether to withdraw approval for the indication and/or to remove the drug from the market. This study compares decisions by the Food and Drug Administration and Health Canada about oncology drugs that were approved using either Accelerated Approval (FDA) or Notice of Compliance with conditions (NOC/c, Health Canada) and that failed confirmatory trials., Methods: Drug/indications approved by the FDA through its Accelerated Approval Pathway and that later failed confirmatory studies were identified from a published study and additional information on these drugs was collected from Drugs@FDA. Health Canada websites were searched on September 11, 2021 for the same group of drugs to determine if they were approved in Canada under the NOC/c pathway for the same indication as in the US. Information from both the FDA and Health Canada about these products was entered into an Excel spreadsheet. Decisions about whether to withdraw the drugs or remove the failed indication for the drug and requirements for confirmatory studies were compared. In addition, the dates of decisions by the two agencies were compared., Results: Ten drug/indications were available for comparison. Regulatory decisions were similar in 4 cases, different in 1 case and could not be determined in the remaining 5, in 1 case because decisions were pending in both countries and in the other 4, because the NOC/c had not been fulfilled in Canada. The requirements for the confirmatory studies were similar in both countries. Decisions were made earlier in the United States., Conclusions: This study shows that decisions made by Health Canada and the FDA about whether to withdraw a drug or remove a failed indication when drug/indications fail a confirmatory trial are usually similar, although the sample size on which this conclusion is made is small. The clinical implications of these similarities and differences should be explored., (© 2021. The Author(s).)

The Comprehensive Economic and Trade Agreement between Canada and the European Union provides for an extension of Canadian patents for prescription drugs by up to 2 years. One of the arguments advanced for longer patent time is to compensate companies for the length of the overall drug development time (the time between patent application and market approval). This study investigates overall development time in Canada for different groups of drugs approved between January 1, 2009 and December 31, 2018 and how many of these drugs are eligible for up to 2 years of patent term extension. Based on a list of patents and dates of market approval, the change in overall development time for all drugs was calculated along with whether there were differences in development time between different groups of drugs. Using Canadian patent filing dates, overall development time for all drugs went from a mean of 2240 days (95% CI: 1832, 2648) in 2009 to 4197 days (95% CI: 3728, 4665) in 2018 (analysis of variance [ANOVA], P <.0001). Using first global patent filing dates, overall development time went from a mean of 4481 days (95% CI: 3053, 5908) in 2009 to 6298 days (95% CI: 4839, 7756) in 2018 (ANOVA, P =.0118). There was a statistically significant difference in the overall development mean time between small molecule drugs (3553, 95% CI: 3361, 3746) and biologics (3903, 95% CI: 3595, 4212), (t test, P =.0487) when using Canadian patent filing dates but not when first global patent filing dates were used. There was no statistically significant change in overall development time among drugs that were substantial, moderate or little to none additional therapeutic value compared to existing drugs. Out of 238 drugs, 218 (91.6%) would have been eligible for patent term extension with 195 (80.7%) eligible for the full 2 years. Patent term extension does not appear to be justified based on changes in overall development time, except possibly in the case of biologics. There are also trade offs in terms of increased expenditures that need to be considered if patent terms are lengthened., (© 2021 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)