Search

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.)

Objectives: This study examines the length of time between when a patent application is filed in Canada for a new drug and when it is available for patients (time to market) and various components of that time. It also looks at whether various factors explain the time between patent application to New Drug Submission (NDS) and compares Canadian and American times. Drugs approved between 1 January 2014 and 31 December 2018 are examined., Design: Descriptive study., Data Sources: Websites from Health Canada, Food and Drug Administration, Merck Index, United States Patent and Trademark Office, WHO and previously published articles., Interventions: None., Primary and Secondary Outcomes: The primary outcomes are time to market, time from patent application to NDS (pre-NDS time), review time, time from approval to availability (postapproval time) and factors that may influence the pre-NDS time. The secondary outcome is a comparison of Canadian and American review times and times between patent application and approval., Results: There were 113 drugs available for analysis. The median time to market was 11.80 years (IQR 9.40-14.05). The component median times were pre-NDS 10 years (IQR 8.05-12.80), review time 0.96 years (IQR 0.75-1.15) and postapproval time 0.15 years (IQR 0.08-0.28). Less than 8% of the pre-NDS time was explained by the factors that were analysed in a multiple linear regression equation. There was no statistically significant difference between Canadian and American pre-NDS times., Conclusion: Once a drug reaches the market, companies have a median of 8.2 years before the patent expires and generics can reach the market. Most of the time between the filing of a patent application and when a drug is marketed is determined by decisions that are largely under the control of the company., Competing Interests: Competing interests: From 2017 to 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 LLP 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 Ltd for books he has written., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pharmaceutical companies engage heavily in promoting their products worldwide, and India is no exception. This article begins with an analysis of the therapeutic value of medications on the Indian market because, by definition, if a drug has no therapeutic value or has a negative benefit-to-harm ratio, then any promotion of that drug is inappropriate. It then examines 2 Indian case studies: drug promotion in Mumbai and the misuse of the World Health Organization logo in promotion. Next it describes specific types of promotion: advertisements in medical journals, brochures, and pamphlets; the actions of sales representatives; and the content of continuing medical education courses and medical conferences. The next sections examine medical students' and trainees' exposure to promotion and their attitudes about promotion; the attitudes of doctors about their interactions with the pharmaceutical industry; and whether promotion has an influence on prescribing. The article concludes with a critique of the existing industry, professional, and government regulatory regimes in India.

In the wake of the withdrawal of the nonsteroidal anti-inflammatory drug rofecoxib, regulators worldwide reconsidered their approach to postmarket safety. Many have since adopted a "life cycle" approach to regulation of medicines, facilitating faster approval of new medicines while planning for potential postmarket safety issues. A crucial aspect of postmarket safety is the effective and timely communication of emerging risk information using postmarket safety advisories, commonly issued as letters to healthcare professionals, drug safety bulletins, media alerts, and website announcements. Yet regulators differ in their use of postmarket safety advisories. We examined the capacity of regulators in the United States, Europe, Canada, and Australia to warn about postmarket safety issues through safety advisories by assessing their governance, legislative authority, risk communication capabilities, and transparency., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following: JL received payment 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. He is a member of the foundation board of Health Action International. LAB is senior editor for research integrity, Cochrane, for which the University of Colorado receives remuneration. CD is an alternate member representing Health Action International on the European Medicines Agency’s patients and consumers working party. MAG reports serving as an expert witness on behalf of Justice Canada in a case about the constitutionality of patented drug price regulation. Provenance and peer review: Not commissioned; externally peer reviewed.

Background: Companies often defending their products when there are concerns about their safety and/or effectiveness., Objective: This study looks at drugs removed from the Canadian market from 1990 onward and examines how companies responded., Methods: This descriptive analysis used a previously published article and a hand search of a Government of Canada website to generate a list of drugs withdrawn from Canada from 1990 onwards. For each product the following information was extracted: brand name, generic name, company, date of withdrawal and evidence base for withdrawal. Google and Factiva searches were used to identify sources containing statements from the company about the withdrawal. Statements were independently graded by two people into the following categories: company agrees with the withdrawal; drug could be used safely with certain precautions; company may reintroduce the drug; company disagrees with the withdrawal. Searches were carried out between September 15-20, 2020., Results: There were 22 drugs for which there were company statements. In 10 statements, the companies disagreed with the decision to withdraw the drug and in 7 they agreed with the decision. In the other 5 cases they felt that the drug could have been kept on the market with restrictions (2 cases) or they might reintroduce the drug (3 cases). The level of evidence for the withdrawal did not seem to influence the companies' position., Conclusion: In 15 out of 22 cases, the company either disagreed with the decision to withdraw the drug or felt that the drug should continue to be available to Canadian patients.

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials is becoming more available, regulators are still reluctant to provide detailed information about how that information is interpreted. As medicines and vaccines come up for approval for treatment of COVID-19, transparency in how pivotal trials are interpreted will be critical in determining how these treatments should be used.

The movement for a national pharmacare plan in Canada is growing, but at the same time the multinational pharmaceutical companies and their supporters are critical of such a move. The three major arguments that they make are that all that is needed is to "fill in the gaps," ie, cover those who currently are uninsured or underinsured, that private drug plans are superior to public ones because they cover a larger number of drugs and that Canada cannot afford pharmacare. This commentary examines each of these arguments and makes the case that none of them is valid and that it is time to get on with implementing pharmacare., (© 2020 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.)

Introduction: Studies of the delay between when companies file a New Drug Submission (NDS) and when drugs reach Canadian patients typically focus on the time in the regulatory review process and do not analyze the time between when approval is granted and the drug is available for purchase (company decision time). This study looks at the length of the two different time periods. Secondarily, it examines whether there is a difference in these time periods for drugs that received a standard review and those that received an expedited review., Methods: A list of all New Active Substances approved in Canada between January 1, 2014 and December 31, 2018 was compiled and the dates when the companies applied for a NDS, the dates when the drugs received a market authorization (Notice of Compliance, NOC) and whether the drugs received a standard review or an expedited review were recorded. The date of original marketing comes from Health Canada's Drug Product Database. Times in days were calculated between NDS and NOC (review time), between NOC and the marketing date (company decision time) and between NDS and the marketing date (total time). The company decision time as a percent of the total time was calculated for all drugs. Times were compared between standard and expedited review drugs using a two-tailed t-test., Results: One hundred and fifty-seven drugs were analyzed, 98 had a standard review and 59 had a priority review. Over 18% of the total time was due to company decisions. All three times were significantly lower for expedited review drugs versus standard review drugs as was the percent of total time due to company decision- 14.4% (95% CI 11.0, 17.8) versus 21.2% (95% CI 17.6, 24.8), p = 0.0102 (t-test)., Conclusions: Over 18% of the total time between when companies file for drug approval until the drug is available is due to decisions made by companies. Company decision times are shorter for drugs with expedited approvals compared to drugs with standard approvals., Competing Interests: In 2016-2019, Joel Lexchin was a paid consultant on two projects: one looking at developing principles for conservative diagnosis (Gordon and Betty Moore Foundation) and a second deciding what drugs should be provided free of charge by general practitioners (Government of Canada, Ontario Supporting Patient Oriented Research Support Unit and the St Michael’s Hospital Foundation). He also received payment for being on a panel at the American Diabetes Association, for a 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 LLP 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 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. There are no restrictions on sharing data.

Purpose: To determine the frequency and characteristics of safety advisories issued by medicines regulatory agencies in Australia, Canada, United Kingdom (UK) and the United States (US)., Methods: This retrospective analysis examines medicines safety warnings issued by the US Food and Drug Administration (FDA), Health Canada (HC), the Australian Therapeutic Goods Administration (TGA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) from January 1, 2007 until December 31, 2016. A database of warnings obtained from regulators' websites was developed and warnings were classified by communication type, drug, or therapeutic class focus, and the risk discussed. Advisories identifying the same drug or therapeutic class and risk were combined into groups termed "drug-risk issues" for comparisons between regulators., Results: Over this 10-year period, 1441 advisories were identified, with the MHRA issuing the most advisories (MHRA = 469, FDA = 382, HC = 370 TGA = 220). Seventy two percent focussed on single drugs (1034/1441) and 58.7% were alerts (846/1441) posted on the regulators' websites. Diabetes drugs, smoking cessation drugs and immunomodulatory agents were the individual drug types most often subject to safety advisories, while antidepressants, antipsychotics, and proton-pump inhibitors were the top three therapeutic classes. Of 680 identified drug-risk issues, 3.8% (26/680) described a risk of death. By body system, cardiac effects were the most frequent: 10.4% (71/680)., Conclusion: We found considerable differences in the use of advisories including frequency, communication type, and focus. Disparities in communication about emergent evidence on risks may mean that clinicians and patients in some countries are less well informed about medicine safety concerns than others., (© 2020 John Wiley & Sons Ltd.)

Previous studies have demonstrated a sex bias when it comes to the portrayal of men and women in medical journal advertisements for prescription drugs for psychiatric conditions. However, these studies have typically looked at ads over a restricted time period and often for a single diagnosis. Here we focus on ads for 3 diagnoses - anxiety, depression, and a combination of anxiety and depression - and cover nearly half a century to examine how the portrayal of patients changed over that time period with respect to sex. We sampled ads for products treating anxiety, depression, and anxiety/depression published in the Journal of the American Medical Association between 1946 and 1990. Our findings confirm other studies showing a marked preponderance of female patient representation during the 1960s in psychotropic drug advertising. However, we also show that from the mid-1970s to the mid-1980s, the proportion of ads for drugs featuring depression and/or anxiety indications depicted male patients significantly more than prior years in which females predominated, demonstrating advertisers' reaction to the critique of gender stereotyping.

Background: The producers of clinical practice guidelines (CPGs) may not disclose industry funding in their CPGs. We reviewed Canadian national CPGs to examine the existence and disclosure of industry-related organizational funding in the CPGs, financial conflicts of interest of committee members and organizational procedures for managing financial conflicts of interest., Methods: For this descriptive study, we searched the asset map of the Strategy for Patient-Oriented Research Evidence Alliance and the CPG Infobase for CPGs published between Jan. 1, 2016, and Nov. 30, 2018. Eligible guidelines had to have a national focus and either a first-line drug recommendation or a screening recommendation leading to drug treatment. One investigator reviewed all CPG titles to exclude those that were clearly ineligible. Two reviewers independently reviewed all remaining guidelines and extracted data. We analyzed the data descriptively., Results: We included 21 CPGs: 3 from government-sponsored organizations, 9 from disease or condition interest groups and 9 from medical professional societies. None of the 3 government-sponsored organizations reported industry funding, and none of their committee members disclosed financial conflicts of interest. Among the 18 disease or condition interest groups and medical professional societies, 14 (93%) of the 15 that disclosed funding sources on websites (3 did not disclose) reported organizational funding from industry, but none disclosed this information in the CPGs; 12 (86%) of the 14 with conflict-of-interest disclosure statements in the CPG (4 did not include disclosures) had at least 1 committee member with a financial conflict (mean proportion of committee members with a conflict 56%); and for all 8 CPGs with identifiable chairs or cochairs (chairs or cochairs not reported for 10) at least 1 of these people had a financial conflict of interest. None of the guidelines described a plan to manage organizational financial conflicts of interest., Interpretation: Canadian CPGs are vulnerable to industry influence through funding of producers of guidelines and through the financial conflicts of interest of committee members. The CPG producers that receive industry funding should disclose organizational financial conflicts in the CPGs, should engage independent oversight committees and should restrict voting on recommendations to guideline panelists who have no financial conflicts., Competing Interests: Competing interests: Katharine Elder formerly worked as the administrator of the Canadian Task Force on Preventive Health Care (CTFPHC), which was the producer of one guideline included in the present study (cited as reference 41). Brett Thombs, Ainsley Moore and Sharon Straus are the chair, vice-chair and director of knowledge translation, respectively, for the CTFPHC. The present work was not commissioned or funded by the CTFPHC, and the authors participated in the study outside of their responsibilities with the CTFPHC. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)