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Aducanumab, Accelerated Approvals & The Agency: Why The Fda Needs Structural Reform, Matthew Herder

Articles, Book Chapters, & Popular Press

The US Food and Drug Administration’s controversial decision to grant accelerated approval to aducanumab (Aduhelm), a therapy for Alzheimer’s disease, has motivated multiple policy reforms. Drawing upon a case series of other drugs granted accelerated approval and interviews of senior FDA officials, I argue that reform should be informed but not defined by aducanumab. Rather, structural reforms are needed to reshape FDA’s core priorities and restore the regulatory system’s commitment to scientific rigor.

Twenty Years After Krieger V Law Society Of Alberta: Law Society Discipline Of Crown Prosecutors And Government Lawyers, Andrew Flavelle Martin

Articles, Book Chapters, & Popular Press

Krieger v. Law Society of Alberta held that provincial and territorial law societies have disciplinary jurisdiction over Crown prosecutors for conduct outside of prosecutorial discretion. The reasoning in Krieger would also apply to government lawyers. The apparent consensus is that law societies rarely exercise that jurisdiction. But in those rare instances, what conduct do Canadian law societies discipline Crown prosecutors and government lawyers for? In this article, I canvass reported disciplinary decisions to demonstrate that, while law societies sometimes discipline Crown prosecutors for violations unique to those lawyers, they often do so for violations applicable to all lawyers — particularly …

‘A Most Equitable Drug’: How The Clinical Studies Of Convalescent Plasma As A Treatment For Sars-Cov-2 Might Usefully Inform Post-Pandemic Public Sector Approaches To Drug Development, Quinn Grundy, Chantal Campbell, Ridwaanah Ali, Matthew Herder, Kelly Holloway

Articles, Book Chapters, & Popular Press

Interventional clinical studies of convalescent plasma to treat COVID-19 were predominantly funded and led by public sector actors, including blood services operators. We aimed to analyze the processes of clinical studies of convalescent plasma to understand alternatives to pharmaceutical industry biopharmaceutical research and development, particularly where public sector actors play a dominant role. We conducted a qualitative, critical case study of purposively sampled prominent and impactful clinical studies of convalescent plasma during 2020-2021. We found that studies were mobilized and scaled at record pace due to well-connected investigators who engaged in widespread sharing of clinical trials resources, regulatory facilitators, and …

Permissive Regulation: A Critical Review Of The Regulatory History Of Buprenorphine Formulations In Canada, Abhimanyu Sud, Meghan Mcgee, Barbara Mintzes, Matthew Herder

Articles, Book Chapters, & Popular Press

Suboxone (buprenorphine-naloxone) is an opioid product approved in the US and Canada for the treatment of opioid use disorder. The drug is considered an important response to the opioid overdose epidemic with consistent calls for wider prescribing and deregulation. The history of Suboxone regulation in Canada has not been critically examined. Part of the rationale for doing so stems from the US regulatory experience, with documented irregularities, or what some have called abuses, that support profit-making by Suboxone's manufacturers. This regulatory analysis allows us to determine how opportunities to address health crises through drug innovation are managed at a federal …

On What Basis Did Health Canada Approve Oxycontin In 1996? A Retrospective Analysis Of Regulatory Data, Jessie Pappin, Itai Bavli, Matthew Herder

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The marketing and sale of oxycodone (OxyContin) by Purdue Pharma has commanded a great deal of legal and policy attention due to the drug’s central role in the ongoing overdose crisis. However, little is known about the basis for OxyContin’s approval by regulators, such as Health Canada in 1996. Taking advantage of a recently created online database containing information pertaining to the safety and effectiveness of drugs, we conducted a retrospective analysis of Purdue Pharma’s submission to Health Canada, including both published and unpublished clinical trials. None of the trials sponsored by Purdue Pharma sought to meaningfully assess the risks …

From Sandbox To Pandemic: Agile Reform Of Canadian Drug Regulation, Ipek Eren Vural, Matthew Herder, Janice E. Graham

Articles, Book Chapters, & Popular Press

Public health urgency for emerging COVID-19 treatments and vaccines challenges regulators worldwide to ensure safety and efficacy while expediting approval. In Canada, legislative amendments by 2019 Om- nibus Bill C-97 created a new "agile" licensing framework known as the "Advanced Therapeutic Pathway" (ATPathway) and modernized the regulation of clinical trials of drugs, vaccines, and medical devices. Bill C-97′s amendments are worthy of attention in Canada and globally, as health product regulation bends to COVID-19. The amendments follow reforms elsewhere to accommodate health product innovation, how- ever, the Canadian ATPathway is broader and more flexible than its counterparts in other jurisdictions. …

Exploring The Food And Drug Administration’S Review And Approval Of Entresto (Sacubitril/Valsartan), Ashley Eadie, Keith Brunt, Matthew Herder

Articles, Book Chapters, & Popular Press

Federal regulatory agencies such as the United States Food and Drug Administration review pharmacological evidence to ensure the safety and efficacy of new and repurposed pharmaceuticals prior to market approval. The discussions, disagreements and procedural decisions contained within such reviews offer unique insight into a pharmaceutical's strengths, weaknesses and opportunities, yet are often overlooked as a significant source of pharmacological information for research and development. To highlight the value of such resources, we present a case study on Entresto, a first-in-class angiotensin receptor-neprilysin inhibitor for the treatment of heart failure with reduced ejection fraction, and explore the regulatory rationale underlying …

In The Name Of Public Health: Misoprostol And The New Criminalization Of Abortion In Brazil, Mariana Prandini Assis, Joanna Erdman

Articles, Book Chapters, & Popular Press

This article explores the criminal regulation of misoprostol as a controlled drug in Brazil as a new form of abortion criminalization. A qualitative analysis of Brazilian case law shows how the courts use a public health rhetoric of unsafe abortion to criminalize the distribution of misoprostol in the informal sector. Rather than an invention of the local bench, this judicial rhetoric reflects global public health discourse and policy on unsafe abortion and the double life of misoprostol as both an essential medicine and a controlled drug. In contrast to previous studies, the article shows that abortion criminalization is not the …

Securing Safe Supply During Covid-19 And Beyond: Scoping Review And Knowledge Mobilization, Matthew Bonn, Natasha Touesnard, Brianna Cheng, Michael Pugliese, Emilie Comeau, Claire Bodkin, Thomas D. Brothers, Leah Genge, Matthew Herder, Candis Lepage, Ayden Scheim, Dan Werb, Sheila Wildeman

Articles, Book Chapters, & Popular Press

Background

Safe supply is defined as the legal and regulated provision of drugs with mind and/or body altering properties that have been typically accessible only through the illegal drug market. In response to the coronavirus disease 2019 (COVID-19) pandemic and related social/physical distancing measures, efforts have been made to scale up and increase access to safe supply programs in an effort to reduce overdose and other drug- and drug policy-related risks. However, it remains unclear whether these efforts taken thus far have meaningfully mitigated the barriers to safe supply experienced by People Who Use Drugs (PWUD), both during and beyond …

Transparency Of Regulatory Data Across The European Medicines Agency, Health Canada, And Us Food And Drug Administration, Alexander C. Egilman, Amy Kapczynski, Margaret E. Mccarthy, Anita T. Luxkaranayagam, Christopher J. Morten, Matthew Herder, Joshua D. Wallach, Joseph S. Ross

Articles, Book Chapters, & Popular Press

Based on an analysis of relevant laws and policies, regulator data portals, and information requests, we find that clinical data, including clinical study reports, submitted to the European Medicines Agency and Health Canada to support approval of medicines are routinely made publicly available.

Dispute Settlement Under The African Continental Free Trade Area Agreement: A Preliminary Assessment, Olabisi D. Akinkugbe

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The African Continental Free Trade Area Agreement (AfCFTA) will add a new dispute settlement system to the plethora of judicial mechanisms designed to resolve trade disputes in Africa. Against the discontent of Member States and limited impact the existing highly legalized trade dispute settlement mechanisms have had on regional economic integration in Africa, this paper undertakes a preliminary assessment of the AfCFTA Dispute Settlement Mechanism (DSM). In particular, the paper situates the AfCFTA-DSM in the overall discontent and unsupportive practices of African States with highly legalized dispute settlement systems and similar WTO-Styled DSMs among other shortcomings. Notwithstanding the transplantation of …

Disagreements Within The Us Food And Drug Administration Regarding Approval Of Novel Therapeutic Agents, 2011-2015, Andrea Macgregor, Audrey D. Zhang, Joshua D. Wallach, Joseph S. Ross, Matthew Herder

Articles, Book Chapters, & Popular Press

Thirty days after a novel therapeutic agent, a new molecular entity, or original biologic is approved, the US Food and Drug Administration (FDA) must publicly disclose its approval package, including scientific reviews completed by FDA disciplines (eg, pharmacology, statistical, and medical reviewers) and any available assessments by agency leadership.1 Although reports of internal disagreement have surfaced,2 it is unclear how often such disagreements occur. Disagreements document differing points of view or engaged discussion and may, thus, capture important scientific debates or signal challenging decisions within the agency. We sought to determine the frequency of disagreements within the FDA regarding approval …

Regulators, Pivotal Clinical Trials, And Drug Regulation In The Age Of Covid-19, Joel Lexchin, Janice Graham, Matthew Herder, Tom Jefferson, Trudo Lemmens

Articles, Book Chapters, & Popular Press

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 …

Transparency Too Little, Too Late? Why And How Health Canada Should Make Clinical Data And Regulatory Decision-Making Open To Scrutiny In The Face Of Covid-19, Sterling Edmonds, Andrea Macgregor, Agnieszka Doll, Ipek Eren Vural, Janice Graham, Katherine Fierlbeck, Joel Lexchin, Peter Doshi, Matthew Herder

Articles, Book Chapters, & Popular Press

Hard-won gains in the transparency of therapeutic product data in recent years1 have occurred alongside growing reliance by regulators upon expedited review processes.2 The concurrence of these two trends raises fundamental questions for the future of pharmaceutical regulation about whether the institutionalization of transparency will foster improved oversight of drugs, biologics, vaccines, and other interventions, or else, provide cover for a relaxing of regulatory standards of safety, effectiveness, and quality.3 The urgency of the COVID-19 pandemic, however, has brought this tension into immediate and sharp relief. During the course of the global health crisis, regulatory bodies have markedly expanded the …

Pharmaceutical Drugs Of Uncertain Value, Lifecycle Regulation At The Us Food And Drug Administration, And Institutional Incumbency, Matthew Herder

Articles, Book Chapters, & Popular Press

Policy Points

• The US Food and Drug Administration (FDA) has in recent years allowed onto the market several drugs with limited evidence of safety and effectiveness, provided that manufacturers agree to carry out additional studies while the drugs are in clinical use.
• Studies suggest that these postmarketing requirements (PMRs) frequently lack transparency, are subject to delays, and fail to answer the questions of greatest clinical importance. Yet, none of the literature speaks directly to the challenges that the FDA—as a regulatory institution—encounters in enforcing PMRs.
• Through a series of interviews with FDA leadership, this article analyzes and situates those challenges …

What Is The Purpose Of The Orphan Drug Act?, Matthew Herder

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The Orphan Drug Act (ODA) [1], first enacted in the United States in 1983, was set up to encourage the development of drugs for rare diseases. At that time, drug therapies for such diseases were rarely developed. Three decades later, a growing proportion of industry research and development (R&D) [2] and regulatory drug approvals [3] target diseases affecting fewer than 200,000 persons in the United States, the prevalence-based threshold of rare disease under the ODA.

In a new article published in PLOS Medicine, Aaron Kesselheim and colleagues document an embedded trend: within the …

Denaturalizing Transparency In Drug Regulation, Matthew Herder

Articles, Book Chapters, & Popular Press

In the arena of pharmaceutical drug regulation, transparency is the favoured focus of many current policy initiatives. Transparency is predominantly understood in terms of information disclosure. Requirements to register clinical trials, publish summary results, share clinical trial data, and disclose physician-industry relationships as well as rationales behind regulatory decision making are each predicated upon this idea that imparting information will both inform and deter unwanted behaviours. In this paper, I argue that understanding transparency qua disclosure has clear limitations and suggest transparency can and should serve an additional function - namely, of enabling standard setting through a more participatory, public …

When Everyone Is An Orphan: Against Adopting A Us-Styled Orphan Drug Policy In Canada, Matthew Herder

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Putting aside whether diseases that affect only small numbers of people ("rare diseases") should be prioritized over diseases that are otherwise orphaned, in this paper I argue that a new approach to rare, orphan diseases is needed. The current model, first signaled by the United States’ Orphan Drug Act and subsequently emulated by several other jurisdictions, relies on a set of open-ended criteria and market-based incentives in order to define and encourage drug therapies for rare, orphan diseases. Given a) the biopharmaceutical industries’ growing interest in orphan diseases, b) progress in the sphere of personalized medicines enabling more and more …

Regulating Prescription Drugs For Patient Safety: Does Bill C-17 Go Far Enough?, Matthew Herder, Elaine Gibson, Janice Graham, Joel Lexchin, Barbara Mintzes

Articles, Book Chapters, & Popular Press

Canada was the last developed country in the world to remove thalidomide from the market, and doing so required an Act of Parliament. At the request of Health Canada’s then Food and Drug Directorate, thalidomide’s two manufacturers voluntarily withdrew the drug from the market on Mar. 2, 1962. However, most of the drug’s distribution was in the form of free samples to medical professionals, which the directorate had no legal authority to control. Therefore, to avoid similar situations in the future and to stop sales of thalidomide, on Dec. 4, 1962, the Parliament of Canada amended the Food and Drugs …

A Conflict By Any Other Name Would Smell As Foul: A Comment On The Appointment Of A Vice-President Of Pfizer To The Cihr Governing Council, Jocelyn Downie

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If one had to pick the pharmaceutical company most associated with unethical and illegal conduct this past year, it would likely be Pfizer. So it seems reasonable to respond with disbelief and outrage to the federal government’s October 5, 2009 appointment of Dr. Bernard Prigent – Vice President, Medical Director and registered lobbyist for Pfizer Canada – to the Canadian Institutes of Health Research Governing Council (CIHR GC). This is the body that sets the strategic direction for most federally funded health research in Canada. A senior executive from a for-profit pharmaceutical company should not be given a seat at …

Demythologizing Phosita: Applying The Non-Obviousness Requirement Under Canadian Patent Law To Keep Knowledge In The Public Domain & Foster Innovation, Matthew Herder

Articles, Book Chapters, & Popular Press

The Supreme Court of Canada recently revised the doctrine of non-obviousness in a pharmaceutical “selection patent” case, Apotex Inc. v. Sanofi-Synthelabo Canada Inc. Although cognizant of changes to the same doctrine in the United States and the United Kingdom, a critical flaw in how the doctrine is being applied in Canada escaped the Court’s attention. Using content analysis methodology, this article shows that Canadian courts frequently fail to characterize the “person having ordinary skill in the art” (PHOSITA) for the purpose of the obviousness inquiry. The article argues that this surprisingly common analytical mistake betrays a deep misunderstanding of innovation, …

Book Review Of Passion: An Essay On Personality , Richard F. Devlin Frsc

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Passion is a cogently structured, compel Jingly argued and seductively enthralling masterpiece which, in years to come, will undoubtedly stand out as an inspirational source for many who seek social transformation. Unger's style, in this essay at least, is lucid and inviting. Substantively, Passion demonstrates not only the depth of his penetrating intellect but also his command of an array of' disciplines. Unger's polymathy is all the more impressive when we remember that ours is an era in which idiosyncratic specialization is the norm.