Matthew Herder

Unlocking Health Canada’s cache of trade secrets: mandatory disclosure of clinical trial results

Health Canada should publicly disclose information about the safety and efficacy of pharmaceuticals, biologics and medical devices, and should especially disclose the designs and results of clinical trials. This disclosure is necessary to preserve public trust, address weaknesses in the evidence base, and protect Canadians from harm.A prime example of the need for this disclosure involves selective serotonin reuptake inhibitors (SSRIs). Health Canada did not authorize SSRIs for sale to people younger than 19 years because of data from clinical trials showing risks of harm, including self-harm, associated with use of SSRIs in that age group. But Health Canada also did not publicly disclose that evidence, and by 2004 SSRIs were being widely prescribed for teenagers. Physicians had no idea they were invoking their discretion to prescribe “off label” on the basis of incomplete information — the balance of which Health Canada had in hand.Assessing how often harm results from nondisclosure is difficult because reporting of adverse events remains poor. What is clear from several analyses is that there is often a chasm between the published scientific literature (which is biased toward positive results) and the information that regulators possess about a given drug.Why does Health Canada not divulge information from clinical trials until reports surface of widespread off-label prescribing? The reason is legal: the companies that manufacture these therapeutic products and devices claim that information is “confidential business information” or a “trade secret,” which they own, and which Health Canada is not free to disclose.I witnessed this pas de deux while attending Health Canada’s “technical discussions on regulatory modernization” held between October 2010 and January 2011. Each proposal put on the table by Health Canada to increase transparency — from making final decisions regarding applications for market authorization publicly available, to creating an online register of therapeutic products — was met with proprietary claims from MEDEC, BIOTECanada or Rx&D, the respective associations of medical device, biotechnology and pharmaceutical companies in Canada. Each time, Health Canada acknowledged that the law controlled what they could and could not disclose.In this article, I argue that the law, in fact, poses a minimal barrier to the disclosure of the designs and results of clinical trials. I begin by illustrating Health Canada’s tendency to keep third-party information secret, then show why — insofar as protecting third-party information has prevented the disclosure of the designs and results of clinical trials — this goes beyond what the law requires, in principle. I go on to highlight institutional barriers to changes in policy.

Regulating prescription drugs for patient safety: Does Bill C-17 go far enough?

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.[1

Who will implement WHO's statement on public disclosure of trial results?

www.thelancet.com Vol 385 June 13, 2015 2353 developed countries, after all cancers combined and other cardiovascular causes. When professional emergency medical services arrive after cardiac arrest—which can be after 8–12 min or more—the brain has already started to die. Thus, a time window for lay resuscitation exists. In 60–80% of cases, a lay bystander witnesses the cardiac arrest, and 60–70% of cases occur at home. Lay resuscitation can fill the gap between cardiac arrest and arrival of emergency medical services in most cases. In fact, initiation of resuscitation by a lay bystander is associated with a two to four times increase in neurologically intact survival. Perhaps more than 100 000 deaths per year could be prevented if members of the public, beginning with school children, were educated about how to do CPR. In countries where educating school children in CPR is mandatory, lay resuscitation is done in 60–75% of cases, and survival after out-ofhospital cardiac arrest can be tripled. Inspired by, and on the basis of this information, the European Patient Safety Foundation, the European Resuscitation Council, the International Liaison Committee on Resuscitation, and the World Federation of Societies of Anesthesiologists developed their joint “Kids Save Lives” statement for training of school children worldwide in CPR. We asked WHO to lend support to this statement. On Jan 13, 2015, we received a letter from WHO stating that “...approval has been granted for the WHO to endorse the statement on Kids Save Lives”. We recommend in this statement that school children be educated in CPR from the age of 12 years or younger for 2 hours per year. This endorsement will help to save thousands of lives worldwide, thanks to many individuals, colleagues, organisations, initiatives, and the WHO.

Orphan drug incentives in the pharmacogenomic context: policy responses in the USA and Canada

INTRODUCTION The US Orphan Drug Act1 is a policy response to diseases that have been orphaned under ordinary market conditions, and thus remain unmet medical needs.They create special, streamlined regulatory pathways and incentives such as grant funding, tax credits, and market exclusivity in order to encourage drug researchers and firms to develop interventions that address these unmet medical needs. As with any system of incentives, concerns have been raised about ‘noise’ in the system from the start of the orphan drug regime.2 The worry is that firms will take advantage of the increased knowledge they have (relative to regulators) about the safety and efficacy of a drug and its potential impact on one ormore forms of disease in order to securemultiple orphan drug designations and approvals, extracting greater revenues over time.This is known as ‘salami slicing’.3 The classic example is Epogen, an orphan drug approved in 1989 to treat anemia linked to end-stage renal disease but subsequently widely prescribed for all kinds of anemia, quickly becoming a blockbuster drug.4 Several commentators have suggested that the shift toward ‘pharmacogenomics’ in drug research anddevelopment (R&D)portendsmore salami slicing.5Theclaim is that findings from genomics and related fields of research will make it easier for industry

Against vaccine assay secrecy

Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canadas access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors.

Toward a Jurisprudence of Drug Regulation

Efforts to foster transparency in biopharmaceutical regulation are well underway: drug manufacturers are, for example, legally required to register clinical trials and share research results in the United States and Europe. Recently, the policy conversation has shifted toward the disclosure of clinical trial data, not just trial designs and basic results. Here, I argue that clinical trial registration and disclosure of clinical trial data are necessary but insufficient. There is also a need to ensure that regulatory decisions that flow from clinical trials - whether positive (i.e., product approvals) or negative (i.e., abandoned products, product refusals, and withdrawals) - are open to outside scrutiny. Further, a jurisprudence of drug regulation is needed. I develop two arguments motivated by (1) innovation concerns and (2) the value of good governance in support of openly publishing all final decisions for approved, abandoned, refused, and withdrawn products. After articulating why greater transparency in regulatory decision-making is needed, I distil four essential features of a jurisprudence of drug regulation that prescribe policy changes in terms not only of the transparency of regulatory outcomes and the underlying reasoning, but also regulatory organization.

Policy Design for Human Embryo Research in Canada: 1989–2015

In Canada, research involving human embryos is circumscribed by law and research guidelines. This chapter describes the development of these policy instruments over the past 20 years and analyses this history using a typology of modes of public consultation developed by Eric Montpetit. (2003) Over time, the degree to which the views of Canadian residents and citizens on human embryo research have been solicited as part of the policy-making process has diminished significantly. We expect this trend to continue given the presence of powerful interest groups and policy communities “speaking for” Canadians.

Fair pricing of “old” orphan drugs: considerations for Canada’s orphan drug policy

New Canadian regulations for orphan drugs are expected soon, after implementation of the orphan drug framework proposed in 2012 was delayed because of patient safety legislation that has now passed.[1][1] Traditionally, laws for orphan drugs have been intended to encourage research and development

Cancer Genomics and Biobanking: Exploring Key Ethical and Legal Issues

Large-scale cancer genomics research projects raise a range of ethical and legal issues. We focus on two emerging themes challenged within genomic research: (1) issues surrounding the return of research results to research participants, whether in summary or individualized form, and (2) issues connected to the commercialization of research, including the patenting of biomedical discoveries and biological materials. We examine current thinking in these areas and highlight areas for further exploration.Large-scale cancer genomics research projects raise a range of ethical and legal issues. We focus on two emerging themes challenged within genomic research: (1) issues surrounding the return of research results to research participants, whether in summary or individualized form, and (2) issues connected to the commercialization of research, including the patenting of biomedical discoveries and biological materials. We examine current thinking in these areas and highlight areas for further exploration.

Proprietary Interests and Collaboration in Stem Cell Science: Avoiding Anticommons, Countering Canalyzation

In this chapter I explore how proprietary interests and commercialization norms can impede collaboration in stem cell science. I begin by outlining three layers of property in stem cell science—stem cell data, stem cell materials, and stem cell patenting—and explain how they are intertwined in practice. I then present two stem cell research initiatives, the Cancer Stem Cell Consortium (CSCC) and Stem Cells for Safer Medicines (SC4SM). Using two conceptual frames, the “tragedy of the anticommons” and “patent canalyzation,” I analyze the extent to which the CSCC and SC4SM appear to address proprietary or commercialization-related impediments to collaboration. Whereas the anticommons frame, and empirical methodologies it has spawned to date, tends to capture costs imposed upon the scientific fields as a whole, patent canalyzation focuses on the individual scientist, hypothesizing that patenting and other commercialization behaviours may (re)constitute the scientific self. The chapter concludes by highlighting three intellectual property-related best practices intended to facilitate collaboration in stem cell science.