Pharmaceutical transparency in Canada: Tired of talk

Health Canada has been talking about improving the transparency of information around pharmaceutical drugs for years. And for years the drug regulator has failed to back up that talk with commitment and action.

The lack of transparency around pharmaceutical drugs continues to undermine patient safety and public health. Unless a drug’s full safety and effectiveness profile is transparent, physicians and patients alike are at best misinformed. At worst, patients could suffer significant harm—even death—after taking a government approved, physician prescribed drug and taxpayers will be left to foot the bill.

The problem stems from the fact that lots of evidence about a drug’s safety and effectiveness is never published: sometimes because journals don’t accept it for publication, other times because the researchers and company sponsors choose not to disclose it, especially if the outcome of the study would be perceived to negatively affect sales. In other cases, it is published in a manner that does not accurately reflect what actually happened.

Government regulators do evaluate both published and non-published evidence but only in confidence with drug manufacturers—a model that has proven deeply flawed. Whether it was evidence of heart attack risks with the pain relief drug rofecoxib (Vioxx) of the late 1990s and early 2000s or studies of children and teenagers’ use of the antidepressant paroxetine (Paxil), time and again, patients have been exposed to serious risks while regulators have been slow to act, were being misled by the companies involved, or simply missed gaps in the evidence—all behind closed doors.

Greater transparency is needed so that researchers can independently assess a drug’s safety and effectiveness and doctors can examine the data to ensure the appropriateness of their prescribing, while investigative journalists and civil society at large put public pressure on regulators and industry to improve their practices.

Several countries (for example, the United States), regulators (for example, the European Medicines Agency), and international institutions (for example, the World Health Organization) have made important transparency commitments followed by concrete action. Transparency remains a work in progress, but laws have been put into place and are beginning to be enforced.

In contrast, until recently, Canada has done little more than talk. Following numerous parliamentary committees, auditor general reports, journalist investigations, and academic researchers calling for greater transparency, Health Canada has offered up several supposed transparency initiatives. But each has failed to deliver meaningful change.

In late 2014 Canada’s parliament finally made a commitment to improving transparency around pharmaceutical interventions by enacting “Vanessa’s Law.” Inspired by the death of former MP Terence Young’s daughter, Vanessa, the law gives the minister of health and in turn Health Canada several new and important powers in the name of patient safety. This law has great promise to finally turn things around and open up the black box of medicines’ safety in Canada.

One provision in Vanessa’s Law, section 21.1(3)(c), gives the minister of health the power to disclose information that companies and Health Canada have kept confidential to any person “who carries out functions relating to the protection or promotion of human health or the safety of the public” provided thatthe purpose of the disclosure is related to the protection or promotion of human health or the safety of the public.

Section 21.1(3)(c) is discretionary: the minister may disclose such information. It also treats—in our view wrongly—clinical data as “confidential business information” (CBI), thereby confirming secrecy as the norm. However, the provision is otherwise worded very broadly. It has the potential to open up reams of information that companies and the regulator have—again, wrongly—treated as private property for decades. Unless and until parliament explicitly excludes unpublished drug studies as CBI, section 21.1(3)(c) has a critical part to play in fostering greater transparency.

Once again though, Health Canada is threatening to undo Vanessa’s Law’s commitment to transparency. In March it published its draft guidance about how it intends to interpret section 21.1(3)(c), cementing an approach that has already stymied access to safety and effectiveness drug information.

Contrary to the provision’s broad wording and the purpose of Vanessa’s Law, Health Canada’s draft guidance narrows who is eligible to ask for drug information, while requiring the few that the regulator deems eligible to make a request to sign a strictly worded confidentiality agreement and demonstrate efforts to obtain the information from “all other possible sources” before receiving the information.

In response to Health Canada’s call for public commentary on its draft guidance, we wrote and coordinated a series of submissions—from clinicians and researchers, representatives of civil society, and legal scholars—calling on Health Canada to remove these limitations and exclude drug safety and effectiveness from the category of CBI. The draft guidance is, in legal terms, deeply flawed and may violate the Charter of Rights and Freedoms.

Unless Health Canada listens to our submissions, Vanessa’s Law will become just the latest example of transparency talk rather than concrete commitment and action. At that point continuing to talk transparency will itself become harmful, obscuring the absence of real change.

Health Canada must return to the drawing board. Canadians have a right to know how safe and effective—or unsafe and ineffective—their medicines are. Anything less will come at a great cost to patient safety and public health.

Matthew Herder, associate professor, Health Law Institute, Faculties of Medicine and Law, Dalhousie University, Canada. Twitter: @cmrherder

Trudo Lemmens, professor and scholl chair in health law and policy, Faculties of Law and Public Health and Joint Centre for Bioethics, University of Toronto. Twitter: @TrudoLemmens

Joel Lexchin is currently a professor in the School of Health Policy and Management at York University in Toronto, Canada, where he teaches health policy. In addition, he has worked in the emergency department at the University Health Network, also in Toronto, for 28 years. He is the author or co-author of over 150 peer-reviewed articles on a wide variety of topics concerned with Canadian and international pharmaceutical policy.

Barbara Mintzes, senior lecturer, Charles Perkins Centre and Faculty of Pharmacy, The University of Sydney.

Tom Jefferson, honorary research fellow, Centre for Evidence Based Medicine, Oxford.

Competing interests:

Matthew Herder is the principal investigator on a grant awarded by the Canadian Institutes of Health Research (EOG 123678) entitled “Emerging health researchers and the commercialization of academic science.” MH is a member of the Health Policy Translation research group of the Canadian Center for Vaccinology (CCfV), which has carried out a number of clinical trials sponsored by vaccine manufacturers. MH has not been involved, in any way, with the conduct of these trials, nor received any funds from CCfV to carry out research. He has no other personal, organisational, or relational conflicts of interest to disclose.

Trudo Lemmens presented in 2016 as a plenary speaker on the regulation of research ethics review at a symposium organised by La Asociación de Médicos Especialistas en la Industria Farmacéutica, A. C. (Ameifac), CANIFARMA (Cámara Nacional de la Industria Farmacéutica), and the Universidad Autonoma de Mexico. His travel and hotel costs in Mexico were paid by the organisers; TL asked the speaker fee to be forwarded directly by the organisers to a Mexican indigenous social advocacy organisation.

Joel Lexchin has no competing interests to declare.

Barbara Mintzes has acted as an expert witness for the legal teams representing plaintiffs in two Canadian class action suits: on hormone replacement therapy and breast cancer risks, and on testosterone and cardiovascular risks. She has no additional competing interests to declare.

Tom Jefferson was a co-recipient of a UK National Institute for Health Research grant (HTA – 10/80/01 Update and amalgamation of two Cochrane Reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children—http://www.nets.nihr.ac.uk/projects/hta/108001).

TJ receives royalties from his books. TJ is occasionally interviewed by market research companies about phase I or II pharmaceutical products. In 2011-13, TJ acted as an expert witness in a litigation case related to oseltamivir and in a labour case on influenza vaccines in healthcare workers in Canada. He has acted as a consultant for Roche (1997-99), GSK (2001-2), Sanofi-Synthelabo (2003), and IMS Health (2013) and in 2014 was retained as a scientific adviser to a legal team acting on oseltamivir. In 2014-15 TJ was a member of two advisory boards for Boerhinger. He is a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial.

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  • Larry D. Sasich

    Pharmaceutical Transparency in Canada: Tired of Talk

    The recent posting appearing in the BMJ Blogs [1] notes that predictably the effective implementation policies to improve clinical trial transparency in Canada through the passage of Vanessa’s Law appear to be failing. Unfortunately and indefensibly this will continue to leave the Canadian public in the dark about the safety and efficacy of many of the drugs they are prescribed.

    Suggestions to improve transparency through Vanessa’s Law seem to be stymied by the definition of Confidential Business Information (CBI) that Health Canada relies on to withhold clinical trial information from the public. A similar prohibition exists in the US for the release of what is called Confidential Commercial Information. In the US, the release of detailed analyses of clinical trials submitted to the FDA in support of new drug approvals, including unpublished trials and analyses, is achieved by recognizing that the data submitted by sponsors belongs to sponsors and is not released. However, the FDA’s detailed analyses of new drug applications must be placed in the public domain by law. Is such a strategy possible in Canada?

    Rofecoxib (Vioxx) is cited as a failure of the US system regarding the disclosure of the cardiovascular risks of this drug, which it certainly was. The failure to disclose this information appeared to be sponsor driven and political, as the FDA reviewers were concerned about the safety of the drug during the early review of rofecoxib. [2] Ultimately, Congressional hearings were conducted on the rofecoxib issue. Now, all patients receiving a non-steroidal anti-inflammatory drug (NSAID), the same class as rofecoxib, are required to receive FDA approved written safety information for patients with each new and refill prescription that includes the cardiovascular risks of these drugs.

    Also, cited as a transparency failure is Study 329 that examined the use of the antidepressant paroxetine (Paxil) in children and adolescents. This study concluded that the drug was safe and effective in these age groups.[3] A reanalysis of this trial was published in 2015 that came to an opposite conclusion compared to the original published study [3] and confirmed what was publically first known about the drug in the US since 1998.

    This was certainly not a regulatory failure but rather the failure of prescribers to read the FDA approved professional information for this drug. The drug was being prescribed for an unapproved disapproved use in younger populations. In the US, this drug was never approved for depression in children and adolescents and the FDA refused approval for the use of paroxetine in younger populations. This information is freely available in FDA documents and the professional product label for the drug. [4,5]

    What should be suggested for Canadian consumers until Health Canada improves drug transparency? Perhaps drug safety and consumer advocates can provide the motivation to Health Canada by recommending accessing FDA approved professional labels at https://dailymed.nlm.nih.gov/dailymed/ and safety information for over 200 drugs at http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm.

    References

    1. Herder M, Lemmens T, Lexchin J, Mintzes B, Jefferson T. Pharmaceutical Transparency in Canada: Tired of Talk. The BMJ Blogs June 6, 2016. At

    http://blogs.bmj.com/bmj/2016/06/06/pharmaceutical-transparency-in-canada-tired-of-talk/. Accessed June 7, 2016.

    2.Testimony of David J. Graham, MD, MPH before the United States Committee on Finance, November 18, 2004. At http://www.finance.senate.gov/imo/media/doc/111804dgtest.pdf. Accessed June 7, 2016.

    3. 2. Keller MB, Ryan ND, Strober M, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry Jul 2001;40(7):762-772.

    3. Le Noury J, Nardo JM, Healy D, et al. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015; 351: h4320.

    4. Dubitsky GM. Food and Drug Administration Review and Evaluation of Paroxetine Controlled Released Tablets, July 17, 1998. At http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-936_Paxil_medr_P1.pdf. Accessed June 7, 2016.

    5. Apotex Corp. Professional Product Label: Paxil CR (Paroxetine), June 2014. At http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=483bd97f-c4d0-4e23-aaa8-6334f4471e0c. Accessed June 7, 2016.