Licenses, Vaccines and Ebola: the Delay, Explained

Posted By Chris Laliberté

The process of researching and developing a new product, weaving it through government approval procedures, and finally bringing it to market demands a substantial investment of both money and time. This long, convoluted process affects all regulated industries, including the pharmaceutical industry. Arguably, these hurdles stand as an accepted cost that accompanies innovation in Canadian business. Pharmaceutical development differs from most other industries, however, in that millions of lives depend on the products “Big Pharma” delivers.

Given this dependency on access to effective medical materials, one would hope that, in the event of a crisis, governments and corporations would have provisions in place to cooperate and serve the best interests of the people. Unfortunately, this does not seem to be the case. Despite the urgent need to contain Ebola, experimental materials necessary to combat the spread of the disease through West Africa have been held captive by a commercial contract.

NewLink Genetics

Iowa-based company NewLink Genetics is a small pharmaceutical company that specializes in cancer immunotherapy treatment. It has “no experience bringing a product through the regulatory process and […] no vaccine production capacity of its own.” And yet, for the past 4 years, it has owned the rights to the Winnipeg-developed VSV-EBOV vaccine – an experimental vaccine that treats Ebola – under a licensing agreement with the Canadian government.

At the time the license was granted in 2010, the urgency for a vaccine seemed low. Still, given the high threat that Ebola poses to the lives of those infected by the disease, the Canadian government expected that NewLink would complete clinical trials, take the vaccine through the regulatory approval procedure, and bring VSV to market. It has not.

Little has been done in the four years since NewLink acquired the license. In fact, NewLink only began human clinical trials in the third quarter of this year. Instead, NewLink has been focused on its more profitable cancer-treatment research, as evidenced by their deal with Genentech, potentially worth over $1 Billion USD. Increasingly, it has become clear that the Ebola vaccine is simply an “afterthought” for NewLink.

At issue is a stockpile of prepared VSV doses as well as confidential details regarding the manufacturing process required for the regulatory approval process. Of 1500 doses owned by the Canadian government, 800 have already been donated to the WHO for clinical trials in Switzerland, and trials are ongoing. Those owned by NewLink would bolster the available resources to help accelerate development, if other organizations could access them and assist NewLink. The recent Ebola outbreak calls for immediate action.

Why does such a small company hold the VSV license in the first place?

The main issue seems to lie with the low commercial value of the vaccine. Prior to this outbreak, fewer than 3000 confirmed Ebola cases emerged over the past four decades; pharmaceutical giants with the tools and the bankroll to complete VSV testing in a quick and efficient manner would not risk the substantial cost for such a low return.

The sudden demand for VSV could prove in the best interest of NewLink, who think it “not unreasonable” that they should retain control over development. However, with 13,268 total cases confirmed this year, the public need for such a vaccine far outweighs any commercial interest. In this case, NewLink’s potential for financial gain seems at odds with the best interest of the affected nations and healthcare professionals whose lives are at risk.

Law professor Amir Attaran of the University of Ottawa has spoken out against the apparent idleness of the Canadian government in exercising possible options to transfer rights to the vaccine. Certain provisions in the agreement allow Canada to terminate the license if NewLink proves incapable of developing the vaccine in a satisfactory manner. Even with the license in effect, however, Canada could issue a non-commercial license to another company, or allow other manufacturers to produce VSV in response to emergencies such as the current one in West Africa. Why the government has failed to exercise any of these options remains unclear, and the source of Attaran’s frustrations.

Despite calls for action to transfer the rights into more capable hands, NewLink has retained their license and begun human trials in Maryland. A recent statement by CEO Charles Link offered some cause for optimism when he relayed NewLink’s intent to collaborate with a larger company that could “complement and enhance” VSV development.

NewLink proved true to their word Monday with the announcement of a partnership with pharmaceutical giant Merck. Merck’s international presence and wealth of experience should see the vaccine made available sooner than if NewLink had proceeded alone; critics argue, however, that earlier government intervention would have allowed the vaccine to come to market even sooner.

Policy Considerations

The NewLink situation raises concerns as to how governing bodies ought to structure agreements with private organizations while keeping public interest the primary concern. In this instance, those with the most resources—the big pharmaceutical companies—take no interest in developing a commercially unviable product, despite the necessity of this vaccine as the most effective means to contain a health crisis; on the other hand, smaller companies willing to take on the financial risk lack the resources and experience to develop the vaccine in a timely and efficient manner.

Even if the Canadian government had revoked NewLink’s license, they would still have faced the obstacle of finding a large company willing to incur the licensing fee as well as associated development costs without substantial return. While Merck’s involvement should now accelerate the development process, the cost of weeks of idleness remains to be fully understood.

If it is the government’s duty to ensure public health and safety through quick and decisive action in the event of a crisis, then perhaps in the future the government should take care that preexisting agreements do not prevent the most capable candidate from delivering the required medical materials to those in need in the most efficient manner. Commercial contracts for medical research and development should serve to hasten, not halt, the process of saving lives.

The SCC Revisits the Right to Die in Carter v Canada (Attorney General)

Posted By Sabrina Mach

Twenty-one years after upholding a criminal prohibition on physician-assisted suicide (Rodriguez 1993), the Supreme Court of Canada must once again consider the constitutionality of s. 241(b) of the Criminal Code in Carter v Canada (Attorney General). Under s. 241(b), anyone that “aids or abets a person to commit suicide” is guilty of an indictable offence and liable to imprisonment for up to fourteen years. Lee Carter and Gloria Taylor joined with others in bringing this claim challenging the constitutionality of s. 241(b) of the Criminal Code, as well as ss. 14, 21, 22, 222, and 241(a), which collectively, with s. 241(b), prohibit physician-assisted suicide in Canada. Ms. Carter’s mother and Ms. Taylor both suffered from intractable and degenerative diseases.

The Supreme Court heard the Carter case on October 15th, 2014. An overview of the main points in the lower court decisions indicates that the Supreme Court’s decision could radically change the state of assisted suicide in Canada.

Trial Court Decision

The main hurdle for Justice Smith was to assess whether or not Rodriguez was binding precedent. In Rodriguez, the Supreme Court held that s. 241(b) was constitutional because it complied with s. 7 and s. 15 of the Charter. If Rodriguez were binding, then the civil claim would fail. However, Justice Smith found that the emergence of different social facts and legal principles since the 1993 decision allowed her to re-evaluate the constitutionality of s. 241(b). She noted that the right to “life” in s. 7 was not considered in Rodriguez. Neither were the principles of fundamental justice of overbreadth and gross disproportionality. Additionally, Justice Smith found that a violation of s.15, the equality provision, was never properly found in Rodriguez; rather, it was simply assumed to have occurred and was then justified under s. 1.

With respect to s. 7 of the Charter, Justice Smith held that the right to life was engaged because the prohibition had the effect of causing some people to end their lives sooner than they would have if physician-assisted suicide were available. With respect to s. 15, Justice Smith found that the impugned provisions created a distinction on the basis of physical disability. It did so by denying physically disabled individuals access to physician-assisted suicide, which was necessary for them to commit suicide, while able-bodied individuals had no legal restrictions to committing suicide. These violations could not be saved by s. 1. The trial judge declared impugned provisions to be of no force or effect due to their violations of ss. 7 and 15 of the Charter. The declarations of constitutional invalidity were suspended for one year to allow Parliament sufficient time to draft and consider new legislation.

With regards to the risks of physician-assisted suicide, Justice Smith suggested that sufficient safeguards could be put into place, such as employing properly qualified and experienced physicians to assess the competence of patients seeking physician-assisted death, identifying inappropriate influences on the patient’s decision, as well as assessing informed consent.

Court of Appeal

The majority found that the trial judge was bound by stare decisis to apply Rodriguez. Consequently, for the most part of the judgment, the court reaffirmed the findings established in Rodriguez.

With respect to s. 7, the court held that “life” was already considered in Rodriguez in relation to liberty and security of the person. The ability to make personal decisions regarding one’s body fell under “security of the person”, which made it unnecessary for Justice Smith to consider the right to “life” under s. 7. As for s. 15, they accepted Justice Smith’s finding of a violation, but concluded that it was justified under s. 1 of the Charter. The Court applied the same s. 1 analysis as in Rodriguez, emphasizing that s. 241(b) clearly had a pressing and substantial legislative objective grounded in the need to protect human life, and that it was rationally connected to its purpose. Thus, the provision is constitutionally valid.

Although the Court of Appeal upheld the prohibition, they did suggest that the legislature should consider adding a constitutional exemption where warranted. This exemption might be in favour of “those who are clear-minded, supported in their life expectancy by medical opinion, rational and without outside influence, and protected by a court process” (para 333).

Supreme Court of Canada hearing

The Supreme Court has yet to release its own decision regarding the constitutionality of s. 241(b) and the other impugned provisions. Nevertheless, following the hearing on October 15th, many media sources have already commented on the direction the court will take:

“Government’s stance on assisted-suicide runs into skepticism from Supreme Court” (Sean Fine, Globe and Mail)

“A tough day at the Supreme Court for supporters of a ban on assisted suicide” (Emmett Macfarlane, Maclean’s)

The Supreme Court has a big decision ahead of it – to follow Rodriguez or distinguish from it. Earlier this year, Quebec became the first province to legalize physician-assisted suicide by passing Bill 52, An Act respecting end-of-life care. With the changing political and social climate regarding assisted suicide in Canada, the Supreme Court has a lot to consider. The Harper government may have to brace itself for another tough loss at the Supreme Court.

Mind the Gap: Bridging Evidence and Policy in Health

Posted By Lana McCrea

One of the big issues confronting the health system is how to translate evidence into sound policy. It sounds deceptively easy, but in reality, there is often a yawning gap between what the science says and the strategies actually implemented. The Institute for Health and Social Policy is taking on this question with its new Evidence to Policy Speaker Series in 2014-2015. What are the best ways to tame the widening gyre?

The Problem

In an ideal world, health policy would be driven by a linear model of knowledge transfer, and compelling new scientific evidence would garner swift, effective policy responses. But the actual action cycle rarely resembles the ideal paradigm. Research is often misapplied or simply ignored. Public perception skews the focus of policymakers: issues like Ebola garner attention that is wildly disproportionate to the actual risk it presents to Canadians. Practical considerations underlie these problems as well: underfunding, decentralization, and the effort required for transforming raw research into real-world applicability.

The Dangers of Knowledge Transfer

It is easy to think that more knowledge and evidence leads to better policy. But are there any hidden dangers to consider? Once published, preliminary scientific evidence can be widely and quickly disseminated through the Internet and social media. Policy decisions may be made prematurely in response, and even if the evidence is retracted from peer-reviewed sources, the ramifications can remain. For example, there was an article in Science postulating that xenotropic murine leukemia virus-related virus (XMRV) was a causative agent for chronic fatigue syndrome (CFS), which in turn triggered blood donor deferral policies targeting individuals with any history of CFS. These policies may still apply, despite the fact that the science no longer supports the association. The MMR vaccine-autism link has long been debunked, but the impact of that information is felt to this day; people are still protesting the vaccine and many parents refuse to vaccinate their children. The distribution and application of evidence is not always optimal. Cultivating a healthy dialogue and regulating knowledge transfer are essential to avoiding premature or misguided responses.

The Appetite for Progress

One of the first hurdles to confront when moving evidence to policy is the appetite for progress. As Maureen O’Neil pointed out at the IHSP launch, research will not be implemented if there is no capacity to address the issue from a political standpoint. Even the most perfect knowledge transfer mechanisms cannot ensure that sound policy will result. The federal government’s response to Insite, North America’s first safer injecting facility (SIF), could be seen as an example of this problem. The health minister would not grant Insite anything more than a 6-month extension for the legal exemption from Canada’s drug laws, despite clear scientific evidence showing the efficacy of the service. Policy remained unaffected by research. So the preliminary questions are: Where is the appetite? Are there conflicting policy considerations? How can we approach the question of why certain approaches are taken in the first place? What happens when there is no appetite for progress?

Concerns about the diminishing role of science in policymaking have provoked some political action. Proposed in December 2013, Bill C-558 would create a Parliamentary Science Officer who answers directly to members of parliament and provide them with sound information and expert advice on scientific issues. The goal is to encourage more transparent and evidence-based policymaking. The bill has not seen much success yet, but hopefully it will not be the last initiative of its kind.

Bridging the Knowledge-to-Policy Gap

The good news is that technology can be used to bridge the gap between policy and evidence by facilitating knowledge transfer. For example, Scientific Director of the Institute of Health Services and Policy Research (IHSPR), Dr. Robyn Tamblyn, spoke about their Policy Rounds. Created by the Canadian Institute of Health Research, the IHSPR hosts webinars to create a dialogue between researchers, healthcare policymakers, and other stakeholders on pressing topics. Ms. Tamblyn also spoke about the Evidence-Informed Healthcare Renewal (EIHR) Portal, which is a comprehensive repository of documents on healthcare renewal. The portal offers a single point of access to the burgeoning body of evidence that can feed policy in this domain. Lastly, the Evidence to Policy Initiative (E2Pi) created by the Global Health Group aims to facilitate the synthesis of evidence and policy by providing the tools and information necessary for policymakers to make informed decisions. Where there is a clear demand for recommendations, E2Pi steps in to translate evidence into sound strategy options.

Alternatives to Policy

Policy isn’t necessarily the best or only route for applying evidence on the ground. Influencing patterns of work by engaging motivated teams and encouraging education may be just as effective. At the IHSP talk, Maureen O’Neil spoke about the CFHI’s flagship EXTRA program, which targets health service professionals in senior management positions. The program engages nurses, physical executives, and other health administrative executives, and develops their capacity to optimize the use of research in managing healthcare organizations with the goal of increasing evidence-informed decision-making in the health system.

Going Forward

There will always be challenges when transferring evidence into policy. The key solutions seem to be facilitating dialogue, optimizing resources, and working to create a stable structure for implementing research that is both vertically and horizontally integrated.