Medical Records — Dossiers médicaux

Posted By Lauren Hanon & Prof. Shauna Van Praagh

In the McGill Journal of Law and Health’s pilot episode of Medical Records, Journal Executive Lauren Hanon interviews Professor Shauna Van Praagh on the legal and social issues that arose surrounding the events of the tragic death of Éloise Dupuis in October of last year. In this episode, Professor Van Praagh discusses informed consent, the right to refuse treatment, religious freedom, and how we, as a society, engage with these issues when there are conflicts between what is right in law, and what feels right morally.

New Policies On the Horizon for Clinical Trials Data Sharing: Is the McGill Community Ready?

Posted By Adrian Thorogood

The International Committee of Medical Journal Editors (ICMJE) recently proposed that journals should require researchers to share patient-level data from clinical trials as a condition of publication. Full disclosure of supporting facts has long been “the bedrock for scientific discourse”. Open science – making research data accessible to a broader community of scientists – is enjoying a renaissance in this era of cloud computing and infrastructure science. The ICMJE joins a chorus of researchers, research institutions, funding agencies, and regulators calling for open and timely clinical trials data sharing, in order to accelerate biomedical innovation and enhance scientific transparency. How will this policy sea change affect innovation, the obligations and careers of researchers, and the privacy of participants?

On Thursday, October 27th, 2016 the Faculty of Medicine’s Research Ethics Office (Institutional Review Board) convened a forum of researchers and ethicists to discuss clinical trials data sharing. The forum was chaired by Dr. Shari Baum (Associate Dean Research – Faculty of Medicine) and organized by Sacha Young (Ethics Review Administrator). Speaker presentations are available here.

Ms. Jane Burpee, who leads research data curation services at the McGill Library, began by recounting shocking tales of fraud in biomedical science. Researchers topping the charts of infamy on RetractionWatch.com built successful careers on fraudulent science. And they would have gotten away with it, too, if it wasn’t for a gang of meddlesome researchers who inspected the raw data. In sum, can we really trust research results without access to all the data: the summary (peer reviewed article), the code and the raw data?

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The quality and reliability of published research depends on peer review of not just the findings, but also the clinical trials data that support them. || (Source: B.A. Nosek et al. | Science 2015:348)

The Canadian research community is waking up to the possibility of a data sharing policy. The Tri-Council Agencies’ 2016 Statement of Principles on Digital Data Management gives helpful guidance, while pointing out that infrastructure and support needs to be established before data sharing policies are implemented. McGill Library Research Data Service and the Canadian Association of Research Libraries are working tirelessly through collaborations like the Portage network to encourage researchers to preserve, annotate, and share their data responsibly.

Dr. Serge Gauthier – McGill Professor in the Departments of Neurology & Neurosurgery, Psychiatry, and Medicine, and Director of the Alzheimer Disease and Related Disorders Research Unit of the McGill Center for Studies in Aging – shared his perspectives on ethical aspects of data sharing in dementia research, gained through his experience with the Canadian Consortium on Neurodegeneration in Aging (CCNA). The CCNA is a Canadian Institutes of Health Research (CIHR)-funded five-year study following a diverse cohort of 1600 subjects.

The CCNA plans to give primary investigators one year to analyze the data before sharing with the wider scientific community. Agreements will be in place for sharing of both data and samples to ensure users protect the privacy of participants and acknowledge the contributions of the biobank. How should researchers identify and communicate “clinically meaningful findings” to participants, especially when samples and data may be shared and re-analyzed for decades? Guidelines determining clinical relevance are liable to change over time. Further, how should disclosure rules and processes be explained to participants when obtaining consent?

Professor Richard Gold, James McGill Professor at the Faculty of Law, who specializes in intellectual property in the life sciences, addressed ethical transparency in open science. While the primary goal of openness is to accelerate research speed, it can also improve the monitoring of research. However, participants will not know, at the time of consent, what research will be conducted, by whom, and for what goals; all of these points raise questions about informed consent. Professor Gold chairs an independent committee to oversee the McGill Neurological Institute’s “open science” policy.

How should researchers identify and communicate “clinically meaningful findings” to participants, especially when samples and data may be shared and re-analyzed for decades?

The MNI’s policy is to make all data (including models and code) publically available when the first article on a dataset is published, even where the data is generated through industry partnerships. The MNI policy discourages researchers from patenting and does not provide them institutional support to do so. The MNI recognizes that it is itself an experiment in innovation. Will openness increase the use of MNI data and materials? Attract sustainable funding, and leading researchers? Lead to new innovation? Inspire other institutions to follow the MNI’s lead?

I spoke to the inherent tensions between openness and participant privacy. This tension often preoccupies research ethics boards (REBs) who oversee open science protocols. Indeed, data sharing calls into question assumptions that research data can be kept anonymous and confidential. Is anonymity feasible – or even desirable – in a Big Data era, where research is fueled by voluminous individual-level data, linked across various sources, and tracked over time? Is confidentiality meaningful where research data is available to wide communities of scientists, bound together by loose organizational relationships and immature IT networks?

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Granting peers access to clinical trial data is an essential step in the life-cycle of data management for clinical trials. || (Source: Matthias Töwe | ETH-Bibliothek)

In light of these uncertainties, how do REBs oversee data sharing? They may be able to assess data sharing plans, to ensure security safeguards and accountability mechanisms are in place. They could also assess data sharing plans to ensure data will be made available in a timely and streamlined fashion. To hold researchers accountable for openness, REBs could even withhold approvals from researchers who consistently fail to share data that has consent to be shared.

The questions posed to the panel reflected a mix of enthusiasm and anxiety about data sharing among the McGill community. While data sharing principles have been articulated, many attendees were unsure what data sharing will mean in practice for innovation, researchers, and patients. What does “open” really mean? What types of data will be shared, with who, and when? What technical infrastructure and governance structures are needed? Who will pay for it? Will researchers be encouraged to share, or forced to do so? How will generation of valuable research data be recognized and rewarded? What incentives will be in place for researchers to share?

There are many possible directions. Funders could inspect investigators’ history of sharing and the quality of data sharing plans during grant applications. An “impact factor” could be developed to measure a researcher’s contribution of valuable data to the research community. To make it easier to identify researchers who fail to share, policies can include a clear deadline (e.g. data must be shared within 18 months of publication). This makes it easy to identify who has failed to share in a timely manner, but may not offer flexibility for different research contexts. Data quality was another prominent concern. Publications are peer reviewed, but there is no clear arbiter for the quality of individual-level patient data shared through a repository.

The emergence of citizen science presents new opportunities for individuals to engage with research, by sharing their health data through web portals, or by accessing and analyzing datasets. This raises new questions about the bounds of “openness”: who can be trusted to use clinical trials data appropriately, and keep it safe?

Data sharing also impacts the relationship between researchers, participants and society. It remains unclear if participants in clinical trials will be given a choice to opt-out of data sharing, or if sharing will be a mandatory component of participation. Special considerations are needed for data generated through partnerships with developing countries that emphasize benefit sharing and capacity building. The emergence of citizen science presents new opportunities for individuals to engage with research, by sharing their health data through web portals, or by accessing and analyzing datasets. This raises new questions about the bounds of “openness”: who can be trusted to use clinical trials data appropriately, and keep it safe?

While it is still early days for clinical data sharing, it is reassuring to see that there is already a diverse and passionate community at McGill keen to move towards open science. It is time we aligned our efforts.Adrian Thorogood is Coordinator of the Regulatory and Ethics Working Group of the Global Alliance for Genomics and Health, a public-private consortium developing technology and forward-looking policies to promote the international sharing of genomic and health-related data. (Bio.)

Three’s a crowd? Three-Parent Babies and the Future of Assisted Reproduction in Canada

Posted By Liam Harris

Earlier this year, a team of doctors successfully carried out a new fertility technique that resulted in the birth of a child containing the genetic information of three people: the mother, the father, and a female donor. The technique allowed the intended parents to have a healthy baby after all of their previous children had died of Leigh syndrome, a debilitating neurological disease.

However, the mitochondrial replacement technique (MRT) remains highly controversial, both medically, due to unknown side-effects, and ethically, because the donor’s genetic information will be passed on to future generations. In fact, American doctors performed this procedure in Mexico to bypass an American ban. MRT is illegal in Canada under the Assisted Human Reproduction Act (AHRA), but other jurisdictions such as the UK have legalized the technique.

What are the risks and benefits of MRT? And what can these developments tell us about our reproductive legal regime in Canada?

The Science

The vast majority of human genetic information is carried in the cell’s nucleus. However, there is also DNA contained in sub-cellular structures called mitochondria. Unlike nuclear DNA (nDNA), mitochondrial DNA (mtDNA) is inherited exclusively from the mother. While mtDNA accounts for a very small portion of the genome (about 1%), mutations in these genes can cause serious disease due to the mitochondria’s critical role in cellular energy generation and signalling.

Leigh syndrome is one of these diseases. Patients with Leigh syndrome experience a progressive loss of movement and neurological function. This decline often begins in early childhood, resulting from the inability of their neurons to metabolize energy effectively. These patients will rarely live more than a few years.

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This new procedure allows prospective parents to conceive a child from their own genetic materials without the risks carried by faulty mitochondrial DNA. || (Source: CBC News)

MRT aims to prevent Leigh syndrome in the children of mothers carrying mutant mtDNA genes. The mother’s egg is harvested and the nucleus, which contains the vast majority of genetic information she would pass to her child, is removed. The rest of the egg, including the disease-causing mitochondria, is discarded. The nucleus from the mother is then inserted into a donor’s egg. This hybrid egg, containing the mother’s nDNA and the donor’s mtDNA, is then fertilized by the father’s sperm, resulting in an embryo that is implanted in the mother through in-vitro fertilization (IVF). The result is a child whose nDNA comes from both parents, but with a mitochondrial genome inherited from a third party. This genetic material will, in turn, be passed on to future generations if that child is female and has biological children of her own.

The Risks

Opposition to MRT is based on two main arguments, one medical and one ethical. First, because the technique is new, its side effects are heretofore unknown. Some suggest that it could result in higher rates of cancer or early aging. While experts have no evidence showing the technique to be unsafe, uncertainty persists.

The result is a child whose nDNA comes from both parents, but with a mitochondrial genome inherited from a third party. This genetic material will, in turn, be passed on to future generations if that child is female and has biological children of her own.

Second, critics decry the alteration of the genome in a way that can affect future generations. Slippery slope arguments suggest that this is the first step down a road to “designer babies”, where parents modify the genome of their offspring to meet their every whim. In the case of MRT, it is important to remember that mtDNA accounts for only a tiny portion of the genome and that these genes control basic cellular functioning rather than the types of defining traits often pictured in the case of designer babies. This concern may therefore prove less relevant to this particular genetic change. However, caution is warranted whenever a heritable alteration occurs, because this permanently changes the composition of the gene pool, recognized as the common heritage of humanity.

The Law

The replacement of the egg’s mtDNA with that of the donor alters the genome in a way that is potentially inheritable, placing the technique within the ambit of prohibited practices in Canada. Section 5(1)(f) of the AHRA states that “[n]o person shall knowingly alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants”. Doctors carrying out the procedure in Canada could face harsh penalties: up to $500,000 and a ten-year prison term.

The outright criminalization of heritable genetic alterations seems less and less tenable as new techniques are developed that offer significant medical benefits and manageable risks. In addition to MRT, recent advances in human gene editing have fuelled hopes that inheritable genetic diseases could be eradicated forever, but these procedures would be prohibited under the AHRA for inducing inheritable genetic alterations.

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Doctors combine the mother’s nucleus, the donor’s egg, and the father’s sperm to produce a viable embryo for the mother to carry to term. || (Source: Science News)

Meanwhile, the promise of these techniques has begun to attract legislative and regulatory attention worldwide. Last year, the UK Parliament carved out a specific exemption from its prohibition to allow MRT. This legislation addresses a number of practical matters, including the right of the child to request medical information about the donor, and it clarifies that the child is not related to the donor despite the contribution of genetic information. Earlier this year, a report commissioned by the FDA recommended allowing clinical trials of MRT in the United States.

This technique and others like it certainly merit close regulatory attention due to the implications they have for our collective genetic heritage and the uncertainty regarding their side-effects. However, it is impossible to ignore the treatment potential of these techniques in the case of diseases like Leigh syndrome. These developments shine a negative light on the restrictive reproductive landscape in Canada. The embattled AHRA provides neither the flexibility nor the clarity needed to confront these new regulatory challenges. Patients, medical professionals, and the public deserve clear rules that properly manage the risks while securing the benefits associated with this promising new medical frontier.

Improving Organ Donation Rates in Canada: Barriers & Solutions to Federal Involvement

Posted By Jonathan Adessky

Canadians have increasingly been donating organs over the past ten years. Shouldn’t we be celebrating? According to the Canadian Blood Services’ early September report, Canada has seen a 23% increase in donations over the past decade. While this is definitely good news, we mustn’t be fully satisfied with our country’s progress on donation rates. According to the International Registry on Organ Donation and Transplantation, Canada lags behind its contemporaries by a large margin. This leads us to wonder: what are we doing wrong? How can Canada catch up to organ donation levels in other Western, industrialized nations?

Canadian Blood Services is a non-profit organization that manages and coordinates national blood and organ donation. We should take pride in the impressive results of their work. According to the organization’s 2015 report, “the national deceased donation rate has risen from 14.1 to 18.2 donors per million population (DPMP)” since 2006; most would agree this counts as an achievement. Nonetheless, the fact remains: Canada has some catching up to do.

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An increasing number of Canadians have registered as organ donors over the past ten years. Shouldn’t we be celebrating?|| (Source: Flickr // Share GK)

The question remains: how and to what extent can the Federal Government help further Canada’s progress? At least one Canadian parliamentarian, Ziad Aboultaif, believed that a federally mandated organ donor registry would help drive growth in the donation rate. In drafting this bill, he put his heart into his work; or, more accurately, his liver, a piece of which Alboutaif donated to his son. The proposed bill intended, in part, to establish a national promotion strategy for organ donation. The Minister of Health would be tasked with producing an annual report detailing the success level of the previous year’s strategic plan, with a set of recommendations for further improvement.

Despite broad support for the its stated goals, Aboultaif’s proposed private member’s bill was defeated in June. Parliament faced a major obstacle in that organ donation falls ultra vires federal jurisdiction. One doesn’t need to consult a learned lawyer to reach such a conclusion; a glance at the Constitution Act, 1867 would suffice. Provincial authority over matters relating to organ donation flows from jurisdiction to legislate on hospitals, as per section 92 of the Act.

Given these constitutional limitations, what role can the Federal Government play in furthering Canada’s progress promoting interest in organ donation? Records of the House debate indicate strong moral support for the Bill; for example, Kamal Khera, Parliamentary Secretary to the Minister of Health, admits that Aboultaif’s initiative is worthy of praise. She elaborates on how the Trudeau government is committed to further supporting the Canadian Blood Services, and how a formalization of the existing interprovincial sharing guideline is underway. Clearly, Ottawa is determined to help reform the system, but the ‘how’ remains murky.

Parliament faced a major obstacle in that organ donation falls ultra vires federal jurisdiction.

According to Canadian Blood Services, most of the provinces already have high registration rates. To add to that, CEO Dr. Graham Sher states that a federally-coordinated national registry alone may prove insufficient to realize the projected gains. If this holds true, the Federal Government need not worry about organizing a centralized registry; a truly daunting task. What alternatives can Ottawa turn to in its efforts to improve the organ donation system, besides the creation of a registry?

International best practice comparisons may prove useful in this endeavour; for example, one might wonder how Spain’s DPMP rests at more than double that of Canada, at a rate of 39.7. The key to Spain’s success may result from the manner in which its intensive care units operate. Kim Young, director of donation and transplantation for Canadian Blood Services, points to the staffing of Spanish ICU facilities with donation specialists as a the key to their success. Clearly, it would be wise and fair to make this approach a priority in tackling subpar growth in Canadian organ donation.

Ottawa has proven generous in directly funding third party organizations, and where money flows, influence follows. This relationship holds true especially as organizations depend more and more on these funds in their financial planning. Since 2008, the provinces and the Federal Government have collectively invested $64 million in the Canadian Blood Services. While the aforementioned constitutional limitations restrict Parliament from direct intervention, Ottawa is still in a good position to effect change from the sidelines.

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Jurisdictional boundaries do not necessarily fence off healthcare from federal involvement. || (Source: Flickr // mhambourger)

The weight placed on federal input is largely driven by its generosity and on the system’s dependence on external financial contributions. If the Canadian government wants to advance a strategic plan, its voice will surely be heard as it continues to provide funding. If the Trudeau government is as passionate about the issue as Khera makes it out to be, then it will consider reworking its strategy. Federal funding ought to entail guidelines that factor in best practices established by medical professionals in Spain.

Through deconstruction of the issue at hand, a subtle and important insight emerges: jurisdictional boundaries do not necessarily preclude federal involvement in healthcare. Yes, these matters fall under provincial jurisdiction. No, the Federal Government cannot directly manage national programs that clearly fall outside of its jurisdiction. Just because it cannot hop the constitutional fence, however, what barrier exists to prevent federally-supported third-party charities from taking action where the government cannot?

Saved By Delatestryl: The Importance of Accessible Hormone Replacement Therapy (Part 2)

Posted By Florence Paré

In last week’s segment, I explored the various extra-legal barriers to accessing hormone replacement therapy for trans individuals, for whom hormones are an essential part of their psychological and physical well-being. The discretion held by the provincial government over insurance coverage of prescription drugs also poses a significant risk to access to hormones, as there is a concern that the government will decide to delist hormones from provincial insurance coverage.

The potential delisting of hormones from insurance coverage is a recurrent fear in trans communities. At the political level, this seems unlikely, as trans rights have entered the progressive collective consciousness and cannot be openly opposed by governments who wish to appear progressive. Furthermore, insurance coverage for medication is largely done on a per-medicament basis, rather than based on the reason for the prescription, and drugs used in hormone replacement therapy are frequently used for other purposes, such as treating polycystic ovary syndrome or hypogonadism, both fairly common illnesses.

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Many trans Canadians choose hormone replacement therapy to help manage dysphoria. Given the disproportionate financial disadvantages trans Canadians face, delisting hormones would further threaten their safety and well-being. || (Source: Susan Bein // wizmosis)

Delisting hormone treatments could arguably be contrary to the Canadian Charter of Rights and Freedoms and to the Québec Charter of Human Rights and Freedoms, CQLR c. C-12. The Canadian Charter prohibits discrimination on the basis of sex at section 15. Human rights tribunals across Canada have long held that the term “sex” in human rights acts includes transgender persons, and would otherwise almost certainly be protected as an analogous ground of discrimination (Andrews v. Law Society of British Columbia, [1989] 1 SCR 143).

In Québec (whereas in the past trans persons have been protected from discrimination under the basis of “civil status”, “disability”, or “sex”) gender identity and expression are explicitly included in the Charter‘s section 10 as of June 10th, 2016.

The potential delisting of hormones from insurance coverage is a recurrent fear in trans communities.

The delisting could also be challenged through judicial review of administrative action. A serious argument can be made under either Charter, most notably pursuant to the Canadian Charter which includes a proportionality criterion (Loyola High School v. Quebec (Attorney General), 2015 SCC 12, [2015] 1 SCR 613 at paras. 38, 40): a slight cost reduction compared with the totality of Public Drug Insurance expenditures is hardly proportional to the lives and well-being of trans people, given that trans people account for less than 0.6% of the total population, and not all trans people wish to take hormones. The Supreme Court of Canada’s decision in Eldridge v. British Columbia (Attorney General), [1997] 3 S.C.R. 624 also supports this argument.

Hogan v. Ontario (Health and Long-Term Care), 2006 HRTO 32, 58 CHRR 317 shows how uncertain guarantees under the Canadian Charter and Québec Charter can be with regards to trans healthcare. While the delisting of genital reassignment surgery in Ontario was found to be prima facie discriminatory, and would likely also have been found discriminatory under the Canadian Charter, it was saved by the bona fide justification analysis.

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Trans rights groups have long battled for the human rights protections now entrenched in Canadian law. Governments have a duty to stand by these protections, including access to healthcare. || (Source: Wikimedia Commons)

We are here confronted not with clearly invalid potential regulations, but potential regulations which only may be invalid despite being imminently immoral. As for Hogan itself, I do not believe that it correctly applied the law. Despite the strong legal arguments that can be levied against delisting, Hogan shows a very real risk that any regulations delisting trans healthcare will be upheld as valid by the Courts, a risk that should not exist given the unnecessary anxiety it causes and the moral landscape of hormone replacement therapy in relation to trans well-being.

Ensuring access to hormone replacement therapy is a difficult and multifaceted task, and if improperly handled provides a fertile soil for the exacerbation of trans people’s vulnerabilities. On the legal plane, trans issues surrounding hormone therapy show the limitations of human rights law both in supervising the decisions of governments and private actors who may too easily bestow help on the least vulnerable of the vulnerable, instead of the most vulnerable of the vulnerable, and in addressing broader systemic issues arising from the interrelations between various public and private bodies. In the end, we can only hope that the government takes seriously the words of the Supreme Court of Canada in Eldridge: once the state provides a benefit, it is obliged to do so in a non-discriminatory manner.