Saturday, November 21, 2015

Future Infectious Catastrophic Disease Outbreaks: Ethics of Emergency Access to Unregistered Medical Interventions and Clinical Trial Designs

The mass media excitement about Ebola has receded. The 2014-2015 West African outbreak has been brought under control not thanks to the deployment of successful treatment regimes, because there are none that are known to work. I participated recently in an international meeting of experts debating the ethical and methodological issues pertaining to trial designs for emerging infectious diseases like Ebola. It was both astounding and also immensely frustrating that to a large extent the controversies that exercised the minds of the delegates of this meeting exercised the minds of many an AIDS activist and clinical trials’ expert prior to the advent of highly active antiretroviral therapy, a good quarter of a century ago.[1] [2]Are placebo controls an ethically defensible methodological tool when patients face a terminal illness? Different alternative trial designs involving placebo controls, adaptive trial designs, and multi-stage approaches involving active controls were discussed during the meeting. The heated nature of some of these debates reminded me strongly of the passion that was on display during the early HIV trials. It turns out, despite decades of informed debate about these issues, a number of significant normative questions have not been settled.

A cluster of difficult ethical questions that engendered justifiably a lot of debate has to do with the use of placebo controls in trials involving patients facing a very high mortality risk (some in excess of 90%) and a fast-acting infection resulting in the death of these patient within 2-8 days after admission to a treatment centre. This scenario mirrors the sobering reality faced by a subset of Ebola Virus Disease patients. This issue was already highly contentious during the early HIV trials, and then patients and clinical investigators were faced with a virus that was nowhere near as fast-acting as the Ebola virus. The ethical conflict that arises here is this: We know that those randomized into the placebo arm face the same greater-than-90%-risk of death within a few days as those who receive the standard of care treatment. In some trial design the placebo control arm could be identical to the gold standard of (unsuccessful) clinical care provided in a particular clinical setting. Given that those who are randomized into the arm featuring the unregistered medical intervention might do better, or might do worse, or might do roughly as badly as those in the placebo control arm, the ethical question remains whether a trial design featuring a placebo control is ethically justifiable, given the almost certainty of imminent death faced by those randomized into the placebo arm. During the meeting I alluded to earlier a fairly contentious debate arose also over the question of whether trials producing less reliable results than placebo controlled trials might be acceptable under such circumstances.

What exacerbates the ethical challenges for those who undertake such trials is that their trial participants are arguably not true volunteers. Their – dying - trial participants are not given the opportunity to choose between participating in the placebo controlled randomized trial versus accessing the unregistered medical intervention on their own volition outside the trial process. It is perfectly conceivable that some patients might choose to participate in such trials in order to facilitate the development of a successful intervention capable of helping future patients like them. Or they might accept that there exists true clinical equipoise between the trial arms and they might be volunteering to be randomized under such circumstances. In the absence of alternative access routes to the unregistered medical intervention, we can never be certain that the patients agreeing to be randomized are not simply responding to what constitutes a coercive offer.

Clinical investigators colluding in this process, and arguably benefiting from it, are not absolved of their ethical responsibilities because they did not create the regulatory frameworks that gave rise to the problem. It is true that they did not create the regulatory framework under which they operate, but they undoubtedly benefit from its existence. We could respond to this kind of argument by pointing to the societal need for sound trial designs and the detrimental impact of permitting patients to access unregistered medical interventions outside the clinical trials’ system. The likely impact of permitting patients access, as a senior biostatistician attending the workshop rightly pointed out to me, would be a significant slowing-down in the trial recruitment process. Some trials might never be able to recruit sufficient patients, because most patients might be voting with their feet and opt to take their chances with the unregistered medical intervention. Surely that is not quite what is in the best interest of any society battling an emerging infectious disease such as Ebola. Does this justify coercing dying people into particular trial designs? I do not think so, but this is a contentious issue where reasonable, well-informed people can justifiably differ. A WHO panel looking at this question argued that while it would be ethically defensible to offer emergency access to unregistered medical interventions to Ebola patients, this should be subject to that emergency access not slowing down trial recruitment.[3] The panelists (not featuring a single expert or disease survivor from the affected countries) took a policy line here that mirrors US regulations. Other countries, including Canada and South Africa do not make this a threshold condition for emergency access. As it is with these sorts of panels, the advice it rendered on this controversial topic is not actually reasoned for, so policy makers and regulators as well as patient rights advocates aiming to balance the competing interests of access versus trial recruitment in a fair manner will be left wondering about the ethical reasons for this policy stance taken by the WHO panel, assuming there are any.

There are other ethical issues that arise in this context: Some experimental agents existed at the time only in insufficient quantities, for instance ZMapp, an unregistered medical intervention composed of monoclonal antibodies, was only available in very limited quantities. In light of this situation, is it acceptable to prioritize patients in comparable clinical circumstances who are willing to be randomized in a placebo controlled trial over patients clamoring for direct emergency access, given that the available quantities of this unregistered medical intervention would have been used up in the placebo controlled trial?

And here is another difficult question: While the AIDS activists of days gone by were highly educated about their disease and about the available unregistered medical interventions considered for expanded access programs, this is not quite the case with regard to the average West African Ebola patient. These patients were unlikely able to provide valid first person informed consent, because they were unable to demonstrate a reasonable person understanding of what was known about the unregistered medical intervention, about their options and so on and so forth. This is the case both because of educational limitations as well as disease progression. Are short-cuts to informed consent ethically justifiable under such circumstances? Given that time is of the essence and proxy consent might not be feasible due to family members being deceased or in a far-away village, are our informed consent requirements reasonable under such emergency circumstances?

The WHO panel suggests that evidence from nun-human primate experiments might be sufficient to justify offering a particular unregistered medical intervention for emergency access. Is that an ethically justifiable stance, given the high mortality rate and fast-acting nature of the infection?

Let me leave you with a final difficult question to ponder: Imagine you were running a medical NGO providing access to unregistered medical interventions to patients you care for in your emergency medical centre. By some fluke your unregistered medical intervention permits some of your patients to survive, but that survival comes at a high price, debilitating after-effects of the Ebola virus as well as of the unregistered medical intervention. Given concerns about your patients’ capacity to provide valid informed consent, should you accept responsibility for the patients’ future care and upkeep, given the lack of state infrastructure to assist these patients? If you accept responsibility for their care, say, by taking out an insurance package from some provider for them, you will expend a fair amount of donor monies on these patients (potentially for decades) that you cannot use to assist patients also facing life-threatening illnesses in other parts of the world. In other words, you face another ethical challenge, a resource allocation challenge. How should that medical NGO go about addressing this challenge?

Monday, November 16, 2015

Trudeau Curtails Harper's Anti-Choice Activist End-of-Life Panel Activities

This is brilliant. Former PM Stephen Harper appointed in the dying weeks of his government a smallish panel of anti-choice activists to advise his government on how to implement the Supreme Court of Canada's ruling on assisted dying. The CBC reports today that PM Trudeau's government has moved to curtail this panel's scope of activities. It doesn't want advice from the panel on possible legislation any longer, the federal government simply asks the panel members to summarise the results of its consultation. I'm pretty sure the results of this panel's activities will be filed away right after that. Game over for these anti-choice activists. Here is some more background information on two of them. Note that both of them were expert witnesses on behalf of the Harper government fighting the case against assisted dying in our courts. Their expertise sank without a trace when the Supreme Court decided unanimously that depriving us of access to assisted dying violates our Charter rights. Mind boggling the amount of tax monies that were wasted on their activities.

Finally out - my new bioethics textbook

After a year's worth of intensive sourcing of new content and a year's worth of intensive deliberations with Helga Kuhse and Peter Singer, the new edition of Bioethics - An Anthology is finally out. In case you care about bioethics, check it out. Amazon currently has the Kindle version on sale, but I understand that the print copy is arriving in warehouses as I write this.

Friday, October 30, 2015

Do we need a delay on the implementation of assisted dying in Canada?

There's movement on the assisted dying frontiers. Yesterday representatives of religious organisations held a press conference declaring that they are opposed to assisted dying and that we ought to strive to improve palliative care. As far as I can see they are not insisting any longer - democracy be damned - that assisted dying must not come to Canada, no matter what. The reason for this, presumably, has also to do with the fact that their own followers are in favor of the decriminalization of assisted dying. Other than that, they stated the obvious, it's a good idea to improve the state of palliative care in the country. It's not an either-or type situation, of course. We can have assisted dying and improved palliative care!

We also had a federal election that turfed out Stephen Harper and his merry band of evangelical government ministers. After the Supreme Court judgement declaring the bits of our criminal code that criminalize assisted dying unconstitutional - government was given 12 months to change relevant legislation - Mr Harper did nothing to implement the ruling. Eventually, in the dying days of his government, and seeing the writing on the wall for a return to power, he quickly installed fellow anti-choice activists as a federal panel to advise his government on the implementation of the Supreme Court ruling. His political calculus with regard to this panel might well be paying off. Its chairperson was yesterday on the CBC's Power and Politics and announced that he thinks his panel is still appointed to report to government, alas, the government that appointed him doesn't actually exist any longer by the time it plans to release its recommendations. Because it's also so very partisan in terms of its membership, it's unclear why anyone would want to take its views as anything other than the utterances of people who supported the Harper government's efforts during the Supreme Court hearings. They worked tirelessly to prevent Canadians from exercising their constitutional rights. Well, that's true for two of the three panelists.

Comes Justin Trudeau, our Prime Minister elect. He will ask the Supreme Court to give him another 6 months to implement the ruling. Initially I thought that that was not unreasonable, but then I wondered. The delay is supposedly needed for his government to decide on how to regulate the matter. The question is whether that is actually needed. The Supreme Court declared parts of the criminal code invalid. Health care is a provincial matter. The provinces and territories have established a task force aimed at advising them on how to implement the Supreme Court judgment. Quebec's legislation is already in place. Once the other provinces have put their legislation and regulations in place, there does not seem any need for federal regulations.

So, why wait?

Wednesday, October 28, 2015

Quixotian attack on Bioethics journals leads to retraction

I have blogged a few weeks ago on this website about a Quixotian attempt by a team of authors aimed at blaming leading mainstream subscription based bioethics journals for their alleged imperialist nature and what not else. A version of this blog entry has since been published here. I pointed out that the analysis of said article rested essentially on a questionable letter by the same team of authors that manipulated categories of the Human Development Index in order to generate a particular result plus false empirical claims about the availability of these journals through access schemes administered by the World Health Organisation.

I am pleased to report that the journal that published said article as a peer reviewed output has since retracted said content. There is no shame in retracting content found significantly wanting.

Discussion of 'Treatment resistant depression and assisted dying'

Readers of this blog might recall that Suzanne van de Vathorst and I published a paper in the Journal of medical ethics arguing for the desirability to make assisted dying available to competent treatment resistant depressed people. There has been a bunch of responses, namely this and this and this and this and this to which we responded here. Since then Frank Miller also offered a thoughtful commentary here to which we responded here.

Today a website dedicated to mental health issues has published a lengthy summary of the debate in the hope of triggering a discussion about our analysis and those of our critics.

Check it out when you have a minute, well worth reading.

Sunday, October 25, 2015

Mustn't we talk in universities about whether trans women are women?

I have been watching for some time with ever-growing horror a movement of - let's be honest, mostly progressive - folks, aka my friends, that strives to limit what we can and cannot debate in university settings. It happens on various levels and is quite insidious. There's the thing about trigger warnings where we are supposed to warn our students each time they might encounter something in class that might deeply upset, disturb or even distress them. Well, I teach bioethics, there's a fair chance that that could happen in every class that I teach. My students are also all of mature age, so should I really aim my classes at not upsetting their emotional well-being or should I aim to challenge and potentially even upset them? It's a rhetorical question. I begin my classes by issuing a general trigger warning for the rest of the course, including every class without exception. Box ticked. Sorted. Would I change my content based on whether a student might be deeply disturbed by the topic, or a case scenario, or a video clip? Not a chance. What's the point of taking a bioethics class and not being challenged frequently to reconsider how you look at the issues we are considering in class. There is no way to run a class on, say, the ethics of animal experimentation, abortion, euthanasia, even cochlear implants, without upsetting someone.

I'm not a junior faculty member in a tenure track position, 'student led' teaching evaluations will neither make nor break me. I doubt junior colleagues would be able to afford doing the same.

Part of this ongoing campaign to keep universities conflict free, and to avoid 'offending' students are no-platform events. No-platform events are events where particular speakers are no platformed, meaning they are prevented from speaking on campuses. This is either achieved by student organisations declaring particular speakers persona non grata, or by university administrations preventing invited speakers from speaking due to 'security' concerns. This has been going on for some time, mostly in the UK, not so much in North America. Initially the objective was to keep neo-Nazi organisations off college campuses. No platform to the BNP or the KKK, that sort of thing. More recently though the victims were secularist speakers aiming to address Muslim fundamentalism on college campuses (including enforced seating arrangements for men and women attendees, enforced head covers, and other such medieval niceties) and there were invariably 'concerns' expressed and offense taken about their 'racism'. 'Racism' here is the preferred misnomer for critiques of a man made ideology.

The latest round of no-platform campaigning has hit feminist author Germaine Greer. She doesn't think that trans women are women. I do think one can have a legitimate debate about human-made categories such as 'man' and 'woman'. However, I also think it's pathetic that student activists think they ought to prevent such debates from occurring by declaring that people who were born 'male' could now define 'woman' in such a way that it includes some of them and that this should be binding on the rest of society. I understand the desire of trans women that society should see them in the same way as other women, as much as I understand that some feminists as well as other people will find that idea offensive. It's a great debate to have - we should teach classes on this subject.

Alas, trigger warnings will be considered necessary in many universities, student activists queer and otherwise will need to be placated and what not else. None of this is acceptable. If we cannot interrogate (there's that dreaded term) these sorts of concepts and categories in universities, where else should or could we do so? How would we even be able to determine whether our culturally evolved categories about ourselves are fit for purpose? And for what purpose?

What's troubling about this defense of free speech on college campuses is that there is a price to be paid for such open debate, and it is mostly to be paid by trans people, that is people who are subjected already to unacceptable forms of societal discrimination and disapprobation. They will find their claims analysed and critiqued, courtesy of the internets, in ways that will be vicious at the best of times. That is deeply troubling seeing that suicide rates among trans people are as sky-high as they are. And yet, while pleading for civility, I am convinced that a public airing of these issues is what is in the best interest of trans people themselves. It helped liberate gays and lesbians, we had to subject ourselves to debates about normality, and naturalness, whether we suffer from a mental illness, perversion, and what not else. Being able to debunk these falsehoods one by one worked for gays and lesbians. I'm afraid trans people and their allies will have to face these issues head-on, make their case with the best arguments and evidence available and win the argument in the public domain as well as in the academy.

No platforming speakers we disagree with is counter productive. The idea that these issues will go away by suppressing debate about them is naive at best.

Friday, August 28, 2015

Health Care - Not an Issue for Major Political Parties in Canada's Federal Election Campaigns

It's a somewhat surreal election campaign that is currently in full swing in Canada. It stays clear of issues of vital importance to Canada and Canadians. There we have a rapidly ageing population and really we need a national seniors strategy that accounts for that. One can nearly feel sorry for the Canadian Medical Association here. The association tried hard during the last few months to make this issue an issue in the current election campaign. It was rightly supported by sympathetic journalists such as the Globe and Mail's Andre Picard. Yet, for all those efforts, the issue gained no traction with any of the major parties. Our federal leaders' heads remain firmly planted deep in sand, with no effort made to look ahead and address major, dramatic challenges to our health care system. Instead we were treated to a good two weeks' worth of Mike Duffy and the usual corrupt shenanigans that are a hallmark of Prime Minister Harper's political operation.

I spoke yesterday to a journalist interviewing me on the state of federal and provincial planning with regard to the implementation of our Supreme Court's decision  on assisted dying. He asked why the political parties, in my estimation, haven't taken up this issue in their respective campaigns? He was puzzled that an issue that enjoys broad support among Canadians is ignored by the major political parties. What was I to say other than 'I don't get it either'. A new poll, released today, confirms what I told the journalist yesterday, it is not only the case that the vast majority of Canadians want to see the decriminalization of assisted dying, it is also the case that the vast majority of conservative party voters supports the decriminalization. 77% of Canadians generally support decriminalization and a whopping 67% of conservative party voters and 84% of NDP voters. This does beg the question why none of the mainstream parties have leveled with their supporters and the general voting public on how they would implement the Supreme Court judgment. I do still wonder why Prime Minister Harper appointed an advisory panel stacked with discredited anti-choice activists, given that the majority of his party's supporters is in favor of decriminalization. Why on earth would he stack his panel with folks known to be opposed to decriminalization? I sometimes wonder about the credit that is given to Mr Harper who is hailed as a master political tactician. His whole election campaign seems a shambles to me.

Tuesday, August 25, 2015

Surveys and surveys - The Canadian Medical Association should know better

The Canadian Medical Association currently debates the issue of assisted dying. That's a reassuring thing as everything points in the direction of doctors becoming the gatekeepers once assisted dying is regulated and will be made available to eligible Canadians who request it.

Strangely, the Association seems to put a lot of store in an on-line poll it inflicted on its members, where only 29% of those who responded said that they were willing to provide assisted dying to eligible patients while 63% objected. I'm surprised the Association's staff would have even mentioned this survey. It's troubled by obvious ( and quite deadly, pardon the pun) methodological problems that renders it useless.

The Associations Vice President Professional Affairs, Dr Jeff Blackmer produced a 34 slide presentation titled (no doubt to the horror of most living medical ethicists) 'End-of-Life Care in Canada: A Principles Based Approach to Assisted Dying'. There will be only few people left in bioethics who have not come to realize that the much celebrated principles approach to medical ethics guarantees arbitrary recommendations and outcomes. The principles approach is neither action guiding nor action justifying, it's useless as a tool of ethical or policy analysis and justification. Blackmer decided to add random other principles to the Georgetown Mantra, including vacuous nice sounding stuff like the 'dignity of life' (yes, really, he did!). We spent a fair amount of time in our Royal Society of Canada Report on the subject matter dissecting this particular issue.

After delivering to his audience this hotchpotch of principles, there's an unconnected slide with recommendations, followed by 8 or 9 slides reporting the results of the CMA's on-line poll. Blackmer reports that of about 80 000 doctors in Canada about 1400 clicked their way thru the on-line poll. At a minimum the negligible turnout suggests that most doctors in Canada didn't care to complete a survey that they probably realized ultimately tells us nothing about Canadian doctors' views on assisted dying. The reason for this is methodological. These kinds of surveys may or may not be representative, we just cannot know, because the survey participants may or may not be representative. If anything we should be suspicious of these results, because no professional survey organisations ensured that the sample was actually representative. Those who feel strongly about the subject matter - physicians opposed to it - will fire up their supporters to reject assisted dying and proclaim no collaboration.

Other surveys, including one reported in our above mentioned report, suggest significantly higher levels of support. It is all the more disheartening that a seasoned journalist like the Globe and Mail's Andre Picard takes the 29% figure at face value in his twitter reporting of the Blackmer presentation. (See the image above.) Doing that permits the anti-choice activists to feel good about their campaign strategy, their encouraging their like-minded doctor supporters to click thru the survey would pay off if people fell for this nonsense. I left a slightly more polite comment to this account under Blackmer's public slide presentation, but it was quickly deleted. Go figure.

The CMA recognizes that we will be getting assisted dying in some form or shape (determined by the criteria set out in the Supreme Court of Canada judgment on this subject) and that a small number of its members will be called upon to provide assisted dying services to their patients. The Association is rightly concerned about ensuring patient access while protecting its objecting members' conscience choices. There is a precedent for this. Abortion. Objecting doctors will be obliged to transfer their patients to a colleague they know will oblige them, without unreasonable delay. The CMA is apparently supportive of this compromise.

The train toward assisted dying in Canada has departed but hasn't reached its destination yet.