Thursday, November 20, 2014

Ebola and the ethics of research design

A couple of recent articles stimulated my interest on the ethics of conducting ebola research, particularly with those conducted in low-resource settings and having a randomised controlled design. It interested me enough to write a letter to JAMA, where it got bounced.  I thought about submitting to Lancet, but hip replacement surgery got in my way: just too much work. So it goes. Part of what is fascinating about the topic are the underlying issues regarding whether doing anything other than the 'gold standard' of clinical trials is justified. I am diverting this piece to Global Bioethics Blog just in case a reader finds something of value in it. 

Two recent commentaries in this journal argue for and against conducting randomized controlled trials (RCTs) of new Ebola drugs during the current epidemic.[i] [ii] Those in favor argue that only RCTs can deliver the evidence required to treat future Ebola patients in ways superior to the current standard of care, which is largely palliative. Other observers hold a similar view.[iii] Those opposed to RCTs in this context argue that if patients were randomized to study arms of either (a) a new drug or (b) the baseline 70% mortality rate for Ebola, such a trial would not possess equipoise, because (arguably) the intervention arm would likely provide at least some benefit. In addition, opponents argue that local communities ravaged by Ebola – whose trust in authority, including medical authority, has been profoundly shaken -- are unlikely to accept a randomized controlled trial design.  They therefore advocate for experimental drugs to be offered to patients within non-RCT research designs, even if they have not been tested by the ‘gold standard’ methodology.   

On the face of it, this seems like a conflict between advocates of evidence-based medicine and those who understandably, but misguidedly, want to provide less-than-well-tested drugs to the sick as soon as possible. But while the former position seems rational and impartial, history reveals some unsettling patterns. When the HIV epidemic was raging in the United States decades ago, advocacy groups mobilized aggressively for expedited access to new experimental treatments, bypassing the full FDA approval process.[iv] The alternative then, for many AIDS patients, was death. Current policies surrounding ‘compassionate use’ were borne out of this experience. This raises the question: is it easier to take a hard utilitarian position on the need for RCTs when it is someone else’s epidemic?

The faith placed in scientific knowledge to resolve deep social problems is also part of an old pattern. When health crises occur in developing countries, international efforts often focus on fast-tracking biomedical interventions rather than also engaging the social, economic, and political factors contributing to emerging infections. Citizens of low-resource countries have every right to be skeptical here. Drugs to prevent mother-to-child HIV transmission were tested and developed two decades ago; only 57% of women in sub-Saharan Africa currently have access to it.[v] The same (or worse) can be said for a host of other diseases. Access to new Ebola drugs, should they be successfully developed, will likely to follow the same trajectory. Again, the argument that we should only encourage RCT trial designs for new Ebola drugs, out of scientific concern for the evidence base, may be more compelling in places other than Monrovia.

[i]Shaw S. Randomization is essential in Ebola trials.  Lancet 2014; 384: 1667. 
[ii]Adebamowo C, Bah-Sow O, Binka F, et al. Randomised controlled trials for Ebola: practical and ethical issues. Lancet 2014; 384: 1423-1424.
[iii]Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA 2014; 312(13):1299-1300.
[iv]Dresser R. When Science Offers Salvation. 2001. Oxford: Oxford University Press.
[v]WHO/UNICEF/UNAIDS. Global Update on HIV Treatment 2013: Results, Impacts and Opportunities.

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Wednesday, October 15, 2014

Has global health become medicalised?

Many people have heard of ‘global health’. In fact, it is hard to get away from it, particularly on the medical side of college campuses, in health policy discussions, or the media when a newsworthy epidemic breaks out somewhere. Global health is generally code for (unfair) health disparities and the unhappy tendency of health crises walk or fly across national borders. Perhaps less familiar is the concept of ‘medicalization’. Roughly speaking, it is the process by which human problems are understood as (or ‘reduced to’) medical problems. For example, one could view diabetes as a purely medical problem, for which better treatments are needed, rather than (say) a condition implicating a host of social, political and economic factors, such as the low-cost of processed food, changes in work conditions and the structure of built environments. So what happens when you put ‘global health’ and ‘medicalization’ together?

Jocalyn Clark has written some intriguing exploratory pieces on the links between medicalization and global health in the online journal Global Health Action. Do global health initiatives tend to medicalize the problems that they set out to tackle? And if so, what effects does this process of medicalization then have? Certainly there is a tendency to seek technological (‘innovative’) solutions to health problems in developing countries, often with mixed results. To the extent that the determinants of poor and better health are social, political and economic, purely medical interventions are likely to have superficial impact. I wonder if there is also something else at play: not just medicalization, but the allure of objectivity and neutrality – think Red Cross -- associated with Western medicine. Coming into a developing country with medical interventions seems far less politically fraught than proposing large-scale changes to ways of life. So there is a tension between a major tenet of global health (that health is socially determined) and the political implications of trying to improve health globally. The tendency towards medicalization may paradoxically reflect a need to look for a ‘safe space’ for global health practice.

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Friday, October 10, 2014

Responsibility for collateral ebola damage

I guess that as far as bioethics and Ebola goes, resistance is futile. As someone interested in bioethics, right now you apparently have three choices: ignore that the Ebola epidemic is happening, join the noisy crowd of disease control bioethicists clamouring for attention, or point out ethical issues that are neglected or lie on the margins of the mayhem. The first option seems irresponsible. The second option seems superfluous: how much of that do we need, really? The third option, on the other hand, might have something to it. So in that vein ...

Those infected by an infectious disease during an epidemic are the object of immediate concern. Those they expose to infection are an important, secondary concern. But there are further knock-on effects that may be less obvious than (say) the overall economic impact. The Ebola epidemic raising havoc with the older, chronic, HIV epidemic in West Africa. Reliable access to HIV treatment has always been a struggle, but now HIV-positive persons in places like Liberia need to travel to get their drugs. Since only some of those in rural areas have the time/money to do that, treatment interruption and its consequences (viral rebound, etc.) are inevitable. In this way, Ebola leads to death by HIV. But it is not just HIV. Ebola in these regions is compromising health systems that were very fragile to begin with, a reversal of hard-won achievements may be faced on many fronts: malaria, diarrhoea, maternal and child mortality.

So the ethics question: when international and local agencies are engaged to control Ebola in West Africa, should they concentrate on Ebola alone, or do they also have some responsibility to deal with the collateral damage that Ebola has caused?

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Saturday, October 04, 2014

A raging epidemic of bioethical commentary

I don't think I have seen so much bioethics commentary about a single topic -- in such a short span of time -- since I got interested in the field. Talk about Ebola is spreading and multiplying far faster and wider than the virus. It is definitely flavour of the month, and as for how many infectious disease bioethicists there are out there, who knew?  Even the ones I thought were more into enhancement or face transplants or some other shiny object of bioethical curiosity are getting in on the action. Decent analyses are being written, it's not that. It is more about where they all were for the last decades, or even in the last years, when cholera, ebola, dengue, malaria and other (neglected) disease threats have been popping up all around developing countries. Does it really have to (frankly) affect a couple white folks from the North before it gets hot and happening? I already knew that Western media outlets are self-absorbed ambulance chasers but ...

OK, I am being overly harsh. I just hope there is more to the bioethics coverage than what-measures-are-appropriate-to-combat-spread-of-terrifying-disease-or-stop-it-from-getting-to-our-shores. The ethics of urgency, Ethics 911. Ebola's rise and spread in Western Africa is a symptom of what kind of shape those countries are in, not just their health care systems but the social and political circumstances in which those systems are embedded. Ebola can only thrive in messed up places. My prediction is that once Ebola has been contained, attention to the driving forces of poor health in developing countries will get as much attention from bioethicists as it generally gets. Plus ca change.

P.S. Now this is more like it ...

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Friday, September 26, 2014

Living large, living long and just getting by

Ezekiel Emanuel has written a controversial piece in The Atlantic entitled Why I Hope to Die at 75: An argument that society and families -- and you -- will be better off if nature takes its course swiftly and promptly. I never thought that I would write about it on this blog, given its developing world focus. And yet, as I read Emanuel's piece, it was hard not to wonder how his thoughts would be regarded from the Global South.

Let's jump to the punch line. Emanuel's conclusion is that he does want to live beyond the age of 75 and, when he reaches that age, he will forgo all medical interventions that aim to prolong his life. Transposing the conclusion to policy, Emanuel concludes that raising life expectancy in a society beyond the age of 75 is not an appropriate public health goal. More attention should be spent on ensuring that sub-groups (like African American males) attain a life-expectancy of 75 years or improving the statistics on infant and adolescent mortality.

These are his conclusions, but how does he get there? What reasons are offered for the 'hope to die at 75' on personal and policy levels? The main reasons are that as people age beyond 75, they experience various degrees and types of physical and mental disability. We all know this, of course, but Emanuel has an especially self-revealing way of mapping this out. A noteworthy fact: the average of Nobel Prize winners is 48. Other noteworthy fact: studies on creativity have shown that classical composers write their first major works in their twenties, peak in their 40's, and then go into irreversible decline. Except for a few outliers, creativity, originality and productivity go downhill after the age of 75. Our thoughts either run along the same well-worn neutral pathways, or the pathways themselves start to fray and fall apart. Sure, one can take other roles, like mentorship, and yet doesn't this too simply reflect (as Emanuel puts it) the "constricting of our ambitions and expectations"? But not only do we progressively become dull as dishwater and daft as brushes. We become burdensome to others, particularly our children, who increasingly have to care for us as we edge further and further into decrepitude. How can they win the Nobel if they have to deal with our shit (pun intended)? And to top it all off, those around us have to bear painful witness to our descent, which (according to Emanuel) has the effect of erasing memories of what we were like when we still had the juice. Because that is the underlying philosophy of life here: don't live long, live large, and get out before you embarrass yourself and burden others.

Yes, this is the philosophy of life of a white male, driven, affluent and privileged, whose career has been marked by important achievements and prestigious positions in academia and government. It is understandable to be concerned about decline when you are so high up in the socio-economic-cultural-political stratosphere. And probably you do not get to that position unless you have always been very strongly convinced that thinking, creativity, productivity, achievement, making social contributions (rather than friendship, love, dancing, hanging out, laughing, skinny dipping, eating pudding) are what is to be most valued in a human life. But what about the rest of us, whose life achievements are unlikely to even get close to the composers, the Nobel Laureates or Emanuel himself? Probably Emanuel at age 75 will be scoring better on all the indices (creativity, productivity, etc.) of the reasons for living than a lot of (younger) people globally, particularly those without the same opportunities, whose capacities have been stunted by oppression. If he does not have a reason to prolong his life then, neither do we.

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Friday, August 22, 2014

Susceptible to Ebola, immune to criticism

Karl Marx famously wrote that "... philosophers have only interpreted the world, in various ways. The point, however, is to change it." The quote by Marx is sometimes used to bash 'academics' in the name of world-changers, men (and women) of enterprise, the 'hands-on' types, interveners, implementers, and so on: what we need is action, not thinking! This, of course, this turns Marx into a cartoon. If he knew the shortcomings of thought without action, Marx also recognised the perils of action without thought. Marx was a German philosopher. He thought for a living. But that hasn't stopped lesser minds from treating action as if it were a good in itself, something we should not distract with reflection or critique. Just do it.

I read today an opinion piece in US Today that brought the above thoughts to mind. In it, Franklin Graham, the head of the evangelical/relief organisation Samaritan Purse, claims that there is no ethical issue involved in providing Dr. Kent Brantly (employee of Samaritan Purse) privileged access to a experimental drug for his Ebola infection. Those who think there are ethics to debate here are merely intellectual elites ('academics' , 'talking heads' ) far removed from 'primitive deathbeds' in Africa, and the ethical debate -- politically correct analysis from the cozy confines of America -- does nothing to help save people at death's door. Dr. Brantly, the piece goes on, left the comforts of America to provide medical assistance in Liberia, got infected with Ebola in the process, and what happens when he gets access to the scarce experimental treatment? People debate about whether that is ethical or not. This is outrageous, because:

this drug is being used to save a doctor who will say thank you by returning to some of the darkest, dirtiest, loneliest places on earth to bring hope and healing to others. What is the ethical dilemma in that equation?

It is hard to know where to start. I suppose the first point to consider would be the neo-colonial, 'Heart of Darkness' description of someone else's country as the 'darkest, dirtiest, and loneliest places on earth.' Apparently the dark, dirty and lonely people should simply be grateful for whatever help they manage to get, and if American academics say anything, they should be singing the praises of the organisation's humanitarian actions. Therein lies another assumption: if you save the lives of individuals, or if your organisation has the mission to save the lives of individuals, then any critical perspective on you or your organisation is inappropriate. Medical humanitarian organisations sometimes take this defensive stand, despite empirical studies that have shown that they are (predictably) a complicated source of good and bad, rife with ethical challenges, like any other sort of human institution. And as for the assumption is that only faraway American academics have the luxury to raise ethical concerns about giving privileged access to experimental treatment to an American doctor and missionary, i.e. people unfamiliar with and untouched by African realities ... think again. The ethical questions around this issue are being debated within Africa, by Africans, as well. Africans also think about issues of global inequality and injustice when they see socio-political elites being whisked off to superior health care, not just when Westerners get sick and get evacuated to the better hospitals in the brighter/cleaner/happier countries, but also when their own political leaders get sick and are flown up to fancy clinics in Paris or London. It is not politically correct analysis, it is painful reality.

The story about the Americans gaining access to the experimental Ebola treatment does reveal something about the state of the world, including its ethics. Debating the ethics is not inappropriate, nor does it hinder efforts to control Ebola. To see this though, you have to move beyond the missionary position.

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Thursday, August 07, 2014

Ebola ethics

Interesting to see the kinds of attention that has been given to the most recent Ebola outbreak in Africa. Part of the reason is that it is a serious epidemic, causing nearly a thousand deaths so far, and it is occurring in West Africa, rather than its usual stomping ground of the Democratic Republic of Congo and thereabouts. Another reason is that some Americans overseas have been infected, and medically evacuated back home, so the story involves not only the familiar 'death exoticism' of faraway anonymous Africans, but has a US domestic component as well.

Perhaps because it involves American citizens, bioethicists have been more active in commenting on the ethics of Ebola control than they were during outbreaks of times past. Two of the infected Americans have been treated with an experimental Ebola drug, the access to treatment being aided and abetted by the National Institutes of Health and the Centers for Disease Control no less. Bioethicists, chronic worriers that we apparently are, worry about this development. If the drug has not been FDA approved, how do we know that it is safe and effective? Even if the conditions of the American patients improve, how do we know whether the drug itself is responsible, if no rigorous clinical trial has been conducted? Why would people continue to join clinical studies if they could gain access to experimental drugs outside the FDA's vetting system?

All fine and good, as worries go. But I wonder what would happen if the Ebola outbreak happened in Louisiana rather than Liberia. Would the American public and leadership -- including its bioethicists -- be so sanguine about waiting years for the results of clinical trials before trying some promising-looking drugs out? Faced with an infectious disease with a very high mortality rate, would we revisit and loosen the rules or hold firmly to the tenets of evidence-based medicine? Is the latter what happened, say, early on during the US HIV epidemic? Or is the ethics a bit different when it is largely somebody else's deadly epidemic? For its part, the World Health Organisation seems more open to the use of not fully tested treatments, for Africans, given that the current alternative for most of those affected is (as the Director of the Wellcome Trust put it) a tepid sponge bath and the promise of a nice burial.

UPDATE: The Scientist issued a short piece on the subject of Ebola and ethics last night, and USA Today has a piece up, with reader comments.

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