Wednesday, March 04, 2015

Whose risk/benefit ratio is this, anyway?

It's a good question. An analysis of risks and benefits for study participants is considered central to the ethics of research, but how risks and benefits are determined remains tricky. Part of the job description of research ethics committees is to make such determinations, and the Belmont Report encourages use of quantitative risk data whenever possible, but it is unclear how often that actually happens. Anecdotally, there is a lot of eyeballing and back-of-the-envelope estimation of risks, if not outright speculation and magnification. And as for benefits, there is much disagreement as to what should count as a benefit in the risk/benefit assessment. Compensation and inducements are traditionally thought to be inadmissible; benefits that come with study participation ('inclusion benefits') are permitted in the mix by some, ruled out by others.

The problem of risk/benefit determination is not just a problem about how, but also about who. Traditionally, the work of making such judgments is something reserved for experts: bioethicists, researchers, research ethics committees, policy makers. This is one area in which the whiff of paternalism in research ethics is particularly strong. If anything, the perspectives of research participants and communities are regarded as ethically dangerous and problematic, particularly in cases where communities are poor and the prospective participants are hoping to gain medical benefits by joining research studies. An article in a recent edition of Tropical Medicine and International Health suggests that local communities make their own risk/benefit calculations about particular studies, which go far beyond whatever risks and benefits may be directly connected to study interventions. For example, the thought "How could my participation in this study possibly benefit my family?" is a consideration unlikely to appear in your standard risk/benefit discussions. What could be a benefit for participants may, from the perspective of an ethics committee, be literally invisible.

The authors state that much more research is needed into the complex links between socio-economic vulnerability, access to health care and the freedom to decide on participation in medical research. Seems reasonable. But whether such research will lead to a participant perspectives being more determinative of 'official' assessments of the risks and benefits of health research remains to be seen.

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Saturday, January 10, 2015

Big Pharma feeling misunderstood

The CEO of Bayer, Marijn Dekkers, was last month reported to have said the following:

"We did not develop this [cancer] drug for Indians. We developed it for Western patients who can afford it."

What Dekkers said was in response to a question about a decision by an Indian government official to grant a compulsory licence to patents on said cancer drug, on the grounds that Bayer's price for it ($65,000) was far too expensive for Indian patients. Dekkers added that he thought the move towards a compulsory licence -- permitting low-cost generic equivalents to be produced and sold by companies other than Bayer -- was "essentially theft."

A couple of websites condemned the comments as the usual 'profits before persons' standpoint of Big Pharma, albeit stated much more brutally than CEOs of major drug companies generally do.  It turns out that Bloomberg News, who originally ran the quote, actually manipulated it a bit. What Dekkers actually said was:

"Is this going to have a big effect on our business model? No, because we did not develop this product for the Indian market, let's be honest. We developed this product for Western patients who can afford this product, quite honestly. It is an expensive product, being an oncology product." 

Plus compulsory licensing is theft. Bloomberg News rightly corrected itself, although if anything the actual quote sounds even worse.

What is really ironic is that Dekkers' statement was made at a conference called Buffering the Pharma Brand: Restoring Reputation, Rebuilding Trust. It could alternatively been called: we make you sophisticated drugs, that you can't make yourself, so where is the love? The participants in the conference seem bewildered that the public trusts pharmaceutical companies less than producers of alcohol and tobacco. How is this possible? In this regard, Dekkers' statement may have inadvertently been the most insightful 'take home' message of that particular get-together.



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Wednesday, January 07, 2015

New Year ruminations on global bioethics

The New Year is a good time to reflect on where one has been and where one is going. What have I accomplished or failed to accomplish? What can I do better? It is hard to know whether Julian Savulescu wrote his recent essay in the Journal of Medical Ethics (‘Bioethics: why philosophy is essential for progress’) in a bit of a fin d’annee funk. But it certainly sounds like it: his conclusion is that bioethics and medical ethics as fields have largely failed, and he seriously doubts that he as a bioethicist has made much of a positive impact over the past two decades. What is the malaise, and what is the antidote?
According to Savulescu, bioethics and medical ethics have failed because the philosophical engine that powers ethics has been allowed to wither. In fact, much of his article is devoted to deftly exposing what he considers crappy ethical reasoning. While one may not be a fan of Savulescu’s brand of consequentialism, and/or why he thinks certain positions are untenable, you cannot fault him for failing to present clear ethical arguments in support of his views. This is part of his point: bioethics is being overrun by intellectual laziness in the form of unreflective adherence to ethical-sounding catch phrases (‘humans have dignity’), slavish appeal to existing codes and regulations, or failures to distinguish empirical claims from normative ones. The paragraph that really struck me was the following:
I left a promising career in medicine to do bioethics because I had done philosophy in 1982 and attended Peter Singer’s lectures in practical ethics. The field was new and exciting and there were original proposals and arguments. Singer, Glover, Parfit, Lockwood and others were breaking new ground, giving new analyses and arguments. Now medical ethics is more like a religion, with positions based on faith not argument, and imperiously imposed in a simple minded way, often by committees or groups of people with no training in ethics, or even an understanding of the nature of ethics.
The remedy for this, according to Savulescu, is to go back to basics. Bioethics is a branch of ethics. Ethics is a philosophical discipline, and philosophy (certainly in its Western, Socratic form) is all about critically examining claims and offering the best arguments one can. 

To the extent that Savulescu’s diagnosis is right, bioethics may be in globally rough shape. To make my own start-of-the-New-Year confession, I have been involved with initiatives to strengthen bioethics in sub-Saharan African countries for a decade now. One of the greatest challenges faced by those initiatives is to stimulate critical philosophical thinking. Trainees often expect the ‘right answers’ or ‘correct values’, which are then to be applied mechanically to particular problems.  This may be due to educational systems that elevate professors high above students, and encourage learning by rote while downplaying critical engagement with what is being taught. In addition, I have found that much of the interest in ‘bioethics’ in developing countries too often boils down to the (institutional) interest in establishing and sitting on research ethics committees. Whatever the causes of the trend may be, the net result may be the globalization of a diluted bioethics that ‘is more like a religion.’ Those of us involved in such initiatives need to seriously reflect on this phenomenon, to what extent we contribute to it, and what can be done to minimize or counteract it.

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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. http://apps.who.int/iris/bitstream/10665/85326/1/9789241505734_eng.pdf?ua=1

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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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