Global bioethics blog

The ethics of drug addiction research in China

2012-05-12T22:09:00.002-04:00

Reports about what goes on in 'drug rehabilitation centers' in China have been dribbling into the media for some time now. Arrest for illegal drug use in China can lead to compulsory treatment (for a minimum of 2 years) at detention centers that, according to a New York Times piece in 2010, function as de facto penal colonies where inmates are fed substandard food and denied basic medical care. The detentions are enforced by police, where the drug user has no opportunity to have a trial, face a judge or raise an appeal. When a drug user leaves detention, the problems do not end there: their having been arrested for drug use is noted on their national identification card, making future employment difficult and leaving them vulnerable to frequent and humiliating searches by police. This is not a rare phenomenon: according to the Joint United Nations Programme on HIV/AIDS (UNAIDS, 2010), half a million people are confined in drug detention centers in China at any given time. Perhaps it would be marginally better if those with drug addictions received effective treatment during thier detention, but the most reports point in the other direction: 'treatment' may come in the form of unpaid labor in chicken farms or shoe factories, or in the form of untested 'therapies' like sandbox play, art, or boxing. The 'treatment' looks like punishment, exploitation, or merely lame.

Question: would it be ethical to conduct research with drug user detainees in such circumstances? In the abstract, those with substance abuse problems are vulnerable persons in poor health, and it would be good to have research on effective interventions to combat drug addiction. But in practice, it gets complicated. The journal Science recently published an article entitled 'A memory retrieval-extinction system to prevent drug craving and relapse'. The study was conducted at Beijing Ankang and Tiantanghe Drug Rehabilitation Centers, but these are two of the facilities that have raised concerns about human rights violations over the past years. Human Rights Watch has published a Letter to the Editor in Science that raises concerns about research being done within institutions suspected of human rights abuse. Should a new intervention be tested against the local standard of care, where there are serious doubts about the effectiveness of that care? In these circumstances, is voluntary informed consent of participants really possible? Are researchers who conduct research in these facilities complicit in the ill-treatment of drug users at the hands of Chinese authorities?

The story is made murkier by the involvement of the US National Institute for Drug Abuse (NIDA) in the study. Two of the authors on the study are from the NIDA, who apparently helped with data analysis and the writing of the article. Since they were significant enough contributors to the research to warrant authorship, should the study have also been reviewed under the (rather stringent) US regulations governing prisoner research, and if it did, would it have passed muster? It will be interesting to see how this case evolves as the facts become clearer.

Blog hiatus

2012-05-12T22:09:00.001-04:00

I have been away from the Global Bioethics blog for longer than usual. It was a matter of converging demands: the end of the semester and teaching duties, plus the grant-writing season was in full swing. The latter is a form of temporary insanity, short-term OCD: your life is consumed not only by designing a proposal, collaboratively with others (and all the give and take that involves), but the mad paper chase of getting up-to-date CVs, writing budgets, budget justifications, scopes of work, letters of support, progress reports, and much else besides, and then packaging it all in the right way to submit it all to the funding authorities, whose pockets are getting shallower all the time. Those who think that academia is all about cushy tenured positions for life with guaranteed income ought to take a look in the trenches at (what I call) us soft monkey monkeys, i.e. those who spend an inordinate amount of time and energy cobbling together enough soft (grant) money to stay at least 75% employed -- you lose your medical insurance coverage if you drop further than that. But that is over, for the moment, and this blog needs feeding.

Research ethics as a sideshow

2012-03-22T18:32:00.007-04:00

There seems to be a new approach to the publication of research studies that have been conducted in a questionable way from an ethical point of view, or are otherwise regarded as 'ethically hot.' Call it the pre-emptive strike approach: you still publish the paper, but you also simultaneously publish editorials that criticize the researcher's ethics. A way of having your cake and eating it too. The researchers and their scientific readership are happy, because they get to look at the data; the ethics people are happy-ish, because at least the problems with the study have been raised. I am reminded of the male circumcision and HIV studies in 2007, where an article was first rejected by the Lancet, and then subsequently published in PLoS Medicine with accompanying ethical commentary.

This time around, it is a tuberculosis treatment study. In the most current issue of the International Journal of Tuberculosis and Lung Disease, Aung et. al. describe how their operational research compared two treatment regimes, in order to evaluate the value of extending the intensive phase of anti-TB treatment for one month. The researchers did not ask participants for informed consent, arguing that: (1) neither of the treatment arms were likely to cause harm (2) the participants were be unlikely to be capable of making a rational choice to decide to participate (3) asking them to participate might lead to selection bias. The study was approved by the Bangladesh Medical Council Ethics Review Committee, and published by the International Journal of Tuberculosis and Lung Disease in full knowledge that informed consent was not sought. And published along with two (not one, but two) editorials that reject all three of the justifications given for not obtaining consent from participants.

So it goes. Another possibility would have been not to publish the article; a possible option now is to retract it. But I doubt this will happen. It seems that if an article looks sufficiently important, as long as the research was approved by an ethics committee (even if they admittedly dropped the ball), then it is acceptable to publish, as long as there is an accompanying ethics sideshow.

Globally embarrassing bioethics

2012-02-28T21:00:00.006-05:00

February continues to be a trying month in bioethics circles. This week we have a firestorm concerning an article published a couple of days ago in the Journal of Medical Ethics, entitled After-Birth Abortion: Why Should the Baby Live? The authors Alberto Giubilini and Francesca Minerva argue that as a matter of consistency, if we accept that fetuses can be aborted for certain reasons (severe abnormality, psychological or financial burden on the family) then we must rationally accept that newborns can be put to death for the same reasons, because both fetuses and newborns have the same moral status as non-persons. Reactions from non-fans of infanticide have been swift and ugly, with the usual accusations of Nazism and dire assessments of where the world is headed when intellectual life is not constrained by religious faith. Editors at the JME, laughably, act as if shocked by all the fuss, as if they seriously expected all readers to receive the paper in a spirit of cool, robotic detachment.

What I found surprising about the paper was how old the main arguments are. Check the references: the philosophical papers cited are all between 20 and 30 years old. Peter Singer and Michael Tooley made the same basic arguments with the same basic premises and with the same rationalistic mindset. So it is not clear why what makes this paper especially publishable, unless the publishers were thinking the time was ripe for stirring up the culture wars (yet again) with a big, fat stick.

But the editors at JME are right that it would be good, ultimately, have a reasoned debate about the article's content. There is plenty in the article to question, including the key premises that our attitudes towards persons is based on their possession of mental capacities (especially their ability to plan for the future) and the idea that our moral sentiments (including our feelings towards newborns) ought or can as a general rule be governed solely by logic and consistency. Those outraged by the Giubilini and Minerva article should take some consolation in the fact that those old arguments by Singer and Tooley did not exactly popularize infanticide, even among other academics. To the extent that the new article has a shock value, the old article has had little effect on common morality.

There is another concern, though: how this all looks to those outside North America and Western Europe, the traditional bastions of bioethics. High-minded arguments in favor of dispatching unwanted babies (and other non-persons) setting off a torrent of mud-slinging and breast-beating. Bioethics: so that's how you do it.

Update: the Journal of Medical Ethics Blog has published some further responses to the paper by Giubilini and Minerva in an apparent effort to open reasoned dialogue on the subject. Giubilini and Minerva have published an open letter to clarify their position, interestingly claiming that they only meant their audience to be other bioethicists familiar with abortion/infanticide debates, emphasizing that they were only making an academic argument, without any practical implications for policy, law, or for what people ought to do.

Research ethics committees in developing countries: something old, something new

2012-02-25T23:11:00.008-05:00

February has been a rough month for bioethics in the USA. Alleged conflicts of interest at the American Journal of Bioethics -- the top ranked bioethics journal -- has lead to a kind of feeding frenzy of accusation, distain and soul-searching in regard to the whole idea of bioethics and how it is practiced in it's most powerful home. Is bioethics a lousy kind of philosophy? Does it just consist in rationalizing the newest biotechnology that comes along, and running intellectual roughshod over whatever traditional values (often religious) might be threatened by that technology? Is that why bioethicists are lured to agencies and institutions that are part of one might call the military-industrial-university-biotech-pharma complex? Is bioethics losing ability to speak truth to power, because they are part of (or eating hors d'oeuvres with) the 1%?

Perhaps on another occasion there will be room for reflection about whether all this should be a cautionary tale for bioethics in other countries in the world, how much of it is true, and how much of it is overblown to serve the interests of other agendas. For my part, I have been lying low, staying away from bioethics news, and looking at what other journals have been putting out. A recent research ethics article in the Journal of Medical Ethics caught my eye, called 'Ethical Approval in Developing Countries is not an Option' (Online First, requiring subscription, goddammit).

What struck me initially was the obviousness of the title: how is that news? It is like having an article called 'Eating people: some arguments against'. And in a certain way, the point of the article is obvious: when there is an appropriate body in developing countries to review human subjects research conducted by anyone (local or from abroad), then it should be reviewed. The authors cite a published article about research conducted in Nepal, which did not have local Nepalese research ethics committee approval. It doesn't sound like a very risky study, but that is not the point. Nepal has an ethics committee that could have reviewed it, and it was not even submitted.

What makes the article publication-worthy are the underlying issues. Central among them is who should have ensured that the study was submitted to local review. Ethics committees are not detective agencies, who scour the community to find out who is doing research on what. Researchers have to volunteer this information; they also have to know that there is a committee to submit their research to. In many developing countries, this is not straightforward: in some settings, research ethics committees may not exist; where they exist, they may only review certain kinds of (biomedical) studies; and even if they do exist and they could review a certain study, getting information about them and their procedures can be unreasonably taxing for scientists. Compounding the problems, some committees may be dysfunctional and intolerably slow, undermining motivations to bother looking for them.

Perhaps if a study is conducted by a developed world institution, their own research ethics committee should ensure that scientists make good faith efforts to get their research reviewed where it will be conducted, or help them get it reviewed. Or journals should not publish articles in which researchers failed to get their research reviewed where it really is human subjects research, and there really is an adequate body that can appropriately assess its ethics. The authors rightly point out that if researchers from Nepal were to do a research study in the UK or USA, but only sought ethics approval for it in Nepal, and published it, this would be considered scandalous -- but when developed world institutions do the same in the developing world, there is far less concern, even when committee members do not know much more about Nepal than Everest expeditions.

So it is not news that local ethics committee review in developing world ought to be reviewed; the news is how this requirement continues to fall through the gaps.

Foreskins, clamps, and stabbings

2012-02-01T22:21:00.003-05:00

Part of the interest in getting Google Alerts, at least as far as I am concerned, is that they provide diverse (if not surreally clashing) news items about the same topic. This week, I received a couple of links about male circumcision as HIV prevention strategy in low-resource, high HIV prevalence countries. A few years ago, three randomized controlled trials in Africa indicated that being circumcised significantly reduced risk of female-to-male HIV transmission. Male circumcision was then all the rage for awhile, but soon slipped off the front pages as it passed from 'research innovation' to 'yet another intervention to be implemented.'

Some countries in Africa are making male circumcision part of their HIV prevention strategy, though informing/convincing men to have their foreskins removed for this purpose, and actually getting it done, has proven slow going. There is some movement to change this. The New York Times has an article about new methods to speed the process of circumcision, complete with pictures of what to the untrained eye look (predictably?) like cock rings of a fairly utilitarian sort. The most promising of these devices seems to be the PrePex, which basically involves putting a ring around your Johnson, and cutting off blood circulation to the foreskin, until the latter comes off 'like a fingernail' as one proponent so sensitively put it. Apparently the clinical trials on male circumcision and HIV gave birth to a growing industry in foreskin removing clamps, from China's somewhat sinister sounding Shang Ring to the exoticism of the Turkish Ali's Klamp, to the device that terrorized many a South African penis a few short years ago, the infamous Malaysian Tara KLamp. That is the new story: which plastic gadget most cost-effectively whips off the African foreskin?

The other story on my Google Alert really goes in another direction. The Citizen, a Tanzanian newspaper has an item entitled 'One Hacked to Death in Male Circumcision Confrontation'. Apparently traditionalists in Tanzania are (very) opposed to the idea of medicalizing male circumcision and treating it similarly to an appendectomy; after all, circumcision in Africa is commonly viewed as a rite of passage for males, where the pain of circumcision is part of its meaning, and the act is part of a ritual performed by traditional practitioners. A crowd of those who have this 'old school' view of male circumcision confronted someone who was treating it more as a medical, disease prevention intervention, and things got ugly. Modernity meets tradition. So the clinical trials on HIV and male circumcision have not only given rise to plastic gadgets, but also some measure of inter-tribal conflict.

Failing to treat TB, until TB treatment fails

2012-01-13T00:43:00.004-05:00

There are reports coming out of India of patients who have tuberculosis that responds to none of the existing drug regimes. When you have MDR (multidrug resistant) TB, the first-line drugs will not work on it, and your physician has to resort to second-line drugs that tend to be more expensive, less effective, have more side effects, and take longer to cure you from TB. When you have XDR (extensively drug resistant) TB, there is no point in you taking the first-line drugs as well as several of those in the second-line. Your clinical options and prognosis dwindle. Now there is the concept of TDR (totally drug resistant) TB, where patients are cast back into medical history, back to the time of the sanitorium and folk remedies.

TB is curable and, as is well recognized, failure to cure has to do with non-adherence to lengthy TB treatment, poor diagnostics, weak health care systems, and lack of political will. TB, in principle, could have been as prevalent today worldwide as polio. Instead, primary TB continues to kill millions every year, and if that is not bad enough, we now apparently have pockets of TDR in the world to control and contain. It is striking that a recent letter to Clinical Infectious Diseases states that systematically poor clinical management -- lack of medical ethics at the most basic level -- is helping to fuel TB drug resistance:

The vast majority of these unfortunate patients seek care from private physicians in a desperate attempt to find a cure for their tuberculosis. This sector of private-sector physicians in India is among the largest in the world and these physicians are unregulated both in terms of prescribing practice and qualifications. A study that we conducted in Mumbai showed that only 5 of 106 private practitioners practicing in a crowded area called Dharavi could prescribe a correct prescription for a hypothetical patient with MDR tuberculosis. The majority of prescriptions were inappropriate and would only have served to further amplify resistance, converting MDR tuberculosis to XDR tuberculosis and TDR tuberculosis.

Playing good cop/bad cop with Guatemala

2012-01-10T23:33:00.005-05:00

Last year, the discovery that abusive sexually transmitted disease (STD) research was funded and conducted by the US government in Guatemala in the 1940's was headline news. This week, we are hearing two quite different responses to those events in the press. The US Department of Health and Human Services announced that it will commit roughly 1.8 million to strengthen public health activities on HIV and STDs in Guatemala as well as help bolster ethical protections for research participants in that country. It is hard to see this newfound interest in Guatemala, STDs and ethics as a coincidence, and also hard not to see it as partly driven by public relations interests. But if it does good, it does good.

Then there is the other voice. Hundreds of Guatemalans who were participants (or family members of participants) are suing the American government for compensation. The US Department of Justice is apparently having none of it. The DOJ is quite willing to state that the research in Guatemala was shameful, unethical and downright wrong, but also quite happy to draw a very firm line between morality and legality: what is immoral is not necessarily grounds for a legal claim. So the DOJ is asking a federal judge to throw out the lawsuit. You can see the reasoning: President Obama and Secretary of State Clinton already formally apologized for the US government's role. President Obama set up a commission to express, to the countries in the world where the US does research as well as the American electorate, that those abuses are being taken seriously and steps are being taken to ensure no repeat performances. Isn't this enough?

Not everyone is comfortable about sticking purely with moral outrage and disapprobation when it comes to serious abuses of persons in biomedical research. Doesn't the whole pious talk about 'respect for persons' just blow hot air around if there is no place for punishment and compensation, at least in the most egregious cases? Obama's Commission itself seems to think that compensation for harm -- which governments and private companies have historically shied away from for obvious reasons -- needs to be rethought. We will see in the coming years which voice about Guatemala makes itself heard.

Bioethics of food in the DR Congo

2012-01-03T23:27:00.004-05:00

An article in the New York Times about the Democratic Republic of Congo had me thinking about bioethics on a very basic level. As organisms, humans need food to survive. This is clear. So if a society has become incapable of providing conditions where its citizens -- even formally employed ones -- can reasonably gain access to food for themselves and their families, something has gone really terribly wrong. This situation is not something that gains much attention in bioethics, despite the known impacts of undernutrition on health. For sure, nutrition makes an appearance once in awhile, say when discussing laws to ban trans fats in restaurants or sweetened beverages in schools. And the obesity epidemic will raise the profile ethical questions surrounding food production and consumption in the coming years. But the New York Times piece is not about how to regulate the consumption certain kinds of foods in order to promote health; it is about people being forced to chose who can get anything to eat at all. Choosing which of your children can eat today: that is a bioethical dilemma in a very raw sense.

Tracking the bioethics of food in the Democratic Republic of Congo would require a truckload of philosophy, history, anthropology, and most of all, economics and geopolitics. The well-known irony of the DR Congo is that it is one of the world's worst-off countries with one of the greatest reserves of precious natural resources. But it is not really an irony: it is closer to a causal relationship. Since colonial times, the Congo's lucrative natural resources (cobalt, coltan, gold, uranium) have drawn the attention of local and foreign governments away from the Congolese people and towards their own gain. The end result at this point in history is a kind of reductio ad absurdum of libertarianism: a country where the average citizen does not pay taxes, and is subsequently free not to receive much help from the government at all, in terms of roads, sanitation, education, health care, agriculture or food security. The recent farcical election in the DR Congo and the shameful near-silence about it in the aftermath indicates that it is not in the interest of any major power to change the status quo. So there will be food dilemmas and empty stomachs in Kinshasa households for the foreseeable future.

Ethically dubious business practices at Boingo

2011-12-19T23:19:00.007-05:00

This is a post about ethics, but not bioethics.

On my recent trip to Madagascar, I needed to get online at airports in order to do email and surf the web, in preparation for the planned bioethics and public health ethics workshop at the Institut National de Sante Publique and Communautaire in Antananarivo. So I signed on for a 'pay as you go' plan with Boingo, a company that enables you to gain access to internet hotspots at a price. You can find Boingo hotspots in airports from Malawi to Moscow to Jakarta. But the company, as I later found out, charges you outrageous prices for every access; has an app that facilitates without mentioning the precise financial implications of doing so (basically draining your bank card); intentionally makes unsubscribing to the service an ordeal, i.e. in my case a greater-than-one-hour wait on the customer service line. I was finally able to cancel my account, after the customer service representative offered that I pay 'only' about half of the bill that I was smacked with. So they made a juicy profit out of services I hardly used, and I am not alone in this. I wonder how those in lower-income countries, with undoubtedly less resources to extract themselves from the practices of dodgy companies, fare in such cases.

Amazingly, the company is celebrating its 10 year anniversary. If a research institution was found to treat research participants as Boingo treats its customers, heads would likely roll. I guess this is a difference between research ethics and business ethics: the former still clings to old-fashioned ideals like respect for persons, transparency and accountability. The latter is happier with 'buyer beware.'

Well, I feel somewhat better now. Back to global bioethics issues soon ...

Unhealthy ethical signals in India's clinical trial world

2011-11-13T21:59:00.005-05:00

Maybe I have been in this business a bit too long: I am starting to regard journalistic exposes about exploitive global health research in developing countries with (at least initially) with a jaded eye. This week The Independent newspaper is featuring a piece entitled Without consent: how drug companies exploit Indian 'guinea pigs'. The title itself is pushing all sorts of buttons: big Pharma + bad ethics + the vulnerable poor. But, as it stands, the content of the article only partially lives up to its vivid title. For those who read the original, consider the following:

The authors accuse researchers in India of not obtaining proper informed consent; participants are said to be not fully understanding what they sign up for. But full understanding is ever achieved in clinical trials conducted anywhere, including those with well-off, literate participants. There is more than a decade of bioethics literature on this.

A number of times, the authors state that there have been a number of deaths in clinical trials in India, and then later state that there has been no confirmed link between the deaths and study participation (including the use of the investigational drug). Unless a link is empirically proven, this is guilt by innuendo.

A number of persons provide soundbites about the Indian regulations of clinical trials being violated 'at every level' and on a regular basis. But concrete examples demonstrating grievous and widespread abuse -- or even detail on precisely what guidelines are being violated -- are not really on offer.

On the other hand, the journalists may have unearthed a couple of unethical nuggets. The Gates Foundation permitted local health authorities to empower headmasters to consent for their teenage girl students, i.e. the students were vaccine research participants without their or their parent's knowledge. If true, this is wrong. Since early this year, there have been accusations of 'enrolling' former victims of the Bhopal disaster into clinical trials without their knowledge. Again, if true, this is wrong. The editor of the Indian Journal of Medical Ethics states that he encountered fellow research ethics committee members unfamiliar with the practice of reading the protocol of the study they were reviewing. The practice of researcher/doctors investigating serious (fatal) adverse events in their own studies -- rather than having an independent body do so -- is cause for alarm. The concern about drugs being tested on those least capable of affording them is not new, but is still worth pointing out. And there have been numerous articles about the ethics of the clinical trial culture in India over the past five years: all this accumulative 'noise in the system' may reflect some serious and systematic wrongdoing. But you need verified and detailed facts to make it all stick.

There is an ethical tension in journalism between the pursuit of truth and the marketing of a compelling story. The whole narrative of global health research as a form of neo-colonialism, where the bodies of the poor are used and abused to make medicines for the bodies of the rich ... this story may be too attractive to pass up. The dodgy relationship between big Pharma and developing countries should be continually investigated, but we also need journalists who rake up some real dirt.

A struggle over samples in Taiwan

2011-11-08T22:11:00.003-05:00

Taiwan is experiencing an interesting confrontation about biorepositories. In some cases, it appears that, in the past, biospecimens were obtained and stored for research purposes without gaining consent for their use. In other cases, people consented to have their samples studied for some specific use, but researchers went on to use the samples to explore something else without informing them. Both practices run afoul of a rather conservative law has newly come into force, and that requires written informed consent of all biospecimens. In order to be compliant with the law, researchers must go back and locate the persons whose specimens were collected, and 'reconsent' them in order to use their samples for specific purposes. If they do not or cannot do so, they must destroy the specimens, and here we are talking about millions of specimens. Researchers are understandably concerned about the loss of a valuable scientific resource; advocacy groups are worried about exploitation and violations of human rights, given recent scandals of unconsented use of biological samples from indigenous populations in Taiwan.

Globally, issues about consent and biorepositories are still a work in progress: should there be consent for all specimens, including blood leftover from routine clinical examinations? When there is consent, should it specify certain limited uses of the specimen for research, or leave it unspecific and open to any kind of future research? The Taiwan example shows that the ethical and policy issues are best thought carefully through before biorepositories are created, and not when the horse has already left the stable.

Where the cheap babies are

2011-10-06T00:22:00.007-04:00

The New York Times has an interesting short piece about surrogate mothers in India. Apparently surrogate motherhood is becoming big business over there, big enough for the government to start regulating it. Or apparently, big enough for the government to draft laws to provide some measure of protection for impoverished women who rent out their wombs, but not so much legal protection that the lucrative surrogacy business climate would feel the pinch. The assisted reproductive industry in India brings in some $450 million dollars annually.

It is interesting how proponents of the industry regard the transaction between surrogate mother and clients as a 'win-win' situation. The mother gets money -- more than an annual income -- from the deal, and clinics supporting commercial surrogacy have every good reason to take good care of her, probably much better care than she would receive if she was having a baby of the old-fashioned (non-income generating) kind. But in order to see this as a win-win, there are large chunks of reality you need to forget: the poverty that motivates having a child for someone else (often from abroad) and the lousy standard of health care that typically goes with it.

The transaction is a 'win' that is quite compatible with losing, seeing as someone else gets the baby, and the life circumstances of the surrogate mother are unlikely to change dramatically. And it seems the legislation proposed is not going to help her much if something goes wrong: the law is silent on what happens in the case of miscarriage or other complications, for instance. As it stands, the regulations seem to send the message that everyone other than the surrogate mother -- the private clinic, the local government, the clients -- ought to be the real beneficiaries of this form of global baby trade.

Research ethics committees and the power of complaint

2011-09-17T23:54:00.004-04:00

Research ethics committees have had a bit of a rough summer. The Advanced Notice of Proposed Rulemaking (ANPRM) mentioned below implies that US research ethics committees working with the current version of the Common Rule are somewhat wrongheaded. When you are told that you need 'streamlining' in order to 'increase efficiency', it is hard not to conclude that you are bloated, misguided and ineffectual. It is noteworthy that the ANPRM is the first major revision of an influential research ethic regulation that is driven more by (researcher) criticism than by scandals (involving participants). The recent report by the Presidential Commission for the Study of Bioethical Issues -- centered on abusive US-funded research in Guatemala from 1946-48 -- does not seem to have motivated or made much of a mark on the proposed changes to the Common Rule.

That the ANPRM is complaint-driven, rather than scandal-driven, shows: there seems to be more emphasis overall about making ethical review of research more user-friendly for researchers than enhancing research participant protections. It remains to be seen where this 'deregulation' of ethical review is headed, and whether deregulation in this domain will have more positive effects than deregulation in financial circles.

The complaints and doubts about research ethics committees also seem to be going global. The current issue of the Indian Journal of Medical Ethics is largely devoted to the ethics of research ethics committees. How democratic are they? What gives them legitimacy? How should their roles be defined and their power monitored? These are all valid and fundamental questions. Such committees are hardly beyond criticism. But there should also be skepticism about the skepticism towards research ethics committees, or at least we should not only evaluate the reasons for the criticisms, but also where the criticisms are coming from and where they might be leading us.

Global implications of proposed revisions to the Common Rule

2011-08-10T00:53:00.006-04:00

For decades, criticism have been directed at Institutional Review Boards (IRBs) and the federal regulations they apply for the protection of human participants in scientific research. The procedures are thought to be too cumbersome, too bureaucratic, and too inconsistently applied. Studies that are low-risk are treated almost on a part with those of higher risk by the regulatory system, and in this way attention can get distracted from the main event, i.e. research studies in which participants really could get harmed. The IRBs were seen to be either losing their mission (with procedures that did not seem to help protect research participants) or expanding their mission in illegitimate ways (examining research methodology, tracking down potential conflicts of interest, etc.). Some researchers, of course, mostly railed at IRBs for being too damned slow, and impeding the progress of their (brilliant, earth-shattering) research.

But some of the more serious criticisms must have hit the mark, because the US government's Office of Management and Budget convened a working group to brainstorm revisions to federal regulations ('Common Rule'), and the group drafted an Advance Notice of Proposed Rulemaking (ANPRM) for public comment. The ANPRM appears in dense type for 20 pages in the Federal Register, and contains a daunting 74 questions for comment. For those not yet ready to dive headlong into the regulatory depths, Emanuel and Menikoff have published a useful summary of highlights in the New England Journal of Medicine.

Personally, I was wondering what the impact the proposed new revisions would have on international research. Changing the US Common Rule is no purely domestic matter; much research covered by the US federal regulations takes place abroad, and its provisions influence the regulations of other countries -- in this way the Common Rule has tremendous global reach. On the face of it, the proposed revisions don't have much of an international flavor to them, but I have been reflecting on possible implications.

Changes to annual review. The ANPRM floats the idea that there be no annual ethical review for studies involving minimal risk, unless an ethics reviewer can justify the need for continuing review. One would generally take it on faith that the research is proceeding as planned, with no modifications that could impact on the well-being of research participants. In my experiences in developing world settings, this is already happening in many cases: once a study is approved, it is approved pretty much forever. This is at least partly because continuing review requires infrastructure and monitoring (and file cabinets) that ethics committees in some settings just don't have. So some parts of the world are ahead of the curve on this one. What ANPRM might call streamlining, others might call poverty.

The new category of 'excused' studies. The ANPRM proposes a new category of review: studies that are excused from being reviewed by IRBs. These are studies in which the risks are 'informational', i.e. the risks are mainly from leaked disclosure of information rather than research interventions. Again, research ethics committees in developing countries might be ahead of the game here. The majority of social and behavioral studies have mainly 'informational' risks, and in many resource-poor countries, such studies are not reviewed at all. The whole category of non-biomedical research has been 'excused.' So if the revision goes through, this will be a confirmation of what is already happening, or rather, what is not happening.

Centralizing multi-site studies. Some studies have very many sites, and having the study reviewed by different IRBs at the different sites has often been a nightmarish experience. The ANPRM sensibly proposes that multi-site studies should have one IRB of record. What does this mean for international research? The ANPRM does not propose that a US IRB be the sole IRB of record when research is taking place at a foreign site. Local ethics committee review still makes sense '... because it might be difficult for an IRB in the US to adequately evaluate local conditions in a foreign country that could play an important role in the ethical evaluation of the study.' Why this could not also be true within a country as vast and diverse as the United States is not clear, but at least it means that past efforts to establish ethics committees abroad have not been in vain.

Control of biospecimens. The ANPRM is basically proposing one-time, general and 'open' consent processes in which participants agree to all their samples to be used by researchers in the future (for as yet unknown purposes) without reconsenting them. Here one might have some pushback from developing countries: the ownership of samples is still very much up in the air, and when samples are collected in many developing countries, they tend to end up in refrigerators in Maryland.

There is much more to be thought about -- this is just a first stab of what this wind of change in research protections may be bringing about.

Combatting and creating vaccine distrust

2011-07-27T14:57:00.005-04:00

NPR has an interesting piece on distrust of vaccines this week in developing countries. Apparently there are a growing number of anti-vaccine groups in resource-poor countries, with links to like-minded folks in more affluent nations. This development is alarming and depressing, because suspicions towards effective vaccines are more likely to have negative effects where health indicators are poor, infectious agents are prevalent and health infrastructure is fragile. The risk of negative consequences of a child not being vaccinated depends where the child happens to be; a parent's decision to forgo a child's polio or MMR vaccine is not the same in Baltimore and Lagos. Such parental decisions are less ethically controversial if the parent is working from a reasonable assessment of the risks and benefits of vaccination, rather than distrust based on hearsay, rumors or shoddy science. Researchers at the London School of Tropical Medicine are apparently studying the social determinants of vaccine distrust, and what is even more tricky, developing practical ways to combat distrust when unreasonable. If successful, this sort of applied social science could assist in the prevention of much morbidity and mortality in developing countries. As with other health interventions, it is not enough that a vaccination is efficient, even life-saving: to be integrated into practice, it has to be accepted in the hearts and minds of communities.

The piece includes a quite amazing, related story: that the CIA used a hepatitis vaccination program in Pakistan as a front in an effort to obtain DNA from bin Laden's family. The effort seems to have been double failure: failure to obtain the DNA and failure to vaccinate children sufficiently. It may well have succeeded in undermining the legitimacy of humanitarian organizations in the region, particularly those funded by the US. Is the potential exacerbation of vaccine distrust in developing countries justified by the (eventually successful) goal of assassinating the world's top terrorist?

Update: the New York Times has printed an editorial on the fake vaccination ploy by a former US Ambassador for HIV/AIDS and Assistant Director-General of the WHO on HIV/AIDS, tuberculosis and malaria. And, coincidentally, a piece in on the BBC news website has appeared about the global struggle to prevent and treat hepatitis.

Doing what is right when the result of research is death

2011-06-10T01:34:00.003-04:00

There is something intrinsically sacrificial about participating in biomedical research. Research exposes participants to some risks and often offer little no individual benefits. In some rare and extreme cases, research participants make the ultimate sacrifice: they die as a result of the intervention being tested. When this happens, there is a strong intuition that the participant's family should receive compensation for their loss. The intuition is also embedded in influential ethics guidance that researchers and their funders are supposed to adhere to: those conducting clinical trials are required to have insurance to cover such eventualities.

A column in the Times of India suggests a serious gap between regulations and reality. The records of the Drug Controller General of India (DCGI) indicate that 25 people died in clinical trials as direct result of study participation, but only the five families received any compensation. Of the minority who received compensation, the financial compensation for research-related death was quite low: between 3400 and 6700 US Dollars. The DCGI is apparently ready to take the major pharmaceutical companies on, having organized a meeting on June 6 to discuss lack of adherence to regulations. It will be interesting to see who wins this clash between for-profit and regulatory powers in India, where rapidly increasing numbers of clinical trials are taking place.

Avoiding the missionary position

2011-05-26T23:48:00.004-04:00

An intriguing book has just been published by Oxford University Press, edited by Catherine Myser, and entitled Bioethics around the Globe. The book examines, from loosely anthropological or sociological perspectives, variations in how bioethics is conceived and practiced in different parts of the world, as well as attempts to spread 'Western-style' bioethics globally. In regard to the latter, Raymond de Vries and Leslie Rott have written a provocative essay in which bioethics training programs (in the United States, continental Europe and the UK) are compared with old-style missionary work in developing countries. Either bioethics experts are flown into developing countries to spread the 'good word' of bioethics, or the natives are flown to Western centers of bioethics excellence, where they gather and return home with the 'right' bioethics notions and approaches.

If there was only one true way of doing bioethics, that those in the more affluent countries of the north just happened to latch onto, this would be less problematic. But as the rest of the book makes plain, bioethics wherever it is practiced tends to be heavily flavored by local morality, social conditions, and cultural norms. This means that attempts (however well-intentioned) to transfer Western bioethics into non-Western settings is going to be a bit weird at best, and harmful at worst. De Vries and Rott speak of various ills: blindness of Western bioethicists to the shortcomings of their own culture and to the cultural assumptions embedded in conceptions of informed consent and autonomy; the lack of cultural fit between what budding non-Western bioethicists get taught and what is relevant in their own culture. And what might be seen as relevant may arguably be relevant for the wrong sort of reasons. Learning how to set up an IRB might be interesting for those in the developing world hoping to attract funding and resources from research agencies, but that seems to miss the ethical point about protection of human participants in research. In these post-colonial exchanges, much is lost in translation.

How can the missionary trap be avoided? It is no simple thing. The dominant bioethics culture in the world is Anglophone, European-American, and secular with Christian overtones. Developing countries who want to expand their understanding and skills in this area are confronted with that particular world in the 'classic' texts, the most prestigious programs, and high-impact journals. Those interested in bioethics in the developing world need to be encouraged to (critically) tap into the 'Western' style of bioethics while also (critically) engaging with their own local moral traditions for guidance and inspiration. Only in this way will alternative bioethics traditions emerge. Those -- like the author of this blog -- involved in bioethics capacity-building projects in developing countries may still have a delicate role to play as facilitator or catalyst. In any case, the bioethics missionary has to be phased out, and replaced by those willing to listen as much as lecture.

Globalization of health research: old story, new twists

2011-05-16T18:05:00.003-04:00

When a story comes out called Big Pharma's Global Guinea Pigs, you can be sure of a number of things. There will be talk about the Tuskagee syphilis study, and if the author has been getting out lately, reference to the recent revelations about abusive US-led research in Guatamala during the 1940's. There will be mention of pharmaceutical companies outsourcing their research to cut costs, avoid red tape (read: institutional review boards) and gain access to research participants who are 'drug naive' (read: do not have regular access to adequate health care). The fact that FDA makes overseas site inspections as frequently as solar eclipses is brought in, giving the impression that when trials take place abroad, no one is really at the regulatory wheel. There is a good deal of truth to all of this, and perhaps it needs to be said repeatedly, given the challenges that the 24-hour news cycle poses to human retention. But it does get pretty tedious, so at this point I tend to scan these sorts of texts in search of a new twist.

The new twist in this particular news item is this:

In the United States, the Justice Department has mounted an investigation under the Foreign Corrupt Practices Act to see if drugmakers are offering overseas bribes, and clinical trials are firmly in the spotlight. That's because doctors in many countries are government employees and therefore any payments to them deemed above fair market value might be viewed as bribes. Britain, too, is introducing a strict new Bribery Act in July that also covers such overseas payments.

This is new, because most news items about global health research are focused on the possibility of research participants being exploited. Here, it is about alleged harm caused to medical institutions and patients by paying health care workers too much. Because just paying persons too much is not in itself a bribe: it is a bribe when the person starts bending rules for money, like a policeman on the take. And the rules being bent might come down to harm to research participants in the end, such as when overseas physicians in the pocket of Big Pharma 'massage' inclusion criteria for studies in order to satisfy the need for large sample sizes. As the global health research market grows, gets more diverse and complex, and the usual suspects get increasingly aware of the usual criticisms, the emergent ethical problems appear as new wrinkles in the old story.

The globalization of research ethics committees: paternalism, ethical imperialism or partnership

2011-04-16T00:26:00.004-04:00

Research, the story goes, has become increasing global: there is more clinical and behavioral research involving human participants in more places in the world now than ever before in human history. These things don't just happen, so it is interesting to reflect on the meaning of the march of research to all points of the compass. Is it because there is an overwhelming humanitarian concern about those who are sick in the most impoverished areas of the world? Or is it because far-flung (at least, from North America and Europe) countries are a friendly business environment as health-related research becomes more and more about developing profitable interventions and devices?

As research projects and institutions are rapidly springing up around the world like mushrooms, the development of ethics committees to review such research globally is moving at a much more leisurely pace. In many places in Africa, for instance, there is no local body with the authority or expertise to conduct an adequate ethical review of a scientific protocol. In this month's issue of Tropical Medicine and International Health (subscribers only, alas) Ravinetto et. al. argue that there always ought to be a double ethics review of research conducted/sponsored by foreign institutions in developing countries. The requirement for 'local' review -- in addition to review in the sponsor's institution -- appears in some ethics guidelines, and it does happen a good percentage of the time. But why ought it to happen? According to Ravinetto et. al., it ought to happen in order to produce a more comprehensive and balanced review process, which in turn better fulfills the central mission of ethics committees, i.e. to protect research participants and benefit communities affected by the research. A collaborative double review can avoid ethical imperialism (imposition of ethical standards of the richer countries on the poorer ones) and paternalism (in the assumption that only ethics committees in richer countries can really review research adequately). The current problem with double review (according to Ravinetto et. al.) is not just the unpleasant fact that some ethics committees in developing countries may be operating at a low standard. The problem is that ethics committees involved in the review of research often do not correspond with one another at all, and the possible benefits of collaboration are missed.

The points are well taken, but the paper seems to underrepresent some of the ethical challenges of ethical review in a context of global inequality. It should be remembered, for example, that sponsoring countries hold the purse-strings, including the portion of the budget that is supposed to go to the local institutions for administrative support (including financial support for the local ethics committee). When there are conflicts between foreign and local ethics committees, which one is more likely to have the greatest say? The ethical playing field, parallel to the political and socio-economic playing fields, is very uneven. What might help, besides greater collaboration between ethics committees, is greater investment in local scientific institutions in order to prevent the vast majority of research being funded and conducted by developed world institutions.

The unbearable fragility of HIV treatment access

2011-04-09T22:14:00.004-04:00

It has taken a tremendous effort, over the course of many years, to give HIV-positive persons in sub-Saharan Africa access to antiretroviral treatment. On the World Health Organization's latest reckoning, over five million persons are now on treatment worldwide. However, the success is partial: another ten million persons in need of treatment currently do not receive it, and the pool of those who will need treatment in the future is expanding furiously -- over 7000 new HIV infections take place globally every day.

Even the partial success in access to treatment is very, very fragile. The global HIV treatment initiatives are generally bankrolled by the developed world's financial heavyweights who (after debilitating their own economies) are calling for austerity and belt-tightening, and programs supporting the lives of distant others are looking vulnerable.

But the challenges to maintaining and expanding HIV treatment programs apparently come from all angles. AllAfrica, that great warehouse of online African news, gives two recent examples. Kenya has been hit by a rise in food prices and a drought. Nearly two and a half million Kenyans are regarded as food-insecure, as prices have risen 15 percent; herders are losing their livestock in the dry north-east of the country, and some are fleeing to Uganda. For those who are food-insecure, HIV-positive and in need of antiretroviral treatment, the situation is grim: even for those who can access treatment, the pills are very hard to tolerate (and less effective) on an empty stomach. Some people would rather go off treatment than deal with the side-effects, though this could lead to resistant strains of HIV; others are reluctant to start treatment, which is likely to lead to poor clinical outcomes. In Tanzania, another twist: a sizable patients taking antiretroviral treatment may fail to adhere to treatment in their quest for the latest miraculous herbal cure. A former Lutheran pastor in the village of Loliondo has concocted something which has stirred a great deal of excitement, as would any substance promising to cure diabetes, tuberculosis and HIV. The ingredients are unknown, but the Tanzanian Drugs and Food Authority, the National Institute for Medical Research and the Muhimbili National Hospital endorse the herb as fit for human consumption. But there is no proof of its efficacy. No matter: people with HIV are flocking there by the thousands, some persons literally dying to get there. The Tanzanian authorities are struggling to convince people to continue taking their drugs, and not succumb to the siren song of an HIV/AIDS cure. (It is always more pleasant to imagine an indigenous cure than deal with the reality of depending on products of foreign multinational pharmaceutical companies.) With all these pressures -- economic crises, natural disasters, rising new infections, strange cultural manifestations -- is it reasonable to expect the pool of those accessing HIV treatment to continue to expand? What is the plan B if the bubble bursts?

New report on a forgotten non-pandemic

2011-03-13T19:26:00.007-04:00

There are certain things we know about the avian flu scare back in 2009. First, that the initial fears, amplified tremendously by the media, culminated in a non-pandemic. When the World Health Organization (WHO) announced that H1N1 was no longer a global health threat, the news appeared somewhere deep in the back pages of newspapers. Second, pharmaceutical companies made a massive amount of money by producing and distributing Tamiflu in vast quantities. Third, critics suspected the World Health Organization of being in the pockets of pharmaceutical interests by whipping up fears of mass infection and death on the one hand, and fully integrating private for-profit companies into the global response on the other. The fact that advisors to WHO's Emergency Committee had undeclared potential conflicts of interest with pharmaceutical firms did not help matters.

Last year, an International Health Regulations (IHR) Review Committee was convened, consisting of an independent panel of 25 experts, to examine the WHO's response to the avian flu threat. The draft report is now available online, and it seems somewhat unsatisfying to conspiracy theorists and defenders of the WHO alike. The Committee contends that while the WHO could have done a better job in managing apparent conflicts of interest among its advisors, there is no evidence that the advisors' judgments were adversely influenced by their drug company connections (though one wonders what would count as evidence). There is also no hard evidence that the WHO 'sexed up' the data on avian flu in order to make the epidemic appear more threatening; there was no way of knowing at the beginning that the rate of new infections would fizzle out rather than explode. The report is less about ethically criticizing the relationship between the WHO and big pharma, and more about practicalities of improving global pandemic response in the future. The avian flu scare exposed serious weaknesses in systems of global pandemic control. In other words, the IHR report seems to mimic the pattern of the 2009 avian flu scare: the prospect looks urgent and compelling at first, but on closer inspection, there seems to be less to meet the eye, at least from an ethical perspective.

The President's Commission ponders global safeguards in research

2011-03-07T22:18:00.007-05:00

An article by Mike Stobbe on global research ethics is doing the rounds: my Google Alert has been sending me its many incarnations, as the piece seems to have been sold and resold to various news outlets. Titles vary from 'Ugly US medical experiments uncovered' to 'Shameful past of medical trials prompts new US investigations' and all sorts of other permutations. The first line of the article, though, is not promising:

Shocking as it may seem, US government doctors once thought it was fine to experiment on disabled people and prison inmates.

It should not be too shocking, because the National Institutes of Health sponsor and conduct research studies involving the disabled and prisoners right now. It was not just the populations that were the problem with those experiments, of course. It were the procedures, and more specifically, studies in the past that involved deliberate infection of healthy (but vulnerable) persons. Stobbe has himself sniffed around in the archives to find some more skeletons in the US research closet, and adds them to the scandals we already know: Tuskegee, Willowbrook, the Jewish Chronic Disease Hospital, the AZT trials, the Trovan study. He leavens his account with an indication of how health research has gone global: drug studies, once almost exclusively conducted in the US on prison populations, has been redirected to developing countries in order to evade stricter regulations at home and to hold down study costs.

This potted history is a lead-in to last week's meeting of the Presidential Commission for the Study of Bioethics Issues. The Commission devoted an afternoon to comments and discussion about global health research ethics, Commission having been given two tasks by President Obama: to investigate dubious US government funded studies in Guatemala in the 1940's, and to see what system of protections and safeguards exist to ensure that similarly abusive research does not happen. This is an enormous task, and the Commission has little time to complete its mission. They did invite an amazing array of experts for the session on March 1st that is well worth watching. What struck me, however, was the public comment session: a fair number of people stood up to give personal testimony of how they were subjected to secret government experiments, involving electroshock treatments, mind control, torture and so on, followed by way too much information about physical and psychological symptoms. Either mentally unbalanced persons are drawn to commissions about abusive research like moths to a flame, or there is much more abusive research taking place in the United States than we know about.

UPDATE (March 10th): I was amazed by the testimonies during the public comment session of the Presidential Commission. Those over at Are You Targetted? are not amazed at all by the content of the testimonies, where citizens claimed to be victims of abusive and covert state-sponsored research, but are amazed by the fact that the news outlets did not seem to cover this part of the proceedings at all. It is strange that the high drama and vividness of these testimonies was not considered newsworthy.

Pneumoccal vaccine in Africa: one step forward, one step back?

2011-03-04T23:20:00.003-05:00

It is pretty well known that many routine medical interventions in the world's more affluent countries make infrequent appearances -- or sometimes none at all -- in the world's poorer ones. The publicly-financed health care systems in some sub-Saharan Africa look to be decades behind the United States, Canada or the United Kingdom when it comes to devices, drugs and procedures. For that reason, initiatives that seek to close the gap are, in principle, to be welcomed. Oftentimes, however, these initiatives are accompanied by moral baggage.

Take for instance the launch of a new pneumoccal vaccine among children in Africa. Considering the number of childhood deaths attributable to pneumonia in this part of the world, the effort has an initial air of nobility. Many lives will be saved, many illnesses avoided. But if one looks more closely, serious ethical problems seem to emerge. There are two multinational pharmaceutical companies involved in the campaign -- GlaxoSmithKline and Pfizer/Wyeth -- who have agreed to sell 30 million doses every year for ten years at $10.30 per child vaccinated. These companies also stand to each gain $225 million in subsidies through their involvement in this scheme. Doctors Without Borders worries that this price for vaccination is very high for many countries, and that the lock on the market exercised by GSK and Pfizer/Wyeth will strongly discourage local companies from developing cheaper generic equivalents. The companies are establishing their brand under favorable circumstances to themselves; after that, all bets are off.

Some people argue that pharmaceutical companies should be given incentives to focus greater attention on developing countries, otherwise they will simply develop whatever is likely to sell to richer consumers elsewhere. But the pneumoccal vaccine example can make you think twice about the wisdom of 'incentivizing'. In the short term, many children will be vaccinated. But in the long term, unless prices are made to go down, children of wealthy elites within developed countries are most likely to benefit. The usual pattern threatens to repeat itself: big business wins, the higher classes win, and the rest struggle on.