Friday, January 11, 2008

The ethics of research on neglected children in Romania


Probably many people remember television images of abandoned children in crumbling Romanian 'care' institutions after the execution of Ceau┼čescu. In 1967, the late dictator ill-advisedly decided to rapidly increase the nation's population (partly by banning sex education, contraception and abortion), and by the time the Eastern Blok went into an economic meltdown in the 1980's, the number of children in state care had reached 100,000. Images of lice-ridden, malnourished children, some tied to cribs, led to an outpouring of sympathy, and the 1990's saw thousands of 'rescue adoptions' of Romanian children from families in Western Europe and America. Unfortunately, sympathy was gradually perverted by the law of supply and demand: between 1989 and 2001, it seems that a good number of poor Romanian families (30,000 on some accounts) were basically handing over their children to Romanian institutions for cash, and the latter were making money by brokering adoptions of these so-called orphans to well-off Westerners. When that story broke -- not coincidentially related to the Romanian application to join to the European Union -- the government were pressured into banning international adoption, started overhauling its child care system, and embarked on a controversial national policy of forcing parents to take their abandoned children back. In 2007, Romania was finally accepted into the European Union, prematurely according to some, because many of its child care institutions, particularly in regard to disabled children, still struggle to meet adequate care standards.

How does the idea of involving institutionalized children in Romania in medical research sound? Probably not very good, especially among those acquainted with the history of research ethics in the United States, and the hepatitis experiments among institutionalized children at Willowbrook State School in the 1960's. Romanian orphans seem like the very embodiment of the concept of a vulnerable population, and therefore a ethical hot potato. Researchers who choose them as study participants -- in this age of intensified ethical scrutiny -- would seem to have a career death-wish.

Science last month published the results of a US-sponsored research study on institutionalized Romanian children along with an accompanying ethics commentary. The main research question of the study was the effects of institutionalization vs. foster care on cognitive development in children. A number of institutionalized children were randomized into two groups: a group that would remain institutionalized and a group to be placed in foster care. Especially for those without a subscription to Science, an excellent detailed description and analysis of the study can be found at the Adventures in Science and Ethics blog. Unsurprisingly, the children under foster care scored significantly better on cognitive tests than their institutionalized counterparts.

A number of things struck me about the study. First, there seems to be a trend in publishing ethics commentaries in conjunction with studies anticipated to be controversial. That happened with the first randomized controled trials on HIV and male circumcision too. Even if such commentaries sometimes glide between analysis and rationalization, they at least show the researchers acknowledged ethical concerns and tried to resolve them. It opens debate. What is not mentioned by the researchers or the commentary is that the study was challenged from an ethical point of view already far back as 2002. So they had some time to hone their arguments.

Second, the study reopens the debate about unduly protecting vulnerable populations from research that could ultimately benefit them -- itself an unethical outcome. Some may have the kneejerk reaction that Romanian orphans should not be participants in research, period. But the researchers seem to have done at least a passable job of moving through the ethical labyrinth, proactively addressing ethical concerns surrounding the participants, and the study results are likely to benefit Romanian orphans (and institutionalized children elsewhere) in the future. It may not be to everyone's taste, but it is no Willowbrook.

Lastly, research is a dirty business, and no good deed goes unpunished. Now that the Bucharest Early Intervention Project and the commentary are out there, potential ethical shortcomings may be laid bare by observers. There can be questions about equipoise -- was there really uncertainty that foster care was better than institutionalization? -- especially when the researchers themselves stipulated that (for ethical reasons?) children in the foster care group could not be switched back to the institutionalized group. There is little word of what happened to the children in the institutionalized group. Are they still there? Did the researchers arrange foster care for them, which might have benefited them, albeit belatedly? The research had local health ministry support, but apparently no local ethical review -- is that something the researchers or their funders should have done something about? And so on. The Bucharest Early Intervention Project should prove an interesting research ethics case for years to come.

Thursday, January 03, 2008

The virtues and perils of putting HIV/AIDS into perspective

It looks like 2008 will be a strange year in HIV/AIDS circles. The prospects of controlling the rise of new infections have been dimmed: 2007 was marked by a series of painful setbacks in HIV prevention research, particularly in regard to microbicides, diaphragm and vaccines. Estimates of the scale of the epidemic have been redrawn: the numbers of persons living with HIV/AIDs (most notably, in India) are still in the tens of millions, but found to be substantially lower than previously estimated by the World Health Organization and UNAIDS, raising doubts about these organizations and their statistics. Last year also saw the publication of two high-profile books by Helen Epstein and James Chin that took dead aim at flaws (and some sacred cows) in HIV-related research, policies and programs.

Continuing the dark trend into the New Year, Daniel Halperin has written a New York Times editorial ('Putting a plague in perspective') that gives voice to a very real concern, namely that more mortality and morbidity in developing countries could be reduced if some of the billions of dollars currently devoted to HIV/AIDS in developing countries were spent on other things, such as clean water provision, nutrition or less fashionable (but no less serious) diseases. The pendulum seems to be swinging: since the beginning of the epidemic there have been continuous and passionate calls for greater financial resources to fight against HIV/AIDS from researchers, activists and policy-makers. And their calls have gradually been answered, to the extent that there is now talk of HIV/AIDS being an industry in itself, with its own big agencies (like UNAIDS) and big programs (like PEPFAR and the Global Fund) and big conferences (like CROI and the World AIDS Conferences). But now it looks like a new zeitgeist has arrived, where HIV/AIDS is starting to be viewed as one important global health priority among others. A big killer, yes, but no longer the king of the jungle.

There is an important truth in Halperin's perspective. The struggle against HIV/AIDS should be embedded within a larger political and ethical struggle to raise the health and well-being of populations in developing countries generally. Millions of people continue to live their lives in absolute poverty, millions of people die annually of preventable and treatable diseases, and the gulf between the affluent and the poorer nations is widening. The point of 'putting the plague in perspective' is not to downplay the significance of HIV/AIDS as a worldwide public health problem, but to expose global inequality and injustice, and to develop effective research, policies and programs engaging with the most pressing needs of communities.

But at this point, a skeptic may wonder. Will this expanded vision sell? How many funders be interested in combatting (very unsexy) diarrhea in Tanzania? Where are the activist groups for leishmaniasis, schistosomiasis and onchocerciasis? Can we imagine the US Congress (or the European Union, for that matter) approving billions to something so mundane as water improvement in Malawi or combatting deforestation in the Congo? And what, ultimately, is the difference between what Halperin is saying and those in development circles have been trying to do for decades, and which has hardly been a glowing success in Africa? From this skeptical perspective, 'putting the plague in perspective' is like going from the frying pan to the fire: if you think HIV/AIDS is bad, wait until you see the larger picture of long-standing and intractable problems.

Maybe there is a way of putting the HIV/AIDS epidemic in proper perspective without falling into paralyzing skepticism. The year is young ...