Failing to treat TB, until TB treatment fails

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

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

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.

Top 10 HIV and ethics stories for 2011

I was looking on the web today hoping to find a top-10 list of bioethics stories for 2011. It is time of the year for such lists, and you would think that someone would be busy compiling bioethics stories of global significance, like whether extremely obese kids should be removed from their parents, the identity issues raised by face transplants or those pesky animal-human hybrids. Alas, I can't seem to find anything. There is always the Top 10 Evil Human Experiments, but beside the question of how these are determined (is there an Academy of Evil?), this is not specific to 2011. Of all places, IRIN/PlusNews, the humanitarian news and analysis service of the United Nation's Office for the Coordination of Humanitarian Affairs, has put out a top 10 list of the HIV/AIDS stories of 2011. And we can go with that, since the global significance of HIV/AIDS, and it only takes a certain degree of tweaking to turn it into an ethics list. It is in no order of importance:

1. HIV/AIDS turns 30. In June 1981, the CDC published a report in its Morbidity and Mortality Weekly Report (MMWR) about cases of what would later be called AIDS. Despite three decades of research and program implementation, both often hindered by politics and alternative public and private priorities, millions continue to be infected by HIV and die of HIV-related causes each year, particularly in low-resource settings like sub-Saharan Africa. How many died who could have been saved during this period, were it not for stigma associated with the condition and the stubborn preference among the world's wealthiest nations for military rather than health-related expenditures?

2. ARVs as prevention. Prior to 2011, there was already some evidence that being on antiretroviral treatment reduced the risk of a HIV-positive person transmitting the virus to others. The HPTN 052 study, a randomized controlled trial with sero-discordant (i.e. one partner HIV-positive, the other not) couples sealed the deal in 2011, indicating a 95% reduction of risk. The real ethical challenge now is implementation: should we target antiretrovirals for prevention purposes at those most likely to transmit the virus? How is this fair to those (such as children) who need such treatment but are unlike to pass it on to others?

3. AIDS funding. Research breakthroughs like the HPTN 052 study come at a painfully ironic time: just when real progress is made with HIV prevention research, we have an economic downturn that seriously threatens funding for studies and initiatives. The Global Fund for HIV/AIDS, Tuberculosis and Malaria just ditched its round of funding for 2011-2013, citing lack of sufficient contributions from supporting countries. What does this mean, ethically? Over the last decade, there has been a tremendous increase in the numbers of persons gaining access to anti-retroviral treatment. Cutting into programs could mean cessation of treatment, with serious potential impact on individuals and public health (in terms of rise of drug-resistant HIV strains).

4. Disappointing HIV prevention trials. The idea of giving antiretroviral drugs to HIV negative persons in order to prevent them from acquiring HIV has been kicked around for awhile, but 2011 has been an awful year for this line of research. Last year, the CAPRISA microbicide study looked very promising. But this year saw the crash and burn of two important studies (FEM-PREP and VOICE), tossing the whole pre-exposure prophylaxis approach to HIV prevention into serious disarray. Besides, if you want to (ethically) do a study with those exposed to HIV infection, doesn't HPTN 052 now imply that you ought to provide antiretroviral treatment to their partners? The mind boggles.

5. Gaffe prone politicians. Yes, this was on last year's list. It is still allowed, as long as you come up with fresh gaffes, and politicians are all too happy to help. Helen Zille, premier of the Western Cape (South Africa) apparently aimed for the title of most gaffe-prone this year. After stating that all HIV positive persons who knowingly infect others should be charged with attempted murder, she came up with a spectacular encore: the creation of an HIV lottery of sorts, where you get a chance of a cash prize if you get tested for HIV. For those not ready to regard these as gaffes, there is always Christine Ondoa, Uganda's new Minister of Health, who claimed in August to have known three persons cured from HIV by prayer. Top that one.

6. Anti-gay legislation. Anyone can make a gaffe. But attempting to make laws that discriminate against persons at heightened risk for HIV on the basis of sexual orientation is another matter. In sub-Saharan Africa, there is a perception that being gay is 'anti-African', as if same-sex orientation would be a Western import along with Volvos, Ipads and hot yoga. Mindless prejudice tarted up as defense of traditional values is nothing new or especially African, but the ferocity of the denial, as well as its negative public health consequences in the midst of an epidemic, might end up having a special African character. But not in a good way.

7. Threats to generic ARVs. HIV is tricky, and it takes a great deal of research investment to create drugs to control it. Those with the deepest pockets -- Big Pharma -- are most likely to develop antiretroviral drugs. While having cheaper generic versions of these drugs are in the interest of poor individuals and nations, it is not in the financial interest of the multinational corporations concerned. 2011 saw conflicts between generic ARV manufacturers in India and European Union, where the EU is widely seen as not being on the side of the angels. In 2012, mathematical modelers should examine the 'persons vs. patents' consequences of whatever policies come to pass.

8. Contraception and HIV risk. Some philosophers wonder if our urge to have children has any rational or ethical basis, but most take this conception as an unquestionable value. But in regions where HIV is highly prevalent, how to conceive without the mother and child risking HIV infection? A condom reduces risk of both HIV and conception. In 2011, a study suggested that a popular contraception drug (Depo-provera) increased risk of HIV acquisition and transmission. Back to the drawing board for researchers perhaps, but in the real world, couples continue to be torn between conception and HIV risk.

9. Medicines Patent Pool. As the IRIN/PlusNews report puts it, 'The patent pool was established in 2010 by the international health financing mechanism, UNITAID, and aims to stimulate innovation and improve access to HIV medicines through the negotiation of voluntary licenses on medicine patents that enable generic competition and facilitate the development of new formulations.' Quite a mouthful, but the point (see #7) is the impact this initiative has on patient access to HIV medicines in actual practice. Gilead should be commended for dipping its toe into this new pool in 2011. We will see if other big pharmaceutical companies follow suit.

10. New HIV targets. Yes, it is easy to get cynical about ambitious targets set by international health agencies, when you consider they rarely if ever get met. In June, the United Nations came out with the language: 'Zero new infections, zero stigma and zero AIDS-related deaths." On the face of it, a bit ridiculous: really, zero? Can we believe that any more than zero-teenage pregnancies, zero-drug abuse, or zero-drinking and driving? In reality, it is more a rallying cry or slogan than a goal. Goals have numbers on them, and the numbers are generally not 'zero'. Doubling the numbers of those on ARV treatment, halving TB-related deaths among HIV positive persons, bringing mother to child transmission of HIV down towards zero, and increasing prevention options among the vulnerable are valuable goals. This may be deja-vu for resource poor countries in Africa, and in an economic downturn the probabilities are altered. But it is better to have targets than none at all, as long as there is some commitment to pursuing them. Something like New Year's resolutions?

Ethically dubious business practices at Boingo

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

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

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.