Exciting new bioethics research topic: the Pope

Former South African president Thabo Mbeki and his fellow ideological travellers in the South African Ministry of Health encountered much domestic and international criticism for their positions on HIV/AIDS. Mbeki once claimed that he 'knew no one who died of AIDS' (it was poverty that did them in) and was cosy for awhile with a fringe group of researchers who deny that HIV exists, or if it exists, that it causes AIDS. The former president was soon clever enough to realize that these positions were very unpopular in a country with a raging HIV/AIDS epidemic, and so left it to various health authorities in the country to express similar beliefs. The former Minister of Health, Manto Tshabalala-Msimang, famously suggested that HIV virus could be treated with lemons and garlic, and that anti-retrovirals were poison, and only benefitted the pharmaceutical companies that produced them. But these were only the most flamboyant characters in the tale. The less-known story is how this absence of leadership, or just plain obstructionism, immobilized the South African health system in regard to HIV prevention and treatment for years, or what the true cost of that paralysis really was in terms of human morbidity and mortality.

Recently, however, two studies have put numbers where there was only speculation and accusation. A mathematical modelling study at Harvard University estimates that Mbeki and company's stance was responsible for the deaths of 330,000 people. A paper by Nicoli Nattrass at the University of Cape Town comes to roughly the same figures: 343,000 lives would have been saved over 9 years if the South African government was not engaged in 'genocide by sloth.'

Which brings us to ... the Pope. The Pope is visiting Africa this week, where he has declared that the use of condoms is not the answer in the fight against HIV/AIDS, and the answer is abstinence. Of course, Pope Benedict is not the first Pope to talk to Africans about how to have (or not have) sex, or the first to say that the distribution of condoms 'can even increase the problem.' As usual, these statements will infuriate many in the HIV prevention community who regard abstinence as a largely failed approach and regular condom use as a crucially important element in the struggle against HIV/AIDS.

But instead of getting angry, researchers should do with the Pope what was done with Mbeki: devise rigorous studies to quantify the number of deaths and new HIV infections that have resulted from the Vatican's position. How many new HIV infections and AIDS-related deaths might have been averted due to the Papal condemnation of condom use, particularly in Christianized African communities? And how does the resultant carnage of preventable deaths square with Christian values? It is not enough to complain: we must study the Pope and his effects, just as we would any other global health hazard.

Bioethics and the stimulus package

Last week, the National Institutes of Health (NIH) announced to great fanfare its new Challenge Grants program. The grant program is funded, to the tune of 200 million dollars , by the Obama administration's American Recovery and Reinvestment Act -- part of the 'stimulus package' we have been hearing so much about. This new grants mechanism will support studies on what are called 'challenge topics', i.e. specific high impact biomedical, social and public health research areas.

Shockingly, bioethics is considered one of those areas. Applications are requested for proposals about informed consent and data access policies; ethical issues of emerging technologies; ethical issues in health disparities and access to participation in research; ethics of sharing of electronic health information; ethics of translating genetic information into clinical practice; the ethical issues involved in the blurring of research and treatment; and research on recontact issues in genotype and genome-wide association studies. Those of us working in international bioethics and research ethics were especially excited by the sentence " ... studies are needed to assess the impact and ethical considerations of conducting biomedical and clinical research internationally in resource-limited countries." This is certainly a challenge topic, and no doubt relevant, given the increasing amount of US-funded or facilitated research taking place around the world, especially in the world's poorer countries.

And then came the fine print. A couple of days ago, the NIH added a notice to the request for applications. It reads:

Funding for this program is provided under the American Recovery and Reinvestment Act of 2009 (Recovery Act). The purposes of the Recovery Act are to preserve and create jobs and promote economic recovery in the United States, and to provide investments needed to increase economic efficiency by spurring technological advances in science and health. Consistent with these goals, domestic (United States) institutions/organizations (i.e., those located in the 50 states, territories and possessions of the United States, Commonwealth of Puerto Rico, Trust Territory of the Pacific Islands, or District of Columbia) who are planning to submit applications that include foreign components should be aware that requested funding for any foreign component should not exceed 10% of the total requested direct costs or $25,000 (aggregate total for all subcontracts and subawards), whichever is less.

This does not mean that you cannot propose an international research ethics project involving foreign collaborators and institutions. It just means that you have to find collaborators and institutions willing to swallow the fact that, even if the topic is about health disparities and research in low-income settings, 90% of the grant money must stay in the United States. Dealing with that painful irony may be a challenge in itself.

How friendly can Big Pharma be to developing countries in a down economy?

Pharmaceutical companies are easy targets of ethical criticism, and it is easy to see why. They invest vast amounts of capital to develop drugs that can be crucial for health, and seek a profitable return on their investment through consumption of the drugs by patients. Profitable returns are only likely when significant numbers of consumers suffer from the condition the drug aims to treat, and when those consumers have sufficient buying power. From a profit-seeking pharmaceutical perspective, there is little incentive to develop drugs for conditions that are prevalent in countries where few people have the wherewithal to purchase the drugs. There may be an urgent health need for such medicines, but if there is no market for them, no return on investment, then it is unlikely that pharmaceutical companies will develop such drugs or faciliate access to them. Unless, of course, developing such drugs and increasing access to them is part of a public relations ploy, meant to enhance the company's brand.

The head of GlaxoSmithKlein (GSK), Andrew Witty, apparently caused a stir at Harvard Medical School last month by promising that his company would make essential medicines accessible to developing countries and commit more resources to research on neglected diseases. More precisely, GSK will take 20% of its profits from sales in developing countries and reinvest back in local health care infrastructure, and patented medicines produced by GSK will be sold at 25% of their market value in the 50 poorest countries of the world. In addition, there was talk of a 'patent pool' for neglected diseases, i.e. an agreement between various patent-holders to share (for some fee) those patents with each other and with third parties.

These promises may make GSK look saintly, but the impression largely fades on reflection. 20% of GSK's profits in developing countries does not amount to much; an editorial in the Lancet calculates it as less than 0.1% of GSK's total profits, and the folks at Policy Innovations see this as boiling down to about $50,000 per country, hardly a generous investment in local health infrastructure. Selling patented medicines at a quarter of the usual (bloated) price may not be of much help either to those who live on a few dollars per day. And while giving access to patents sounds nice, the road from possession of patent information to research to marketing is a long and winding road paved by a great deal of money. Who has that kind of money? The big pharmaceutical companies, like GSK. But they won't really invest to create drugs for conditions affecting developing countries because the profit margin would be meagre. We come full circle.

Gestures of philanthropy towards the world's poorer nations, on the part of aggressively profit- seeking pharmaceutical companies, is to be taken with a grain of salt at the best of times. In a down economy, when pharmaceutical companies are merging for their own survival, full-blown skepticism is in order.

The ethics of outsourcing clinical trials, one more time

Since the mid-1990's, and clinical trials on drugs to prevent mother-to-child transmission of HIV in Africa, there has been a growing academic literature on the ethics of clinical research in developing countries. Of course, this is an academic literature, which means that only a vanishingly small number of the world's population has actually read any of it. But the general popularization of the economic practice of 'outscorcing' has raised public awareness of the debate somewhat, together with the steady stream of scandals and suspicions emerging out of India, which seems to be a lightning rod of ethical concern about clinical trials lately. The global clinical trial outsourcing phenomenon is a wild and woolly affair: it is not known precisely how much of it is going on, precisely what sorts of studies are taking place, how regulatory oversight works (or doesn't) in actual practice, and what to think -- from an ethical point of view -- about the whole messy business. And it is important to get some clarity on this subject: given the vast health and other inequalities between the agencies funding and institutions largely conducting clinical trials in developing countries, how can such studies avoid plunging into one or another ethical pitfall? So it is timely that the New England Journal of Medicine published a commentary entitled 'Ethical and scientific implications of the globalization of clinical research' a couple weeks ago.

However, a piece in the New York Times on the NEJM commentary was not very positive, and it is not hard to see why. The authors breezily trot out the usual ethical problems in clinical trials: relative lack of understanding of research procedures by research participants; possible undue inducement by financial compensation offered to the poor; large differences in standards of care and possibility of ethical double standards, i.e. study designs in developing countries that would be allowed in more affluent ones; uneven research oversight by local ethics committees; drugs tested on participants not being responsive to local health needs; drugs developed from the research not being accessible to the communities who participated in the research. All of these are legitimate concerns, or at least can be, in particular clinical trials. But the NEJM article does not add anything here to current debates engaging with more fundamental questions: how much understanding is 'enough' for informed consent, in any research study, with any population? What makes an inducement undue? Are all cases of double standards wrong? What does it mean for a study to be 'responsive' (or not)? Are all cases of communities not having (immediate?) access to study drugs necessarily ethically wrong?

Whenever the commentary departs from old concerns, it seems to glide into hot water, particularly when it offers recommendations to address the ethical problems raised by the globalization of research. The authors suggest that clinical trials are outsourced largely because of bureaucratic regulations in developed countries, which adds to research costs, and therefore these regulations should be 'streamlined' in order to de-incentivize doing clinical trials abroad. It is a charming idea that ethics committees would be responsible for stimulating the globalization of research (and indirectly, the ethical problems that go with it), but it seems more likely that streamlining the processes at home will simply increase the number of trials abroad, as long as the economic disparities between countries remain in place. You will simply get your IRB approval faster. Besides, if you want to 'de-incentivize' clinical trials abroad, why not build up ethical review in developing countries, or force pharmaceutical companies to pay to build local health infrastructure and capacity as a cost of doing business, rather than scaling down IRB processes at home?

There is a sneaking sense in the NEJM commentary that the ethical problems raised by the globalization of clinical research is 'our' problem -- i.e. that of the more affluent countries -- and that it our responsibility to fix it:

Industry sponsors, contract research organizations, and the academic community can meet the challenges of globalization by accepting full responsibility for the ethical conduct and quality oversight of these trials.

There is little hint that such responsibility needs to be -- for ethical and practical reasons -- shared with local communities in which research takes place, as well as national governments, ethics committees, research institutions, NGOs, and other stakeholders. Developing world researchers enter the picture indirectly, and mostly passively, as the recipients of training in conduct of clinical trials. True, there is talk of 'reaching international consensus' on the ethics of global clinical research, perhaps in conferences held by the WHO or Institute of Medicine, and folks from the developing world could come too. But in the end, with this sort of top-down (and North-South) approach, the chances that the recommendations will be taken up, put much of a dent in the ethical issues surrounding outsourcing of clinical research, seems pretty dim. And the fact that this commentary about ethics and the globalization of research seems to have been penned exclusively by US researchers is not necessarily damning, but also not very encouraging either.