Scale up and follow up: the struggle to stay on AIDS treatment in Africa

Not so long ago, the number of HIV-positive persons in Africa who had access to antiretroviral drugs was painfully low. Through important initiatives such as the US President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria, millions have been put on AIDS treatment in the past few years. Available graphs on treatment access show a healthy upward trajectory, flatter in some parts of the developing world, and steeper in others, but nevertheless going up. And up is good.

A recent report in the New York Times shows another side of the story. Getting people started on antiretroviral drugs is one thing, keeping them on the treatment is another. HIV treatment, as it currently stands, is lifelong. Once you start, there is no stopping: or rather, there is stopping, but with disasterous consequences for the health of individuals and potentially for the community (if expensive to treat resistant strains of HIV thereby emerge). But keeping people -- increasingly vast numbers of them -- from defaulting on their treatment is a tremendous challenge with many obstacles. It is hard to know how many are 'lost to follow up', but if it is as the report states (between 15-40%), then we are talking about millions.

The agencies that are to be praised for efforts to increase treatment access may also shoulder some of the blame for the current situation. For years, 'numbers of persons on treatment' were the stuff of progress reports, the ultimate marker of program success, and where efforts and funding were to be largely concentrated. The focus was not on keeping people on their treatment regimes. If hell is not to be paved with good intentions, attention is going to have to subtly shift, the causes of loss to follow-up will have to be thoroughly explored, and support will have to provide to those tracing treatment defaulters and coaxing them to take their drugs.

Final day, ASBH conference

A thick mist hangs over the buildings and it is lightly drizzling. San Diego, since the beginning of the conference on Friday, has been doing a pretty good imitation of Belgium. Today is only a half-day, and a good number of conference attendees come with their carry-on bags, enabling them to bolt towards the taxi stand at a moment's notice. They have already entered into liminal space, neither here nor there.

One of the early morning sessions is rather bruising, though the topic lent itself to this: whistleblowing in bioethics, what to do when we discover unethical practices. Carl Elliott spoke about the suicide in 2004 of 26-year old Dan Markingson, who was enrolled in a University of Minnesota led, industry-funded, clinical trial of the antipsychotic drug Seroquel. The tale he told appears in the September issue of Mother Jones, and the case reveals not just faulty informed consent but a broader, systematic rot: clinical trials are increasingly becoming a plaything for pharmaceutical companies, which function not so much science as marketing tools, where the data gets massaged and researchers are lining their pockets. The participants get the short end of the stick, and when things go south, the pharmaceutical companies call their legal department and limit whatever recourse wronged participants or their family members may have. The IRBs stand idly by, either unwilling or powerless to intervene, despite their central mission. A compelling tale, but I almost needed anti-depressants myself afterwards. Alice Dreger and Ellen Feder discussed two controversial research studies they have brought to public attention lately: clitoroplasty studies and the experimental (but not IRB approved) use of dexamethasone, a risky Class C steroid aimed at female fetuses that may have a form of congenital adrenal hyperplasia (CAH). It got heated: an audience member accused Dreger of presenting falsehoods, which she denied, and Dreger accused the audience member of bullying those who criticized the dexamethasone studies, which he denied. Those (like me) who had no independent information may have felt that they were witnessing an obscure family dispute. The whole session reminded me: despite appearances sometimes, bioethics questions are not merely 'academic'. When there is a real conflict, it is a political conflict, with money and reputations and well-being at stake.

Ethics consultation services. If there is one area in bioethics that stands a chance of being professionalized, this is it. At this conference, I got the impression that no one wanted to enter into the old fashioned (philosophical) discussions about the possibility and meaning of 'ethical expertise'. We have moved on, apparently, and now the question is how to best operationalize the expertise we possess. In an affinity meeting on Saturday, there was much talk (but little discussion) about a proposal to develop certification procedures for clinical ethics consultants. What is needed, it was said, was non-negotiable standards for clinical ethics consultation, have current practitioners take some sort of examination, and get officially certified in a way that will (it is hoped) enhance their professional status and authority. How this is to be funded, and how to make medical institutions care about this, was unclear. The value of research ethics consultation, independent of sticky certification questions, was made clear in the last session on Sunday. Members of the NIH's research ethics consultation service provided a peek at their internal activities, challenges and lessons learned. From the looks of it, the decisions made were very likely more sensitive and better informed than they would have been otherwise, and that is probably all you can really ask for.

A four-beer lunch with the delightful Marin Gillis (fellow graduate from the University of Leuven, and currently at the University of Nevada), and I headed towards the hotel, towards the laptop, and home.

ASBH, Day Two

How long it takes me to get to the conference hotel in the morning amazes me. It is not the distance: a short way through the Gaslamp Quarter, and I am there. It is not the time spent on the treadmill up in the Indigo Hotel fitness center, overlooking the early morning mist from the ninth floor. Whatever it is, I get to the Hilton Bayshore just as breakfast is wrapping up, and bury a couple of greasy french toasts and two cups of black coffee before the plenary starts. In a mood of haste and impatience.

The plenary was on creative engagement with persons suffering from Alzheimer's. Not something I had thought about before, but it makes perfect sense. Everyone knows the horror stories of older men and women being plunked down all day in front of television sets, and much worse forms of neglect or abuse. So engaging Alzheimer's patients in theatre, painting, songwriting and dance is in stark contrast with other tendencies in Alzheimer care, including early diagnosis and initiation for medication: with the old in general becoming a rapidly growing target market for the pharmaceutical industry, medicalizing approaches tend to predominate. A strength of the presentation was reference to empirical research indicating positive outcomes in 'non-medical' or cultural approaches, and a highlight was the speaker's call for pharmaceutical companies to devote 1% of their operating budgets to programs enhancing a 'sense of purpose' among Alzheimer's patients. Wishful thinking, but a nice thought.

Highlight of the day: a piece of good old fashioned philosophy. In a session on cognitive enhancement, we had two presentations of surveys conducted on attitudes of various populations towards cognitive enhancement, particularly medications for school performance. They were solid presentations, revealing the predictable, i.e. we are in two minds about using drugs to stimulate our minds. This was followed by a talk like a gust of fresh San Diego sea air: Tom Buller from the University of Alaska started asking some fundamental questions about the very idea of cognitive enhancement. Can we make people smarter with 'smart drugs' anyway? Improved memory and concentration is not equivalent to improved intellect. Even if drugs (somehow) improved intellect or knowledge, how valuable is that? Would it make us better people or better societies? Is there such thing possible as moral enhancement through medications? Muller offered skepticism of the best sort: patient, rational questioning of (inflated) claims about what enhancement is supposed to do for us or to us.

A panel discussion about ethics and quality improvement (QI) studies does not sound particularly riveting, but Saturday's session proved otherwise. Quality improvement studies, because they are so closely entangled with ordinary health care delivery, can pose problems for IRBs because it is not always clear whether they fit the definition of 'research' according to the Common Rule. According to the panel members, some IRBs treat QI as health research interventions like any other, requiring at least expedited review, consent forms and all the rest, even when they are very low risk. There was much grumbling about expedited reviews taking too long, and this unleashed a string of negative comments about IRBs, raising the impression of a groundswell of criticism against the Common Rule. There was even talk (gasp) of research institutions opting out of adhering to the Common Rule for all their research activities. However, an official from OHRP in the audience was having none of it: the official argued that there were already provisions in the Common Rule that could handle QI studies, and no overhaul of the regulations was necessary or desirable. If IRBs fail to implement the provisions or if they are not reviewing applications fast enough, that is their problem, and not problems with the Common Rule itself. I had to admire someone willing to stand up for their organization's mission in a room chock full of discontent.

ASBH, Day One

One thing about the American Society for Bioethics and the Humanities conference was clear after just one session: don't expect a very deep discussion about anything. Not that there is a lack of quality speakers. To the contrary. It is just that within a 15-20 minute time-frame, there is only so much room for maneuver, and in fact the abbreviated time slots inspire speakers to race through their talks at a manic pace -- this conference comes but once a year, and they are going to get all the information out, come hell or high water. Ideas can get blurred or hollowed out this way. So it is best to let intellectual expectations drop somewhat and regard the sessions as 'samplers', where you are offered tastes of a diversity of themes and directions in bioethics.

Choosing what to taste is always difficult. Do you go to sessions on topics you already know something about? Or on something that you are clueless about? Both have potential pitfalls and benefits. A session on vaccines offered little information beyond the usual puzzlement (on the part of scientists) about why there are people who refuse to have their children vaccinated; I quickly took off to a large, thinly populated and appropriately spooky hall where the discussion focused on the ethics of using human remains. The idea was floated of a market in cadavers, and I involuntarily recalled what is said to happen in South Africa, the stealing of body parts from cadavers to be sold and used for muti, a sort of witchcraft. The session was rounded off by an interesting talk on the images of (and fascination with) the vampire in popular culture, and what vampire fiction could mean for bioethics. I thought of the persistent image, in Africa, of foreign researchers as vampires, coming to literally suck blood of locals.

The exhibit hall had an impressive display of well-stocked book stalls, conveniently located at a short distance from the coffee. My browsing experience, however, was somewhat disrupted by a couple of booksellers who were both selling what you might call 'other-help' books (as opposed to 'self-help') about clinical ethics decision-making. They both were aggressive, in their own ways: one was quite literally in my face, smiling and waving brochures, while the other was greasing the wheels of trade by offering free sunglasses and hand sanitizers. And both merchants featured books with algorithms and flow-charts, their own preferred paths to successful ethics conflict resolution. All very cheerily practical, like those who sell vegetable cutters in supermarkets. There really is a market for everything.

Low point of the day: a talk on international health research that was all over the map, conceptually muddy and in places, factually wrong. The cringe factor was high, and it was a pity, given that there is no little international bioethics on offer here. Fortunately, the session had two redeeming and stimulating talks after that, on the challenges faced by those wishing to provide compensation for research-related injuries (Jonathan Jay) and another on the parallels between moral responsibilities of photojournalists and international health researchers towards their respective 'subjects' (Valarie Blake). I was thus cheered up by presentations which were, on the face of them, pretty depressing.

Highlight of the day: the session on ethics and pain treatment. The general consensus among the speakers was that pain is undertreated in the US, at least partly due to the inability to visualize any physical source of pain by medical devices. A question of out of sight, out of practice and policy. The affable Daniel Goldberg (who writes his own excellent Medical Humanities blog) stormed merrily through his talk, making a strong case for a need to cultivate (political, socially and policy-wise) a greater receptivity to the subjectivity of pain, rather than merely tweaking current opiate policy. I couldn't help but think if pain is undervalued and undertreated in the US, what must the situation be in the developing world, where there are less diagnostics and less availability of opiates. A new twist on the phrase: a world of pain.

Field trip: the ASBH Annual Meeting in San Diego

Normally I don't do this sort of thing. When I am not off to the DR Congo, Malawi, South Africa, Burundi, Madagascar or some other far-flung place, I am pretty much parked on my perch in North Carolina. Travel within the United States over the last decade has been very limited, and travel to domestic bioethics conferences pretty much absent. When you are already jetlagged, and poisoned by (increasingly) small bags of salted peanuts, why drag your sorry self to Cleveland or Nashville?

This week marks an exception. The annual meeting of the American Society for Bioethics and Humanities is being held in San Diego from October 21st-24th. My decision to go was not due to Glenn McGee's vigorous but somewhat unbalanced call last week for bioethicists to attend the event on the American Journal of Bioethics Blog. I had already signed on. And it is not due to the location, though I heard that it is sweet. For me, it is more about learning what practitioners of this odd activity in the United States are up to, think and care about, and believe others should think and care about. Connecting names and reputations with faces and fashion choices.

So, in the next few days, this outsider and first-timer will be posting reflections on the ASBH conference. How objective it will get depends on who mixes the cocktails.

The 'Guatamalan Tuskegee'

When news broke about unethical syphilis studies being conducted by US government agencies in Guatamala back in the 1940's, I was not sure how to take it. My first (well, questionable) reaction was that some research ethics modules and textbooks would need an upgrade, and maybe some lectures on the infamous Tuskegee study might become less tedious, now that the well-worn scandal had both a precursor and an international twist. My second reaction was that I would have no choice but to write something about it, because it got so much press, and because the Guatamalan government received apologies from the US Secretary of State Hilary Clinton and President Barach Obama in a very big hurry. But reading the paper by the historian who broke the story, Susan Reverby, gave rise to deeper reflection on the moral landscape of health research between developed and developing countries, and how in some ways that landscape has not radically changed over the last sixty-some years.

As usual, the ethical problem was not so much with the research question itself. Trying to find a way of preventing men from acquiring syphilis after exposure by using penicillin had some merits. The use of captive and highly vulnerable populations -- prisoners, orphans, soldiers, and mental patients -- without gaining much semblance of informed consent is another story. As were some of the methods. Attempting to infect prisoners by means of deliberately selecting syphilitic prostitutes to visit them in prison, and conducting what sounds like a quite uncomfortable procedure of inoculating the penises of mentally ill patients: this is morally out of bounds. Sweetening the deal by offering the Guatamalan authorities supplies and infrastructure, as well as handing out cigarettes (yes, this was a public health study) to the prisoners, sounds like crossing the line between providing 'research benefits' and greasing the local wheels. There are important ethical differences the Guatamalan studies and Tuskegee: in the former, you had healthy participants being deliberately infected, whereas in the latter, the participants were already infected prior to being recruited. However, in the Guatamala case, those who became infected were all treated with pencillin (albeit without follow up), whereas treatment was infamously withheld from Tuskegee participants for decades.

What is striking in Reverby's paper is how the researchers know what they are doing is -- from a perspective they try to downplay and discredit -- ethically wrong. Reverby quotes a letter written in 1948 by the Public Health Service physician R.C. Arnold to a researcher involved in the Guatamala studies:

I am a bit, in fact more than a bit, leery of the experiment with the insane people. They can not give consent, do not know what is going on, and if some goody organization got wind of the work, they would raise a lot of smoke. I think the soldiers would be best or the prisoners for they can give consent. Maybe I’m too conservative....Also, how many knew what was going on. I realize that a pt [patient] or a dozen could be infected, develop the disease and be cured before anything could be suspected...In the report, I see no reason to say where they work was done and the type of volunteer.

The recipient of the letter, Dr. John C. Cutler, would go on to take a lead role in the Tuskegee syphilis studies and defend them to the end against accusations of wrongdoing.

At the end of her paper, Reverby muses about why this new addition to the history of research scandals matters. She raises two important points. First, US researchers in the Guatamala studies did things that they would not dare to do back home, not even in Tuskegee. In such studies, there is an implicit distinction between (as Reverby puts it) what is morally thinkable in the metropole and what is morally thinkable in the periphery. That distinction between what may be acceptable abroad -- but not at home -- is still very much with us in global health research. Second, we have to be wary about what is done with the case of the Guatamalan syphilis studies. Tuskegee gave rise to the Belmont Report, which strongly informed the Common Rule, arguably the most influential research ethics regulations worldwide. It gave birth to the IRB system. Many take issue with the provisions (and predominance) of US research regulations, and Reverby suggests the scandal in Guatamala -- particularly if it is misrepresented -- could give rise to Frankensteinian effects. But in truth, it is too early to know what this newly revealed scandal will come to mean.