Sunday, August 26, 2007

Eat your greens, take your medicines

You cannot treat HIV/AIDS simply by eating good food. This seems like a pretty straightforward thing to say. So why would this statement be considered newsworthy?

Place the statement in the South Africa, add a background ideological struggle about traditional medicine vs. modern biomedicine -- itself a proxy for disputes about the legacies of colonialism and neo-colonialism on the African continent -- and the banal statement suddenly becomes charged with new meaning. The current South African Health Minister, Manto Tshabalala-Msimang, has long touted the benefits of beetroot, garlic, lemon and African potatoes for HIV and AIDS patients while warning about the toxicities of anti-retroviral treatments. Unfortunately, her beliefs about the benefits of nutrition and the evils of pharmaceuticals have watered down her commitment to increasing access to drugs for HIV-positive South Africans. There was always the suggestion that the garlic (and the like) could act as substitute for AIDS drugs, the sort of fatal advice you might expect from a sociopath, not a health minister. Speaking of which: when the deputy minister, Nozizwe Madlala-Routledge, started making unambiguous statements about the relationship between HIV and AIDS, and made a serious efforts to prevent and treat HIV/AIDS across the country, there was only one reasonable course of action: find some dirt on her, and have her fired.

Opponents of Manto Tshabalala-Msimang needed to find a way of promoting healthy nutrition to strengthen the immune system of HIV positive persons without contributing to AIDS denialism. Last week, the Academy of Science of South Africa issued a report entitled HIV/AIDS, TB and Nutrition. In it, a fifteen member panel concludes that while proper nutrition is important for general health and the link between nutrition and the human immune system should be the object of further research, the claim that any food or food supplement can substitute for anti-retroviral therapy has no scientific basis whatsoever. In this way, the Academy paid the Minister a compliment: they treated her like a lousy scientist, rather than a madwoman.

Tuesday, August 14, 2007

The ethics of health research and practice, postmodern style

It is not enough to do good; you also have to be seen to do good. Increasingly in biomedical research, and especially when conducted in the developing world, the challenge of ethically conducting a complex clinical trial is compounded by the need to control even the appearance of wrongdoing. In sensitive studies that inevitably lead to negative health outcomes for some participants -- such as HIV prevention research -- managing the appearances seems almost a quixotic endeavor. A recent article in PLoS Medicine describes reactions to the failure of a multi-site (South Africa, India, Uganda and Benin) trial of cellulose sulphate, a microbicide gel for use by women. In a major setback, the trial was stopped when it was unexpectedly discovered that more women became HIV-positive in the microbicide arm than in the placebo arm. The authors of the paper -- who led the trial -- describe the precautions put into place, the misunderstandings, attempts to allay fears, and lessons learned for future research. One sobering lesson of the article is that years of careful preparation on the part of researchers may be undone by an ambiguous phrase or uninformed media comments.
Clarity of communication among all stakeholders is essential, but hard to maintain, especially in settings where there is some suspicion towards biomedical research (particularly studies involving foreign researchers), and where lurid stories of 'third world exploitation' sell newspapers and increase hits on blogs. Of course, the authors of the article are partly defending their study and their response to its results, and not just describing them. There is no need to take their word on faith. But that is just the point: any suspicion of wrongdoing has to be backed up by evidence, otherwise there is a risk of undermining community trust and hindering promising medical research. That would be unethical itself.

In a similar vein, this week's Lancet carries a report of a deworming initiative in Ghana being derailed by community rumor and erroneous media reports. The initiative involved
trained teachers supervising the administration of a single 500 mg mebendazole tablet (imported by UNICEF) to nearly 4 and a half million children, aged 3–15 years in 28,043 public schools. Hours after the program started, there were reports on local radio stations about deaths and serious side-effects affecting several children in three administrative regions. These reports led to considerable public disorder. Some teachers were attacked and schools were shut. I will quote the part of the report describing the reaction of health authorities (the Lancet requires subscription):

The Ministry of Health immediately commissioned the independent pharmacovigilance centre at the University of Ghana Medical School to investigate. The investigators, in collaboration with the WHO Programme for International Drug Monitoring, found no deaths, three admissions to hospital for suspected Plasmodium falciparum malaria, and scattered reports of mild stomach aches, nausea, and cramps (known adverse events of mebendazole). The investigators also noted localized mass hysteria, including parents rushing their children to hospital or giving them palm oil in the belief that it would induce emesis, attacks on teachers by irate parents and carers, and attendance at hospital by over 350 children, all of whom were reassured and discharged. A possible source of the rumours was the emergency activities associated with the death of a child, killed by a falling wall, 2 h after the start of the deworming exercise. The report by the investigating team was presented by the Deputy Minister for Health at a press conference. The news that the Ghana Health Service had asked an independent team to investigate helped restore confidence and calm nerves. Other assurances came from UNICEF, which attested to the safety of the drug and widespread coverage of these findings in the print and electronic news media seemed to assure parents and calm the situation.

Thursday, August 09, 2007

An Indian summer?

Maybe it is selective perception, or coincidence, but over the summer I kept seeing bioethics and research ethics items about India. Three medical ethics items that were hard to overlook: in two, surgeries were performed not by qualified health professionals, but by their family members. In one case, a 15-year old performed a Caesarean section under the watchful eye of his parents, both physicians. After the case hit the media, the boy's father, unrepentant, said he wanted his son to be in the Guinness Book of Records as the youngest ever surgeon, and that he had been training his son since the boy was 12. It is not clear what the patient thought about this arrangement or (aren't you curious?) how the operation went. In the other case, a doctor in the northern Indian city of Lucknow allowed his daughter-in-law to surgically remove a woman's 5 month old dead fetus. She botched it, and the patient eventually had to have her uterus removed. In a third story, a man had to deliver his own child when doctors in Meerut found out his pregnant wife was HIV-positive. The hospital staff refused to get anywhere near the woman, but were willing to give advice from the other side of the room. These incidents have led to much soul-searching and many questions in regard to the protections Indian patients have against malpractice, negligence and discrimination. The Indian trade in transplant organs is well-known, though publicity does not stop such trade from taking place. Perhaps less known is the stigmatization and exclusion of HIV patients by some health care workers and institutions; last month saw a man having to deliver his own child, when hospital staff refused to come into contact with his HIV-positive pregnant wife.
Then there is the biomedical research scene in India. An article in the May/June issue of the New Left Review by Kaushik Sunder Rajan, entitled Experimental Values: Indian Clinical Trials and Surplus Health, describes the scramble of international and local commercial research organizations (CROs) to conduct clinical trials in India, and basically argues (via some neo-Marxist conceptual gymnastics) that Indian participants get the raw end of the deal: the trials increase the benefits and lower the risks of yet-more medications targetted at affluent 'consumers of health', the CROs make a nice profit, the pharma industry makes an even nicer profit, while Indian research participants will be lucky if they can gain reliable access to old medicines, not to mention the newly tested ones. The introduction of ethics codes and consent forms, according Sunder Rajan, will leave these power imbalances untouched. The article came out in the summer, but it is clearly not for beach reading. It is not the first time such concerns have been raised. Meanwhile, there is the familiar dialectic of research scandals and calls for more ethics education. A study in which the genitals of children were examined without assent of the children or parental permission -- the data apparently to be used for purely commercial interests -- came to light during July. The rapidly increased volume of research in India seems to have provoked the Indian Council of Medical Research (ICMR) to issues new ethical guidelines last year.

It is hard to underestimate the challenges involved in strengthening the ethical conduct of biomedical research and medical practice in a country that is geographically large with a high population density, is marked by tremendous ethnic and religious diversity, has vast gaps between the rich and the poor, struggles with substantial gender inequality, and which has become a magnet for global pharmaceutical companies.