AZT Trials in Developing Countries (13)
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Research groups trying to identify alternatives for the expensive
ACTG076 zidovudine regimen in developing countries, are under heavy
ethical fire. North American "Public Citizen's Health Research Group"
has stigmatised 15 studies as unethical because of comparing a short
regimen of zidovudine to a placebo. Nine of the 15 studies are funded
by the US government, 5 by other governments and 1 by UNAIDS. The
authors refer to US regulations and ethical standards as if the US
regulations are the only valid standards in the world overruling
ethical committees in other countries. On the apparently superior
holy grail of American ethics they mix different study designs with
antiretrovirals, vitamin A, intra partum vaginal washing and HIV im-
mune therapy, and serve it to the world with a spicy sauce of unethi-
cal flavour.
Let's look at some of the points made in the New England Sounding
Board of September 1997:
1. The authors state that the trials 'will lead to hundreds of pre-
ventable HIV infections in infants'. Clearly, this is a nonsense
statement because children are not exposed because of the trials
but because of their mothers HIV status, and they do not have ac-
cess to antiretrovirals in real life. Hence, placebo controlled
AZT studies reduce the risk of transmission in 50% of the study
participants who receive the active medicine instead of increasing
the risk for the others.
2. The alternative for a placebo is an equivalence study in which
shorter zidovudine regimens are to be compared to a longer proven
effective regimen. This is obviously a better study design but im-
possible to carry out in most African countries because women at-
tend late in pregnancy, because of compliance issues, cultural and
health behavioural aspects, side effects of zidovudine such as
anaemia already highly prevalent in some populations due to ma-
laria and iron deficiency.
3. Vaginal washing studies and vitamin A interventions are also sub-
ject to ethical criticism despite the fact that these studies are
looking for affordable alternatives applicable to the entire popu-
lation of pregnant women without having to carry out an HIV test.
Has it now become unethical for western researchers to be involved
in collaboration with their local counterparts in placebo con-
trolled trials of e.g. locally affordable potential effective
painkillers in labouring women because American women have access
to epidural anaesthesia which has become standard of care in West-
ern countries? Why can locally available and affordable potential
HIV interventions not be tested as such without having to intro-
duce zidovudine as the standard of care while this is only avail-
able to pregnant women in the west? In other words, who sets the
standards and the rules? Clearly, vaginal washings and vitamin A
interventions will have a weaker effect - if any- than retrovirals
but are the only potential affordable candidates while waiting for
vaccines and sexual behaviour changes.
Ethical and moral concerns in the area of research in developing
countries are very important and justified as clearly demonstrated by
Marcia Angell in the same New England Journal issue. However, the
concerns should watch over *relevant* issues. The argument that the
study results may contribute to the world-wide implementation of
shorter regimen is not good enough as most developing countries will
still not be able to afford a short regimen zidovudine for their
pregnant population. Even if zidovudine were freely distributed at no
cost at all to all pregnant women in the world, the costs of imple-
menting these programmes will still vary between 260 and 900 USD per
case averted depending on the model and the assumptions used.
Resource poor setting will have it difficult to organise and manage
pre-and post-test counselling and testing for HIV, and to provide ex-
tra personnel to cope with the additional burden on the health sys-
tem. Obviously, besides other interventions, dose-response studies
have to be undertaken for the sake of mankind because it is likely
that shorter zidovudine regimen will be as effective as the longer
ones, but ethical considerations should aim at setting well defined
criteria for conducting the studies. The populations under study
should have access to minimal standards of health care, and there
should a minimal likelihood that funds and methods for implementing
the results of the study will be available. This kind of criteria
will automatically limit the eligible research sites to countries in
transition and exclude the poorest groups in societies from only be-
ing used as guinea-pigs.
Also, local partners should raise their voices and defend what they
feel is a priority for their own populations instead of adapting a
western dominated research agenda, and strengthen the capacities of
their own local ethical and research committees.
Marleen Temmerman, MD, PhD
International Centre for Reproductive Health
University of Gent, Belgium
De Pintelaan 185, Poli 3, 1ste verdieping
9000 Gent
Belgium
Tel: +32-9-240-3564
Fax: +32-9-240-3867
mailto:marleen.temmerman@rug.ac.be
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