EARLIER this year, The New England Journal of Medicine took an
unusual step: in an editorial, it queried the ethics of an AIDS study published
in the same issue. This study, which took place in Uganda, focused on 415
couples in which one partner was HIV-positive. It sought to find out why some
HIV-positive people transmitted the virus to their partners, while others did
not. Ninety people who were not infected at the start of the trial contracted
HIV during it. The researchers concluded that the key to transmission was the
concentration of virus in the blood.
What troubled Marcia Angell, the journal鈥檚 editor at the time, was that for
two-and-a-half years several hundred people with HIV were being monitored as
part of the trial鈥攂ut not treated. The researchers also left it up to the
HIV-positive participants to inform their partners about their infection. 鈥淪uch
a study could not have been performed in the United States,鈥� said Angell.
No one denies that new drugs and vaccines are urgently needed to curb the
spread of HIV and other infections. UNAIDS, the UN programme on the disease,
estimates that 16 000 people are being infected with HIV every day, and that 90
per cent of them are in the developing world. But it is worrying that this
urgency is being used to justify the lowering of ethical standards in clinical
trials. The Ugandan trial follows a trend in which the rights of trial subjects
in developing countries鈥攚here drugs companies carry out many of their
trials to save costs鈥攁re compromised in the name of medical progress.
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This has culminated in an attempt by drugs companies and mostly American
researchers to dilute the Helsinki Declaration, which was drawn up by the World
Medical Association (WMA) in 1964 and has since remained the standard for
ethical research conduct. There are also moves鈥攃arried out mostly in
secret鈥攖o modify the guidelines of the Council for International
Organizations of Medical Sciences (CIOMS), which set out how the declaration
should be implemented.
The Helsinki Declaration states that all volunteers who take part in clinical
trials must have access to 鈥渢he best proven diagnostic and treatment methods鈥�.
Last year, the WMA proposed that this clause be changed to 鈥渂est proven
diagnostic, prophylactic or therapeutic method that would otherwise be available
to him or her鈥�. This would mean that if no treatment were available in the
country where the trial was taking place, the researchers would not have to
provide one. The rationale was that the high cost of providing best proven
treatments in countries where they were not normally available would discourage
the industry from carrying out trials for new drugs and vaccines. Moreover, it
was argued, scientists have no ethical obligation to provide more than what is
locally available鈥攄espite the fact that the rigid pricing policies of
drugs companies are a primary reason for the lack of medicines in these
countries.
The suggested change has since been dropped from the draft of the revised
declaration after widespread protests. However, the change likely to replace it
is far more subtle, but just as worrying. In the latest draft, which the WMA has
just released, 鈥渂est proven diagnostic and treatment methods鈥� has been replaced
with 鈥減roven effective prophylactic, diagnostic and therapeutic methods鈥�. This
effectively means that trial subjects in the industrialised world will continue
to receive best proven therapy, while those in the developing world will receive
anything proven鈥攚hich in many countries could mean anything available.
Could there be a more clear-cut case of double standards? This latest
proposal would still mean that drugs companies and research teams could get away
with providing participants in a trial with less than the best care.
The drift towards lower standards also applies to the use of placebos. As it
stands, the Helsinki Declaration allows researchers to use a placebo alongside a
trial drug when no known effective treatment exists. The 1999 draft revision
allowed the use of placebos in all cases except where the outcome of the
condition being studied was death or disability. In other words, a placebo was
permissible so long as the volunteer was expected to survive the trial
uninjured. It justified this dramatic loosening of standards 鈥渙n the basis of . . . efficiency鈥�.
鈥淓fficiency鈥�, in this case, means making drugs trials less expensive, less
time-consuming and needing fewer volunteers. That is what this debate is all
about. The pressure to lower standards is based on economics and not on ethics
or science. Yet the fear that maintaining high ethical standards will hinder the
progress of medicine is misdirected and amounts to protectionism for drugs
companies and research agencies. Very often, claims about the inordinate costs
of treatment are made without any attempt to determine them.
For now, the revised placebo clause has been dropped from the current draft
of the declaration, but the threat has not disappeared. A final decision will be
made at a meeting of the WMA in Edinburgh in October. The use of placebos in
developing countries鈥攅ven when a known and effective therapy
exists鈥攊s justified on the grounds that the people there cannot afford
proper treatment anyway, so their medical condition will not worsen as a result
of the trial. But this is just a way of pretending that the subject鈥檚 problems
are not the researcher鈥檚 business.
In 1994 the National Institutes of Health in the US tried to persuade a team
at the Harvard School of Public Health to use a placebo in a trial in Thailand.
The trial was looking into various treatment regimes involving zidovudine, which
had previously been shown to reduce HIV infection in infants born to
HIV-positive women. If the NIH had got its way, it would have been sanctioning
the use of a placebo in the full knowledge that an existing drug treatment was
more effective鈥攕omething that could never have happened in the US.
The proposals to weaken the declaration underline a desire among drugs
companies and some researchers to legitimise trials that are fundamentally
unethical. This trend must be resisted. Trials with a new drug or vaccine should
only ever be carried out where the best possible means of care are already in
place, or can be raised for the trial. Cost is no excuse for exploiting the
vulnerable.
Dirceu Greco is professor of internal medicine at the Federal University of
Minas Gerais in Brazil, and chair of its ethics review committee