ISIS Report 01/09/06
FDA in Third World Drug Trial Scandals
Experimental tests are conducted in developing countries on sick and
vulnerable children under the guise of free and ethical treatments sanctioned
by the FDA and complicit medical institutions. Sam
Burcher and Dr.
Mae-Wan Ho
A fully referenced
version of this report is posted on ISIS members’ website. Details
here
Unapproved GM rice serum tested on sick infants
Two children suffered serious allergic reactions after being used as guinea
pigs by the California-based company
Ventria Bioscience in Lima, Peru [1]. The children were part of a clinical
trial of a genetically modified (GM) rice serum containing
two synthetic human proteins lactoferrin and lysozyme (normally found in human
milk and other bodily fluids), not yet approved for testing in the US or anywhere
else in the world.
Ventria had
experienced stiff opposition for growing the GM rice in its home country.
It was driven out of California and southeast Missouri in 2005, but managed
to grow the GM rice in North Carolina [2] (Molecular Pharming - the New Battlefront
over GM Crops , SiS27).
The company was hoping to sell the GM rice
as a “nutraceutical” presumably on grounds that it provided extra nutrition.
Nevertheless, it was unlikely to gain approval for a clinical trial in the
US; so, like other companies, it decided to target Third World countries where
regulations are lax.
Trials of proteins known to be unsafe
There are reasons why Ventria’s trial should
never have been allowed, anywhere in the world, least of all, on vulnerable
infants suffering from diarrhoea. Prof. Joe Cummins [3] had drawn attention
to the potential hazards of these particular GM rice proteins ( Human Proteins in GM Rice Linked to Diseases , SiS22).
Lactoferrin participates in the regulation of immune functions and controls
pathogens by binding iron required for bacterial growth. But it has been implicated
in asthma with fatal consequences. Lysozyme breaks down the cell wall material
of bacteria, but may contribute to emphysema. By far, the greater danger is
that the transgenic proteins are only approximations of the natural proteins
in amino-acid sequence and glycosylation
(carbohydrate chains added to the proteins during processing), and may therefore
provoke immune reactions. Glycosylation
differs between species; hence transgenic proteins are bound to exhibit differences
in glycosylation patterns from the natural protein. It was indeed the difference
in glycosylation patterns that turned a normally harmless bean protein into
a potent immunogen when transferred to pea, causing debilitating lung inflammation
and food sensitivities in mice [4] (Transgenic Pea that Made Mice Ill , SiS29).
Other serious breaches in protocol suspected
The trials in Lima were carried out at the
Institute for Child Health and at the Nutrition Research Institute. Ventria
had experimented on 140 children from the age of 5 months to 3 years suffering
from diarrhoea. It is doubtful whether informed consent was obtained.
One child is now so ill
that according to his mother, Diana Canessa Garay, he is allergic to many
foods such as fruit and chocolate. She said [5], “I do not know what will
happen to him later, the Ministry of Heath must follow up investigation of
his health.” She was told that her child was receiving rice serum, which is
medically documented as an efficacious treatment for diarrhoea. No mention
was made of its transgenic origins. The case is under investigation by the
public prosecutor.
A US paediatrician Jim Diamond
suspects that the reason that the children in the control group were given
a less effective glucose solution was to make the positive effect of the transgenic
rice appear more dramatic: 5.21 days to recovery in controls as opposed to 3.67 days with GM rice
serum [1]. Ventria wasted no time in announcing theresults.
Professor Flora Gonzales, who specialises in genetics, fears that the tests
could have untoward long-term consequences. She believes that children given
the GM rice serum could suffer degenerative diseases like Alzheimer’s because
of damage incurred by the altered proteins.
Not only have unethical drugs trials been pushed onto
developing countries, but also so has pharm crop production itself. GM pharm
crops such as rice, maize, tomato and tobacco crops started in California,
but were rapidly moved on to other states
such as Hawaii [6] ('Pharmageddon' / Risks of Edible
Transgenic Vaccines , SiS17),
and now France [7] (Transgenic
Maize with Monoclonal Antibodies Grown in France, this issue). The government
in Bangladesh has just announced that its National Biotechnology Policy aims
to introduce GM rice production into the country by 2010 [8].
Nuremberg Code breached by financial incentives
The ethical obligations to protect the best interests of children (and
adults) in clinical procedures are defined by The Nuremberg Code [9]. The
Code was developed in the aftermath of atrocious human experiments during
World War II, and provides guidance
for protecting human experimental subjects from injury, disability or death.
Its main principle is the necessity to obtain voluntary informed consent from
the patient.
The latter day
US Government, however, offers powerful incentives to pharmaceutical companies
to test on children. Companies that voluntarily test drugs on children are
given a “paediatric exclusivity provision” which adds six months of patent
protection or market exclusivity to their product, and means more profits
[10].
The FDA also
imposed a “paediatric rule” that require companies to test on children under
certain circumstances. The rule includes the likelihood that the drug tested
could be used on a substantial number of children and in different paediatric
age groups, leading to high volume sales. The trials in Peru of a remedy
for diarrhoea appear to fulfil the criteria of this rule; as do the trials
of an unapproved antibiotic for meningitis in Nigeria (see below).
Unregistered antibiotic tested on children
The Washington
Post revealed recently that d rug
giant Pfizer Pharmaceuticals was
accused of conducting unethical clinical trials on children in Nigeria in
1996 [11]. This accusation was made in a Nigerian government report instigated
by a whistleblower.
It’s a real life story echoing the sentiments of
the recent hit film The Constant Gardener
(SiS 30)[12] that highlights the
exploitation of African patients enrolled on drugs trials, often without informed
consent.
An experimental antibiotic, Trovan, was given to the children
in a field hospital in Kano where they were treated for a meningitis epidemic.
The parents were not told of the drug’s unapproved status and they only
gave verbal consent to the nurses for its use on the understanding that it
would help their children.
The report,
which lay buried for five years, revealed that five children died after being
given Trovan. Six other children also died while taking the comparison drug.
The pharmaceutical company later concocted and backdated a letter
of approval from a Nigerian Ethics Committee.
Deadly deviations of clinical protocol
One child in particular was subject to serious deviations in clinical
trials protocol. A ten year-old
girl, identified in the report as patient 0069, received only three days
worth of Trovan. When her condition deteriorated she was given no further
treatment of any kind, and subsequently died.
Pfizer maintains that its presence in the Kano hospital
was ostensibly a philanthropic one to fight an epidemic that had claimed the
lives of up to 15 000 people.
However, as soon as the trial was over the company withdrew. This action,
coupled with the fact Pfizer never obtained authorization from the Nigerian
Government to test Trovan on nearly 100 children and infants, amounts to an
opportunistic and illegal trial of an unregistered drug on vulnerable patients.
According to the Nigerian government report, Pfizer
has violated Nigerian Law, the International Declaration of Helsinki, and
the UN Convention of the Rights of a Child. The discovery of the report has
breathed new life into a court action against the
company initiated by 30 Nigerian families involved in the trials.
Drug tested on African children first
The US Food and Drug Administration (FDA) subsequently never approved
Trovan for use in treating American children
implying that the drug was tested first
on African children before being
considered for the American market. It continued a worrying trend of testing drugs on Africans,
both in Africa and America [13-15]
(US Foster Children Used in AIDS Drugs
Tests ; NIH-Sponsored AIDS Drugs Tests on Mothers
and Babies ;
Guinea Pig Kids
in AIDS Drugs Trials ; SiS27)
The FDA non-approval was a blow to Pfizer, which was
looking to gain a billion dollars
per year from sales. The drug was cleared for adult use in the
US, but its use
became severely restricted
after reports of liver damage and deaths. Trovan is now banned in Europe.
Tom Lantos is a senior Democrat on the International
Relations Committee. He describes the report findings as absolutely appalling.
He said [11], “I
think it borders on the criminal that the large pharmaceutical companies both
here and in Europe are using these poor, illiterate and uninformed people
as guinea pigs”.
The FDA is
under fire from another senior democrat who has denounced its links with drugs
corporations through the House of Representatives [16]. Not only that, some
of the FDA’s own scientists have reported that they are under enormous pressure
to alter findings in scientific documents [17, 18]. (See FDA Under Fire for Corporate Links that Compromise Science,
SIS31)
HIV-tainted drug dumped on developing countries
The FDA is also
implicated in a controversial story involving drugs giant Bayer Corporation, brought to light
by the New York Times [19].
It is alleged that Factor VIII, a drug for treating mostly child haemophiliac patients was contaminated
with the HIV virus during the 1980s. When American haemophiliacs contracted
HIV after using the injected,
blood-clotting drug made from unheated blood concentrates, the FDA recommended
that Bayer dump their surplus on Japan, Malaysia, Singapore, Indonesia and
Argentina. That way the company could still reap profits from sales, despite
it being pulled from the US market.
In Hong Kong and Taiwan
alone it is estimated that over one hundred haemophiliac patients, including
a two-year old child, contracted HIV after using the tainted medicine.
New stocks of the drug were made using heat-treated
blood concentrates (which kills the virus) for the American market while the
remainder of the old stock went off to France and Spain. Two French officials
were later imprisoned for approving the use of the contaminated, unheated
Factor VIII. The FDA was neither subject to investigation no r indictment and wanted the problem “quietly
solved without alerting Congress, the medical community and the public.” Bayer
maintains that it behaved responsibly and ethically.
Drugs trials boom in developing countries
By 2010 it is estimated that some two million people in India will be
taking part in clinical trials [20]. Most of the world largest pharmaceutical
companies have established a presence in India, where they are increasingly
recruiting patients and outsourcing trials.
The BBC recently screened a documentary (27 April 2006) called Drug Trials:
The Dark Side that showed the woeful lack of informed consent by Indian
patients, many of whom were taken off their existing medication to take part
in drug trials commissioned by US companies. The patients were under the impression
that their usual drug was no longer available and the new drug was merely a
continuation of their treatment.
Typically, the patients interviewed by the BBC reporter Paul Kenyon were in
awe of their d octors, and because of ill health and poverty, were willing to
agree to anything they were asked to do. Most consent forms were written in
English, which many patients could not read, let alone understand, and some
were able to give only a thumbprint as their acquiescence to the clinical trial.
One patient who agreed to take part in the placebo part of the trial did so
because he believed that if his doctor was administering the pill, then it must
somehow do him good.
None of the patients received any money for their involvement, and when the
trials finish, there is no guarantee that their treatment will continue, nor
that the drug will be available to the wider population as a whole.
Need for global regulation in clinical research
There are serious
breaches of ethics and protocol in clinical trials, especially those conducted
in Third World countries, though by no means restricted to those countries,
as the recent London drug trial catastrophe so clearly demonstrates
[21] (Clinical trial on trial series, Science in Society 30).
There is a need for global regulation in
clinical research, so that drugs and trials not approved in one country may
not be tested or used in another.
We hope that the WHO Registry of Clinical Trials (SiS30)
[22] will ensure that all clinical trials are at the very least registered
with the World Health Organisation, and that a minimal set of data about the
trial is readily available, should questions of safety and emergency care of trial subjects
arise.
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