Science in Society Archive

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

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.

Article first published 01/09/06


References

  1. Silvia Ribeiro.  Babies as Guinea Pigs: Biotech company turns two Peruvian hospitals into laboratories. http://www.organicconsumers.org/2006/article_1097.cfm
  2. Ho MW. Molecular pharming the new battlefront over GM crops.  Science in Society 2005, 27, 4, https://www.i-sis.org.uk/isisnews.php; also I-SIS report, https://www.i-sis.org.uk/MPTNB.php
  3. Cummins J. Human proteins in GM rice linked to diseases. Science in Society 2004, 22, 30. https://www.i-sis.org.uk/isisnews.php
  4. Ho MW. Transgenic proteins that made mice ill. Science in Society 2006, 29, 28-29, https://www.i-sis.org.uk/isisnews.php
  5. GMO’s already affecting the young. The Republic, Friday 14 July 2006 translated by Claire Robinson, Weekly Watch editor.
  6. Ho M.W. Pharmageddon. Science in Society, 2003, 17, 23-24, https://www.i-sis.org.uk/isisnews.php
  7. Cummins J, Ho MW and Saunders PT. Transgenic maize with monoclonal antibodies grown in France. Science in Society 2006, 31, https://www.i-sis.org.uk/isisnews.php
  8. Obaidul Ghani.  BRRI hopes to introduce golden rice by 2010.  New Age, July 27, 2006 http://www.newagebd.com/2006/jul/27/front.html#4
  9. The Nuremberg Code http://www.hhs.gov/ohrp/references/nurcode.htm
  10. “Panel faults Pfizer in ’96 clinical trials in Nigeria. Unapproved drug tested on children”, Joe Stephens, The Washington Post, 7 May 2006.
  11. Sutcliffe A.G. Testing new pharmaceutical products in children, a positive step, but ethical concerns remain.  BMJ 2003, 326:64-65 (11 January)
  12. Burcher S.  The Constant Gardener, Science in Society 2006, 30, 4. https://www.i-sis.org.uk/isisnews.php
  13. Ho M.W. US foster children used in Aids drugs tests.  Science in Society 2005, 27, 41. https://www.i-sis.org.uk/isisnews/sis27.php
  14. Burcher S. Guinea pig kids in Aids drugs trial. Science in Society 2005, 27, 42-43. https://www.i-sis.org.uk/isisnews/sis27.php
  15. Burcher S.  NIH sponsored Aids drugs tests on mothers and babies. Science in Society 2005, 27, 44. https://www.i-sis.org.uk/isisnews/sis27.php
  16. Wayne Kondro. Conflicts cause FDA to review advisory committees.  Canadian Medical Association Journal, July 4 2006, 175 (1) 23-24
  17. FDA scientists pressured to exclude, alter findings; scientists fear retaliation for voicing safety concerns
    Public health and safety will suffer without leadership from FDA and Congress, July 20, 2006 http://www.ucsusa.org/news/press_release/fda-scientists-pressured.html  
  18. Burcher S. FDA under fire for corporate links that compromise Science, Science in Society  2006, 31, https://www.i-sis.org.uk/isisnews.php
  19. Walt Bogdanich and Eric Koli. 2 paths of Bayer drug in 80’s: Riskier one steered overseas. The New York Times May 22, 2003
  20. Drugs trials outsourced to India. Story from BBC News 24 April 2006 http://newsvote.bbc.co.uk/mpapps/pagetools/print/news.bbc.co.uk/1/hi/programmes/this_world/4924012.stm
  21. Cummins J, Ho MW and Saunders PT. Drug trials on trial series. Science in Society 2006, 30, 41-50. https://www.i-sis.org.uk/isisnews/sis30.php
  22. Saunders P. WHO Registry of clinical trials. Science in Society 2006, 30, 49 https://www.i-sis.org.uk/isisnews/sis30.php

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