Pfizer facing fresh legal battle with Nigeria over child deaths

The case highlights the potential minefield pharmaceutical companies are entering as they increasingly conduct drug testing in the developing world, especially in regard to informed consent.

Five civil claims for damages totalling over $2bn (€1.5bn) have now been filed against Pfizer, and seven of its employees involved in the trials, by the attorney general of Kano, in northern Nigeria, and the Nigerian government has also filed criminal charges against the firm, according to a Washington Post report.

Pfizer vehemently denies the allegations of misconduct surrounding the drug trials, which took place in 1996, and the dispute is not new - Nigeria and Pfizer have been tussling over the matter for years.

The drug at the centre of the furore, Trovan (trovafloxacin), was at the time a late-stage experimental antibiotic treatment for meningococcal meningitis.

It was allegedly given to around 100 children in Kano after the area suffered a large meningitis outbreak.

Prior to this, the drug had already been tested in 5,000 patients elsewhere, said Pfizer.

However, according to the Washington Post, the drug had never before been tested in children with meningitis and Nigerian officials are claiming in the lawsuit that Pfizer's actions resulted in "the deaths of an unspecified number of children and left others deaf, paralyzed, blind or brain-damaged".

"Every surviving child suffered one or more disabilities, the lawsuit says, adding that the state of Kano has incurred major costs caring for the children and otherwise dealing with the drug trial's repercussions".

In addition, the lawsuit claims that researchers did not obtain consent from the children's families, that parents were banned from the ward where the drug trial occurred, and that the researchers knew Trovan had potentially life-threatening side effects, according to the Washington Post.

Furthermore, it is alleged in the court documents that researchers administered the comparison drug in the trial, Hoffmann-La Roche's Rocephin (ceftriaxone), to around 100 children in "dangerously low doses to make Trovan look more effective", and after the completion of the trial, Pfizer took all medical records and "obliterated any evidence".

The Washington Post also said it had obtained internal Pfizer records showing that five children died after being treated with the Trovan, although there is no indication in the documents that the drug was responsible for the deaths and that six children also died while taking Rocephin.

According to the newspaper, in 2000 Nigeria's health minister appointed a panel of experts to look into the trial, and an ensuing report concluded that Pfizer's actions violated Nigerian law, the international Declaration of Helsinki and the UN Convention on the Rights of the Child.

It also said there were no records documenting that Pfizer told the children or their parents that they were part of a drug trial, nor were they told that alternative treatments were available.

In addition, it said an approval letter from a Nigerian ethics committee, which Pfizer used to justify its actions, was a branded as a "sham concocted long after the trial ended".

Nigeria subsequently brought a previous lawsuit against Pfizer in a US court although this was dismissed in 2005 by a federal judge who said the case should instead be heard by a Nigerian court, which this latest lawsuit will be.

In response to the fresh legal challenge, Pfizer issued the following statement: "…the 1996 Trovan clinical study was conducted with the full knowledge of the Nigerian government and in a responsible and ethical way consistent with the company's abiding commitment to patient safety.

Any allegations in these lawsuits to the contrary are simply untrue - they weren't valid when they were first raised years ago and they're not valid today."

"The Trovan study introduced a new meningitis treatment to the region that indisputably helped save the lives of almost 200 children stricken with meningococcal meningitis, a disease that if left untreated, kills four out of every 10 people who contract it."

Pfizer also said that at the time of the meningitis outbreak in Kano its doctors had "solid scientific evidence that it

[Trovan] would provide a safe and effective treatment" against meningitis.

"At a 94.4 per cent survival rate, Trovan performed at least as well as the best treatment available."

Incidently, the drug is not available in Europe and is only available in the US for adults, although its use is restricted due to its reported association with liver toxicity and deaths.

The clinical trials industry in developing nations has exploded over the last few years as drug companies have realised the potential of trials to such regions for fast subject recruitment and major cost savings, however, as a result, situations such as the one now being faced by Pfizer are becoming more commonplace, particularly over the thorny issue of adequate patient consent.

Any companies conducting a clinical trial must make sure they are following the internationally accepted Nuremberg code, laid down in 1947, citing 10 standards to which physicians must conform when carrying out experiments on human subjects.

The code, states that voluntary consent of the person is absolutely essential.

The person should have legal capacity to give consent and be able to exercise free power of choice, without any coercion; and should have sufficient knowledge and comprehension of the elements involved as to enable them to make an enlightened decision.

However, evidence from those involved in trials in developing regions is suggestive that many patients may be falling through the cracks of the Nuremberg code.

It has been reported that even when consent forms are signed by participants, many of them were signed without the patients really knowing or understanding what they were doing.

Issues such as language barriers and level of education have also been cited by clinical trial doctors as problems they experience in making patients understand what they are signing.

Blind trust in doctors and desperation for access to otherwise unattainable medications and medical care are also often contributing factors to "uninformed" clinical trial participation.

GlaxoSmithKline (GSK) is also currently facing allegations that some of its vaccines have been tested illegally and against good clinical practice (GCP) in children in Russia.

Embroiled in the controversy is The Railway hospital in Volgograd, in Russia's south, that the UK drug giant contracted for a reported $50,000 to run clinical trials on its behalf, in the absence of any suitable contract research organisations (CROs) in the region.

Testing at the site has now been suspended as the local Russian authorities have stepped in to investigate the claims.

Meanwhile, the hospital and GSK are both appealing against the decision.

It is alleged that clinical trials, which were approved by the Russian regulatory authorities in 2005, were carried out by the hospital on healthy children as well as those with pre-existing health problems, when a condition of the trial approval was that only healthy children could take part.

It is also alleged that a handful of children have experienced health complications and/or developed learning difficulties after receiving the vaccines.

Responding to the allegations, GSK strongly denied any wrongdoing or breach of GCP: "As far as we are concerned these reports are untrue and unfounded," a GSK spokesperson told Outsourcing-Pharma.com in an earlier interview.

Furthermore, various media reports have been surfacing suggesting that the clinical trials being conducted in India often target poor, illiterate and sometimes mentally incapacitated patients, many who are unaware they are even taking part in clinical trials that could be detrimental to their health.

Certain trials carried out in India on Johnson & Johnson's anti-psychotic drug, Risperdal (risperidone), were among several suspect trials that were singled out in a BBC report last year.

As part of the report, allegations were made that patients have been killed or severely injured from some of the trials that have been carried out in India on behalf of international drug firms and that some of the drugs being conducted have not even being tested before in animals.