The UK’s drug watchdog, the Medicines and Healthcare Regulatory Authority (MHRA), said that drug giant GlaxoSmithKline (GSK) will not face criminal prosecution for allegedly withholding information on its widely prescribed antidepressant, Seroxat.

The government’s drug regulator said it will strengthen the law to force drug companies to report safety issues as soon as they know them.

The drug company reported to the MHRA in May 2003 results of clinical trials that showed under 18-year olds treated with Seroxat had a higher risk of suicidal behaviour than those treated with placebo.

The same data also showed that Seroxat was no more effective than placebo at treating depression in the under-18s.

The drug had never been approved for pediatric use, but doctors are allowed to prescribe unapproved drugs “off label”. Seroxat was however banned after these results were made available.

The MHRA criticized the company, Europe’s largest drug manufacturer, for not handing the results over earlier, but GSK deny that they withheld information irresponsibly.

Kent Woods, Chief Executive of the MHRA, said in a press statement that the authority will “take immediate steps to ensure the law is strengthened, so that there can be no doubt as to companies’ obligations to report safety issues,” reported the Telegraph earlier today.

Woods said that drug companies had an “ethical responsibility” to reveal this kind of information sooner. He said he was disappointed that GSK did not do this:

“I remain concerned that GSK could and should have reported this information earlier than they did,” Woods told the media in a BBC report. He added that:

“All companies have a responsibility to patients, and should report any adverse data signals to us as soon as they discover them.”

The MHRA carried out a four year investigation that involved reviewing over a million pages of reports.

Woods said the investigation discovered “important weaknesses” in the legislation that was in force at the time, and that is the main reason a prosecution cannot be brought. However, since then the weaknesses have been partially addressed but more laws are needed to plug some remaining gaps.

Dr Alastair Benbow, Medical Director for GSK Europe said in a statement that the company believed it had acted responsibly by “first carrying out this important clinical trials programme and then informing the regulatory agencies when we identified a potential increased risk of suicidal thinking and behaviour in patients under 18.”

Benbow added that:

“Whilst there are substantive and rigorous requirements in place regarding disclosure of clinical trial data, it is clear that there is a need and benefit to strengthen the confidence of decision-makers and the general public that all pharmaceutical industry clinical trial data are disclosed promptly and transparently.”

He said the company was committed to working with the government, other agencies and companies to improve the appropriate laws and policies in this area.

Chief executive of the Mental Health Foundation, Andrew McCulloch told the BBC it was “totally unacceptable” that young people may have taken their own lives because a drug company was not sufficiently transparent about its trials.

An investigation by the BBC programme Panorama that aired last year showed internal company emails that revealed the drug company had “distorted trial results” and alleged the company knew there was a problem with giving Seroxat to children five years before it was banned in the UK.

The BBC reported that Health Minister Dawn Primarolo also said the government would act immediately to strengthen laws in the UK and Europe. She said drug companies should “disclose any information they have that would have a bearing on the protection of health,” regardless of how tight the legislation was, echoing the “ethical responsibility” statement made by MHRA’s Woods.

GSK said it carried out nine clinical trials altogether, over an eight year period. These looked at the effectiveness and safety of Seroxat in children under 18 with depression and other psychiatric disorders. There are few drugs available to treat this vulnerable group, said the company.

GSK said no suicides were reported in any of the nine trials it carried out, and neither the company nor independent investigators considered any individual trial to have shown a “clinically meaningful increase in the rate of suicidal thinking or attempted suicide”.

However, as the MHRA confirmed in the conclusion of their own investigation, it is only when all the data from all the trials is viewed together, at the end of the whole programme, that an increased rate of suicidal thinking or attempted suicide in paediatric patients taking Seroxat becomes apparent, said the company.

GSK said they brought this information to the attention of the regulatory authorities, including in the UK, and rejects “any suggestion that it withheld drug trial information as results from its paediatrics studies were documented and submitted to regulators in accordance with regulatory requirements”.

GSK emphasized that:

“Seroxat has never been approved by UK or European regulators as a medicine for those under 18 years of age.”

The company points out in a statement on its website that UK product labelling for the drug shows clearly that:

“The use of Seroxat in children is not recommended, as safety and efficacy have not been established in this population.”

Any decision to prescribe the drug for pediatric use is taken by doctors “on the basis of his/her clinical judgement and the interests of their patient,” they said, and they declare they have never promoted the drug to UK doctors for non-authorised use.

Seroxat is a selective serotonin reuptake inhibitor (SSRI) that helps to stabilize levels of the mood chemical serotonin in the brain. Recent research has shown SSRIs are no better than placebo at treating mild and moderate depression but they may benefit people with extremely severe depression.

The MHRA instructed UK doctors to stop prescribing Seroxat to under 18s when they received the results of the clinical trials from GSK in May 2003. This warning was increased to include all SSRIs at the end of 2003.

Click here for more information on the MHRA investigation.

Sources: BBC News, Telegraph, MHRA, GSK press statement.

Written by: Catharine Paddock, PhD