GlaxoSmithKline may have escaped the threat of prosecution after being accused of delaying the submission of safety data concerning the antidepressant Seroxat but the firm’s reputation, and indeed that of the whole industry, is under scrutiny again.

As we reported yesterday, the Medicines and Healthcare products Regulatory Agency, after a four-year probe, said that GSK had delayed providing it with clinical data showing that patients under the age of 18 taking Seroxat (paroxetine) were at a higher risk of suicidal behaviour than those given a placebo. The company vehemently disputes this claim, saying that it complied with all the regulatory norms.

Specifically GSK points out that it conducted nine studies, over eight years, to examine the use of Seroxat in treating patients under the age of 18 with depression and other psychiatric disorders, and no suicides were reported in any of them when reviewed individually (GSK’s italics). The firm goes on to say that none of these trials were considered “by GSK or independent investigators to show a clinically meaningful increase in the rate of suicidal thinking or attempted suicide.”

Indeed, “as has been confirmed by the MHRA”, it was only when all the data became available and were analysed together that an increased rate of suicidal thinking was revealed, and GSK brought this analysis to the attention of the regulatory authorities, including in the UK. However the firm’s defence brought a stinging rebuke from the MHRA’s chief executive Kent Woods.

In a letter to GSK’s chief executive Jean-Pierre Garnier, Prof Woods started by saying that “there is obviously a need to tighten the law to make it absolutely clear that pharmaceutical companies have a legal responsibility to inform the regulator of any information that changes the benefit:risk profile of their products, regardless of whether the information relates to a licensed indication”.

Seroxat was never approved on a paediatric basis, though doctors had prescribed it off-label to some 8,000 teenagers before GSK handed over its analysis to the MHRA in 2003. The latter said that there was insufficient evidence of the drugs giant actively promoting the off-label use and GSK again has strenuously denied such claims.

Moral responsibility
However, back to the letter and this is where Prof Woods twists the knife. He says that a tightening of the law “should be unnecessary in an industry which relies so heavily on public trust and aspires to high ethical standards. I would have thought it self-evident that such information should be made available promptly to the regulator in order that action can be taken to protect public health. However, that moral responsibility now needs to be to be insisted upon by the unambiguous force of law."

The MHRA chief then goes on to challenge Dr Garnier to let him release all the documents submitted by the firm to the investigation which are presently covered by secrecy rules. “Quite legitimate public interest in this case” demands this step, he believes but “this of course requires your consent. GSK has regularly asserted that it has nothing to hide in this matter, and so I should be grateful if you could confirm in writing your consent to the release."

GSK – “we acted properly and responsibly”
Strong stuff and at the time of writing, GSK had not yet responded to his request. Indeed the firm was conspicuous by its absence in the myriad discussions held on UK television and radio news programmes. However, Alastair Benbow, medical director for GSK Europe, issued a statement saying that “we firmly believe we acted properly and responsibly in 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”.

Nevertheless, and perhaps most interestingly, he went on to say that while 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”.

Dr Benbow concluded by noting that GSK is “committed to working with the Government, appropriate regulatory authorities and other pharmaceutical companies to take whatever action is necessary to improve legislation and policy in this area”. The debate about disclosure is now well and truly back on the agenda.