Drug regulation faces enormous change, writes medical correspondent Dr Muiris Houston
It has been a difficult year for the pharmaceutical industry. The safety of the new generation of antidepressants called SSRIs is still being questioned.
Two products in particular have been the focus of much media publicity. Although vigorously defended by their respective manufacturers, questions about the appropriate prescribing of Seroxat and Prozac continue.
These have focused on areas such as the prescribing of SSRIs for teenagers and children and the possibility that some drugs might, as part of their therapeutic effect, lead to suicidal behaviour.
But it was the withdrawal of the widely prescribed anti-inflammatory drug Vioxx in September that began a period of intense focus on the regulation of the global drug industry.
Vioxx (rofexcoxib) is one of a number of drugs used to treat arthritis. Called Cox 2 inhibitors, they were licensed here in the late 1990s and heavily marketed as offering a significant advantage on the standard non-steroidal anti-inflammatory drugs (NSAIDS).
Ironically, in view of subsequent events it was the Cox 2's reduced potential to cause bleeding from the gastrointestinal tract that was their main selling point. Their commercial success was revealed in a paper published last week in the medical journal, Archives of Internal Medicine, which found that within two years of the introduction of Cox 2 inhibitors in the US, they achieved a 61 per cent share of the anti-inflammatory market.
On September 30th the manufacturer of Vioxx, Merck Sharp and Dohme (MSD), withdrew the drug. The reason given was an increased risk of cardiovascular side effects, namely heart attack and stroke, in people taking it for 18 months or more.
However, concerns about Vioxx and the whole group of Cox 2 inhibitors had been circulating in medical circles as far back as 2000. An article in the Journal of the American Medical Association in December 2001 from the Department of Cardiovascular Medicine of the Cleveland Clinic found that patients taking Vioxx were almost two and a half times more likely to have a heart attack or stroke than those taking an older NSAID.
The authors based their conclusion on analysis of a large trial of 8,000 patients published in the New England Journal of Medicine in November 2000. An article in the British Medical Journal in March 2003 suggested "harms outweigh benefits of Cox 2s for many patients".
But this was just the beginning. In the months since the withdrawal of Vioxx, medical journals have been full of trials evaluating the safety and effectiveness of other Cox 2s. Pfizer, the manufacturer of Celebrex and Bextra, said Celebrex was associated with a doubling of the risk of cardiovascular side effects when taken in higher dosage. It issued new contra-indications for Bextra.
The influential and independent review of medical treatment, the Drugs and Therapeutics Bulletin, said in January: "We can see few, if any, situations in which Cox 2 [ inhibitors] are unequivocally indicated... We see potential hazard in prescribing a Cox 2 to a patient who is at risk from cardiovascular disease."
The drugs are currently being reviewed by the Food and Drug Administration (FDA) and by the European medicines regulatory agency and it is expected the anti-inflammatory agents will have their licences severely restricted.
Responding to recent developments, the Association of the British Pharmaceutical Industry (ABPI) said drug companies may withdraw vital medicines and cut investment in R&D of new drugs if the threat of litigation and public hostility continues.
Dr Richard Barker, director general of the ABPI, says some companies may decide it is not worth the legal or financial risk of launching new drugs if they are liable for the side effects patients' experience.
"The aggressive programme of class-action suits which have emerged must be factored into a company's decision-making."
One thing is certain. The drug regulatory environment has changed. The days of drug regulators doing business with the pharmaceutical industry behind closed doors are numbered.