A BMJ investigation into the top-selling diabetes drug rosiglitazone (Avandia) raises concerns about its safety and the whole system by which drugs are evaluated, regulated, and promoted around the
BMJ Editor in Chief, Dr Fiona Godlee,
believes that the drug should not have been licensed and should now be
withdrawn. She also calls for more robust regulatory processes and better
access to the raw data used to license drugs to allow scrutiny by the
The investigation reveals that in July the
Commission on Human Medicines advised the MHRA to withdraw the drug as the
"risks of rosiglitazone outweigh its benefits and that it no longer has a place
on the UK market".
In light of these concerns, doctors are also
advising that no new patients should be started on rosiglitazone, and patients
already taking it should be reviewed and alternative treatments considered.
Those at higher risk of heart disease should be advised to stop taking the
Rosiglitazone, manufactured by Glaxo
SmithKline (GSK) was approved by the US Food and Drug Administration (FDA) in
1999 and by the European Medicines Agency (EMA) in 2000 to help lower blood
sugar levels in patients with type 2 diabetes.
Since its approval, several studies have
suggested that rosiglitazone may lead to a small overall increase in the risk
of heart attacks, but in July an FDA scientific advisory panel recommended that
it was safe enough to stay on the market.
In her report, Dr Deborah Cohen
investigations editor of the BMJ, obtained documents under the Freedom of
Information Act that note a paucity of evidence during the European approval
process and outline concerns from some panel members about the long term risks
and benefits of rosiglitazone. Other experts have since remarked on the poor
evidence base and lack of long term data on cardiovascular safety.
The report also raises concerns about the
quality of the data used by GSK to show that rosiglitazone did not lead to
increased heart problems compared to other diabetes drugs, the lack of publicly
available trial results for independent scientific scrutiny, a lack of
transparency in the European system, and the ability of the European regulator
to assess individual patient data.
Pressures on regulatory agencies by
diabetologists to approve rosiglitazone, and failures by the agencies to act
swiftly on emerging safety information are also highlighted in the report.
Two experts comment on today's report.
Professor Nick Freemantle at the University
of Birmingham, calls for an overhaul in the standards of regulatory trials to
minimise the risk of a similar situation occurring in other clinical areas in
the future. "In order to learn from our mistakes, we must improve the quality
of safety data from clinical trials on all new health care interventions, not
just antidiabetic drugs," he says.
Professor John S.Yudkin of University College
London believes doctors must focus on what matters to patients. "Ten years after
the release of rosiglitazone, we still cannot accurately quantify the harm to
which we were exposing our patients," he says. He admits that some of the blame
lies with clinicians for not insisting on better proof of long-term benefit,
and adds: "We need to be absolutely certain that our long term treatments for
type 2 diabetes are not causing the very harm they are meant to prevent. And if
the regulatory bodies do not insist on clear evidence of greater benefit than
harm, they are failing in their basic purpose."