Need for a better system of drug evaluation

Jun 17 2007

The current drug surveillance system needs to be fixed, argues an editorial in the British Medical Journal.

The call follows a recent analysis of the diabetes drug rosiglitazone (Avandia) which raised serious questions about the drug's safety.

Rosiglitazone was approved by the US Food and Drug Administration (FDA) in 1999 and by the European Medicines Agency (EMEA) in 2000. Its popularity has increased steadily, with more than one million prescriptions written in the one year period ending March 2006 in England alone.

But last month an analysis of 42 trials of rosiglitazone, published in the New England Journal of Medicine, found that the drug was associated with an increased risk of heart attack and death from cardiovascular causes.

These emerging safety concerns highlight the need for a better system of drug evaluation both before and after approval, says Dr Dhruv Kazi from the London School of Economics.

He argues that the current approach relies heavily on passive surveillance and is based on reports of unusual adverse events from consumers, practitioners, manufacturers, and national regulatory authorities. Alternatively, the regulatory authorities may require further (phase IV) trials after approval, but these are often not completed in a timely manner, he says.

This results in a fractured regulatory process, where postmarketing surveillance falls short of the standards the agencies set for themselves.

This is exemplified by the case of rosiglitazone, which comes from a family of drugs with well documented side effects, he writes. However, postmarketing safety data seven years after regulatory approval consist of a patchwork of heterogeneous manufacturer sponsored trials, many of which are unpublished.

The system needs to be fixed, he says. This will require systematic rethinking of the existing regulatory and funding processes, and expediting changes currently in the pipeline.

In the meantime, doctors will need to revisit the indication for the drug on a case by case basis, bearing in mind that several alternatives are cheaper, supported by robust evidence, and now perhaps safer, he concludes.