La FDA y la EMA son las agencias encargadas de proteger la salud de los estadounidenses y los europeos respectivamente en lo vinculado a la autorización de medicamentos y aparatos sanitarios.
El British Medical Journal acaba de publicar el trabajo
- Drug Regulation
what went wrong?
At the hearing in July, the FDA panel voted that the available data supported a conclusion that rosiglitazone increases cardiac ischaemic risk in type 2 diabetes patients. However, they voted to continue the TIDE trial—a study commissioned by the FDA to assess rosiglitazone’s cardiovascular safety—which some argue the FDA should have asked for at the outset. This trial has since been put on “clinical hold” by the FDA.
Los datos para suspender el TIDE y retirar la rosiglitazona del mercado estaban disponibles desde el año 2007.
To date, the FDA and the EMA have decided that the drug is safe enough to stay on the market. But the story reflects badly on almost everyone involved: the regulators, the manufacturer, GlaxoSmithKline, and the clinical community. It has also raised a host of questions. Why did the regulators accept such poor evidence on benefit and safety for rosiglitazone? Did GlaxoSmithKline mislead the regulators? Should the drug have been licensed in the first place and should it now be withdrawn? Why haven’t patients in the UK and Europe been made aware of the concerns about rosiglitazone’s effects? And is the current drug regulatory system up to the job?
According to John Yudkin, emeritus professor of medicine at University College London and endocrinologist; “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 drug.”
In comments sent to the EMA approval meeting in 1999, one expert adviser noted that without a long term study with hard primary endpoints it was not clear whether rosiglitazone would have any beneficial impact on cardiovascular disease. This adviser also questioned whether you could put a drug on the market without these long term data and was unconvinced that rosiglitazone in combination therapy offered any advantages over what was already available—metformin and sulphonurea combined, or insulin.
Silvio Garattini, a member of the EMA panel in 2000 that approved the drug and director of the Mario Negri Institute for Pharmacological Research, told the BMJ that the documentation presented for approval was initially poor and that the studies were of a relatively short duration. The initial decision to reject the drug was overturned despite there being no new evidence, he says.
When rosiglitazone was approved, even clinicians who were nominally supportive of the drug remarked about the poor evidence base and lack of long term clinical trials.
Given these concerns and the lack of good evidence, why did the EMA approve rosiglitazone?
Garattini said that rosiglitazone is “an example of what happens for drugs that have large commercial interest such as the antidiabetic drugs.”
When appealing against a decision not to approve their drug, Garattini says pharmaceutical companies bring forward opinion leaders who are obviously favourable. These paid advisers give presentations to the regulators and companies turn to them whenever an oral presentation is required.
On receiving the negative opinion Jan Leschly, chief executive officer of SmithKline Beecham, told the press it was “a temporary setback,” adding that “in the coming months we will be working with the committee to address their concerns. We are confident that by the end of March we will have demonstrated Avandia’s unique benefits in the treatment of type 2 diabetes to the CPMP [Committee for Proprietary Medicinal Products]