Archive for 28 septiembre 2010

Créase o no: criterios de inclusión en el TIDE

septiembre 28, 2010

Entre los criterios para incluir pacientes en el TIDE (sí, leyó bien, para incluir, no para excluir), figuran

Inclusion Criteria:

  • Age ≥ 50 years and evidence of vascular disease defined as ≥1of:
    • prior myocardial infarction
    • prior stroke
    • coronary, carotid or peripheral artery revascularization ≥ 4 years earlier
    • previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation

    Sin embargo, lo que se pensaba desde el trabajo de Nissen et al era que la rosiglitazona aumentaba el riesgo cardiovascular.

¿Qué ocurre con la rosiglitazona en la Argentina?

septiembre 28, 2010

Hace 24 horas la ANMAT sacó un comunicado. Veremos que difusión recibe en las páginas de “salud” de los medios de comunicación.

Atendiendo  la  nueva  información  científica  disponible  a  nivel  nacional  e
internacional,   que   sugiere   un   riesgo   elevado   de   eventos   adversos
cardiovasculares asociados al consumo del principio activo rosiglitazona, la
ANMAT informa que ha dispuesto una serie de restricciones relativas a las
especialidades medicinales que contengan la droga mencionada.

La información científica estaba disponible desde el 2007 para quien quisiera buscarla en las revistas médicas más conocidas.

Las  medidas  adoptadas  por  esta  Administración  Nacional  respecto  a  la
rosiglitazona, un principio activo utilizado para el tratamiento de la Diabetes
Mellitus tipo II, son las siguientes:

1-  Reformulación  de  determinados  items  contenidos  en  el
texto del prospecto, que implican limitaciones en su utilización.

2- Modificación de su condición de venta, que en adelante será bajo
receta archivada.

3- Instrumentación de un plan de farmacovigilancia estimulada o Plan
de Minimización de Riesgos.

Por otra parte, se ha decidido que no se dará curso a los ensayos clínicos
que involucren a  la droga en cuestión. De todos modos, cabe aclarar  que
actualmente  no  existe  ningún  estudio  clínico  aprobado  o  en  realización
vinculado al fármaco de referencia.

Sin embargo, el estudio TIDE figura en la página del registro de ensayos clínicos de USA como ensayo a realizarse en más de 20 centros en la Argentina, sobre un total de 741 sitios.


Radiografía de la corrupción

septiembre 28, 2010

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?

Clinical implications

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]

Garattini, who was on the panel, was not convinced. “There was no need for another antidiabetic drug—there are so many already that are more or less the same,” he told the BMJ. And as one adviser from the FDA said at an advisory meeting, it’s for the regulators to protect public health and not to equip physicians with a broader array of medicines for clinical choice.
Y aquí está la clave de todo esto:
At the end of 2006 and beginning of 2007, the sales of Avandia were up. It was GlaxoSmithKline’s second biggest drug, making an estimated $3billion per year. And it was outselling its rival, pioglitazone.
As part of a settlement with the state over GlaxoSmithKline’s nondisclosure of possible heightened suicide risk among teenagers taking antidepressant paroxetine (Paxil) the company had to put all its recent clinical studies on a website. O sea que no tuvieron más remedio, y se publicó un meta-analysis of GlaxoSmithKline’s study reports by Steve Nissen and Kathy Wolski in the New England Journal of Medicine.19 It claimed that rosiglitazone was “associated with a significant increase in the risk of myocardial infarction” compared with placebo or other antidiabetic regimens.
Finalmente han tenido que suspender un ensayo clínico muy grande (TIDE), y restringir el uso de rosiglitazona.
Esto es una radiografía de un sistema corrupto (la relación estados-empresas farmacéuticas), dentro de otro sistema corrupto (el capitalismo). Todo se justifica para seguir vendiendo.