The Avandia scandal

An investigation by the BMJ published this week calls for the withdrawal of the daibetes drug, Avandia, immediately from the market because of the concerns that it may increase the risk of myocardial infarction and the paucity of good evidence to support its use.

Rosiglitazone, also known as Avandia, was GSK's second biggest selling drug, introduced in 1999 and is widely used to lower blood glucose levels in patients with type 2 diabetes. It was approved by the EMA in 2000 despite concerns over its safety.

In 2007, several studies found Avandia having harmful effects and issued serious health warnings. The researchers questioned why Avandia is still available on the market and why physicians would prescribe it to diabetic patients when there are other drugs without these side effects. They called for Avandia to be withdrawn from the market. Since then, the sales of Avandia fell sharply.

The BMJ investigators found that in July, the UK Commission on Human Medicines advised the MHRA to withdraw Avandia as the risks of Rosiglitazone outweigh its benefits. This has raised a lot of questions about the quality of the data used in the studies and the lack of trial results made available to the public. The investigators also ask why the regulators accept such poor evidence on benefit and safety, why patients in the UK and Europe are not make aware of the concerns about this drug and whether the current regulatory body is doing its job properly. They said that doctors are advising that no new patients shoud use this drug, existing diabetic patients should review their options and those at high risk of heart disease should stop taking it.

In the accompanying editorial, the authors said that clinicians had focused on the wrong endpoint and lost sight of the main reason for treating this disease, "which is not to reduce glycaemia but to prevent complications". They went on to say that clinicians need to be "absolutely certain that the long term treatment for type 2 diabetes are not causing the harm they are meant to prevent" and should insist on robust evidence of benefits and harms.

Professor Freemantle noted in the accompanying commentary that the Avandia studies were hindered by inadequate data due to high levels of loss to follow-up. He wrote "In order to learn from our mistakes, we must improve the quality of safety data from clincal trials on all new healthcare interventions, not just antidiabetic drugs" and an overhall in the standards of regulatory trials is needed.


Sources : free f/t
Rosiglitazone: what went wrong? BMJ 2010; 341:c4848 (Published 6 September 2010) Editorial - Licensing drugs for diabetes BMJ 2010; 341:c4805 (Published 6 September 2010)
Commentary: What can we learn from the continuing regulatory focus on the thiazolidinediones?BMJ 2010; 341:c4812 (Published 6 September 2010)

Free drug samples to children

Researchers analysed the data on more than 10,000 US children under 18 years old from a 2004 national survey that included questions on receipt of free drug samples.


They found that 1 in 10 children who take prescription medications received free samples and 1 in 20 children overall got free samples. The study showed that wealthy and insured American children who had access to medical care and saw doctors in private offices rather than in hospitals or clinics were more likely to get free drug samples although drug companies argue that free samples help uninsured and low-income people get the medications they need.


The author said that most free samples were new and expensive drugs, in her previous study on free samples for adults, Vioxx topped the list but was later withdrawn from the market due to dangerous side effects. She concluded that "Poor and uninsured children are not the main recipients of free drug samples. Free samples do not target the neediest children selectively and they have significant safety considerations."


Source: "Free Drug Samples in the United States: Characteristics of Pediatric Recipients and Safety Concerns" ( Published online October 1, 2008) Pediatrics Vol. 122 No. 4 October 2008, pp. 736-742

Calmer approach to Avandia : The Lancet

Since the NEJM paper ( see posting on 25 May 2007) was published on May 21, frightened diabetes patients flooded their doctors with calls, many patients have stopped taking Avandia or switched to a rival drug Actos although some experts caution there is no urgent need for diabetes patients to stop taking Avandia.

The Lancet published an editorial online on May 23, 2007 to point out that there are important weaknesses in Nisson's meta analysis and call for "a calmer and more considered approach to the safety of Rosiglitazone" in response to the alarm raised by Dr Steven Nisson in NEJM.

According to The Lancet, the 2 most reliable studies to inform decision-making are ADOPT (published by NEJM) and DREAM (published by The Lancet). Although the results of these studies "indicate the need for more reliable information about rosiglitazone's safety", patients should calm down and wait for the results of the RECORD trial, a multi-centre study designed to monitor cardiac risk.

Avandia and myocardial infarction

A leading cardiologist, Steven Nissen, found that Avandia (generic name: rosiglitazone), a diabetes drug, "was associated with significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance."

The study concluded that despite the study's limitation, " patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes."

His findings were based on an analysis of 42 RCTs and published online on May 21 by NEJM. "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes". The article will appear in the June 14 issue of the Journal.

Avandia is a top-selling diabetes drug manufacturered by GlaxoSmithKline, introduced in 1999 and is widely used to lower blood glucose levels in patients with type 2 diabetes mellitus. Nissen’s analysis on Avandia has caused the Glaxo stock down more than 6% in midday trading.

Dr. Nissen is a strong critic on drug safety, he and colleague, Eric Topol, a well-known cardiologist, raised concerns about the safety of Vioxx in JAMA in 2001 that led to the withdrawal of the drug from the market in 2004. Dr Topol lost his job after testimony against the drug manufacturer Merck in federal trial.