Since rosiglitazone was approved for use in controlling blood sugar in Type 2 diabetics who did not have success with front line treatments in 1999, studies have shown that this drug (included in trade name drugs Avandia, Avandamet and Avaglim) increases the risk of heart disease in users. This is of particular concern because most Type 2 diabetics die from heart disease. It is estimated that 60,000 to 200,000 people have suffered from heart disease due to these drugs.
A black box warning was placed on these drugs, but not until November 2007. The European Medicines Agency recommended that the drug be suspended from European markets in 2010, and the drug was withdrawn from New Zealand markets in 2011. What took so long?
We can attempt to add some clarity to this issue by viewing it in a Cause Map, or visual root cause analysis. To begin this analysis, we look at the impact to the goals from the point of view of the manufacturer. The patient safety goal is impacted because of the increased occurrence of stroke, heart attack, and death. The compliance goal is impacted because – according the Senate Finance Committee – trial results that would have indicated the increased risk for cardiovascular disease were not publicly released in a timely manner. Reduced sales as a result of the risk are estimated to be more than $2 billion (an impact to the organizational goal) and lawsuits (an impact to the patient services goal) are projected to cost more than $1 billion.
Although the actual mechanism that is causing the increased risk of cardiovascular disease is unknown, the cause of the increased occurrence of heart attack, stroke and death is due to use of the drug rosiglitazone. Although rosiglitazone has been found to be an effective second-line treatment for Type 2 diabetes, it is unlikely that doctors would have prescribed it as readily had they known about the increased risk of heart disease. Instead, they were likely swayed by a multi-million dollar advertising campaign, while test results that showed increased cardiovascular risk were allegedly covered up.
Unfortunately, it’s not the first (or last) time this has happened. In early 2012, the British Medical Journal raised concern about research misconduct – including cases where poor results from clinical trials are not released to the public. In the US, it was found that less than half of studies – including those funded by the government – are publicly released in a timely manner. Although there are regulations that require publication of studies, they aren’t always (or even usually) followed. Some consideration of what can be done to ensure that these regulations are effective is ongoing.
Meanwhile, rosiglitazone has been removed from Europe and New Zealand markets. In the US, new regulations went into effect making the drug extremely difficult to come by. A different drug – Actos – is said to have similar effects on controlling blood sugar without the increased cardiovascular risk. However, patients should consult with their doctors.
To view the Outline, Cause Map, Solutions and Timeline, please click “Download PDF” above. Or click here to read more.