The safety of Actos, an oral diabetes drug that increases the body’s sensitivity to insulin, has been increasingly called into question since 2010. That was when the FDA announced that it was “reviewing data from an ongoing, 10 year epidemiological study designed to evaluate whether Actos (pioglitazone) is associated with an increased risk of bladder cancer.” The results of FDA study did not show an over-all increased risk of bladder cancer with Actos use but did establish risk among patients with the longest exposure to Actos and in those exposed to the highest cumulative dose of drug.
Last year, health officials in the United States and Europe issued warning on the cancer risk that long-term use of Actos poses, and now patients are seeking redress for bladder cancer caused by drug. New research supports the Actos-cancer link, but the plaintiff lawyer must also have a thorough understanding of the etiology of bladder cancer and a detailed knowledge of the client’s medical history.
The FDA issued a warning in June of 2011 that Actos use for more than one year may be associated with an increased risk of bladder cancer , and the French Medicines Agency suspended the use of Actos in 2011based on the results of a retrospective cohort study conducted in France by the national Health Insurance Agency. Research oublished in Diabetes Care last year reaffirmed the drug's risk; researchers evealuated adverse events reported to the FDA from January 2004 to December 2009 and found that the reporting odds ratio (a measure applied to databases to estimate relative risk) of bladder cancer was increased in Actos patients by 330 percent. The European Medicines Agency, promptedby an increased number of spontaneous reports of bladder cancer, concludedthat the evidence provided a clinically relevant signal that required further evaluation.
Takeda Pharmaceutical Co., the manufacturer of Actos, disoutes the link between the drug and bladder cancer. The company relies on a flawed industry- funded study conducted in 2005; researchers in that study foundthat bladder cancer in the Actos group versus the placebo group did not reach the statistical significance required to support causation.
While the study's data and safety monitoring committee reviewed cases with "external experts," it excluded highly relevant data-such as tumors that occurred in patients within one year of enry into the study. Thos exclusion is not valid because the latency period between exposure to a carcinogen and the development of transitional cell carcinoma- the most common form of bladder cancer-varies between nine months and 23 years. This exclusion makes the study suspect and vulnerable to scrutiny on cross examination. Comittee reviewers also excluded cases that had "known risk factors in their history (Smoking, exposure to potential carcingens, family history, previous tumor, urinary tract infection)" in finding that bladder cancer was not likely to be a safety issue with Actos.
Takeda researchers revvisited the study data in 2009 and reported new finding supporting the company's view- that Actos does not cause bladder cancer. " In fact," the researchers wrote, " in vitro studies suggest that pioglitazone may actually inhibit the growth of some neopllastic human urothelial cell lines."
A significant weakness of the 2005 study is the exclusion of patients merely because they had one or more risk factors for bladder cancer. Independent researchers recalculated the Actos versus placebo data, adjested it to take into account concomitant potential risk factors and treatment duration and, in a 2001 letter to the editor published in the Lancet, report "a significant relation between pioglitazone and bladder cancer, which has not been presentedin the ( industry-funded) study reports." The indepenndent researchers opinedthat bladder cancer in patients taking actos contracted between 2005 and 2010 could have been prevented, but the industry-funded researchers failed to properly asses and report the results of the industry study in 2005.