Conflicting Bisphosphonate Studies Raise Esophageal Cancer WorriesMay 3, 2012 | Parker Waichman LLP
In 2010, two studies on oral bisphosphonates reached differing conclusions regarding the drugs’ association with an increased risk of esophageal cancer. One study, published in the Journal of the American Medical (JAMA) Association, found no increased risk for esophageal cancer among patients who used oral bisphosphonates like Fosamax. Three weeks later, the second study, which found a doubling of the risk, appeared in the British Medical Journal.
Strangely enough, both bisphosphonate esophageal cancer studies drew data from the same source - a U.K. patient data base. So why the different conclusions?
According to a report published in The Wall Street Journal, the answer could lie in the way the studies were conducted. Both were observational studies, in which the researchers analyzed previously gathered data and drew conclusions, the Journal said. Observational studies are not considered the told standard in medical research - that distinction belongs to randomly controlled experimental studies. For one thing, observation studies are vulnerable to bias. Their conclusions usually are not easy to replicate, and flaws are usually not spotted - or corrected - when observational studies are published. Yet this research method is increasingly popular, possibly in part to their lower cost compared to experimental studies.
According to the Journal, both bisphosphonate esophageal cancer studies suffered from flaws. In the JAMA study, oral bisphosphonate users were identified first, then matched to random people of the same sex and age in the population, and then tracked until some developed cancer. The authors of the study acknowledge that their work has less statistical power than the BMJ paper, and that "poorly measured or unmeasured causes of bias may have masked an association" between the drugs and cancer.
In the JAMA, cancer cases were identified first, and then researchers looked at the drugs subjects had been given in the past. According to the Journal, the study suffered because it reported on three different variables at once, which could introduce errors due to "multiple testing." The study's lead author told the Journal the team did not adjust for multiple testing, and she acknowledged that because information about the patients isn't consistent, "this database may not be the ideal place to look," the Journal said.
It could also turn out that neither study has any validity because they both followed patients for less than five years. The findings of both would be rendered useless if it turns out that esophageal cancer develops after longer periods of bisphosphonate years, say 10 years or more.