Thursday, January 14, 2010

If there Really is a Possible Association between Sinemet & Gambling, Why Is It not Being Publicized?

Further detail on the question of why this is not being publicized if it's true, given that the FDA clearly knows about it...

In early 2006 a research letter to the editor*, which is not peer-reviewed, was published and publicized across the Internet. This letter was written in support of a 2005 paper claiming to have found an association between dopamine agonists and gambling based on the fact that 11 people gambled while taking dopamine agonists.

The authors of this 2006 research letter had mined the FDA's adverse event reporting system database looking for correlations between gambling reports and drugs. The adverse event reporting system is a database of reports of adverse drug events.

The authors say they found exorbitantly high correlation between reports of gambling and mirapex. They did not find a correlation between gambling and any other drugs, including levodopa.

What the authors of the study did not reveal was that of the 39 reports linking gambling and mirapex, 38 of those reports came in after the publication and plastering across the Internet of the first gambling study in 2003.

That means that in the first six years mirapex was on the market, there was only one report linking it to gambling -- 38 came in after the first study was published. Given that huge differential between before and after publicity, and given that virtually no reports came in before the publicity, there is a distinct possibility that these reports at least some of them were generated by the publicity. And when I say generated, I mean that people who would have gambled anyway with or without an agonist might have erroneously attributed to gambling to the drug.

For example, I guarantee you that if someone published a study saying that tetracycline makes you giggle, there would be a deluge of reports linking tetracycline and giggling -- and even if tetracycline did make you giggle really, some of those people would have giggled anyway with or without tetracycline. Not taking this into account would result in artificially high correlation between tetracycline and giggling.

The likelihood that publicity had an effect on the reporting rate was not addressed in a research letter in spite of the fact that one of the authors cautioned her audience against overlooking the possibility of such an effect in a presentation I found on the Internet.

Instead, the data was presented as if it incontrovertibly confirmed an association between the drug and gambling.

Three of the authors worked at the FDA. There was a disclaimer at the end of the research letter saying that these opinions were not necessarily those of the FDA, but nonetheless, the authors were openly associated with the FDA in press coverage of the research letter findings.

Just to call out the most interesting points here -- FDA employees mined the adverse event reporting system database and DID NOT find an association between levodopa and gambling.

FDA employees published a study that fanned the flames of the idea that mirapex and gambling were associated and cautioned people to be on the alert for such phenomenon.

Fast forward to end of 2008 -- the exact same paragraph word for word that has been in the mirapex label for a couple of years now is inserted into the Sinemet label under the FDA's watch and approval, and not a peep -- not a word to the public - all those hundreds of thousands of people who are taking Sinemet who don't know that the FDA now says that the drug they are taking might be associated with pathological gambling.

If it's true, why have FDA employees not published it across the Internet, like they did in 2006 with Mirapex? If it's not true, why did Bristol Myers Squibb/Merck put it in its label, given that it is not coming under any fire whatsoever for an association between Sinemet and gambling?

*“Association Between Pathologic Gambling and Parkinsonian Therapy as Detected in the Food and Drug Administration Adverse Event Database” by Ana Szarfman, MD, PhD, P. Murali Doraiswamy, MD, Joseph M. Tonning, MD, MPH, and Jonathan G. Levine, PhD published in the Archives of Neurology in February of 2006.

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