Monday, May 05, 2008

Pathological Gambling Caused by Drugs Used to Treat Parkinson’s Disease: Yet Another Closer Look, Part Two

Welcome to Part Two of a three part series.

To recap the background provided in Part One, in the 2005 study entitled “Pathological Gambling Caused by Drugs Used to Treat Parkinson’s Disease,” the authors mine records of Parkinson’s patients seen at the Mayo Clinic in Rochester, MN (MCR), between 2002 and 2004, and find 11 people who had developed pathological gambling (PG) - they conclude that the PG was caused by Parkinson's drugs. The authors so completely fail to provide evidence compelling enough to support this conclusion that the fact that this study was published in a peer-reviewed journal boggles the mind. It is available online for free at the Archives of Neurology, if you are interested. It may actually be necessary to read the study for what I am about to say to make sense – I don’t know.

According to the authors of this study, the 11 people who gambled fit the DSM-IV-TR criteria for PG.* They also say that the PG was temporally associated with the commencement, increase, and/or cessation of dopamine agonist (DA) therapy, a type of drug used to treat Parkinson’s disease (PD), and, for a disproportionate percentage of these people, the culprit was a DA called pramipexole.

Finally, the authors provide the results of their survey of the field of literature, and present in a table six studies in support of their conclusion that Parkinson’s drugs cause – not just “are associated with,” but cause PG.

In Part One, I addressed the authors’ failure to adequately support their central assertion, that DAs cause PG, in the context of what criteria must be met to identify a causal relationship. In Part Two, I will address specifically the authors’ failure to provide any indication of the prevalence of this phenomenon and show how that pretty much single handedly invalidates the study. And in Part Three, I will address several other questions that come up when one actually reads the study rather than the press coverage it received.

Prevalence is defined by the Centers for Disease Control as “the number of existing disease cases [or, in this case, adverse events of a specific nature] in a defined group of people during a specific time period.”

So there are three parts to prevalence, each of which consists of a number – (1) the number of existing cases; (2) a defined [read: finite, i.e., quantifiable] group of people among whom those cases are found; and (3) a specific time period.

Prevalence is calculated by dividing the number of existing cases by the quantity of people in the specific population in which those cases were found, which yields a percent of people affected. In this study, the authors provide the number of existing cases, which is 11, and they denote a specific time period, which is 2002 to 2004. However, the authors omit (2), the total number of people with Parkinson’s (PWP) being treated at MCR and taking DAs between 2002 and 2004, and that really makes the claim that an association was found groundless.

In order to illustrate why this is true, and because I was unable to find any relevant stats regarding the MCR, I extrapolated a value for the missing piece of data from information found in various places on the internet, and using this method (which I have detailed below, in case you are interested)** I came up with the number 1195 for the total number of PWP taking DAs that were seen at MCR between 2002 and 2004. 11/1195 returns a prevalence of PG of 0.09% among those who were taking DAs.

But even that is not enough information. The authors also fail to provide the prevalence of PG in the general population or in untreated PD, which is just as crucial as the total number of (PWP) being treated at MCR and taking DAs between 2002 and 2004, because the only way a prevalence in a certain population has meaning is in relation to the prevalence of the same phenomenon in a different population.

So, I looked around and found the following stats for the general population from 1999. Estimates of the lifetime prevalence of PG in the general population in the US in the late 90s range from 1.2-3.9%, while estimates of past year prevalence of PG in the general population range from 0.6-2%.***

As you might have noticed, the prevalence I have extrapolated for the 11 who gambled is far lower than even the lowest estimated prevalence I could find for the general population. One might argue that my method of deriving that prevalence was not scientific, and that may be true.

However, in the absence of the total number of (PWP) being treated at MCR and taking DAs between 2002 and 2004, there is no way of knowing whether the prevalence of PG among those taking DAs is higher or lower than that of the general population.

And if the prevalence really were 0.09%, i.e., significantly lower than that of the general population, then I would think the makers of pramipexole would be doing the victory dance, because they would then be purveyors of a treatment for, not a cause of, PG.

And it is in that way that the authors fail to provide evidence sufficient and compelling enough to support their conclusion.

If I have not explained my thoughts clearly, please let me know and I will try again.

On to Part Three.

* Pathological gambling is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) as follows, and the study does not describe in which five each patient has engaged:

A. Persistent and recurrent maladaptive gambling behavior as indicated by five (or more) of the following:
  1. is preoccupied with gambling (e.g., preoccupied with reliving past gambling experiences, handicapping or planning the next venture, or thinking of ways to get money with which to gamble)
  2. needs to gamble with increasing amounts of money in order to achieve the desired excitement
  3. has repeated unsuccessful efforts to control, cut back, or stop gambling
  4. is restless or irritable when attempting to cut down or stop gambling
  5. gambles as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)
  6. after losing money gambling, often returns another day to get even ("chasing" one's losses)
  7. lies to family members, therapist, or others to conceal the extent of involvement with gambling
  8. has committed illegal acts such as forgery, fraud, theft, or embezzlement to finance gambling
  9. has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling
  10. relies on others to provide money to relieve a desperate financial situation caused by gambling

B. The gambling behavior is not better accounted for by a manic episode

**Based on the fact that Ohio State University’s Dept of Neurology’s 28 physicians see 400 PWP annually, I will extrapolate that the 93 neurologists at MCR see 1328 PWP annually, or 3984 PWP over the three year period in question. And according to the website of a law firm selling its services to folks who have gambled while taking a DA, 30% of PWP are prescribed DAs – which would mean 1195 people on DAs were seen at MRC between 2002 and 2004.

*** 3.9% lifetime; 2% past year ~ National Research Council. Pathological Gambling: A Critical Review. Washington, DC: National Academy Press; 1999

1.2% lifetime; 0.6% past year ~ National Opinion Research Center at the University of Chicago, Gemini Research, and The Lewin Group. Gambling Impact and Behavior Study. Report to the National Gambling Impact Study Commission. April 1, 1999. Table 7, p. 26.

No comments: