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Sorry for the delay in responding. Doing my taxes took me down to the wire this year. Let me address each of Mackenzie’s points. > First, it was not my idea to compare the incidence of PG > (pathological gambling) among those on DAs to that of the > general population - Both Drs. Stacy and Voon (the April > 5th study) held up the indcidence and prevalence, > respectively, in the general population for comparison. > Stacy does not calculate signficance, but he does compare > the two numbers - and derives meaning from the one being > marginally higher than the other. Voon does the same. Arnie> True, but neither draws the conclusion which Mackenzie does, that there is "zero evidence" for any relationship between DAs and PG. Rather, they think it is a real effect and are trying to put the rate of occurrence in context. > Second, perhaps i misunderstand you, but it seems to me > that you are saying two things. > > first, it seems you are saying that statistical > significance is insignificant in that it tells us nothing > more than the degree to which certain results may or may > not have been influenced by random fluctuations, and that > tells us absolutely nothing of worth about the sources > from which the raw data was drawn. > > If i am understanding you correctly, then i have to ask > why the calculation is undertaken as a matter of course in > countless studies, and even more basic than that, why > bother inventing (?) a calculation that merely give us a > number - say, 42 - from which we may derive no meaning > whatsoever? Arnie> Yes, all that a test of statistical significance does is determine whether a result might be due to chance. Check any statistics textbook, or see one of these websites or dozens of others you can find by googling "statistical significance": http://en.wikipedia.org/wiki/Statistical_significance http://www.statpac.com/surveys/statistical-significance.htm I am not saying that tests of statistical significance are useless in general – they would take away my degree if I said that – but that they need to be used appropriately. I suspect I did not explain this very well, so I will try again. Ruling out random fluctuations as the cause of an empirical result is essential to being able to rely on it. But the comparison needs to be appropriate, and there are lots of ways one can go astray. For example, children who grow up in older housing which has lead-based paint do more poorly in school than the population as a whole. But there are many other differences besides lead-based paint: rheir parents are less well educated, they are poorer, fewer of them have intact families, etc. If you don’t take account of all these other factors, you will not be able to correctly determine the impact of lead-based paint (which is, in fact, very important, by the way). If there does not appear to be an association between two variables, there are several possible reasons: there really is no relationship; there is a relationship, but it is smaller than you thought, so you need a larger sample size; and, there is a relationship, but it is being masked by other factors that you are not considering but which impact the factors you are looking at. An example of the third type (this is made up, so don’t go quoting it): The total number of deaths from cancer in the population remains about the same, despite progress in treating it. Other factor: people are living longer, so more of them are reaching the ages where cancer is more common. The general principle here is to be careful when comparing two different populations or two different variables, since they may differ in ways you did not anticipate. This is where the problem is in the "lack of statistical significance" in the Parkinson’s pathological gambling studies, as I will discuss below. > second, it seems to me you may be saying that beyond the > uselessness of calculating significance itself, the two > groups are not appropriate for comparison because, and > please correct me if i have this wrong, PG among PWP is > associated with the starting and stopping of DAs, and PG > among the general population is not. could you clarify > that for me? Arnie> Exactly. I’m glad *something* I wrote was clear. > because such comparisons are standard procedure - take > the question of suicide risk among cancer patients - > epidemiological studies have indicated that the risk of > suicide in cancer patients is higher than that of the > general population. suicide is to the onset of cancer > as gambling is to the onset of dopaminergic medication (in > theory, at least)- and both suicide and gambling occur in > the general population as well. in what way is the > comparison stacy and voon make different from cancer > comparison? Arnie> I am not familiar with the literature on suicide risk among cancer patients, but I would assume that the studies follow standard practice by using a control group or comparison group that is matched or adjusted for variables known to affect suicide risk, such as age, gender,socio- economic status, etc. Thus, the comparison is between cancer patients and a group of non-patients who are as similar to them as the investigators can arrange. In contrast, the comparisons quoted by Mackenzie are between the occurrence rates among the subpopulation who are PWPs getting a particular medication compared to the whole population. The statements were made to indicate the general magnitude of the effects reported and did not pretend to be a complete, detailed analysis. Thus, the distribution of demographic variables is quite different between the PWP group and the comparison group. Pathological gambling has been studied, and, as I wrote earlier, it usually starts in adolescence or early adulthood and builds up over many years until it reaches the point of being "out of control". There typically does not seem to be any particular event that sets off the behavior, and it continues until treatment is sought and is successful. Treatment is usually similar to that for alcohol addiction. Overcoming it is a very difficult, lifelong struggle. By using these comparisons to discount the reality of the experiences of PWPs in these studies, Mackenzie is basically arguing that they are not real *because* a similar proportion of young people without PD experience a long-term addiction to gambling. Obviously, this is not the intention, but it’s what the argument from lack of statistical significance means. According to this argument, a few percent of PWPs taking DAs experience pathological gambling, mostly in their 50s or higher, with sudden onset and rapid resolution, while a few percent of young people experience a long-term addiction to gambling. Since the percentages are similar, there is argued to be "no statistically signficant difference" and hence "zero evidence" of an effect. If someone were to make a comparison of suicide rates among cancer patients with suicide in the total population *and* use it to discount the seriousness of the problem, that reasoning would be equally questionable. I hope I have made it clear that pathological gambling as a result of treatment with DAs is very different from PG in the general population. They start at different ages, have a different pattern of development, and are totally different in their patterns of treatment and the efficacy of treatment in bringing them under control. Therefore, it does not matter that the proportions of the very different populations that are affected by each happen to be similar. > and as far as the difficulty determining whether anyone > has the behavior because of the tendency to lie about it - > people lie about suicidal thoughts, about binge eating, > about starving themselves, about pulling their hair out - > people lie about lots of things and still studies are > done, such obstacles and variables are taken into account > and conclusions are drawn. this situation is no different. Arnie> True, but they are taken into account by recognizing that the study is likely to underestimate the rate of occurrence of the behavior in question and by reflecting this in assessing the meaning of the low rates documented in the study. > regarding the statement that no study has shown an > association btw gambling and levodopa monotherapy, i will > actually put it in all caps - THE MOLINA STUDY found an > incidence of 4-4.5% of PG among those on levodopa - no > other drug is mentioned - just levodopa - and for some > reason it is like that study is invisible. > > anyone wants to read that study, i have it, happy to send > it. Arnie> I would like to see that study. I have not gotten ahold of the full report, but I have seen the abstract and the descriptions by Dr. Dodd, et al. As is noted, no other drug is mentioned, but it does not say that no other drug was used. In fact, Dr. Dodd states that "adjunctive drugs were employed but not listed". Of course, if it turns out that Molina’s patients were receiving levodopa monotherapy, I would have no problem dropping that part of my argument. And, of course, this may be overtaken by events if the study by Voon is replicated and a clear pattern emerges of which drugs are most likely to have which effects. > however, i totally agree with your assertion that whether > or not it is a *real* effect is of tantamount importance, > along with the mechanism of causation (is it mirapex, or > DAs, or levodopa, or some combination thereof?) I also > agree that the frequency of use of a particular drug must > be taken into account when calculating the incidence of a > certain behavior occuring on that drug vs other drugs of > its kind. > > but, i disagree that there is substantial evidence to > support the existence of the association we are > discussing - the Voon abstract *seems* to address some of > the as yet unaddressed issues, but i am going to wait to > read the full study before coming to any conclusions about > that - and until then, the stacy, dodd and szarfman > studies are all we have and they remain just as flimsy as > they have been - in my opinion Arnie> It is generally a good idea to read the full study and not rely on abstracts and press reports. While I certainly remain open to new data, I think the existing studies (even before Voon) show a consistent pattern of behavior that includes onset of pathological gambling after treatment with some PD drug or drugs, at ages usually in the 50s or later, sometimes accompanied by hypersexuality and pathological shopping, which resolves after stopping the medication or reducing the dose. None of these are observed in typical cases of PG in the general population. I would not change the conclusion of my previous post: "The evidence is less convincing than a randomized double-blind trial but goes well beyond isolated anecdotal reports." > anyway - if your takeaway were the final word and the goal > of all of this sound and fury were to alert folks to this > "danger," i think it is VERY safe to say "mission > accomplished." > > would it be nice if that were the final word? but it's > not - not by a long shot - this is going to spawn dozens > of studies (time will tell if i am right) and syphon money > away from research that could really help people - not to > mention the danger of people being frightened away from > DAs and into the arms of that most excellent drug, > levodopa. Arnie> People have lost their life savings and destroyed their marriages as a result of this behavior. If these results can be prevented, that certainly seems to me to be "really helping people". I agree that it would be unfortunate if people are frightened away from DAs, but I do not see any evidence that this is actually happening. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn