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Showing posts with label psychotic major depression. Show all posts
Showing posts with label psychotic major depression. Show all posts

Friday, January 29, 2010

Health Care Resources - Ten statisticians every psychologist should know about

As psychology students past and present will be only too aware, statistics are a key part of every psychology undergrad course and they also appear in nearly every published journal article. And yet have we ever stopped to recognise the statisticians who have brought us these wonderful mathematical tools? As psychologist Daniel Wright puts it: "Statistical techniques are often taught as if they were brought down from some statistical mount only to magically appear in [the software package] SPSS."

To help address this oversight, Wright has compiled a list of ten statisticians he thinks every psychologist should know about. The list is strict in the sense that it only includes statisticians, whilst omitting psychologists, such as Jacob Cohen and Lee Cronbach, who have made significant contributions to statistical science in psychology.

Wright divides his list in three, beginning with three founding fathers of modern statistics. First up is Karl Pearson (pictured), best known to psychologists for the Pearson Correlation and Pearson's chi-square test. He was a socialist who turned down a knighthood in 1935. His first momentous achievement was his 1932 book The Grammar of Science and he also founded the world's first university statistics department at UCL in 1911.

Ronald Fisher was the author of Statistical Methods for Research Workers, which Wright describes as "one of the most important books of science." Fisher was also instrumental in the development of p values in null hypothesis significance testing.

Together with Pearson's son, Egon, Jerzy Neyman produced the framework of null and alternative hypothesis testing that dominates stats to this day. He also created the notion of confidence intervals. Neyman and Fisher were big critics of each other's theories. After a brief spell at UCL with Fisher, Neyman moved later to Berkeley where he set up the stats department - now one of the top such departments in the world.

Wright also lists three of his statistical heroes: John Tukey of post-hoc test fame, who made major contributions in robust methods and graphing (and who coined the terms ANOVA, software and bit); Donald Rubin who has conducted influential work on effect sizes and meta-analyses; and Brad Efron who developed the computer-intensive bootstrap resampling technique.

Wright devotes the last section of his list to four statisticians who have gifted psychology particular statistical techniques: David Cox and the Box-Cox transformation; Leo Goodman and categorical data analysis; John Nelder and the Generalised Linear Model; and Robert Tibshirani and the lasso data reduction technique.

"The list is meant to introduce some of the main statistical pioneers and their important achievements in psychology," Wright concludes. "It is hoped learning about the people behind the statistical procedures will make the procedures seem more humane than many psychologists perceive them to be."

What do you think of Wright's list? Is there anyone he's overlooked?
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ResearchBlogging.orgDaniel B Wright (2009). Ten Statisticians and Their Impacts for Psychologists. Perspectives on Psychological Science, 4 (6), 587-597. [Draft pdf via author website].

Sunday, November 29, 2009

More Evidence for Suppression of Research: the Case of Lamictal for Depression

We recently discussed the severe challenges to evidence-based medicine presented by manipulation and suppression of clinical research to serve vested interests.  I recently (and unfortunately belatedly) came upon yet another example of suppression of research that was unfavorable to a research sponsor's vested interests, suggesting that such suppression may be more prevalent than heretofore believed. 

This example appeared in the journal Evidence-Based Mental Health [Gahemi SN. The failure to know what isn't known: negative publication bias with lamotrigine and a glimpse inside peer review.  Evidence Based Mental Health 2009; 12: 65-68.  Link here.]

The author was able to use the database of clinical trials provided by GlaxoSmithKline as part of a settlement of a suit by former New York state Attorney General Elliot Spitzer that charged that the company had suppressed information about the selective serotonin reuptake inhibitor paroxetine (Paxil).  His interest was the use of lamotrigine (Lamictal) in depression.  His main findings were:
Of the nine lamotrigine related bipolar disorder studies posted on the website (see table 1), two were positive and published supporting the FDA approved indication for delay of relapse in the long term treatment for bipolar disorder patients. A negative study in rapid cycling bipolar disorder and another in acute bipolar depression were published but both emphasised positive secondary outcomes as opposed to the negative primary outcomes. Five other negative studies involving rapid cycling bipolar disorder, acute bipolar depression and acute mania have not been published and are only available on the GSK website.

Failure to adequately publish these negative studies led to the creation of a clinical impression that lamotrigine is an 'antidepressant,' a view innocently expressed to me as recently as last week by an academic colleague. This mistaken impression occurred partly because the prophylactic benefits of lamotrigine for depressive episodes were confused with a presumed acute benefit. Partly it was due to the publication of one apparently positive study, and the non-publication of several negative studies.

The clinical relevance of the lamotrigine studies is notable: taking the negative outcomes into account, as of now, one might say that this agent is reasonably effective in maintenance treatment of bipolar disorder, particularly in prevention of depression. It is proven ineffective in acute mania, rapid cycling disorder and acute bipolar depression.

Note that Dr Ghaemi and colleagues had published a summary of the suppressed negative articles in Medscape Journal of Medicine in late 2008.  [Ghaemi SN, Shirzadi AA, Filkowski M. Publication bias and the pharmaceutical industry: the case of lamotrigine in bipolar disorder. Medscape J Med 2008; 10(9):211.  Link here.]  That earlier article also documented the group's failed attempts to discover whether negative trials of other drugs for depression had been suppressed.

Dr Ghaemi's newer made some additional important points about suppression of clinical research.  The first is that it is occurring with the acquiescence of government regulators. In particular,
It is worth mentioning that the [US] FDA [Food and Drug Administration] has encouraged this state of affairs, by viewing negative studies as uninformative, due to the possibility of being 'failed' rather than truly negative (ie, the sample may have simply been unresponsive, or dosing might have been too low and so on). Thus drugs could have two positive studies, and 10 or so negative ones (as did a number of selective serotonin reuptake inhibitors),8 and the FDA not only allowed approval but it did not require that the pharmaceutical industry publish its negative results. The pharmaceutical industry did the minimum necessary; the FDA set the minimum far below what should have been the acceptable scientific standard.

Furthermore, even though the FDA is supposed to allow access to information about all studies for drugs for which it provides an indication, in fact it still does not allow access to raw data from industry sponsored studies, which are viewed as confidential and proprietary. Rather, in my experience and those of colleagues who have attempted to access such studies, Freedom of Information Act requests are met with abstracted summary results. While summary results are better than no results, full access to scientific data should be the standard at the FDA.

The second is that medical journal reviewers and editors do not seem enthused about publishing articles about how research has been suppressed (an apparent example of the anechoic effect, or perhaps the anechoic effect squared, i.e., discussion of our failure to discuss research studies whose results did not please their sponsors is simply not done.)
In the course of trying to investigate and publicise these negative findings, we ran into numerous roadblocks, as I discussed in an interview for the Carlat Report last year

Instead of repeating what I have said before about the evils of suppressing clinical research, I will offer some concluding quotes from Dr Ghaemi.
Evidence based medicine—or, more simply put, the science of medicine—cannot be taken seriously, and is certainly not valid, if the evidence base is only partial. The scientific literature currently is like an under cooked meal which we think is ready to eat. We never know whether what we see in the evidence is correct or biased in one direction or the other. Meta-analyses of large published datasets are not as meaningful as they seem when unpublished data languish elsewhere.
Manipulation and suppression of clinical research has likely misled doctors and patients into using and paying too much for minimally effective, ineffective, or even harmful drugs and devices.  Manipulation and suppression of research is thus probably a major reason that health care costs much more than its value and accessibility warrants.  To truly reform health care, we should not let those with vested interests in selling health care products or services control the clinical research that purports to evaluate what they are selling.

Friday, November 27, 2009

More Evidence for Suppression of Research: the Case of Lamictal for Depression

We recently discussed the severe challenges to evidence-based medicine presented by manipulation and suppression of clinical research to serve vested interests.  I recently (and unfortunately belatedly) came upon yet another example of suppression of research that was unfavorable to a research sponsor's vested interests, suggesting that such suppression may be more prevalent than heretofore believed. 

This example appeared in the journal Evidence-Based Mental Health [Gahemi SN. The failure to know what isn't known: negative publication bias with lamotrigine and a glimpse inside peer review.  Evidence Based Mental Health 2009; 12: 65-68.  Link here.]

The author was able to use the database of clinical trials provided by GlaxoSmithKline as part of a settlement of a suit by former New York state Attorney General Elliot Spitzer that charged that the company had suppressed information about the selective serotonin reuptake inhibitor paroxetine (Paxil).  His interest was the use of lamotrigine (Lamictal) in depression.  His main findings were:
Of the nine lamotrigine related bipolar disorder studies posted on the website (see table 1), two were positive and published supporting the FDA approved indication for delay of relapse in the long term treatment for bipolar disorder patients. A negative study in rapid cycling bipolar disorder and another in acute bipolar depression were published but both emphasised positive secondary outcomes as opposed to the negative primary outcomes. Five other negative studies involving rapid cycling bipolar disorder, acute bipolar depression and acute mania have not been published and are only available on the GSK website.

Failure to adequately publish these negative studies led to the creation of a clinical impression that lamotrigine is an 'antidepressant,' a view innocently expressed to me as recently as last week by an academic colleague. This mistaken impression occurred partly because the prophylactic benefits of lamotrigine for depressive episodes were confused with a presumed acute benefit. Partly it was due to the publication of one apparently positive study, and the non-publication of several negative studies.

The clinical relevance of the lamotrigine studies is notable: taking the negative outcomes into account, as of now, one might say that this agent is reasonably effective in maintenance treatment of bipolar disorder, particularly in prevention of depression. It is proven ineffective in acute mania, rapid cycling disorder and acute bipolar depression.

Note that Dr Ghaemi and colleagues had published a summary of the suppressed negative articles in Medscape Journal of Medicine in late 2008.  [Ghaemi SN, Shirzadi AA, Filkowski M. Publication bias and the pharmaceutical industry: the case of lamotrigine in bipolar disorder. Medscape J Med 2008; 10(9):211.  Link here.]  That earlier article also documented the group's failed attempts to discover whether negative trials of other drugs for depression had been suppressed.

Dr Ghaemi's newer made some additional important points about suppression of clinical research.  The first is that it is occurring with the acquiescence of government regulators. In particular,
It is worth mentioning that the [US] FDA [Food and Drug Administration] has encouraged this state of affairs, by viewing negative studies as uninformative, due to the possibility of being 'failed' rather than truly negative (ie, the sample may have simply been unresponsive, or dosing might have been too low and so on). Thus drugs could have two positive studies, and 10 or so negative ones (as did a number of selective serotonin reuptake inhibitors),8 and the FDA not only allowed approval but it did not require that the pharmaceutical industry publish its negative results. The pharmaceutical industry did the minimum necessary; the FDA set the minimum far below what should have been the acceptable scientific standard.

Furthermore, even though the FDA is supposed to allow access to information about all studies for drugs for which it provides an indication, in fact it still does not allow access to raw data from industry sponsored studies, which are viewed as confidential and proprietary. Rather, in my experience and those of colleagues who have attempted to access such studies, Freedom of Information Act requests are met with abstracted summary results. While summary results are better than no results, full access to scientific data should be the standard at the FDA.

The second is that medical journal reviewers and editors do not seem enthused about publishing articles about how research has been suppressed (an apparent example of the anechoic effect, or perhaps the anechoic effect squared, i.e., discussion of our failure to discuss research studies whose results did not please their sponsors is simply not done.)
In the course of trying to investigate and publicise these negative findings, we ran into numerous roadblocks, as I discussed in an interview for the Carlat Report last year

Instead of repeating what I have said before about the evils of suppressing clinical research, I will offer some concluding quotes from Dr Ghaemi.
Evidence based medicine—or, more simply put, the science of medicine—cannot be taken seriously, and is certainly not valid, if the evidence base is only partial. The scientific literature currently is like an under cooked meal which we think is ready to eat. We never know whether what we see in the evidence is correct or biased in one direction or the other. Meta-analyses of large published datasets are not as meaningful as they seem when unpublished data languish elsewhere.
Manipulation and suppression of clinical research has likely misled doctors and patients into using and paying too much for minimally effective, ineffective, or even harmful drugs and devices.  Manipulation and suppression of research is thus probably a major reason that health care costs much more than its value and accessibility warrants.  To truly reform health care, we should not let those with vested interests in selling health care products or services control the clinical research that purports to evaluate what they are selling.
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