File Drawering on Psych Med Studies
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SteveGrenard
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So wait a minute. If a study is started and early results looks like it is unpromising and it is stopped, it makes a certain amount of sense. Why would a commercial, profit making enterprise want to continue spending a ton of money on something that predictably will be unpromising?
And if it is unpromising and the study stopped for this reason doesn't it also mean that the company will not be submitting the drug for marketing approval or for approval to add a new indication?
And if it is unpromising and the study stopped for this reason doesn't it also mean that the company will not be submitting the drug for marketing approval or for approval to add a new indication?
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calebprime
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-Doctors rely on the prevailing wisdom and articles in medical journals.
-The medical journals are publishing a higher percentage of studies of trials which seem to show that antidepressants are effective, than studies which show them to be ineffective.
-These are not new drugs we are discussing. They are the antidepressants already sold under the names Paxil, Zoloft, etc.
-There are at least 4 areas of concern with SSRI's--sexual dysfunction, withdrawal symptoms, overall effectiveness compared to other options, long-term effects (and long-term effectiveness). There are others as well.
Suicidality, akathisia.
-For these areas of concern, the drug companies somehow didn't study them, or exaggerated the benefits and downplayed the risks. The studies were short-term. I have read of various methods the drug companies used to slant their data. (This is subtle stuff for me--so I don't recall all the details--but I've read about this quite a number of times.)
-example: Withdrawal symptoms were at first written off as the return of depression. Sexual dysfunction was blamed on depression--or supposedly could be treated with other drugs (!)
-Ought reports that SSRI's are ineffective be considered less interesting than those saying that they are effective? I don't understand.
Whether this is publication bias or "File-drawering", isn't this important evidence that doctors have received skewed information?
Someone more knowledgeable than me, please confirm or explain why not.
-The medical journals are publishing a higher percentage of studies of trials which seem to show that antidepressants are effective, than studies which show them to be ineffective.
-These are not new drugs we are discussing. They are the antidepressants already sold under the names Paxil, Zoloft, etc.
-There are at least 4 areas of concern with SSRI's--sexual dysfunction, withdrawal symptoms, overall effectiveness compared to other options, long-term effects (and long-term effectiveness). There are others as well.
Suicidality, akathisia.
-For these areas of concern, the drug companies somehow didn't study them, or exaggerated the benefits and downplayed the risks. The studies were short-term. I have read of various methods the drug companies used to slant their data. (This is subtle stuff for me--so I don't recall all the details--but I've read about this quite a number of times.)
-example: Withdrawal symptoms were at first written off as the return of depression. Sexual dysfunction was blamed on depression--or supposedly could be treated with other drugs (!)
-Ought reports that SSRI's are ineffective be considered less interesting than those saying that they are effective? I don't understand.
Whether this is publication bias or "File-drawering", isn't this important evidence that doctors have received skewed information?
Someone more knowledgeable than me, please confirm or explain why not.
They also rely on the FDA-approval process and post-marketing surveillance. The FDA had access to the studies even if they were not all published in medical journals. Regardless of what is published, the uses for which a particular drug is approved will have evidence backing that use.
That really only influences the perception of overall effectiveness. And from a practical point-of-view, the absolute effectiveness of a medication doesn't really matter when it comes to prescribing for an individual. You don't really expect an identical response to what was found in an RCT, as an RCT represents a somewhat contrived situation. You just need to know about relative responses - whether it's likely to have a response better than placebo or other anti-depressants, and in what conditions (mild vs. moderate vs. severe depression, for example). Publication bias becomes more relevant when you are talking about off-label uses.
Yes, but it includes the information that went in to deciding whether or not the drugs were approved - i.e. at the time of the studies they were new drugs.
To be fair, that is the point of post-marketing surveillance. It is difficult to discover these effects before there is widespread use of the drug. Side-effects are looked for in Phase I, II, and III trials, but to rule-out uncommon effects or to thoroughly discover the effects of long-term use would be prohibitively expensive and time-consuming. It's a balance between making useful drugs available and ensuring they are as safe as possible.
And regardless of whether drug companies try to suppress the information, the process is too transparent, and too many other people, like physicians, are aware of the information, for it not to become public knowledge.
I think Blutoski answered this question well, already. Unless the information is likely to change practice, it's not particularly interesting regardless of whether it's positive or negative.
Doctors generally assume that they are receiving skewed information, though. This is sort of a formal confirmation of already established suspicions. There tends to be an ongoing re-evaluation of drugs over time, sometimes even over-turning prior practice. That this kind of information comes to light shows that the system is working.
Linda
Dancing David
Penultimate Amazing
On the whole 'effectiveness' issue, the scale that is used to asses depression is crucial, the Beck Depression Inventory is a good gross assessment tool, and it is not a great way to assess levels of depression.
Here is a brief technical discussion of the BDI:
http://www.swin.edu.au/victims/resources/assessment/affect/bdi.html
Here is the Wikipedia article:
http://en.wikipedia.org/wiki/Beck_Depression_Inventory#BDI
This is a very useful tool for assessing the presence of depression, however it will not give you as accurate a picture as a functional analysis or personal interview. People are notorious for under and over scoring.
(For example)
When I did interviews about domestic violence you would ask people a very standard set of question, one of which was “Has there been physical violence?"
Now it is very important when you ask this question to listen and then follow up with a series of behavioral indicators and criteria. I am very serious that people would say "No" and then answer "Yes" to most of the follow-up questions.
Did they strike you? Did they slap you? Did they grab you and restraint you? Did they ever bruise you when they grabbed you or restrained you? Did they throw things? Did they break things? Did they block the doorway? Did they cut you? Did they burn you? Did they choke you?
So this can be a real problem in any information gathering, seriously many victims would say "No" and then when you ask if they have been choked they would say "Yes".
Then there is the issue of how you grade events as an individual who is living with depression. You get used to being depressed and so how you answer questions kind of gets skewed after a while, especially if you have had it for a long time. You begin to notice that 'good' days are really 'not so terrible days'. And so when someone rates their level of sadness this can totally mess up the scoring.
Here is a brief technical discussion of the BDI:
http://www.swin.edu.au/victims/resources/assessment/affect/bdi.html
Here is the Wikipedia article:
http://en.wikipedia.org/wiki/Beck_Depression_Inventory#BDI
This is a very useful tool for assessing the presence of depression, however it will not give you as accurate a picture as a functional analysis or personal interview. People are notorious for under and over scoring.
(For example)
When I did interviews about domestic violence you would ask people a very standard set of question, one of which was “Has there been physical violence?"
Now it is very important when you ask this question to listen and then follow up with a series of behavioral indicators and criteria. I am very serious that people would say "No" and then answer "Yes" to most of the follow-up questions.
Did they strike you? Did they slap you? Did they grab you and restraint you? Did they ever bruise you when they grabbed you or restrained you? Did they throw things? Did they break things? Did they block the doorway? Did they cut you? Did they burn you? Did they choke you?
So this can be a real problem in any information gathering, seriously many victims would say "No" and then when you ask if they have been choked they would say "Yes".
Then there is the issue of how you grade events as an individual who is living with depression. You get used to being depressed and so how you answer questions kind of gets skewed after a while, especially if you have had it for a long time. You begin to notice that 'good' days are really 'not so terrible days'. And so when someone rates their level of sadness this can totally mess up the scoring.
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Just watched a News clip about this. Said 94% of published studies state antidepressants work great, while 96% of unpublished studies show little or no benefit from the same drugs.
http://cosmos.bcst.yahoo.com/up/player/popup/?rn=3906861&cl=5989719
http://cosmos.bcst.yahoo.com/up/player/popup/?rn=3906861&cl=5989719
The SkepDoc
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Here's the abstract: http://content.nejm.org/cgi/content/abstract/358/3/252
I've read the whole article. It doesn't say anything new. We always knew about publication bias, and that's why efforts have been made to get all trials registered. The authors point out that their review did not show that antidepressants were ineffective, it just showed that they may not be quite as effective as we thought. I was intrigued that there did not appear to be any publication bias for Prozac in the table they printed iin the article. Prozac was the first, prototypical SSRI. I wonder what the lack of bias for that particular drug means. I think one of the authors of the new Science Based Medicine blog at http://www.sciencebasedmedicine.org/ plans to discuss this study soon. Watch for it!
I've read the whole article. It doesn't say anything new. We always knew about publication bias, and that's why efforts have been made to get all trials registered. The authors point out that their review did not show that antidepressants were ineffective, it just showed that they may not be quite as effective as we thought. I was intrigued that there did not appear to be any publication bias for Prozac in the table they printed iin the article. Prozac was the first, prototypical SSRI. I wonder what the lack of bias for that particular drug means. I think one of the authors of the new Science Based Medicine blog at http://www.sciencebasedmedicine.org/ plans to discuss this study soon. Watch for it!