FM sufferers dont miss this--A really good study

[Gerwyn]

I'm not sure what you mean here. It has nothing to do with anything I brought up. Perhaps you are commenting on another post...not sure.



.

Again, nothing to do with what I said. The paper I quoted was about Detailing, gabapentin just happened to be the drug in the study because there was abundant documentation available resulting from an FOI request(re detailing...not the drug per se). Of course that is made very clear in the paper, so I'm sure you picked that up when you read it[?]




No. They are not. That is the point.

Please read the papers I cited. Otherwise I don't see the point in commenting.

Here are the salient points;

Of approx 70 applications for FDA approval studies, all were completed but less than half were published. The only ones published were the ones in which the antidepressant performed better than placebo. More than 50%, which were not published had placebo outperforming the antidepressant.

It was based on these studies that next gen. antidepressants have been approved. It is also the basis on which the more recent theories you are bringing up are founded.

This is a very simple synopsis, the complete story is quite a bit worse.

Ok their sampling was biased they did not look at the big prospective studies over the last ten years .you can make meta analysis say virtually whatever you want them to say if you are selective with their data and use the "right" statistical tools.They did both.i read your studies and analysed them.No medic in the UK takes any notice of meta analysis to back up any scientific claim.You need prospective studies.The gabapentin article was a marketing report the like of which i,ve seen many times before 1995 come on!What doctors say when they are being paid to complete surveys and the reality of practice are completely different
There are many reasons why a study is requested by a regulatory authority in phase 1 2 and 3. They are mostly concerned with safety pharmaco kinetics LD 50 and so on.They are almost never published.The authors do not appear to be able to tell classes of antidepressants apart --prozac is hardly a new class I note they did not referr to the older and very cheap monoamine oxidase inhibitors and so on--Why was this "study" carried out?Please dont think that I disagree with you about the nefarious practices within pharma because I do.But we cant rely on studies of this quality to support our(legitamate) arguments when we would severly critise this methodology if used against us..The work on neurogenesis was first carried out re research into the dissociative symptoms in PTSD and nothing to do with depression whatsoever.I promise i will try to find it
people do use gaba pentin off liscence occasionaly because of desperation but its main use is per license because it is very toxic.Experience refutes the detailing theory, that is essentially my point if clumsily put

 

[julius]

they did not look at the big prospective studies over the last ten years

.

They were looking at applications to the FDA used for the purpose of drug approval.
The prospective studies have nothing to do with this. Apples and oranges.
If your studying XMRV you study XMRV, not coconuts.

their sampling was biased... you can make meta analysis say virtually whatever you want them to say if you are selective with their data and use the "right" statistical tools.They did both

Ok, this point is on topic.
But I don't see where they did this. Can you point these out to me.
This is the important point of the conversation. If you can show me where the analysis is flawed or biased I would be grateful.

No medic in the UK takes any notice of meta analysis to back up any scientific claim

Actually, no medic anywhere takes any notice of scientific literature (apart from a very few dedicated professionals). We all know that. If they did, CFS would be a 'real disease' wouldn't it. They don't read literature. They eat what the detailers feed them.

You need prospective studies

Perhaps. But that's not what were applied for by the sponsors, and not what were published/withheld by the sponsor's. So, therefore not in the scope of this study.

The gabapentin article was a marketing report the like of which i,ve seen many times before 1995 come on!What doctors say when they are being paid to complete surveys and the reality of practice are completely different

Personal opinion/experience. I'll give you mine. Two years seeing a psychiatrist (for CFS?), and every time I came to his office, if he had a new pen or pad with fancy drug logo's on it (bing! visit from detailer) I could be sure he would try to prescribe that drug to me, that very appointment. Without fail.

Also, a friend of mine is a detailer, and a successful one. He has told me a lot about his job and how it works. So yes, I know from first hand that they do influence doctors' prescribing choices.

The authors do not appear to be able to tell classes of antidepressants apart --prozac is hardly a new class

???
Prozac is a third generation antidepressant.

"The term "Third generation antidepressant" is sometimes used to refer to even newer antidepressants,[1] often selective serotonin reuptake inhibitors, such as fluoxetine, reboxetine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine."-wiki
http://en.wikipedia.org/wiki/Second-generation_antidepressants

Please dont think that I disagree with you about the nefarious practices within pharma because I do

.

I know. I think for the most part though we are just not on the same page. I am talking about apples and you are talking about oranges. But with your last post we seem to be talking about similar things at least.


I'm kind of digging in here because I know this topic is important to this and other communities.
The basic point being that these drugs are ineffective against any condition, and they are standing n the way of good research and treatment, again for our community and others.

The fact that they are ineffective has been proven by the manufacturers themselves. I haven't seen a single argument to refute that.

 

[Alesh]

In my experience citalopram (SSRI) was the first really helpful medicine I took. The improvement was dramatic but it didn't lead to full recovery. I only regret that I didn't start to take it sooner. If you "google scholar" antidepressants and cytokines you will find that many antidepressants have potent anti inflammatory effectiveness against many cytokines that are arguably involved in ME/CFS pathology.

Next, many antidepressants have neuroprotective, nootropic and neurotrophic effects.

Look at this commentary with a bit overrated title:

http://www.physorg.com/news185727145.html


And of course let's not forget that the first MAOI was a drug against tuberculosis. I think it is a common thing that some drug is effective against many different disorders, e.g., valproic acid is anticonvulsant, mood stabilizer and potential anti HIV medicine or amfonelic acid is both an antibiotic and stimulant. :Retro smile:

 

[Alesh]

And quickly to milnacipran: From a private communications with some psychiatrists I learned that milnacipran is not effective against depression at all. But from the commentary I posted a link to in my last post it should substantially promote neurogenesis so I am going to give it a try.

 

[Gerwyn]

.

They were looking at applications to the FDA used for the purpose of drug approval.
The prospective studies have nothing to do with this. Apples and oranges.
If your studying XMRV you study XMRV, not coconuts.




Ok, this point is on topic.
But I don't see where they did this. Can you point these out to me.
This is the important point of the conversation. If you can show me where the analysis is flawed or biased I would be grateful.




Actually, no medic anywhere takes any notice of scientific literature (apart from a very few dedicated professionals). We all know that. If they did, CFS would be a 'real disease' wouldn't it. They don't read literature. They eat what the detailers feed them.



Perhaps. But that's not what were applied for by the sponsors, and not what were published/withheld by the sponsor's. So, therefore not in the scope of this study.



Personal opinion/experience. I'll give you mine. Two years seeing a psychiatrist (for CFS?), and every time I came to his office, if he had a new pen or pad with fancy drug logo's on it (bing! visit from detailer) I could be sure he would try to prescribe that drug to me, that very appointment. Without fail.

Also, a friend of mine is a detailer, and a successful one. He has told me a lot about his job and how it works. So yes, I know from first hand that they do influence doctors' prescribing choices.




???
Prozac is a third generation antidepressant.

"The term "Third generation antidepressant" is sometimes used to refer to even newer antidepressants,[1] often selective serotonin reuptake inhibitors, such as fluoxetine, reboxetine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine."-wiki
http://en.wikipedia.org/wiki/Second-generation_antidepressants

.

I know. I think for the most part though we are just not on the same page. I am talking about apples and you are talking about oranges. But with your last post we seem to be talking about similar things at least.


I'm kind of digging in here because I know this topic is important to this and other communities.
The basic point being that these drugs are ineffective against any condition, and they are standing n the way of good research and treatment, again for our community and others.

The fact that they are ineffective has been proven by the manufacturers themselves. I haven't seen a single argument to refute that.

IF you look at the detail they constructed P values used the metaanalysis method that exaggerates differences between two groups.

You are wrong about drs not taking notice of science but they do it collectivel if you look closer you will see that the absolute differences between the FDA and the published studies effectiveness ratings were very small but both cohorts were way better than placebo.

The difference in fda effect rating and published effect rating was based on the authors opinion when the scatter bars mostly overlapped.

Phase 2 studies are never published.publication is not just decided by companies.

If you look at the prospective studies the effectiveness is judged by reducing the depreesive symptom indices by about 50%.The old adage about meta analyses is when you look back so see what you want to see.
Prozac is the first SSRI about twenty odd years ago the others SNRI,s etc are the new classes mirtazapine will fall into that category for instance

.The evidence for CFS is still not solid that is the problem so it gives denyers a chance to twist things

.i had much the same experience as you mirtazapine nearly killed me!seisures etc.I am no defender of antideoresents as a first line treatment but for endogenous melancholic kinds of depression they can be very effective

.I haven,t seen any evidence that antidepressents are ineffctive in people with depression.So many people are given that label when they dont have CLINICAL depression.if you see someone like this you will recognize it immediately

.Drug reps have different effects in different countries in the UK their role has been usurped by government sponsored pharmaceutical advisors and Drs are actively encouraged not to see detailers

.They no doubt have an influence but the report in the NY times wasan example of a pharma marketing report and needs taking with some salt.If at the end we get an effective drug a pharma company will provide it

.I find their methods unsavoury but we live in a capatilist world and they must produce ever increasing profits like every other non pharma companies to survive.


If you study the effectiveness of drugs you do so prospectively apples and apples etc meta analysis is a deparure from the scientific method and a major one if used to test hypothesis ok for generation though


.I will post some of the prospective studies and see what you think.I dont quite know how i got myself into this position but bad science annoys me

I fully undersand your position julius .The fact that any of us have any faith left in humanity is miraculous.

i am genuinely sorry about my typing t is one of the first things to go when

 

[julius]

Thanks for that Gerwyn. It's a lot to digest and very hard to read

The fog is rolling in too.

I hope you are right, because it is due to this sort of corrupt behavior that I have lost all faith in humanity. I'm not quite convinced yet, but I'll go over what you wrote.

 

[julius]

I think I see the problem here.

The point i'm talking about in the New England Journal of medicine has nothing to do with scatter/funnel plots. Compensating for publication bias is not an issue, because the paper is specifically about publication bias.

"Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive."


It's a simple matter of adding up all the studies done (74), seeing that only the positive results were published (37) and the negative results were not published (22) or misrepresented (11). And a couple were 'lost'. Very straightforward.


The meta analysis, dealing with data sets is not what I was referring to, and was not the main point of the article;

"Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall."


But, anyways, I think this will just keep going on forever if I don't just stop. So I'm out.

 

[Gerwyn]

I think I see the problem here.

The point i'm talking about in the New England Journal of medicine has nothing to do with scatter/funnel plots. Compensating for publication bias is not an issue, because the paper is specifically about publication bias.

"Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive."


It's a simple matter of adding up all the studies done (74), seeing that only the positive results were published (37) and the negative results were not published (22) or misrepresented (11). And a couple were 'lost'. Very straightforward.


The meta analysis, dealing with data sets is not what I was referring to, and was not the main point of the article;

"Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall."


But, anyways, I think this will just keep going on forever if I don't just stop. So I'm out.

The decision that there was a significant difference was based on opinin and whether this selection bias was real or just a chance observation.They also mention that they referred to studies that were ubpublished when technically they had been published.They included phase two trials as unpublished which is frankly rediculous because they never are! " published in a way THAT IN OUR OPINION conveyed a positive outcome" The science stops there!

 

[starryeyes]

I came across this Petition:

Public Citizen Petition to FDA: Dangerous Fibromyalgia Drug Should Be Pulled From the Market

Medication Has Limited Efficacy, Risky Effects

WASHINGTON, D.C. – The fibromyalgia drug Savella (milnacipran) should immediately be taken off the market because its dangers outweigh its benefits, Public Citizen said today in a petition to the Food and Drug Administration (FDA). The European regulatory authority, the European Medicines Agency (EMEA), rejected the drug’s approval for fibromyalgia in July 2009, stating that its benefits were “marginal” and “did not outweigh its risks.” This was shortly after the FDA approved the drug in January 2009. Since the drug went on the market in the U.S., approximately 250,000 prescriptions have been filled, with doctors writing more prescriptions every month.

In two randomized clinical trials, Savella, also known by its generic name milnacipran, was found to increase blood pressure, heart rate and suicidal thoughts, Public Citizen’s petition said. Among patients who had normal blood pressure at the beginning of the study, 19.5 percent of those who took Savella developed hypertension, compared to 7.2 percent of those on a placebo.

“Because Savella is a drug that produces only a marginal effect on pain, the main problem for which patients seek treatment, and has the potential to be quite dangerous, it is clear that it should not be sold,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “The FDA never should have approved Savella for fibromyalgia and should now immediately order the drug company to remove it from the market before large numbers of people suffer serious harm,” Wolfe said.

To Sign the Petition: http://www.citizen.org/pressroom/release.cfm?ID=3029

 

[Gerwyn]

I came across this Petition:

Public Citizen Petition to FDA: Dangerous Fibromyalgia Drug Should Be Pulled From the Market

Medication Has Limited Efficacy, Risky Effects

WASHINGTON, D.C. – The fibromyalgia drug Savella (milnacipran) should immediately be taken off the market because its dangers outweigh its benefits, Public Citizen said today in a petition to the Food and Drug Administration (FDA). The European regulatory authority, the European Medicines Agency (EMEA), rejected the drug’s approval for fibromyalgia in July 2009, stating that its benefits were “marginal” and “did not outweigh its risks.” This was shortly after the FDA approved the drug in January 2009. Since the drug went on the market in the U.S., approximately 250,000 prescriptions have been filled, with doctors writing more prescriptions every month.

In two randomized clinical trials, Savella, also known by its generic name milnacipran, was found to increase blood pressure, heart rate and suicidal thoughts, Public Citizen’s petition said. Among patients who had normal blood pressure at the beginning of the study, 19.5 percent of those who took Savella developed hypertension, compared to 7.2 percent of those on a placebo.

“Because Savella is a drug that produces only a marginal effect on pain, the main problem for which patients seek treatment, and has the potential to be quite dangerous, it is clear that it should not be sold,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “The FDA never should have approved Savella for fibromyalgia and should now immediately order the drug company to remove it from the market before large numbers of people suffer serious harm,” Wolfe said.

To Sign the Petition: http://www.citizen.org/pressroom/release.cfm?ID=3029


http://forums.aboutmecfs.org/showth...s-this-A-really-good-study&highlight=cymbalta

I think the study was 2010 the benefits did not appear marginal but of course the european agency did not have this info a great many antidepressants cause hypertension It is hard to see if these people have skills greater than those of theFDA I note they attack the hundred top selling drugs branding them as unsafe

 

[starryeyes]

Gerwyn, can you show me where they are "attack[ing] the hundred top selling drugs"?

Here's some more info about Public Citizen:

Public Citizen is a national, nonprofit consumer advocacy organization founded in 1971 to represent consumer interests in Congress, the executive branch and the courts.

We fight for openness and democratic accountability in government, for the right of consumers to seek redress in the courts; for clean, safe and sustainable energy sources; for social and economic justice in trade policies; for strong health, safety and environmental protections; and for safe, effective and affordable prescription drugs and health care.

We have six divisions and one state office. To learn more about each of the divisions and our Texas office, click on the links below.

* Auto Safety
* Congress Watch
* Energy Program
* Global Trade Watch
* Health Research Group
* Litigation Group
* Texas State Office

Gerwyn, I know you originally posted this to show that FMS is not Somatiazion or Depression which is cool. I just thought I'd share this Petition as I happened to come across it today.

 

[*GG*]

Yeah, I have seen this I will not be signing it.

I used to like Public Citizen until I found out where they stand on other issues. I do not need big brother "protecting" me. Like they have done so well with CFIDS?!! Why do we need the FDA anyways? They stop so many drugs that could possibly help the sick. I just saw Stossel on FBN and think he makes some good points. I believe I am a Libertarian and tired of people giving away my freedom to the Govt! The Gov't is bloated and it needs to be taken down in size!

Public Citizen is also pushing for Crap and Trade, that should be really good for us? NOT! Just more regulation and taxation without representation! I mean look how they want to take away our supplements now also?!

If you watch the lamestream media, you will think that Global Warming is settled. Luckily I get my news from other sources and have not been blinded by the barage of settled science. I mean it snows more in DC and this proves Global Warming and then it is warmer than usual and this helps corroberate that Global Warming, so if you are sceptical you are a flat earther or something. I mean to believe that the Earth's climate is going to be static is ridiculous, of course there are going to be hotter and colder years, months, days etc... This issue is not passing the smell test, I used to believe but am more sceptical now that the Science has not been transparent. More of a political issue now, to much political influence in this arena, seems like an agenda is being pushed and it is not going to be good for us pee ons!

I came across this Petition:

Public Citizen Petition to FDA: Dangerous Fibromyalgia Drug Should Be Pulled From the Market

Medication Has Limited Efficacy, Risky Effects

WASHINGTON, D.C. – The fibromyalgia drug Savella (milnacipran) should immediately be taken off the market because its dangers outweigh its benefits, Public Citizen said today in a petition to the Food and Drug Administration (FDA). The European regulatory authority, the European Medicines Agency (EMEA), rejected the drug’s approval for fibromyalgia in July 2009, stating that its benefits were “marginal” and “did not outweigh its risks.” This was shortly after the FDA approved the drug in January 2009. Since the drug went on the market in the U.S., approximately 250,000 prescriptions have been filled, with doctors writing more prescriptions every month.

In two randomized clinical trials, Savella, also known by its generic name milnacipran, was found to increase blood pressure, heart rate and suicidal thoughts, Public Citizen’s petition said. Among patients who had normal blood pressure at the beginning of the study, 19.5 percent of those who took Savella developed hypertension, compared to 7.2 percent of those on a placebo.

“Because Savella is a drug that produces only a marginal effect on pain, the main problem for which patients seek treatment, and has the potential to be quite dangerous, it is clear that it should not be sold,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “The FDA never should have approved Savella for fibromyalgia and should now immediately order the drug company to remove it from the market before large numbers of people suffer serious harm,” Wolfe said.

To Sign the Petition: http://www.citizen.org/pressroom/release.cfm?ID=3029

 

[IntuneJune]

The Gov't is bloated and it needs to be taken down in size![/B

Public Citizen is also pushing for Crap and Trade, that should be really good for us? NOT! Just more regulation and taxation without representation!

If you watch the lamestream media, you will think that Global Warming is settled.............the Science has not been transparent. More of a political issue now, to much political influence in this arena, seems like an agenda is being pushed and it is not going to be good for us pee ons!

I tried to get multiple quotes going, but cannot figure it out and also just got a low battery warning on my notebook, must talk fast. I bolded (I hope) the words that really took my heartbeat up a notch. I so agree with these.

Am going to end this now so I don't lose this post.

 

[IntuneJune]

US Political scene---Who are you really

The parties of the past are not the parties of the present. Unfortunately many Americans have not been able to keep pace with these changes and vote on past beliefs.

Sound bites on the evening news are misleading. Deeper studies need to be done, and done by the voter. Time consuming, yes. Unfortunately if the citizens of the United States do not make the time, we will lose the country we were born into.... with the freedoms we have enjoyed.

The more I paid attention to the deeper facts and not the sound bites, the more I learned, and realized I am not necessasrily a member of the party I believed I was.

Why did I change my mind about mainstream media???? The first tour to Iraq my son made, he came home for his two week R&R and we were watching the "news" together. His statement, "That is not the Iraq I know." He has spent two and a half years there. His opinion of our "news" coverage did not change.

My news watching changed venue and I try, try (brain-fog being high on the list of symptoms) to eek out the WHOLE truth about the issues.

No matter what side of the issue you stand, I would hope everyone would understand that our government -- for whatever reason, cannot accomplish anything efficiently, any business they run takes more money with less efficiency than the private sector.

June

 

[julius]

Gerwyn,

I'm not trying to start this discussion up again, but I just noticed something and wanted to make it clear. The study I was defending didn't actually come out as a link in my original post, so it might have looked like I was arguing about the second study, which I only included as further support, but didn't read too closely.

So, just for clarification, this is the study that I was discussing,
http://content.nejm.org/cgi/content/abstract/358/3/252

Don't know if that changes anything, but when I realized the mistake I really wanted to bring it up.

 

[Gerwyn]

Gerwyn,

I'm not trying to start this discussion up again, but I just noticed something and wanted to make it clear. The study I was defending didn't actually come out as a link in my original post, so it might have looked like I was arguing about the second study, which I only included as further support, but didn't read too closely.

So, just for clarification, this is the study that I was discussing,
http://content.nejm.org/cgi/content/abstract/358/3/252

Don't know if that changes anything, but when I realized the mistake I really wanted to bring it up.

Hi Julian I thought we were missing each other i just couldnt figure out how The NEJM study was fair and balanced the other one was not so we were at cross purposes.It wasnt the conclusions in the other paper that bothered me it was the science