Talk:Study 329

Gratuitous feedback

Just some comments - Cas Liber (talk · contribs) 12:44, 4 May 2015 (UTC)

• I'd put in the eight primary outcomes and other secondary outcomes as footnotes, to give the reader an idea of what was being measured.

• One issue I've been thinking about is the use of sources. Strictly speaking medical articles should be restricted to secondary sources, but I reckon much of this article is about the ethics/law and journalistic aspects and hence the rules are not so strict. Anyway, might be something worth discussing later.

Hi Cas, thanks for the feedback and assessment. This is more a medical ethics article than a medical one. The only primary source used for medical claims is the Keller/JAACAP article, but as that's part of the topic it's unavoidable. I think every time I used it there's an accompanying secondary source; if there are exceptions to that I can easily add one.

Re: outcomes. I was confused about how to present them. There were two primary and six secondary outcomes in the protocol. Later other secondary outcomes were added. Then, according to the sources, the primary and secondary outcomes were conflated. It may be difficult to explain that clearly, but I'll try to draft something. Thanks again for looking at it and commenting. Sarah (SV) ^(talk) 18:49, 4 May 2015 (UTC)

I am thinking that if it were in footnotes, something like the four items at the bottom of Corona Borealis in the Notes section it would be good, as it is interesting info but placing it in the body of the text might disrupt the narrative flow. Cas Liber (talk · contribs) 20:40, 4 May 2015 (UTC)

Yes, that's a good idea. Sarah (SV) ^(talk) 20:41, 4 May 2015 (UTC)

Otherwise I am pleased to say I found surprisingly little to copyedit, however I don't have a good eye for detail and am better at "bigger picture" type things....Cas Liber (talk · contribs) 20:54, 4 May 2015 (UTC)

Thanks, Cas. I might ping you when I get the footnote(s) written about the primary/secondary outcomes. Sarah (SV) ^(talk) 05:59, 5 May 2015 (UTC)

Sure, no problem. Cas Liber (talk · contribs) 11:29, 5 May 2015 (UTC)

Additionally, "STI had worked with SmithKline Beecham on its promotion of paroxetine for years" - vague and somewhat perjorative in tone - be nice to get a more exact time for this sentence Cas Liber (talk · contribs) 02:42, 4 November 2015 (UTC)

Hi Cas, I've changed it to "STI had worked with SmithKline Beecham on its promotion of paroxetine since the early 1990s," and I'll be more precise if I can find a source for a year. If by perjorative in tone you mean the word promotion, I'm not sure how else to phrase it. The company is/was a PR firm, and their work in relation to the drug (that I have seen) involved promoting it. SarahSV ^(talk) 21:11, 4 November 2015 (UTC)

Sorry, should have been more specific, I meant the "for years" bit as sounding a bit pejorative, so clarifying the time fixes this nicely. Cas Liber (talk · contribs) 01:21, 5 November 2015 (UTC)

something to consider

Nice article. yep lots of scandal around this.

probably the most important thing to come out of all this was the black box warning about suicide in kids. please see PMID 24452997

here is the conclusion:

Leon, who was a member of the FDA committee for interpreting the data that became the basis of the ‘black box’ warning, acknowledged that the data were far from ideal for the purpose [51]. He concluded that the FDA had initiated ‘‘… a large de facto public health experiment.’’ He thought the results of this experiment could be evaluated in about 5 years as to ‘‘… whether the black box cost more lives than it saved.’’ As far as we know, such an official evaluation has not yet appeared in print.

However, in the decade following issuance of warnings regarding suicidality among young people taking antidepressants, there have been several observations.

• There was a measurable decrease in the diagnosis of depression and the prescribing of antidepressants in several countries including the US, UK, Canada, Australia, and Sweden.
• There was 'a measurable increase in the numbers of suicides among young people in the same countries, with the exception of the UK.
• There is no evidence of emergence of increased risk of suicide among young people who use antidepressants.
• A large independent study found that antidepressant medication (specifically fluoxetine) was the most

effective treatment for major depression in young people [15]. Also, there was no increase in treatmentemergent suicidality in that study [47]. A new metaanalysis of all fluoxetine studies confirmed both results [18, 48] (emphasis added)

Jytdog (talk) 16:34, 6 May 2015 (UTC)

please do not mush together the bad things that GSK did, with the question of the best way to treat depressed kids. thanks. Jytdog (talk) 17:03, 6 May 2015 (UTC)

• There's a study about the same issue here in the BMJ from 2014. It says there was a rise in attempts, not completed. It would be difficult to make the connection to warnings and reduced SSRI use given that the period coincided with the rise of social media and the enormous change that made to teenagers' lives (e.g. they can be bullied remotely while sitting in their bedrooms). Sarah (SV) ^(talk) 17:09, 6 May 2015 (UTC)

• your making the boxed warning seem like a public health triumph is dead wrong. it hurt people. The actual' conclusion of the BMJ study you cite above is "Undertreated mood disorders can have severe negative consequences. Thus, it is disturbing that after the health advisories, warnings, and media reports about the relation between antidepressant use and suicidality in young people, we found substantial reductions in antidepressant treatment and simultaneous, small but meaningful increases in suicide attempts. It is essential to monitor and reduce possible unintended effects of FDA warnings and media reporting." Translating "simultaneous, small but meaningful increases in suicide attempts" into English - it means more suffering. please do not confuse the bad things that GSK did with the important questions about the best way to treat depressed kids. Jytdog (talk) 17:42, 6 May 2015 (UTC)

Comparing SSRI to TCA is like apples for oranges. — Preceding unsigned comment added by 92.0.75.164 (talk) 09:12, 9 February 2021 (UTC)

Anti-depressants and suicidality

• Can you say why you left out the last sentence of that paragraph? You ended the article with: "Untreated depressive disorder is associated with the risk of completed suicide and impacts on academic and social functioning." But left out the next sentence: "It is not clear that treatment with an SSRI will modify this risk in any significant way." Sarah (SV) ^(talk) 17:19, 6 May 2015 (UTC)

copyying this here for discussion, and am placing a notice at WT:project medicine to get further input.

In 2007 the FDA proposed that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. A 2012 Cochrane Collaboration report on the use of SSRIs in children and adolescents suggested that fluoxetine (Prozac) might be the medication of first choice, although caution is advised because of an "increased risk of suicide-related outcomes in those treated with antidepressant medications."

References

References

I find the partial quote of the Cochrane study to be... a bad thing. I tried to fix it here but it was put back to the status above, here. Jytdog (talk) 17:32, 6 May 2015 (UTC)

You didn't try to fix anything, and I'd appreciate it if you would answer my question above.

I'm in the process of trying to write this. There is still a lot missing. I'm not going to be able to do that if you start the usual problems, so I'd appreciate it if you wouldn't. Sarah (SV) ^(talk) 17:39, 6 May 2015 (UTC)

Not a big fan of block quotes. We should paraphrase. We need to be careful about quotes per Wikipedia:Non-free_content aswell Doc James (talk · contribs · email) 17:41, 6 May 2015 (UTC)

Doc James, it was Jytdog who added the blockquote, and I agree that the section is better without. Before he edited then removed the section, it looked like this (and the point was simply to end the article with a brief note about the current situation):

Anti-depressants and suicidality

Further information: Antidepressants and suicide risk

In 2007 the FDA proposed that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. A 2012 Cochrane Collaboration report on the use of SSRIs in children and adolescents suggested that fluoxetine (Prozac) might be the medication of first choice, although caution is advised because of an "increased risk of suicide-related outcomes in those treated with antidepressant medications."

Sarah (SV) ^(talk) 17:48, 6 May 2015 (UTC)

Yes I know SV was referring to Jytdog edit. Doc James (talk · contribs · email) 17:51, 6 May 2015 (UTC)

SV please discuss content, not contributors. Thanks. Doc James do you have a concrete proposal on this? I find the truncated quote in SV's version tendentious and not reflective of current evidence nor practice. Jytdog (talk) 17:57, 6 May 2015 (UTC)

Doc James, do you feel that section is okay as it is? I'd like to restore it (also the image sizes, if you don't mind, especially as I was just about to send a link to someone who released a couple of images for the article).

The point of the section is just to give the reader an updated sense of the current position with SSRIs and children, so I based it on a Cochrane review. I don't want to go into detail because then it will veer away from the topic of the article. Sarah (SV) ^(talk) 18:01, 6 May 2015 (UTC)

leaving out the part " but the importance of this is unclear as is the association between SSRIs and suicide completion. Untreated depressive disorder is associated with the risk of completed suicide and impacts on academic and social functioning. It is not clear that treatment with an SSRI will modify this risk in any significant way" either a quote or a paraphrase is just terrible. Jytdog (talk) 18:14, 6 May 2015 (UTC)

Jytdog, you left out the final sentence, so that the article ended with "Untreated depressive disorder is associated with the risk of completed suicide and impacts on academic and social functioning." But the next sentence said: "It is not clear that treatment with an SSRI will modify this risk in any significant way."

I asked you above why you did that, and you didn't respond. Sarah (SV) ^(talk) 18:18, 6 May 2015 (UTC)

and i'll be happy to respond if you say why you cut a sentence in half to leave a distorted description of the current picture. Jytdog (talk) 18:20, 6 May 2015 (UTC)

I would replace the quote ""increased risk of suicide-related outcomes in those treated with antidepressant medications." with something more like "although caution is advised because of a possible increased suicide risk" "possible" because of "Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity." andincreased suicide risk because of "Clinicians need to keep in mind that there is evidence of an increased risk of suicide-related outcomes in those treated with antidepressant medications." Doc James (talk · contribs · email) 18:23, 6 May 2015 (UTC)

i think DocJames is correct with the needed wording of the article...(BTW...i also believe the "further reading " section of the article needs better organization)--Ozzie10aaaa (talk) 18:32, 6 May 2015 (UTC)

Doc James, thanks, I'll add that. Ozzie, I'm in the process of writing the article. The contents (and FR section) are likely to change, as there's still material to add. It's not quite at first draft stage yet. Sarah (SV) ^(talk) 18:37, 6 May 2015 (UTC)

Doc James in my view your wording does not reflect the current evidence. Not even Cochrane (which is the most cautious in emphasizing the risk) is that strong. Please see the sources I cite below. The black label has actually been bad for public health. Jytdog (talk) 18:40, 6 May 2015 (UTC)

• (edit conflict) I would accept something like this.

In 2007 the FDA required that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. As a result of the label and media attention on the issue, prescriptions of SSRIs decreased and rates of suicide among children and adolescents increased. The question of whether SSRIs increase the risk, of suicidal thoughts or completed suicide remains controversial, with some authorities flatly denying it and others acknowledging a possible increased risk in suicide ideation of uncertain importance. all authorities agree that undertreatment of depression in children and adolescents is harmful.

References

• That's the industry position, and it's oddly written. Jytdog, this article isn't about the broader issue. It's not about medical claims at all. It's about the history and medical ethics of one series of incidents surrounding study 329 and related research at that time. I'd appreciate being allowed to write it because it's nowhere near done, and this is very distracting. Sarah (SV) ^(talk) 18:54, 6 May 2015 (UTC)

We could begin with "Whether or not antidepressants increase the risk of suicide is controversial. In 2007 the FDA required that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. A 2012 Cochrane review found tentative data of an increased suicide risk. Other reviews have concluded that the risk are invalid.

Observational data sucks. Thus not impressed with that statement by Isacsson. This is an interesteding graph [1] Doc James (talk · contribs · email) 19:03, 6 May 2015 (UTC)

Doc James, I'll add your new wording shortly. Sarah (SV) ^(talk) 19:39, 6 May 2015 (UTC)

Sorry, I went to add it, but don't know what the last sentence means and can't see the source, so I've make that final sentence invisible for now. Will add the rest. Sarah (SV) ^(talk) 19:53, 6 May 2015 (UTC)

I've read the source, and that section is now on Doc James' version, except for a couple of tweaks:

Whether antidepressants increase the risk of suicide is controversial. In 2007 the FDA required that all anti-depressants include a boxed warning of an increased risk of suicidal thoughts and behaviour in young adults (18–24) during the first one to two months of treatment. A 2012 Cochrane review found tentative data of an increased suicide risk. Other reviews have concluded that the risk is not confirmed.

Sarah (SV) ^(talk) 21:06, 6 May 2015 (UTC)

that is great, thanks for working toward consensus. Jytdog (talk) 02:54, 7 May 2015 (UTC)

The sentence "Other reviews have concluded that the risk is not confirmed" is sourced to a review by primary author Göran Isacsson and secondary author Charles L. Rich. His 2010 paper on how "antidepressant medication prevents suicide in depression" was retracted due to errors by the journal Acta Psychiatrica Scandinavica.[2] The authors of this retracted study were accused by their colleagues in the British Journal of Psychiatry of making an argument where their "premises are flawed" and where they have "overstated their case with selective citation and biased interpretation of evidence".[3] More serious allegations against Isacsson were made by Swedish journalist Janne Larsson who uncovered documents alleging a pattern of malfeasance.[4] For these reasons, it seems very, very suspect (and a violation of the reliability guidelines) to cite these same authors who continue to claim "other reviews have concluded that the risk is not confirmed". The entire controversy is covered by Retraction Watch.[5] Viriditas (talk) 04:43, 7 May 2015 (UTC)

Viriditas, thanks for spotting this. Doc James didn't seem keen on that source either, so I'm going to remove it and go back to a summary of the Cochrane review. I chose it as a neutral source to sum up current consensus, so I think it's better to stick to it. Sarah (SV) ^(talk) 15:37, 7 May 2015 (UTC)

GSK's chief medical officer, James Shannon, wrote to child psychiatrist Jon Jureidini in 2014: "I think we both agree that for adolescents treated with paroxetine there is an association with an increased risk of suicide related events ..." So this does seem to be the accepted view. Sarah (SV) ^(talk) 15:44, 7 May 2015 (UTC)

p tags

We had a long discussion about these here [6] and our resident expert on screen readers User:Graham87 suggested a solution I hope will work for all. Doc James (talk · contribs · email) 23:06, 9 May 2015 (UTC)

Outcome Switching

I was trying to find a place to integrate this into the article. Would it make sense to include the definition for Outcome Switching in this article or include a link if it is mentioned elsewhere on Wikipedia?

See ref: http://www.economist.com/news/science-and-technology/21695381-too-many-medical-trials-move-their-goalposts-halfway-through-new-initiative

Shaded0 (talk) 16:29, 29 March 2016 (UTC)

Accuracy and sourcing

I am somewhat concerned by misrepresentations such as the one I have just corrected (1 million documents given as fact was actually an estimate of 1 million pages). Further to this particular example, readers - and editors - may not know that the document supporting a drug approval application to the MRHA typically runs to several hundred thousand pages. I'm not sure that the MRHA's estimate of the amount of evidence they reviewed, especially in such a power-of-ten estimate is actually useful.

Reading on in the same document, the advice not to prosecute was given by independent legal counsel, Mr Robert O’Sullivan and Mrs Miranda Moore QC, not as stated in our article, government lawyers.

All the best: Rich Farmbrough, 23:00, 12 December 2016 (UTC).

I don't have time to adjust for this now, but the "unclear law" also seems a bit dodgy, when looking at the following paragraph form the MRHA papaer cited.

Having considered the advice provided by counsel the Prosecution Division reached the conclusion that no offence has been committed contrary to the 1994 Regulations because the clinical trials conducted by GSK on the paediatric use of Seroxat, and GSK’s alleged failure to provide information from those trials, most likely did not fall within the regime implemented by those Regulations.

The text makes it seem as if an offence was probably committed but would have been hard to prosecute due to unclear law.

All the best: Rich Farmbrough, 21:47, 20 January 2017 (UTC).

bots template

On 6 May 2015 User:SlimVirgin inserted a bots template to deny AWB access to this article. Whatever the issue was should have been resolved by now. A comment on this talk page or an explanation in the edit summary would have been helpful, too. Let's get this cleaned up. Chris the speller ^yack 16:15, 8 August 2017 (UTC)

Hi Chris, it's gone. Thanks for leaving the note. SarahSV ^(talk) 17:56, 8 August 2017 (UTC)

Why 'controversial' and not 'fraudolent'?

I read this:

Published in July 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), which listed Keller and 21 other researchers as co-authors, study 329 became controversial when it was discovered that the article had been ghostwritten by a PR firm hired by SmithKline Beecham; had made inappropriate claims about the drug's efficacy; and had downplayed safety concerns.[8][9][3] The controversy led to several lawsuits and strengthened calls for drug companies to disclose all their clinical research data. New Scientist wrote in 2015: "You may never have heard of it, but Study 329 changed medicine."[10]

A GSK gw that write the 'scientific' paper Study 329 = nothing else than a fraud. And the fact that JAACAP refuse to retract it, shows very much cleary how the GSK power can influence the 'science' as well. Wakefield work was rectracted for much less, so why this study is not retracted and why wikipedia fail to show the real importance of this attitude? When a fraudolent scientific work was discovered and not retracted? If not, then it's not science, but something else. Logical said.

Instead, the incipit/abstract of this article is complex, vague, unclear. What was the 'controversial' part in a total fraud like this one?

For the sake of wikipedia neutrality, a fraud must be called what is it, a fraud. And this is not indicated in the abstract, no word like this at all.