Talk:AllTrials

Sources about sharing clinical trial data, but not about AllTrials

I am not sure where this goes.

• Chalmers, Iain (16 September 2013). "House of Commons - Science and Technology Committee: Written evidence submitted by Sir Iain Chalmers". publications.parliament.uk. Retrieved 26 October 2013.
• Science and Technology Committee (17 September 2013). "House of Commons - Clinical Trials - Science and Technology Committee". publications.parliament.uk. Retrieved 26 October 2013.
• Doshi, Peter; Jefferson, Tom (10 April 2012). "Drug Data Shouldn't Be Secret - NYTimes.com". The New York Times. New York: NYTC. ISSN 0362-4331. Retrieved 26 October 2013.
• Fanelli, D. (2013). "Redefine misconduct as distorted reporting". Nature. 494 (7436): 149. doi:10.1038/494149a. PMID 23407504.

Blue Rasberry (talk) 14:40, 26 October 2013 (UTC)

A new BMJ editorial by Goldacre:

• Ben Goldacre, Carl Heneghan Improving, and auditing, access to clinical trial results BMJ 2014; 348 doi:10.1136/bmj.g213 (Published 15 January 2014)

Hope that helps. --Hroðulf (or Hrothulf) (Talk) 19:54, 6 February 2014 (UTC)

I think (as Bluerasberry suggested below) we need an article on Political problems with the evidence base of medicine or some such. None of the content of Evidence-based medicine seems quite relevant. Does anyone have a suggestion for something snappier? HLHJ (talk) 22:04, 1 August 2015 (UTC)

Another source: Clinical trial participation poses ethical, practical issues (om funding of trials in Canada). HLHJ (talk) 21:45, 2 August 2015 (UTC)

Hard to edit, fix citations please

It's hard to edit this page due to the wall of metatext in some sections, it's so extensive that the article text gets lost. It would be great to reformat the refs to be less cumbersome and more useful; I'm not sure how many citations we need for such uncontroversial claims as "Ben Goldacre... would like to address the systematic flaws in clinical research" and "The project is a reaction to under-reporting of research".

I will try and get around to finding proper secondary sources for the context under "Issues", help welcome.

HLHJ (talk) 23:18, 10 February 2014 (UTC)

Negative media coverage

I'm also having trouble finding some of the negative media coverage I remember seeing; anyone got some links?

HLHJ (talk) 23:18, 10 February 2014 (UTC)

@HLHJ: Goldacre describes some responses here:

• http://www.badscience.net/2013/12/free-here-is-the-new-what-happened-next-update-chapter-from-bad-pharma-2013/

• Equally baffling – but much more important – was the ABPI’s claim, in a press release on the day of the book’s publication, that the cases were all ‘long-documented’, ‘historical’ and ‘long-addressed’.
• Then, in July 2013, an extraordinary document was leaked: it was an internal PhRMA and EFPIA memo, sent to leaders of major pharma companies around the world, setting out their strategy on transparency.22 Under the heading ‘Advocacy’, it discussed a plan for ‘mobilizing patient groups to express concern about the risk to public health by non-scientific re-use of data’. Sample, Ian. Big pharma mobilising patients in battle over drugs trials data. Guardian, 21st July 2013.
• In one interview, the FDA told Nature that the 22 per cent figure is wrong, and that it is only pursuing fifteen cases of overdue results: a tiny proportion. Nature then asked the US government research agency NIH for an informal audit, which found 50 per cent compliance for the industry (and even worse for NIH: it found that it reported only one in five of its own trials).

(Hrothulf doesn't have access to Nature through JSTOR)

• The title of this editorial was unusually direct about the impact on patient care: ‘Blood on Our Hands: Seeing the Evil in Inappropriate Comparators’. The ABPI’s public response to this paper was to say that the industry is very well regulated.8 Inside Health, BBC Radio 4, January 2013.

It is hard for me to disentangle comment on the book from response to the AllTrials campaign.

--Hroðulf (or Hrothulf) (Talk) 10:31, 11 February 2014 (UTC)

David Healy

undue weight. Healy's position on Evidence Based Medicine is fringe and should not be presented as a representative "anti" argument for alltrials

That's odd. The opinion you removed,[1] regarding the difficulty of reporting adverse events in clinical trials and the ability to "hide" them, appears to be well sourced in the literature. While I agree that the source is poor and deserved to be removed, can you discuss why Healy's position is fringe in this matter and in general? Thanks. Viriditas (talk) 01:53, 17 November 2014 (UTC)

First, no. My comments are never "odd". They are thoughtful and considered and intended to provide our readers with accurate medical information. There is nothing odd about that.

Second point. If you read the quote in the article Healy isn't arguing that trials "cover up" side effects just because companies lie about the results (which we've seen plenty of). He's arguing that the method intrinsically fails to uncover adverse events even in the event that the trial is run by saints. He's opposed to the IDEA of clinical trials as a way of measuring efficacy and side effects, and he's the only person I've ever heard express that opinion. If you can find a review article in a Pubmed indexed journal that approvingly cites Healy's opposition to the very idea of running RCTs, I have no objection to re-adding the material in question. Otherwise it is fringe. Formerly 98 (talk) 02:58, 17 November 2014 (UTC)

Sure thing. Just be sure to note that the guy you accused of being "fringe" was director of the psych dept. at the University of Cardiff, and that his opinion about how adverse events are treated is widely reported in the peer-reviewed literature. Viriditas (talk) 02:55, 17 November 2014 (UTC) (Moved from my Talk page Formerly 98 (talk) 03:03, 17 November 2014 (UTC))

There is nothing about occupying a position at a University of significance that means your POV is not fringe. Peter Duesberg is at Berkeley, which is one of the most prestigous universities in the world, and he is widely considered fringe. Though in this particular case I did not call Healy fringe, just his position on clinical trials. Formerly 98 (talk) 03:03, 17 November 2014 (UTC)

You seem to be evading my point with sophmoric flourishes and rhetorical acrobatics. What part of Healy's position on clinical trials and adverse reporting is fringe? I looked up what he said and discovered it is accurate and verifiable. Here is what Healy said. Now, directly address it and show where it is "fringe". Good luck. Viriditas (talk) 03:09, 17 November 2014 (UTC)

I gave you a very direct answer. Let me repeat it. What is fringe about David Healy's position is that he does not believe that clinical trials are a useful tool for determining the safety and effiacy of drugs even if the trials are performed and reported with perfect honesty. As I said, if you think this is mainstream belief among medical experts, find a review that cites this position and comments on it favorably. As near as I can tell, he is the only one who says this. By definition, that makes it fringe. Formerly 98 (talk) 03:13, 17 November 2014 (UTC)

And I pointed out to you with a direct link above that Healy did not say that. That's a straw man you created to justify removing the material. You were given the link to Healy's text above. What Healy said is exactly the mainstream belief among medical experts, namely that "The reporting of adverse events in drug trials is generally poor...Many clinical trial protocols fail to describe a satisfactory methodology for reporting adverse effects...it is almost always impossible to gauge the prevalence of particular adverse events".[2] There are literally hundreds of reliable sources on this subject, many of them directly supporting what Healy said. Some talk about how adverse events may be "hidden".[3] This one in particular is chilling as the sources are of the highest quality and show how the FDA uncovered problems with adverse event reporting. Far from being fringe, Healy merely repeated the mainstream belief about how adverse event reporting is handled. Viriditas (talk) 03:18, 17 November 2014 (UTC)

As you have done in our past interactions, you preface every comment with a personal attack of some sort. I will not continue this discussion. If you like I am willing to do a Request for Comment, but I have no desire to interact with you further. Formerly 98 (talk) 03:31, 17 November 2014 (UTC)

Viriditas, I have to agree with you, and I'd support inclusion of similar material. David Healy's views are unusually strongly expressed, but he is saying:

• that finding adverse effects can be hard. This is conventional wisdom; it's a large part of the reason we have clinical trials. Good trials are hard (bad ones are really easy).
• a specific regulatory and technological interface for accessing data from clinical trials, which he has experienced, is nearly impossible to use to find adverse effects, and he thinks AllTrials should be more critical of this tool. This may be a controversial view (the designers probably disagree), but it isn't fringe. He clearly values clinical trials if he is complaining that his access to their results is poor.
• adverse effects are easily missed in clinical trials, even with the best of intentions; this is not controversial, either. See thalidomide. See also the side effects of steroids on brain injury. No-one was trying to bury the harms here; but some tests failed to find them. Saints aren't infallible.

HLHJ (talk) 20:30, 1 August 2015 (UTC)

Trial publication bias

"Much medical research is done by the pharmaceutical industry, which may experience conflicts of interest reporting results which will hurt sales of their products. There is a measurable bias in reporting; studies have shown that published drug studies funded by pharmaceutical companies are much more likely to support the use of the tested drug than studies with other funding. Industry-funded trials are also less likely to be published[2]["

Perhaps a minor point, but a better reference is needed here. The fact that this particular paper includes a discussion of other people's work does not make it a secondary source: it's primary research. Nor does the paper prove the point that it is cited in support of. All the authors showed was that many large trials remained unpublished. As an example of the relatively poor level of scholarship and refereeing that characterizes many publications about "moral' issues, the authors simply made the assumption that the only reason a "large" trial would remain unpublished would be attempts to hide bad outcomes of trials for commercial reasons. The did not perform any analysis that actually compared the subject or outcomes of the trials that were and were not published.

"By focusing our investigation on studies with at least 500 participants, we greatly limited the possibility that non-publication of trials in this cohort was due to rejection of manuscripts by journals or a lack of time or interest on the part of investigators or sponsors.35 Because of the considerable time and expense required to run these trials and the appeal of such studies to editors, non-publication of the results of large randomized trials is likely in most cases to be a conscious decision made by study investigators and sponsors. Reasons why investigators and sponsors might choose not to publish results include a discrepancy between observed and desired results or the protection of intellectual property rights.36 37 The considerable rate of non-publication even among this group of large trials suggests that decisions by investigators or sponsors are a significant cause of non-publication of clinical trials."

The supplementary material of this article includes a list of the published and unpublished trials underlying this analysis. Of the first 20 unpublished trials listed, there is only a single example listed of a trial of an approved drug in its approved indication (5%). There are two examples (10%) of trials of approved drugs in indications that were never approved. There is one trial (5%) of a generic drug performed for regulatory approval in China. The remainder (80%) are trials of drugs that never reached the market and for which all development activities have ceased. For comparison, about 75% of drugs that are the subject of Phase 3 trials are eventually approved for use in the U.S., so taken in sum, the data actually suggests that the great majority of phase 3 trials of approved drugs are being published.

If this study had actually been done correctly, it would be citable as among the most favorable to the industry of the many scores of papers on this topic. The authors started with a set of assumptions, and stopped analyzing the data when they got a result that appeared to support their presuppositions. Its really quite a sad little paper. Formerly 98 (talk) 12:29, 8 December 2014 (UTC)

Formerly 98 Here is the paper:

• Jones, C. W.; Handler, L.; Crowell, K. E.; Keil, L. G.; Weaver, M. A.; Platts-Mills, T. F. (2013). "Non-publication of large randomized clinical trials: cross sectional analysis". BMJ. 347 (oct28 9): f6104–f6104. doi:10.1136/bmj.f6104. ISSN 1756-1833.

I am not ready to critique this paper, but the claims made in this Wikipedia article are in my opinion shallow and noncontroversial, and I feel that this paper is sufficient to back those claims. Is there some change that you would like to see?

I removed your "medical citation needed" tag because whatever the problem is, there is no medical citation needed here because no health claim is made. That template is for health claims, and this is a business or industry claim. WP:MEDRS applies only to issue directly relating to human health, so in this case, secondary sources are not required as this is a humanities issue. Blue Rasberry (talk) 15:01, 8 December 2014 (UTC)

Oh contraire! Respectfully, if this was just a business or industry claim, no one would give a rat's ass and it wouldn't be mentioned in this article. It's fundamentally a claim that the literature systematically overstates the risk/benefit ratio of therapeutics. And in any case, this reference does not support the claim. Formerly 98 (talk) 15:22, 8 December 2014 (UTC)

Formerly 98 I am not ready to qualify these claims as you are, and would prefer to leave that issue for now. Failing to reflect the cited source is a different complaint entirely, and that is easier to address. Let's check that here:

• Much medical research is done by the pharmaceutical industry, which may experience conflicts of interest reporting results which will hurt sales of their products.
  • source - "The lack of availability of results from these trials contributes to publication bias and also constitutes a failure to honor the ethical contract that is the basis for exposing study participants to the risks inherent in trial participation" (this is not a good match)
• There is a measurable bias in reporting; studies have shown that published drug studies funded by pharmaceutical companies are much more likely to support the use of the tested drug than studies with other funding.
  • source - "Prior investigations have shown evidence of publication bias against negative studies as one factor associated with non-publication"
• Industry-funded trials are also less likely to be published
  • source - "We observed that non-publication is common among large randomized clinical trials." "Non-publication was more common among trials that received industry funding than those that did not"

That first point needs a better citation but I think practically any researcher would still agree with it. It needs a better citation, or perhaps it is not worth stating at all. How do you feel about the other points being summarized?

Also, this article is not the correct place for this discussion. This is an article about an organization or movement, not for critiquing clinical trials. Where should this content and discussion be moved? Blue Rasberry (talk) 15:46, 8 December 2014 (UTC)

Hmm. Perhaps I'm being an intellectual dilletante here, I'm not really even saying that I disagree with the conclusions so much as the evidence presented to support it. Philosophically, I like to see conclusions tied to data and while I am aware of what the "common wisdom" is on many of these issues, I also see a lot of holes in the evidence used to support it. I looked at the supplementary material of this article with an open mind, and was quite surprised at the extent to which the data seemed to suggest that the great majority of phase 3 trials of approved drugs are being published. I had thought it was much lower.

Similarly the conclusion that industry selectively publishes positive data has been shown pretty clearly in a few specific areas, but the evidence cited for this as a general phenomenon is often weak. Published trials done by industry are more often positive than those published by academia, but they are not the same trials. Academia tests hypotheses for the sake of expanding medical knowledge. One expects "positive" results for such trials about half the time (shooting from the hip, anyway). Industry's goal is to approve drugs. Any successful phase 2 trial will be followed up by two phase 3 trials, and these phase 3 trials will likely be successful as well. A phase 2 trial that is not successful does not lead to a phase 3 trial. This creates a natural tendency for a higher fraction of industry trials to be successful that is unrelated to selective publication. I also frequently see it stated that industry trials are more likely to report a statistically significant result favoring efficacy than academic trials, but many of these papers do not explicitly address the well-established fact that industry trials are on average twice as big as academic trials, and thus 1.4x more highly powered to see an effect.

We can continue this on my talk page if you are interested in pursuing it. I'm certainly not denying that commerical interests have sometimes, even frequently been a problem. It's probably more a question of nuance and extent. But having looked at the particular article cited here and concluded it was complete bullshit, I was a little taken aback to find it used as a reference here and felt compelled to WP:SOAPBOX a bit. Probably not entirely appropriate. Formerly 98 (talk) 16:06, 8 December 2014 (UTC)

I wrote those lines. I only intended the source to support the last two sentences; the "Results" section of the abstract seems to me to strongly support both (it's CC-BY-NC, so anyone can read the entire article, but as I recall the abstract was a fair summary). I intended no judgement about motivation; I was using "bias" in the objective statistical sense (I've added links to make that clear). The first sentence seems to me to be pretty obvious (the person selling a product has a COI in providing information about it), but I've found and added two sources for the statement. The new sources also support the inference (which my juxtaposition could be taken to imply) that COIs can cause bias ("The potential of such [COI] relationships to create bias varies from negligible to extremely great"; "When the company is footing the bill, the opportunities for bias are manifold:..."). Please feel free to ping me if you would like to discuss concerns about my edits on an article talk page; I don't take offence easily and I'm happy to discuss it. HLHJ (talk) 21:56, 1 August 2015 (UTC)

Update needed to include AllTrials USA

A sister campaign, AllTrials USA, was officially launched on 29th July 2015: http://www.alltrials.net/news/usa-launch/ Can someone please update the page to include this info? I work for AllTrials [in the UK] and don't want to give the appearance of a conflict of interest by doing it myself. Thanks! Till Bruckner (talk) 16:19, 27 July 2016 (UTC)

Till Bruckner I sent you an email asking for a referral to someone from AllTrials in New York. I think your USA office is in New York, and I wonder if anyone from that office might join any local Wikipedia meetup. I cannot say what if any organizational information should be included in Wikipedia, but I think it would be interesting to have expert information from AllTrials and its network presented in Wikipedia. —Preceding unsigned comment added by Blue Rasberry (talk)