Talk:GW501516/Archive 1

Error in structure
The structure of GW501516 is missing a methyl group on the phenyl ring, ortho to the oxygen in the aryl ether. — Preceding unsigned comment added by 193.157.195.173 (talk) 10:33, 30 November 2012 (UTC)
 * File:Gw501516.svg, currently in the article, appears correct (per article refs and does contain ortho-methyl on the phenol-ether ring. DMacks (talk) 20:37, 31 March 2013 (UTC)

Cancer risk
I have reverted the addition of the suggestion that GW501516 is safe in humans for the following reasons:
 * "although clinical trials in humans published in the medical literature from 2008-2013 have not reported any safety issues. Phase I, II and IV human clinical trials have been completed with no safety issues reported."
 * There have been three clinical trials completed on GW501516:
 * , NCT00158899, 10 mgs/day, 2 week, 6 patients
 * NCT00841217, 2.5 mgs/day, 6 weeks, 13 patients
 * NCT00388180, 10 mgs/day, 12 weeks, 268 patients
 * These are either phase I or phase II clinical trials. Because of the short duration and limited number of patients, these studies would only detect the most common side effects and the most acute/severe types of toxicity. These studies are very unlikely to pick up increased cancer risk which would take years to develop into detectable tumors.  Furthermore it would be unethical to use humans for that purpose.  That is why long term toxicity tests are done in rodents in parallel to the early human clinical trials.  The rodent GW501516 toxicity studies demonstrated a strong tumor promotion effect even at the lowest doses tested.  Because of the these rodent findings, no further clinical trials in humans will be conducted.


 * Thank you for your further input. No drug, in market or pre-market, are without side effects. All research will find supporting and refuting findings and this is not unusual. It is also well known that animal studies may not be a direct comparison to humans. I agree that long term studies on humans are limited, and even today we are discovering the long term safety profiles of aspirin/penicillins etc. The decision to transit from animal studies to humans is beyond the scope of the current discussion. The long term monitoring of new drugs is also a separate discussion.


 * I have cited Phase I, II and IV trial in my earlier version. I have also been in ongoing personal communication with several of the researchers who are experts in the field (some of which were cited above by you) and who have experience with GW501516. I have in addition been in contact with the representatives of GSK, the NHMRC and the Attorney General Office to determine the evidence relied upon in WADA's recent decision. I am also trying to clarify the status of the drug from GSK themselves: There is so far a lack of transparency and clarity from the GSK representatives. They are also unable to confirm or deny third-hand reports that has been published in the media. 220.244.41.132 (talk) 01:05, 29 March 2013‎ (UTC)


 * As stated in earlier edits that has been reverted by BogHog. The above statement is unidentified editor using open IP. As user responsible for reverting comments, BogHog has accepted responsibility/ownership for published statement [IP Admin]
 * The above comments are a permanent part of this talk page's history (diff) and hence can always be retrieved from the history. Per WP:TALKNO, I have restored these comments.  I take no responsibility whatsoever for what others have written. I only take responsibility for my own comments. Boghog (talk) 18:08, 13 April 2013 (UTC)


 * "It remains unclear why WADA issued this warning in Mar 2013 when the matter was known to WADA since 2009"
 * The reason why the warning has been released now is that it has only recently reached the black market. Furthermore WADA first added it to their prohibited list in 2009.


 * "WADA and GSK has yet to provide clarification on the recent concerns, with experts and clinical researchers trialing the drug in humans remaining puzzled over WADA's latest concerns."
 * Which "expert and clinical clinical researchers" are you referring to? It is pretty obvious why GSK has halted further development of GW501516 and why WADA issued a warning to athletes.  GW501516 is a potent tumor promoter and using it will greatly increase your chances of developing cancer. Boghog (talk) 14:02, 28 March 2013 (UTC)

The "drug" has been sold legally through nationally-registered supplement companies online and in brick-and-motar premises. The issue is that it is sold as a nutritional supplement and not a drug. As to the purity and effectiveness of such supplements, that is beyond the current scope of discussion. It is therefore biased and inaccurate to use emotive terms such as "black market" when it is not against the laws in many countries to purchase the supplement through legitimate registered businesses. Whilst I disagree with the double standards of drugs versus supplements in many countries, that is also beyond scope of the current discussion.

As per earlier response, the "expert and clinical clinical researchers" are individuals who have direct knowledge and experience of using the drugs in the trials. I myself am an "expert" in drugs in sports and prefer statements based on evidence and not hearsay or hyperbole. As per earlier comments, there is at present a lack of transparency of the warning and relied "reasoned decision". This is ongoing and I will update once I get verified information from the respective organisations/individuals. Like many, I would like some clarity of the recent WADA announcement. If the issue is known since 2009 (as the cited 2009 reference provided by WADA indicates) what are the new findings in 2013 that prompted the sudden and global alert?

-As stated in earlier edits that has been reverted by BogHog. The above statement is unidentified editor using open IP. As user responsible for reverting comments, BogHog has accepted responsibility/ownership for published statement [IP Admin]

In the cited reference provided by WADA, in your Wiki comments you cited the rat experiments correctly in terms of the carcinogenic effects. However, the issue is that the evidence is based on an abstract of a conference proceeding and not a peer-reviewed article published in a academic journal. The reliability/validity issues are not addressed. Moreover, it is also not balanced in view that the same 2009 conference also published an abstract on the potential beneficial effect of the drug on human pancreatic cancer cells (Study 897 p.185).

To provide a credible discourse on the topic, scientific and legal statements made needs to be evidence-based. At present there is a lack of evidence to credibly accept on prima facie the assertions made. There are two possible view points, both equally valid. I would prefer that a version on Wikipedia that reflects a more neutral stance and offering views from multiple perspectives (media reports, academic journals, expert inputs, reported information, unreported information that needs clarification etc). These views can be updated as more evidence/information becomes available. 220.244.41.132 (talk) 01:05, 29 March 2013‎ (UTC)


 * Here are four articles published in peer reviewed journals that demonstrate that GW501516 is a tumor promoter:
 * – animals treated with the PPARδ agonist GW501516 accelerated mammary tumor formation
 * – GW501516 promotes the formation of metastatic gastric tumors
 * – GW501516 enhances mammary tumorigenesis
 * – activation of PPARδ by GW501516 antagonizes the ability of PPARγ to induce colorectal carcinoma cell death
 * Boghog (talk) 06:11, 29 March 2013 (UTC)


 * 220.244.41.132: Have you read WP:MEDRS?
 * the first statement, about there being no reported adverse effects from the limited clinical trials that have been run so far, i would say should not make it into the article at all. Since there are very few secondary sources on the effect of this research chemical in humans, I would say that any claims that even hint that it is safe in humans would be pretty clearly original research and not permissible.
 * We can certainly point out that the WADA has made statements about the chemical, so long as they come from reliable sources. The sourcing standard for non-medical claims is different from that which summarizes medical or scientific research. We should not speculate as to the basis or sourcing of this, because that would, again, be editorializing equivalent to original research.
 * And if there are companies that have been selling this chemical as a "nutritional supplement" then my non-lawyer interpretation of current US law is that that's pretty clearly illegal, since it is implied that it will be for human consumption. I could offer specific laws but this legality comment is already verging on WP:SOAP. -- [ UseTheCommandLine  ~/ talk  ] # _  06:13, 29 March 2013 (UTC)
 * You're correct about that - this is essentially now a designer drug so people selling it could be liable under things like the Medicines Act 1968. SmartSE (talk) 11:57, 29 March 2013 (UTC)

Thanks again for your further input. Without going into details here, and without knowing your professional background, I would suggest that you review the discussion section and referred citations of human studies cited in the Phase IV trials.

There is no suggestion here that any "drug" is "safe". Every "drug" even "natural foods" have benefits and side effects. The risk profiles are different for every "drug". There has to be a position of being credible and balanced based on the available (scientific) evidence without scare mongering and/or being too nonchalant. That is why I would advise that the editorial here be as neutral and circumspect as possible without overtly biased one way or another, and without using emotive words.

I note your cited references, but these studies are based on lab animals and the animals have been given supra-normal doses. Even Paracetamol/Tylenol given at supra-normal doses (weight equivalent in humans) are toxic despite its relatively "safe" drug profiles. Paracetamol/Tylenol remains on the market in many countries and often sold over-the-counter.

WADA is a global agency set up to harmonise international legislation. As such, it is not appropriate to cite the handling of legal matters in one jurisdiction on other sovereign counties. I believe Wikipedia also caters to a global audience and not just US ones.

Without going into specific examples here, the US FDA has approved different "drugs" deemed "risky" by other countries. The reverse is also true. The US has also approved some substances as "supplements" (but not as a drug) but banned in other countries as both drugs and/or supplements. The reverse is also true.

In the context of what this article is about, the statements made needs to remain as neutral as possible when it comes to politics. The issue needs to be based on scientific evidence and not just (biased) media reporting. And where the (scientific and/or media) evidence is not clear or contradictory, this should be pointed out as so. Supporting one view point and censoring another is not scientific. This is especially since, as an expert on the topic, I find the reported evidence in the peer-reviewed journals limited at best at this point in time (for both perspectives).

The inappropriate extrapolation of animal studies that conflict with human ones needs to be done with caution. Again without presuming your professional background, I think it is best, that until WADA and GSK clarify the basis for their recent reasoned action, that we stick to the available validated information without hyperbole, speculative hearsay, or unvalidated assumptions. We do not know the underlying reasons as yet for the recent alert. If it is sufficiently serious, as you have postulated, then there is an ethical responsibility that all human participants in the trials be recalled for review. But until we get such confirmation and evidence, it is best that we reserve judgment and have a healthy regard as more information unfolds.

Respectfully. — Preceding unsigned comment added by 220.244.41.132 (talk) 07:42, 29 March 2013 (UTC)


 * UseTheCommandLine is absolutely correct. Per WP:MEDRS, medical claims such as safety or even speculation about safety must be backed up by reliable secondary sources.  So far, you have provided none.  Boghog (talk) 08:20, 29 March 2013 (UTC)
 * This alert that mentions "serious toxicities" qualifies as a reliable secondary source. This assertion of "serious toxicities" can only be questioned if a second reliable source can be supplied that challenges the assertion. Boghog (talk) 08:31, 29 March 2013 (UTC)


 * With all due respect, ideally all WP articles are supported by secondary sources. the definition of secondary sources with regards to medical claims, though, is more limited, specifically to things like review papers, meta-analyses, guidelines, etc. I feel like i at least understand the ip editor's concerns with regard to WADA, but I'm trying to point out that those concerns are quite frankly irrelevant to the matter at hand; what is important is that there are no secondary medical sources on the safety of this chemical in humans, so we cannot talk about its safety in humans, period. To suggest that it is safe or not-safe based on scant clinical trials goes against wikipedia's core values. -- [ UseTheCommandLine  ~/ talk  ] # _  08:50, 29 March 2013 (UTC)


 * Because of the GSK rodent toxicity results, further clinical testing in humans is completely out of the question and definitive results concerning long term human safety will never be obtained. Hopefully an article that reviews the animal testing results and discusses the implication for humans will eventually be published. In the mean time, GW501516 has already reached the black market and this alert is secondary, from a reputable source, and provides a rationale for the safety concern. Boghog (talk) 09:16, 29 March 2013 (UTC)


 * 220.244.41.132: I see little evidence that you have familiarized yourself adequately with the policies and procedures that we follow here; despite this, you have endeavored to prescribe a particular course of action with regards to others' evaluation of evidence, and more to the point, the editing of this page. I urge you, before entering another lengthy prescription for the behavior of your fellow editors, please provide at least some evidence that you have done the most basic due diligence in familiarizing yourself with how this community works. I fear that If you do not do so, I or others might simply disregard whatever you have to say. I think that would be a shame, since I imagine that you, like everyone, have at least the potential to contribute something valuable to this community. -- [ UseTheCommandLine  ~/ talk  ] # _  08:36, 29 March 2013 (UTC)

It appears there are multiple response to this post/talk from potentially several writers. It also appears that some of the comments made are obviously from individuals unfamiliar with assessing scientific evidence. For individuals knowledgable of how evidence in science and medicine is used and assessed, assertions made would have been less antagonistic and not so self-assured. Even among the experts in the area, the evidence is not clear, so it is surprising that individuals relying on lay knowledge should be so confident in their perspective. As a very superficial attempt in trying to illuminate the issue, and trying to educate those less familiar with assessing evidence in science and medicine, below are several citations offering a contrasting perspective:


 * http://carcin.oxfordjournals.org/content/28/12/2641.short
 * http://www.sciencedirect.com/science/article/pii/S0300483X07007524
 * http://diabetes.diabetesjournals.org/content/57/2/332.abstract?ijkey=864d643ff35c2f00b9aaf2e6e075e063317adab7&keytype2=tf_ipsecsha
 * http://atvb.ahajournals.org/content/27/2/359.abstract?ijkey=ad073afa9c4fd4ff280cdf93e574a245be460794&keytype2=tf_ipsecsha
 * http://jcem.endojournals.org/content/96/10/E1568.long

The purpose of these citations is not to stake a claim of one view or another. Rather it merely serves as credible examples to show the lack of knowledge amongst the experts in the field at this present time and that alternative evidence exists. Until such time as WADA and/or GSK clarifies the actual reasons for the recent alert, all assumptions are speculative. — Preceding unsigned comment added by 220.244.41.132 (talk) 10:24, 29 March 2013 (UTC)

Glad to read what seems like some sensible professional perspective against all the Dr Googles.

— Preceding unsigned comment added by 149.135.146.111 (talk) 11:30, 29 March 2013 (UTC)


 * Before we continue this discussion any further, it is important that you first familiarize yourself with the relevant Wikipedia policies (WP:PSTS) and guidelines (WP:MEDRS). In short, it is essential to support statements in Wikipedia articles with high quality secondary sources.  This alert that mentions "serious toxicities" qualifies as a reliable secondary source. All five of the citations that you have supplied above are primary.  Furthermore the last three concern efficacy and have nothing to do with safety. It is crystal clear why WADA issued the alert and why GSK has halted further work on this compound: the two year rodent toxicity tests. Boghog (talk) 11:34, 29 March 2013 (UTC)


 * Since when is WADA a reliable source on anything other than its own political and financial interests? :)) Bstard12 (talk) 13:15, 18 June 2013 (UTC)


 * I have reverted 149.135 220.244's edit again. There is no way that things like "Phase I, II and IV human clinical trials have been completed with no safety issues reported in the peer-reviewed journals. Clarification from New Scientist in terms of cited academic/research evidence is pending." belong in the article. All we know is that GSK say that they have stopped researching the compound because it causes cancer - as Boghog has already explained, unless there is a very high-quality source which disputes this, then it is what our article should state. "In addition, the cited reference in WADA's alert referred to a 2009 conference proceeding abstract on rodent experiments and not on human clinical studies. The same conference proceeding also included a laboratory study suggesting the drug's therapeutic effects on human pancreatic cancer cells." is original research - whilst it may be true, it is based off the synthesis of different sources to produce a statement that isn't found in the original sources. It's not our job to decide whether or not it really is unsafe or suggest that the reliable sources are wrong. Unfortunately this article was a mess before the WADA alert was issued, but that's no reason not to make it more consistent with what reliable sources say now. SmartSE (talk) 11:57, 29 March 2013 (UTC)

Reference 2 in the article deals with the secondary source that is reliable and aligns well with statements of 220.244.41.132 — Preceding unsigned comment added by 149.135.146.109 (talk) 12:19, 29 March 2013 (UTC)


 * Reference #2 is essentially a blog and blogs generally are not considered reliable (see WP:BLOGS). Boghog (talk) 13:01, 29 March 2013 (UTC)


 * I think that is probably an RS, based on this which shows that there is editorial control of the content on that site. I am a bit concerned though that looking at 220.244's other edits [wrong attribution] it looks as if they might be the author of the article though which raises WP:SELFCITE/WP:UNDUE concerns. SmartSE (talk) 13:16, 29 March 2013 (UTC)


 * This is a University remote terminal with several thousand users commenting through this IP.


 * Yes, I also noticed some strong similarities in the some of the comments posted above and what has been written in the blog. Boghog (talk) 13:26, 29 March 2013 (UTC)

Is Wikipedia, through the actions of a few editors, purposefully biased in not allowing the options of alternative view points (especially non-US centric) through censorship? Does the citation of secondary resource instead of primary citations run contrary to long-held practice in academia to ensure a credible, unbiased, and accurate reflection of issues?


 * http://conversableeconomist.blogspot.com.au/2012/05/is-wikipedia-politically-biased.html
 * http://www.conservapedia.com/Examples_of_Bias_in_Wikipedia
 * http://insight.kellogg.northwestern.edu/article/is_wikipedia_biased
 * http://www.emeraldinsight.com/journals.htm?articleid=1464270&show=abstract
 * http://reagle.org/joseph/2005/06/neutrality.html
 * http://www.ingentaconnect.com/content/aea/aer/2012/00000102/00000003/art00059
 * http://link.springer.com/article/10.1007/s10676-009-9193-y
 * http://works.bepress.com/cgi/viewcontent.cgi?article=1045&context=laura_quilter&sei-redir=1&referer=http%3A%2F%2Fscholar.google.com.au%2Fscholar%3Fstart%3D40%26q%3Dis%2Bwikipedia%2Bpolitically%2Bbiased%26hl%3Den%26as_sdt%3D0%2C5#search=%22wikipedia%20politically%20biased%22

Is this another example where credible, validated alternative perspective provided by expert authors with insight and understanding of a phenomenon and issues are skewed and purposefully censored/omitted to reflect the views of a particular cohort who may/may not have expertise in the field? If so, then the Wikipedia is but another propaganda tool to propagate the message of the perceived elite Anglo-phile using a socialist paternalistic ethos under the facade of freedom and democracy and true knowledge seeking.

— Preceding unsigned comment added by 220.244.41.132 (talk) 02:03, 30 March 2013 (UTC)


 * You have some major misconceptions both on how Wikipedia and drug development work. Have you read WP:PSTS? Our insistence on using secondary sources is not the arbitrary action of a few editors, but rather a core principle of Wikipedia and applies to all articles, not just this one. If you cannot accept this core principle, then you need to find another venue.
 * WP:SOAP warning: Turning to the issue of drug development, two year rodent toxicity tests are the gold standard to establish the carcinogenicity potential of a drug candidate. As a part of the regulatory requirements to obtain drug approval, the drug sponsor performed these tests on GW501516.  In two species, mice and rats, GSK found that GW501516 had strong tumor promotion effects even at the lowest dose tested.  Furthermore this tumor promotion effect appears to be mechanism based (caused by activation of PPARδ), hence there is unlikely to be any window between the desired therapeutic and undesired tumor promoting effects.  While rodent carcinogenicity tests are imperfect models of human carcinogenicity potential, they are the best we have and are a mandatory part of the drug approval process.  Based on these toxicity test results, no regulatory authority would approve the drug.  The drug is dead.  Hence it is completely understandable why GSK halted further work on this drug.  The only thing that is surprising is that you are surprised. Boghog (talk) 10:42, 30 March 2013 (UTC)

I am quite familiar and have professional experience in the drug approval process. As an informed professional in the field, I do not have any implicit or explicit conflict of interest with regards to the current substance in question. My purpose here is to ensure a balance of perspective based on available, consistent and validated evidence.

If, as you claim, the use of secondary sources is a core principle of Wikipedia, I would appreciate a clarification of the following:


 * 1.	WADA is ultimately a political entity that has a clear and biased mandate. That is its role and there is no judgment here. Authors from other avenues with no direct or indirect links to the issue are not encumbered by such biases. As such, my question is why one secondary source (WADA) announcement is deemed as acceptable, while an academic critique and similar secondary source (not biased by editorial input) is classified as “a blog” and rejected?
 * 2.	If only secondary source is used as the basis of a Wikipedia article, why are the primary source from rodent studies in an abstract of a 2009 conference proceeding used, and primary source from in vivo and in vitro human and animal studies from validated peer-reviewed scientific articles over half a decade of scientific publication rejected on that same basis. Where is the consistency?
 * 3.	Moreover, if the secondary source of a 2009 abstract of an conference proceeding is used (2 rodent experiments), why is another human pancreatic cancer cell study cited from that same 2009 conference proceeding rejected? Again where is the consistency?
 * 4.	The verbatim quotation of “Black market”, whilst necessary for the purpose of the original document, seemed prejudicial in the current context. Correct me if I am wrong, it was my impression from other commentaries of Wikipedia that Wikipedia seeks (ideally) to not be prejudicial based on race, religion, gender, nationalities (and jurisdiction).
 * 5.	How is “Black market” defined? Legislative issues are complex and WADA (and by my impression, Wikipedia) is a global entity and not a US-centric one. That as it may, as noted previously, the US FDA has approved different "drugs" deemed "risky" by other countries. The reverse is also true. The US has also approved some substances as "supplements" (but not as a drug) but banned in other countries as both drugs and/or supplements. The reverse is also true. If there are jurisdictions that have legally approved the sale of certain substance, the term “Black market” needs to be better qualified, otherwise is simply an emotive language used solely to incite prejudicial ("either with us or against us") agendas. I would have preferred, as per my version of the document, to use a more neutral description of the state of affairs and to avoid prejudicial language.
 * 6.	If as is stated, clinical testing in humans will never occur, and according to a GlaxoSmithKline spokesperson as reported in the press, the development was halted in 2006, this seems odd given that several human clinical trials (some approved by the US) have been conducted and reported since 2006 to date. Several of the authors of these trials that have published their results in academic journals were also GSK staff.

I do not disagree that it is possible, although not improbable, that GSK may have terminated the development of the drug. However, this has not been formally validated. Quotes from various GSK staff in the press, whilst indicative, are questionable given the issue of date discrepancies (2006 halted; 2006-2013 human trials). The point is that this should be clarified in the Wikipedia article as such. Unless Wikipedia has a political agenda of seeking to only publish one version of events, rather than a balanced account, then both the stated issues and inconsistencies need to be highlighted.

I also do not disagree that WADA and GSK may have new but undisclosed findings of toxicity of the drug and hence the recent warning. However, all we have so far are generic statements that are not backed with the evidentiary information for that apparent reasoned decision and announcement. This would, I presume, have an ethical implication on past researchers (and participants in trials) who have used the drug in approved clinical trials. As mentioned previously, contacted experts involved have so far not been aware of any (potential) updated issues. Until such time as clarification and further information is provided by GSK and/or WADA, this should be reflected in the Wikipedia article, insofar as not to incite unnecessary panic.

To explicitly clarify, all I seek is that the article in Wikipedia (read by a global audience from diverse personal and professional backgrounds) report relevant issues based on information that is consistent. Where inconsistencies occur, as is the case, by the very least, Wikipedia should have an ethical obligation to report the inconsistencies as well. I believe that would, at its most basic, be in line with the social and corporate responsibility? That is unless, of course, there is a political bias that I am unaware of, and all message needs to stick to a fixed script with all dissenting and inconsistent facts necessarily ignored. — Preceding unsigned comment added by 220.244.41.132 (talk) 03:00, 31 March 2013 (UTC)


 * The following is a statement by GSK posted on their web site:
 * While publication of the GW501516 clinical results occurred after 2006, no patients were dosed after 2006. Boghog (talk) 05:30, 31 March 2013 (UTC)
 * The above statement from GSK is a primary source, however it is allowed by WP:PSTS since it is a "straightforward, descriptive statement of fact that can be verified by any educated person with access to the source but without further, specialized knowledge". Boghog (talk) 05:41, 31 March 2013 (UTC)
 * Here is a secondary source (already cited as reference #5 in the current version of the article) that supports the above primary source: Boghog (talk) 05:53, 31 March 2013 (UTC)
 * This Wikipedia article has it right. What needs to be edited is this blog. Boghog (talk) 06:04, 31 March 2013 (UTC)


 * If you genuinely want to clarify things, then do your due diligence and read our policies before commenting. You have displayed no evidence so far that you are interested in meaningfully contributing to our community. So, not to put too fine a point on it, but until you have and can demonstrate a meaningful understanding of our policies, why we follow them, etc, go jump in a lake. -- [ UseTheCommandLine  ~/ talk  ] # _  05:40, 31 March 2013 (UTC)

Thank you for the further reply and clarifications, unprofessional remarks notwithstanding. The GSK link was useful. Although as referenced in the human clinical trials, the research was not terminated in 2006 as indicated by the GSK statement. In addition, I note that in another research article: Detection of PPARδ agonists GW1516 and GW0742 and their metabolites in human urine
 * Tim Sobolevsky*, Marina Dikunets, Irina Sukhanova, Edward Virus, Grigory Rodchenkov
 * Article first published online: 13 SEP 2012
 * DOI: 10.1002/dta.1413


 * Drug Testing and Analysis
 * Special Issue: Advances in Sports Drug Testing
 * Volume 4, Issue 10, pages 754–760, October 2012

Based on the article's full text, human subjects (healthy volunteers) were administered GW 501516, between 2009-2012 for the study.

I further note that other Peroxisome Proliferator-Activated Receptor drugs are currently in clinical trials:
 * http://clinicaltrials.gov/ct2/show/NCT01261494?term=Peroxisome+Proliferator-Activated+Receptor&rank=49
 * http://clinicaltrials.gov/ct2/show/NCT01271777?term=Peroxisome+Proliferator-Activated+Receptor&rank=48
 * http://clinicaltrials.gov/ct2/show/NCT01275469?term=Peroxisome+Proliferator-Activated+Receptor&rank=47
 * http://clinicaltrials.gov/ct2/show/NCT01271751?term=Peroxisome+Proliferator-Activated+Receptor&rank=46
 * http://clinicaltrials.gov/ct2/show/NCT01694849?term=Peroxisome+Proliferator-Activated+Receptor&rank=45
 * http://clinicaltrials.gov/ct2/show/NCT00872599?term=Peroxisome+Proliferator-Activated+Receptor&rank=10
 * http://clinicaltrials.gov/ct2/show/NCT00926341?term=Peroxisome+Proliferator-Activated+Receptor&rank=7
 * http://clinicaltrials.gov/ct2/show/NCT00745225?term=Peroxisome+Proliferator-Activated+Receptor&rank=1

I reiterate my earlier point that I do not disagree that the statements made by GSK/WADA are probably founded on the premise we have so far discussed. What is at hand is the lack of clarity and information beyond a cursory public-service announcement. Any citation of "secondary" and "tertiary" information should reflect as such. — Preceding unsigned comment added by 220.244.41.132 (talk) 07:20, 31 March 2013 (UTC)

While your attempts at reconciling perceived inconsistencies and subjectivity in Wikipedia are noted, they are nevertheless inconsistent and subjective and previous noted concerns remain. I will refrain from stooping to your level of unprofessional discourse. If you are such a stickler for Wikipedia's protocols of do's and don'ts, then perhaps adhering to the minimum communication standards as dictated therein would not go amiss. — Preceding unsigned comment added by 220.244.41.132 (talk) 06:51, 31 March 2013 (UTC)


 * It's great that you feel you are refraining from "stooping to [my] level of unprofessional discourse" but that horse left the barn quite some time ago with your statement about "individuals unfamiliar with assessing scientific evidence". (For reference, this would be WP:AGF.)
 * Whether a drug in the same class is being tested matters not a whit for what appears to be your intent, which i am interpreting as to cast aspersions on the safety claims made by WADA et al about this drug specifically.
 * Read the policies, and demonstrate that you have done so. then talk. -- [ UseTheCommandLine  ~/ talk  ] # _  07:49, 31 March 2013 (UTC)


 * "I will refrain from stooping to your level of unprofessional discourse" – what an incredibly hypocritical comment. We have merely asked you to acquaint yourself with the way Wikipedia works. In response, you have repeatedly questioned our motives and competences.  Our discourse has been very measured.  Yours is way over the top.
 * Concerning, the purpose of this study was develop an analytic method for detection of its illegitimate use in sports, not to study its safety or efficacy. I do not have access to the article, only the abstract so I do not know the details of this "controlled excretion study". Presumably this study was done with low doses over short time periods so that the carcinogenicity risk would be very low.  It is also important to note that this study was performed by the Moscow Anti-doping Centre, not GSK.
 * Not that it probably matters any longer, but I was finally able to track down the full text of the above citation. The "controlled excretion study" was based on a single 15 mg dose of GW1516 administered to one human volunteer (male, 31 years old). Boghog (talk) 14:55, 21 April 2013 (UTC)
 * Concerning the ongoing clinical trials:
 * NCT00872599: fenofibrate – PPARα agonist
 * NCT00745225: Pioglitazone (PPARγ agonist), telmisartan (angiotensin II receptor antagonist)
 * The above drugs do not have significant PPARδ activity and are therefore not relevant to this discussion. Furthermore GSK has noted that the type of carcinogenicity observed with the PPARδ agonist GW501516 are not observed with either PPARα or PPARγ agonists.
 * NCT01261494, NCT01271777, NCT01275469, NCT01271751, NCT01694849: GFT505 – dual PPAR α/δ agonist
 * We do not know if the carcinogenicity observed with the PPARδ agonist GW501516 is compound specific or a class effect of all PPARδ agonists. Furthermore the fact that GFT505 is also a PPARα agonist may counteract the carcinogenicity potential caused by the δ agonism.  Boghog (talk) 08:15, 31 March 2013 (UTC)


 * Telmisartan is both a PPARγ agonist and also upregulates PPARδ receptors. The science here gets quite complicated and you simply can't make the blanket statements that you continue to make. Without actual testing, these things are mostly unknown. The researchers who are very close to these ideas are possibly the only people on the planet that should be speculating here. Foamyslippers —Preceding undated comment added 17:42, 31 March 2013 (UTC)


 * I do not believe what I have written above qualifies as a blanket statement. Quite to the contrary, what I stated above is that one cannot extrapolate from the GW501516 two year rodent toxicity tests to conclude that all PPARδ agonists are carcinogens. Furthermore a dual PPAR α/δ agonist may (or may not) behave very differently in toxicity tests compared to a pure PPARδ agonist.  Of course we will not know the answer until additional dual PPAR α/δ and pure PPARδ agonists are evaluated in long term toxicity tests. Boghog (talk) 07:36, 1 April 2013 (UTC)


 * So you're suggesting that GSK are lying about when they stopped research on the drug?! Why should we believe you over them? How can the black market be described as anything else? If the drug was developed by GSK then they presumably own the patents and therefore by definition it can only be available through the black market. As we have tried to explain, it is not up to us to decide whether it is safe or not. It would appear that your idea of what Wikipedia is differs from the reality and we're getting to the point where you are refusing to take this on board. The consensus is clearly against you. SmartSE (talk) 09:49, 31 March 2013 (UTC)

[Wrong reference of author], please accept that GW-501516 is toxic and move on. I agree the term 'black market' is stupid and should not be used. The sale of this drug is legitimate, but only in certain context, and should be labeled 'gray market'. 'black market' is a WADA term, but as the drug is not scheduled and openly sold from licensed commercial enterprises, with potential patent and FDA issues, gray market is correct — Preceding unsigned comment added by Foamyslippers (talk • contribs) 15:50, 31 March 2013 (UTC)


 * Just to clarify, GW501516 is a useful research tool for in vitro and animals experimentation and is commercially available to research institutions for that purpose. GW501516 has not been approved for human use and therefore such use is illegal.  There is a legitimate market for the use of GW501516 as a research tool. However any sale intended for human consumption is illicit and therefore can fairly be described as "black marketing". Boghog (talk) 17:49, 31 March 2013 (UTC)


 * There are many black and gray market sources. I would consider may internet sources which are inherently "not for human consumption" or for "research use only" to be gray market. But that's just me. Foamyslippers (talk) 17:56, 31 March 2013 (UTC)


 * Your are correct. After a little more digging, it appears that GW501516 has not yet be classified as a controlled substance, at least in the US. Its sale for human use should probably be classified as grey marketing at least for now. Boghog (talk) 18:28, 31 March 2013 (UTC)


 * There don't seem to be any sources saying grey market, so unless there is something to replace WADA, who say it is for sale on the black market, this is a bit irrelevant. SmartSE (talk) 18:36, 31 March 2013 (UTC)
 * There is an issue of coloring the topic. The "black market" is simply not where GW 501516 is typically for sale. And you only have to use Google for about 10 minutes to figure this out for yourself. Foamyslippers (talk) 03:16, 1 April 2013 (UTC)


 * The distinction between "black" and "gray" market drugs is important. Black market drugs are sold illegally. They are scheduled, or prescription drugs sold without a prescription. Their sale and distribution may be subject to criminal penalties, hence, "black market". Black market == criminal penalties. You go to jail. A gray market drug would be one that is sold for research. It is not going to be scheduled, nor otherwise subject to criminal penalty when distributed for purposes not including human-consumption. The fact that it may violate a patent right is a civil, not a criminal issue. Several drug patent protections are based on usage. They don't cover research (non-human-consumption) use. I know of no case where a company selling "research chemicals", with or without authorization from the patent holder, has EVER been sued in any court. I challenge you to find any example of this. It simply does not happen. There is no money in pursuing a case like this. I'm not saying it's impossible. That's what makes it a "gray" market. Foamyslippers (talk) 03:34, 1 April 2013 (UTC)


 * Operation Web Tryp. Notably, the drugs were marketed as "research chemicals" and thus ostensibly not for human consumption, but they were still prosecuted criminally. There is plenty of other information on this event elsewhere on the intertubes. -- [ UseTheCommandLine  ~/ talk  ] # _  04:41, 1 April 2013 (UTC)
 * I realize in looking at your comment again that this is not exactly the situation you were referring to. but "gray market" does not refer explicitly to violations of civil law, in my experience. and to be fair there are also criminal infringements of copyright law (normally a civil matter) and, presumably, also patent law, though i am unfamiliar with examples of the latter. trying to make a clear distinction is probably unwise, thus the term "gray market" for things that are not clearly black market but also possibly illegal. -- [ UseTheCommandLine  ~/ talk  ] # _  04:51, 1 April 2013 (UTC)
 * Operation Web Tryp was a criminal prosecution. None of these people got in trouble for selling chemicals "not for human consumption" --- quite the opposite. They were set up in stings where many admitted they could be used to replace schedule I substances! I'm talking about the multitude of professional labs that will synth a batch of XYZ-1whatever for a cost, on demand. They don't typically get patent rights and they absolutely never get heat, until the scale gets so large that you end up in Web Tryp. In any event, patent cases are always civil matters. Copyright violation is only a criminal matter in blatant large scale commercial operations, and has nothing to do with any of this. I hope this helps to make my thinking more clear. I'm not saying that a gray market case is always == civil infringement, i'm saying that a black market case does always mean criminal activity, "beyond a reasonable doubt". Foamyslippers (talk) 05:36, 1 April 2013 (UTC)

Thank you all for the further debate on this issue. If I may summarise (open to further clarification if disagreed; but in the interest of moving forward, I hope there is tentative consent and agreement):


 * *We agree that the term of "gray" market would be the least objectionable and most accurate term to describe the status of the substance without being unnecessarily prejudicial.
 * *We agree that GW501516 is likely to be carcinogenic based on some animal studies (known since at least 2009) and that the recent announcement by WADA in 2013 may be a result of such studies. However, this is by inference only and it is not clearly and explicitly stated in WADA's actual announcement.
 * *We agree that human studies on GW501516 are limited, and that the only four known published to date do not show toxicity, but this may be due to the lower doses and shorter follow-up periods. That as it may, animal studies of toxicity have limited GW501516's further development in humans and we are unlikely to ever know.
 * *We agree that GSK has issued a statement that development of GW501516 was ceased in 2006 but published reports in the medical literature suggest that the dates may or may not be accurate and is not clear.
 * *Research into PPAR agonist are still continuing and there is at present limited understanding on how the related α, β, δ and γ agonist drugs work in isolation and in combination. Some PPAR drugs are currently under investigation in human trials. — Preceding unsigned comment added by 220.244.41.132 (talk) 05:05, 1 April 2013 (UTC)


 * I'm not sure what you mean by "unnecessarily prejudicial" here. It is extremely likely to be a significant human health hazard. A poison, even. So, prejudicial against what, exactly? There is not, and there should not be, any presumption of safety in humans. Just the opposite, in fact, especially given what evidence there is. -- [ UseTheCommandLine  ~/ talk  ] # _  05:23, 1 April 2013 (UTC)
 * I suspect the numerous PPAR agonists with similar structures, currently under investigation, all will show some level of carcinogenic activity in animal models. I think GW 501516 is obviously toxic, and so will be many others. Having said that, whether or not this is an issue in human use at therapeutic dose range is simply unknown. Ironically the thousands of guinea pigs testing themselves will help a future generation of diabetic/therapeutic and endurance drug users make informed choices. Foamyslippers (talk) 05:44, 1 April 2013 (UTC)


 * Hear! Hear! I suppose there are some new knowledge gained from others' self-experimenting? Although, the lack of quality control and consistency of the substance makes it hard to interpret. They may just be consuming sugar water! — Preceding unsigned comment added by 220.244.41.132 (talk) 05:58, 1 April 2013 (UTC)


 * From a macro-perspective, since PPAR belong to the NHR super family of receptors, it may be that activations of any NHR simply increases activity of the cells involved. By pure probability of increased in activity alone, the acceleration and risk of cancer is increased. The prevalence of the receptors in different organs, and the susceptibility of each organ to carcinogenic changes, would affect the cancer rate. The ultimate successful PPAR would be a balance of hitting mainly the desired organs (and avoiding others), and hitting it at an appropriate dose so that the benefits (e.g. fat reduction) outweighs the side effects (e.g. cancer)


 * Unambiguous WP:SOAP. -- [ UseTheCommandLine  ~/ talk  ] # _  06:39, 1 April 2013 (UTC)


 * Well more like WP:NOTFORUM but yes, please stay focused on improving the article rather than discussing the compound in general. SmartSE (talk) 16:13, 1 April 2013 (UTC)

It is prejudicial as per Foamyslippers' (accurate) explanation of the two terms. I will not reiterate the discussion. Every substance is also potentially a "poison" in supra-doses or outside its therapeutic range. E.g. water in extreme doses is also a "poison" (see "water intoxication")


 * So you have a dispute about terminology, I suggest you take it to e.g. WP:DRN. I am not inclined to take either your or ' word for it, though it there is consensus elsewhere I am happy to accept that. -- [ UseTheCommandLine  ~/ talk  ] # _  05:42, 1 April 2013 (UTC)


 * emacs or vi? Foamyslippers (talk) 06:05, 1 April 2013 (UTC)

I think the terminology is consistent with that defined within Wikipedia?: "...a third type of "grey market" since it is legal, yet unregulated, and probably not intended or explicitly authorized..." http://en.wikipedia.org/wiki/Grey_market


 * Exactly, who needs to use the DRN when the answer is already here? Foamyslippers (talk) 06:05, 1 April 2013 (UTC)

Regarding "posions", again using Wikipedia: "...Paracelsus, the father of toxicology, once wrote: "Everything is poison, there is poison in everything. Only the dose makes a thing not a poison." The legal definition of "poison" is stricter. A medical condition of poisoning can also be caused by substances that are not legally required to carry the label "poison"...." http://en.wikipedia.org/wiki/Poison


 * WP:WINARS. if you want to continue your dispute about black vs gray market, take it to WP:DRN. -- [ UseTheCommandLine  ~/ talk  ] # _  06:32, 1 April 2013 (UTC)


 * If the terms "black" and "grey" are so contentious, perhaps the article should just state explicitly the intent of the sentence without using labels.
 * - As an example "...GW-501516 has been promoted on bodybuilding and athletics websites[5] and its availability for purchase has so far been unregulated..."

I assume all the other summarised points were agreeable? — Preceding unsigned comment added by 220.244.41.132 (talk • contribs)


 * I agree with the summarized points and also like the draft bits. 204.80.187.227 (talk) 15:22, 1 April 2013 (UTC)

This discussion is getting rather disjointed and difficult to follow. As I stated yesterday - there are no sources calling it a grey market, whereas there are several listed in the draft below calling it the black market, so I certainly disagree with the first point. With regards to the rest, I don't disagree, but it's all WP:OR so I wouldn't support adding anything along those lines to the article - we need to concentrate on finding the secondary sources, rather than coming to our own conclusions. Can we at least decide to follow WP:1RR regarding the cancer info for the moment and continue to discuss any secondary sources here? Then we can get rid of the protection and add more context. SmartSE (talk) 16:13, 1 April 2013 (UTC)
 * It's not the place of amateur editors here to make judgements like "black is a pejorative term, so we'll call it grey". Our job is to fairly reflect what reliable sources say and the source says "authorities should be aware of the facile availability of black market copies of these drug candidates" - so that's the phrase we use. --RexxS (talk) 16:22, 1 April 2013 (UTC)

Page protection
I have protected the page from editing due to the ongoing content dispute and edit warring. Discussion should take place here on the talk page until a consensus is reached and then the article can be unprotected. -- Ed (Edgar181) 12:44, 29 March 2013 (UTC)


 * Seeming as the discussion seems to have fizzled out and there are now plenty more eyes here, I've requested unprotection. SmartSE (talk) 20:00, 2 April 2013 (UTC)
 * I have now unprotected the page. -- Ed (Edgar181) 20:09, 2 April 2013 (UTC)

To the recent IP editors
At the risk of perhaps speaking a little too plainly:
 * Your alleged expertise means squat here unless you can demonstrate it, and you have not done that
 * You have thus far completely failed to demonstrate that you have familiarized yourselves with the norms and rules of this community. Please see the essay "verifiability, not truth"
 * Your eagerness to cast doubt on what appear to be fairly well-founded (if perhaps a bit shrill) safety claims, combined with the recent hints that you may have financial conflicts of interest (and in conjunction with vague comments you have made regarding "nutritional supplements") make me think, despite my efforts to assume good faith, that you are simply snake oil salesmen with nicer suits. Facility with scientific language does not make you a scientist.
 * Your dismissive tone ("Dr. Googles", "obviously from individuals unfamiliar with assessing scientific evidence" ) is neither warranted nor appreciated

I hope, despite a deep innate cynicism, that now that the page has been protected, you will reconsider your actions thus far, and make a genuine effort to engage the community of editors here in coming to consensus about this material. The tone you have struck thus far actively works to make editors oppose you, I think, but some well placed mea culpas would probably get things back on track. -- [ UseTheCommandLine  ~/ talk  ] # _  17:00, 29 March 2013 (UTC)


 * ditto right back at ya mate...pot meet kettle

Similar drugs
Links to similar drugs, such as Telmisartan (PPAR-gamma agonist) and GFT505 (dual PPAR delta/gamma agonist) should be provided. These are likely safer alternatives.

Also there are enough PPAR drugs out there, we need a template to link these together like other major drug groups have.


 * Thanks for creating the GFT505 article. A word of caution however. A lot less is known about the safety of GFT505 compared to GW501516. We will not be able to say if GFT505 is less carcinogenic than GW501516 until a two year tox study is completed on GFT505.  Also telmisartan is a angiotensin II receptor antagonist (reduces blood pressure) and not a PPARγ agonist. This is a bit confusing since NCT00745225 is a combination study of two distinct drugs with two distinct mechanisms of action. Boghog (talk) 17:29, 31 March 2013 (UTC)


 * I bet tox studies are already done on GFT505. It's not that new, at least 5 years of study are already obvious to me. 05:45, 1 April 2013 (UTC)


 * Take a look at some of the materials I added to the GFT505 page. If the Genfit press release is to be believed, they have high confidence in the safety profile of this new drug. Genfit appears to be a sort of research arm of Sanofi Aventis Foamyslippers (talk) 18:04, 31 March 2013 (UTC)


 * Telmisartan is also a PPARγ agonist. I added a reference stating such in the Telmisartan article. This is what makes it unique from other "sartan" drugs.Foamyslippers —Preceding undated comment added 17:35, 31 March 2013 (UTC)


 * Interesting, a dual acting compound that hits both a GPCR and a nuclear receptor. I stand corrected. Boghog (talk) 17:53, 31 March 2013 (UTC)


 * The structure of Telmisartan has some similar features to the patent that I cited on the GFT505 page. Interesting, indeed. Chemicals from the Okinawan Bitter melon are also worth a look. Foamyslippers (talk) 18:01, 31 March 2013 (UTC)


 * I think a table to template of other agonists would be the best solution rather than us trying to judge which compounds are similar, when AFAIK there are no sources discussing similar compounds. I second Boghog in the need for caution regarding safety - I don't think we should even suggest that they might be safer on this talk page. It might be worth citing this paper though: SmartSE (talk) 19:52, 31 March 2013 (UTC)


 * A table sounds like a good solution SmartSE, not sure how one will look like? Even being familiar with the literature and after communicating with several experts in the field, there is still no consensus on the effects in isolation and in combination. — Preceding unsigned comment added by 220.244.41.132 (talk) 06:07, 1 April 2013 (UTC)
 * Woops - I meant template not table. It doesn't need to be complicated - just list all the agonists that have been identified. I found something earlier in google books that would have made an excellent source, but now seem to not be able to find it. SmartSE (talk) 16:48, 1 April 2013 (UTC)

History and context
I have had a search on factiva to see what I could find out about this compound. Below is content that can be added to the article if others don't object. Feel free to copy edit it. SmartSE (talk) 19:48, 31 March 2013 (UTC)


 * Very useful information. Thank you SmartSE. I would hope that the below makes it into the Wiki piece as it provides relevant context (and is interesting). Can we verify the dates WADA recognised GW501516? Based on the recent announcement and the change of the Prohibited list between 2008 and 2009, I would have thought it was in 2008/2009 instead of 2012? I'm not sure here. — Preceding unsigned comment added by 220.244.41.132 (talk) 05:34, 1 April 2013 (UTC)
 * The article is already on this IMO - It was added to the list in 2009 but they changed the category in 2012. SmartSE (talk) 15:50, 1 April 2013 (UTC)
 * This article also provides interesting background info. SmartSE (talk) 22:04, 1 April 2013 (UTC)

Draft
According to R & D Focus Drug News GW 501516 was initially discovered during a research program collaboration between GSK and Ligand Pharmaceuticals that began in 1992.

R & D Focus Drug News reported that GSK began phase I trials of the compound for the treatment of hyperlipidemia in 2000 followed by phase I/II in 2002.

The discovery of the compound was published in a 2001 issue of PNAS. Oliver et al. reported that they used "combinatorial chemistry and structure-based drug design" to develop it. One of the authors was the son of Leo Sternbach who discovered benzodiazepines in the 1960s.

In 2003, Ligand Pharmaceuticals earned a $1 million payment as a result of GSK continuing phase I development.

In a 2004 article in New Scientist Ronald M. Evans from the Salk Institute stated "I suspect that animals training with the drug will increase endurance more rapidly," and that "the potential for this to be abused by athletes is real." A spokeswoman for WADA said it would not be surprising if athletes were to take the substance if it was available. GSK told New Scientist that it had not investigated whether the compound had any effect on endurance. An article the same year in The Wall Street Journal noted that a study published in Nature Medicine had found that GW 501516 increased polyps in specially-bred mice, but GSK said that they had not identified any safety problems with the compound and would continue to develop it.

GSK abandoned the development of GW 501516 in 2007 for reasons which where not disclosed as of 2008.

A sample of GW 501516 purchased via the Internet in 2010 was found to be authentic, but it contained considerably less of the compound than stated on the label.

In 2012, WADA recategorised GW 501516 from a gene doping compound to a "hormone and metabolic modulator".

Reliable source?
What do people think of the reliability of this? https://www.caymanchem.com/app/template/Article.vm/article/2191 It is a bit unusual, but the author looks as if he should know what he is talking about and it is a good secondary source discussing the reasons that it could be used in doping. SmartSE (talk) 20:03, 31 March 2013 (UTC)
 * I would agree that the draft above represents useful, verifiable information that gives a historical context to the drug, although I think the "A sample of GW 501516 purchased ..." is tantamount to trivia. Perhaps the key point from is that by 2010 the drug was available via black-market routes, rather than the customer getting short measure?


 * I like this point. Noted point about Trivia by RexxS, but relevant insight into lab-substances vs online products? — Preceding unsigned comment added by 220.244.41.132 (talk) 05:37, 1 April 2013 (UTC)


 * I kind of agree, but surely one report is better than nothing? But yes, it is a very good source for demonstrating how long it has been available on the black market. SmartSE (talk) 15:50, 1 April 2013 (UTC)


 * The article on the Cayman Chemical Company website looks like a review, but "good secondary sources" are published in peer-reviewed journals with a reputation for fact-finding and accuracy - it's the editorial process and the journal reputation that gives us confidence in the analysis of the reviewer. The author does look like he knows the subject, but that then begs the question why the article is published in CaymanChem, not the NEJM. I personally wouldn't be comfortable using the article as a source for this article. --RexxS (talk) 00:13, 1 April 2013 (UTC)


 * You have a point regarding why it isn't published in a journal, but IRS states that the author is just as important as the publisher. I should have stated what I wanted to cite from it too, rather than just the source, since this is important for deciding whether it is reliable - specifically it would be useful for another source for it being available on the black market (not grey) and that using it in combination with AICAR "leaves plenty of room for unwanted side effects". SmartSE (talk) 15:50, 1 April 2013 (UTC)
 * That's not what IRS states at all. That section simply says that we use the word "source" in three different ways. The sections you are looking for are IRS  and IRS  which tell you that you might use:
 * a statement made outside of a reliable publication by an acknowledged published expert in a field; (Conventionally, we take the minimum requirement for 'expert' is that they have a wikipedia article. Thomas G Brock doesn't meet that minimum.)
 * "general or systematic reviews in reliable, third-party, published sources, such as reputable medical journals, widely recognised standard textbooks written by experts in a field, or medical guidelines and position statements from nationally or internationally reputable expert bodies" as a source for any "biomedical assertions"
 * You might just use it for the black market claim (but you already have and WADA - both much better quality sources), but it is unusable for the biomedical assertion about side effects. --RexxS (talk) 16:49, 1 April 2013 (UTC)

When GSK stopped research
This book:

cites this paper by a GSK employee:

For saying that GSK have abandoned research into 501516. I can't access a full copy at the moment, but hopefully someone at WP:REX can help out. SmartSE (talk) 15:50, 1 April 2013 (UTC)


 * Got it now, will add the info to the draft above. SmartSE (talk) 16:27, 1 April 2013 (UTC)

So when did GSK stop research? 2006 or 2007 or 2008? -UniWiFiTroll — Preceding unsigned comment added by 220.244.41.132 (talk) 04:04, 12 April 2013 (UTC)

GSK states 2006Www.gsk.com/media/resource-centre/anti-doping.html — Preceding unsigned comment added by 149.135.146.23 (talk) 04:09, 12 April 2013 (UTC)

The article should say 2006 then as it came from GSK directly -UniWifiTroll — Preceding unsigned comment added by 220.244.41.132 (talk) 04:12, 12 April 2013 (UTC)

Which is more reliable? — Preceding unsigned comment added by 149.135.146.89 (talk) 05:57, 12 April 2013 (UTC)

Is drug company blog primary source? — Preceding unsigned comment added by 149.135.146.111 (talk) 06:05, 12 April 2013 (UTC)
 * Normally, blogs are not reliable sources (never mind whether primary or secondary). However, the situation where a company makes a statement about itself in a company blog meets our exception for using self-published-sources. (The section WP:ABOUTSELF gives five tests). This is also one of the cases where this clearly isn't a biomedical assertion. I would think that we could safely source a statement about when a company ceased research of a drug to that company's blog, as long as it isn't contradicted by a reliable source. We need to be aware that blogs are not necessarily checked for accuracy, though, and we have to be open to the possibility that a company blog might be an inaccurate recollection. --RexxS (talk) 20:28, 12 April 2013 (UTC)

MEDRS
Too much of this article makes medical claims that are unsupported by reliable secondary sources as required by WP:MEDRS. Specifically:
 * "Scientific findings are often touted in the popular press as soon as the original, primary research report is released, and before the scientific community has had an opportunity to analyze the new results. For a short time afterwards, the findings will be so new that they will not be reflected in any review articles or other secondary sources. If the findings involve phase I or phase II clinical trials, small studies, studies that did not directly measure clinically important results, laboratory work with animal models, or isolated cells or tissue, then these findings are probably only indirectly relevant to understanding human health; in these cases, they should be entirely omitted." (my emphasis)

For example, these claims strike me as inappropriate, particularly as expressed in Wikipedia's voice: The article needs to have secondary sources found for any medical claims, and in their absence should be cut back to what is supportable, presumably the warnings from WADA and not much else. It is not acceptable to try to wikilawyer claims into the article because "it's pharmacological, not medical". The effects and mechanisms of pharmacological products are just as subject to the need for reliable secondary sourcing as any other medical claim.
 * "GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone." (in the lead)
 * "... it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization. This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar."

This article needs to be unprotected and fixed as a matter of urgency: we should not be allowing the unsupported information to remain in this article any longer than necessary. The 'nutshell' summary of MEDRS is clear:
 * "Wikipedia's articles, while not intended to provide medical advice, are nonetheless an important and widely used source of health information. Therefore, it is vital that the biomedical information in all types of articles be based on reliable, third-party, published sources and accurately reflect current medical knowledge." --RexxS (talk) 20:46, 31 March 2013 (UTC)


 * I wouldn't disagree with removing those claims. If you haven't seen it already, you might want to look at these articles as well (there are probably 10s of others too). SmartSE (talk) 20:57, 31 March 2013 (UTC)


 * This is a failed drug that is not approved for human use. Hence no medical claims are being made.  This article falls more within the scope of WP:PHARM than WP:MED.  The animal data teach us a lot about the function of PPARδ and hence are appropriate to include in this article.  Of course, relevant high quality secondary sources should be used whenever possible. Boghog (talk) 21:18, 31 March 2013 (UTC)
 * The second quote talks about "patients" but the citation is to an in vitro study. This sentence should be modified. Boghog (talk) 21:27, 31 March 2013 (UTC)


 * I think it's perfectly reasonable to preface mechanistic claims with factual clarifications like "In $animal models of $disease," in which case I think gives a bit more freedom in writing about the topic, so long as it's also made clear that this should not be extrapolated to humans, danger will robinson. -- [ UseTheCommandLine  ~/ talk  ] # _  21:32, 31 March 2013 (UTC)
 * @Boghog: Nobody who thinks "changes the body's metabolism to favor burning fat for energy instead of carbohydrates" is not a medical claim should be editing these sort of articles. Which bit of "it is vital that the biomedical information in all types of articles be based on reliable, third-party, published sources and accurately reflect current medical knowledge" do you think doesn't apply to this article? --RexxS (talk) 23:28, 31 March 2013 (UTC)
 * @ RexxS: Have your read WP:AGF? Your condescending tone implies you have not.  Furthermore you are putting words into my mouth.  As I have already stated above, it is clear that some of the text in the article needs to be modified and better sources are needed.  However I stand by my statement that not all parts of this article fall within the scope of WP:MED. Boghog (talk) 06:01, 1 April 2013 (UTC)
 * @ RexxS: I think this may be a case of both of us talking past each other. I assumed that you were proposing to remove mention of the animal studies.  You may have assumed that I was defending primary sourcing.  I think both assumptions may have been wrong.  My apologizes for any confusion my comments may have caused.  Boghog (talk) 09:28, 1 April 2013 (UTC)


 * @Boghog throughout this piece you claim that others are rude. Perhaps it's in response to your rudeness to begin with

Agreed


 * @ 220.244.41.132: Can you show me a single example on this talk page where I personally was rude? The only instance that came close was this edit, and I think that response was well justified. Boghog (talk) 08:20, 1 April 2013 (UTC)
 * Boghog, please don't descend to ad hominem. Frankly, your opinion of my tone has no relation to the job of improving this article. If you think I'm passionate about ensuring that this encyclopedia maintains the high standards of sourcing that have been agreed in WP:MEDRS, then you're exactly right. Beyond that, you need to concentrate solely on the points I make. Have a look at the Trip Database: http://www.tripdatabase.com/search?criteria=501516 - it finds 51 results for "501516". There are 4 controlled trials, 45 extended primary research, and 0 secondary evidence. That's zero sources that can be used back biomedical assertions (and that's from WP:IRS, not just WP:MEDRS). If the drug has had primary research articles written about it for the last ten years, but not one review has mentioned its alleged effects or mechanism, then it's a red flag that those issues have no standing in current medical opinion. Our article needs all of those claims removing at the first opportunity. There is a story to be told here, so by all means give the narrative about how the drug was developed; how primary research made claims and WADA recognised potential problems; and so on. All of that is supportable. What is not acceptable is making unqualified statements about how the drug might be bioactive or that it might cause weight loss or extend endurance, because those are biomedical assertions without secondary sources to support them. --RexxS (talk) 17:14, 1 April 2013 (UTC)
 * "Nobody who thinks ... should be editing these sort of articles" is not an ad hominem attack?
 * In any case, the issue is not the sourcing. We both agree that medical claims need to be backed secondary sources. The issue is what constitutes a medical claim.  According to WP:MEDRS:
 * Where in vitro and animal-model data are cited on Wikipedia, it should be clear to the reader that the data are pre-clinical, and the article text should avoid stating or implying that the reported findings necessarily hold true in humans. The level of support for a hypothesis should be evident to the reader.
 * I agree that any medical claim concerning effects in humans should be removed from this article. The only exception is possibly the cancer risk since the concern is well founded.  But it should be OK to have a separate animal studies section.  Will you agree to that? Boghog (talk) 18:23, 1 April 2013 (UTC)
 * You say "no medical claims are being made" (21:18, 31 March 2013 (UTC)); I point to "changes the body's metabolism to favor burning fat for energy instead of carbohydrates". Do you stand by your statement? Are you suggesting that editors who don't understand what a medical claim is should be editing medical articles? Am I right to assume you're asking for agreement to having a separate animal studies section based entirely on primary sources? --RexxS (talk) 21:08, 1 April 2013 (UTC)

There's no need to base it off primary sources - there are plenty of secondary ones e.g. these:



I've only skimmed them, but they look like they should be suitable to write a suitable section on the mode of action. SmartSE (talk) 21:59, 1 April 2013 (UTC)
 * Thanks for that research. Assuming that they explain GW-501516's mode of action, they look to be just the sort of quality sources we need.--RexxS (talk) 22:36, 1 April 2013 (UTC)

From an uninvolved perspective, as a request has been posted on WT:PHARM for "more eyes":
 * Explanation of mechanism of action is by no means a "medical claim", and while secondary sources would certainly be preferable, I don't think primary sources should be entirely dismissed if they are identified as such in the body text. In my humble opinion, there is a striking (and unfortunate) amount of misinformation on the letter and spirit of WP:MEDRS going on right now. We should all remember that it is a guideline; that, as per WP:IRS, secondary sources are ideal, not "the only ones acceptable"; and that primary sources are "difficult to use appropriately", not verboten. WP:MEDREV is abundantly clear on this aspect and provides excellent guidance we should strive to follow.
 * That being said, This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar is completely unsupported by the cited source (which does not meet WP:MEDRS in the first place) and should be removed immediately IMHO. Fvasconcellos (t·c) 17:19, 1 April 2013 (UTC)
 * If no one objects, I'd like to remove the whole "Mode of action" section and post a draft here for consensus editing. Fvasconcellos (t·c) 17:34, 1 April 2013 (UTC)


 * I'm unsure how that will work out, given that we have a number of ip editors here who have in the past 24 hours done things like alter others' comments and remove signatures (which I posted at AN/I about). But I'm game. -- [ UseTheCommandLine  ~/ talk  ] # _  17:40, 1 April 2013 (UTC)
 * '... remove the whole "Mode of action" section and post a draft here for consensus editing.' Yes please - and the sooner, the better. --RexxS (talk) 21:08, 1 April 2013 (UTC)
 * @Fvasconcellos, oddly enough, it was WP:MEDREV that was foremost in my mind when I commented here.
 * "If the findings involve phase I or phase II clinical trials, small studies, studies that did not directly measure clinically important results, laboratory work with animal models, or isolated cells or tissue, then these findings are probably only indirectly relevant to understanding human health; in these cases, they should be entirely omitted."
 * "When in doubt, omit mention of the primary study (in accordance with recentism) because determining the weight to give to such a study requires reliable secondary sources (not press releases or newspaper articles based on them)."
 * And it's exactly when we ignore that advice that we end up with the litany of unsupportable medical claims that make up the bulk of this article. --RexxS (talk) 21:27, 1 April 2013 (UTC)
 * Of course, "medical claims" being the operative term. This is a bugbear of mine regarding WP:IRS; it mentions "biomedical assertions" and "medical claims", but merely links them to WP:MEDRS, which does not explain what constitutes a "medical claim". Perhaps it did at some point—I don't remember, as it's been several years since I was involved in its drafting. Clearly "medical claims" are those concerning quality, efficacy, and actual medical use in humans, not "mechanistic" claims as they are called by CommandLine above, but that's a point for the MEDRS talk page, not this one.
 * IMHO there are two passages in the current incarnation that could be construed as unsupportable medical claims when "in the voice of Wikipedia" as noted above:
 * This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar.
 * GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity. (problematic passage in bold)
 * One other passage is sourced to animal studies and, although noted as such, one could make the case for its being misleading as currently presented:
 * GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone.
 * IMHO these should be removed the most urgently. Fvasconcellos (t·c) 22:07, 1 April 2013 (UTC)
 * Are you also happy with:
 * "It activates the same pathways activated through exercise" - sourced to PMC1386117 (monkeys and mice; states: "it remains to be determined whether long-term administration of PPARd drugs will control body weight in monkeys and humans") and a primary study.
 * "GW-501516 regulates fat burning through a number of widespread mechanisms" - sourced to a single primary study from 2003.
 * "GW-501516 also increases muscle mass" - sourced to a single primary from 2004.
 * We can debate all day about whether these constitute medical claims or biomedical assertions or not; but the fact remains that the sources are just not good enough to sustain those unqualified assertions even in the absence of MEDRS. Doesn't the same logic that drives our preference for high-quality, reliable, secondary sources not apply everywhere in Wikipedia? --RexxS (talk) 22:36, 1 April 2013 (UTC)
 * PMC1386117 is a relatively recent review article published in a high-impact factor journal and thus beyond reproach from a MEDRS standpoint. In fact, it could probably be used extensively to source a new "Mode of action" section or an "In [animal] research" section as proposed by Boghog (which, incidentally, would be in line with WP:PHARMMOS).
 * "GW-501516 regulates fat burning..." no, I wasn't happy at all with that, because it grossly misrepresented the source, which says PPARd regulates fat burning, etc. (not GW 501516).
 * "GW-501516 also increases muscle mass"—not the best source, I agree wholeheartedly. Still, not a medical claim, and could simply be presented with the appropriate qualifiers.
 * These are all moot points, of course, as I have removed the section in question. And yes, we can debate what constitutes "medical claims" or "biomedical assertions" until we're blue in the face (or, more appropriately, sore in the fingers) and it probably wouldn't be constructive for the purposes of this article. However, this is something that will have to be addressed eventually if WP:MEDRS is to reach its full potential as a content guideline. The lack of a clear definition of "medical claims or biomedical assertions" is a glaring omission. Besides, as you note, we have a preference for secondary sources (except when making "analytic or evaluative claims" as set forth in the relevant policy). Most of the time, omitting information that cannot be supported by high-quality secondary sources is the best course of action, and not just in medical articles. Sometimes, however, presenting information that is supported by suboptimal sources can be a "net positive" (as the buzzword goes) if it is done with the appropriate care. That's where editorial judgment and discussion come into play, and it is a practice entirely supported by policies and guidelines. Fvasconcellos (t·c) 01:59, 2 April 2013 (UTC)
 * Yes indeed, I'm sorry if I wasn't clear: I'm very happy about the quality of PMC1386117 as a source - but for mice and monkeys, not humans. Having studied it, I'd be more than happy to see Boghog's In [animal] research section based heavily on its findings. --RexxS (talk) 01:05, 3 April 2013 (UTC)

Mode of action
I am loathe to edit a protected article in a way that does not reflect consensus, but it seems that everyone agrees that the "Mode of action" section is unsustainable as is and leaving its current incarnation in the article would be more harmful than nuking it and then rebuilding from more reliable sources, so I have removed it. If anyone thinks it's salvageable, by all means let me know. Fvasconcellos (t·c) 22:17, 1 April 2013 (UTC)
 * Now that the article is again editable, it would be worthwhile considering if we can create a Mode of action section that is verifiable. Can I pose the following questions:
 * Is there a good secondary source that describes GW-501516's mode of action? I mean actually says "GW-501516 works like this ..."
 * If not, is there a good secondary source that unambivalently states that GW-501516 is a PPARδ receptor agonist?
 * If we then tie that in to a good secondary source that states "A PPARδ receptor agonist works like this ...", are we guilty of WP:SYNTH?, or is that so obvious that SYNTH doesn't apply?
 * I think we probably need to be clear on those issues before we can assemble the sources to write a sustainable section. Thoughts? --RexxS (talk) 01:05, 3 April 2013 (UTC)
 * is secondary and unequivocally states that GW-501516 is a PPARδ receptor agonist. In addition,,  (GSK author),   (GSK author), , and  are all secondary and also all state that GW-501516 is a PPARδ agonist. Boghog (talk) 07:19, 12 April 2013 (UTC)
 * Thanks, I was hoping that number 2 (above) would be easy to prove. Are we then all happy that we are not synthesising if we use a source only describing properties of a PPARδ receptor agonist in general as a means of describing a particular GW-501516 property, even if we have no source that explicitly describes that given property of GW-501516? --RexxS (talk) 21:01, 12 April 2013 (UTC)
 * Sorry for not responding sooner to question #3. Some of the review articles cited above discuss the properties of PPARδ agonists in general and GW-501516 in particular. Therefore I think we will be able to expand the "Mode of action" section without resorting to any synthesis based on the available review articles. I don't have access to the full text at the moment, but as soon as I do, I intend to expand this section.  Boghog (talk) 18:28, 13 April 2013 (UTC)

Use as a performance enhancing drug
Should there be a new section as more athletes test positive for the drug? -UniWifiTroll — Preceding unsigned comment added by 220.244.41.132 (talk) 03:48, 12 April 2013 (UTC)


 * There already is a section on Use in doping in sports that covers this topic. It would be appropriate to add more examples if they are supported by reliable sources. However there is a danger that such a list might become very long and start to overwhelm the rest of the article. If this occurs, I suggest that the list be restricted to the most notable examples that have received the widest press coverage. Boghog (talk) 09:25, 12 April 2013 (UTC)

Potentially defamatory comments
Unidentified editors using IP 220.244.41.132 does not represent the views of organisation. IP Admin of 220.244.41.132 has tried removing potentially defamatory comments as per guidelines but is reverted. As indicated to responsible IP editors reverting comments, the editor reverting the comments will bear legal ownership of the statements made.-IP Admin- — Preceding unsigned comment added by 220.244.41.132 (talk) 07:35, 12 April 2013 (UTC)
 * Please read No legal threats, as you may be skirting close to breaching that policy. The bar is set quite high when it comes to removing other users' comments and the allowable circumstances are set out at WP:TPO. It would be helpful if you were to acquaint yourself with them. The IP 220.244.41.132 appears to be assigned to TPG Internet Pty Ltd in Sydney, Australia, and I seriously doubt that any reader of this talk page is going to take the comments as representing the views of that organisation (it's an ISP). So if you merely want to avoid confusion between yourself and other users who may be able to use the same (static) IP, I'd strongly recommend registering an unique username. It only takes a few keystrokes and carries no obligation, although I should add that usernames containing the word "troll" are likely to be looked upon disapprovingly on Wikipedia. --RexxS (talk) 20:50, 12 April 2013 (UTC)

Under Wikipedia guidelines on Editing comments- http://en.wikipedia.org/wiki/Wikipedia:Talk_page_guidelines
 * Dear User RexxS- Please advise the following:

"Editing—or even removing—others' comments is sometimes allowed. Some examples of appropriately editing others' comments":

* "If you have their permission": As the IP Admin, all users that utilise the free internet service accept that the IP Admin has been granted permission to delete any social media comments using this IP address if the user does not identify him or herself. As IP Admin, this organsation chooses to exert this right to remove any comments made using this IP address that have not been self-identified and/or properly attributed.

* "Removing prohibited material such as libel, personal details, or violations of copyright, living persons or banning policies": As the IP Admin, comments that are made in any social media which the IP Admin feels are potentially libel for this organisation; include either implicit (by identifiable content) or explicit details that attributes this organisation as source; violates copyright and moral right material owned by this organisation; and explicit under user agreements and ICT policies of all users of this IP for condition of use, as the IP Admin, this organisation chooses to exert this right under the Forum's guidelines to remove any comments made using this IP address that have not been self-identified and/or properly attributed.

As IP Admin, it is not the intent of this organisation to threaten any editor on this forum. We merely seek to remove content posted under our IP address that we feel do not reflect the position of this organisation. We were alerted to the presence of this forum by a complaint from a member. From our reading of the Forum's policies based on the two cited subsections above, we understand that this is allowed. We do not seek to remove any content not from this IP. We also like to clarify that the user "UniWifiTroll" is NOT this IP Admin.

Please advise if our interpretation of the Forum's policies is different from what has been stated above. - IP Admin - — Preceding unsigned comment added by 220.244.41.132 (talk) 14:19, 14 April 2013 (UTC)


 * There are a couple of problems with this line of reasoning. Per WP:TPO "But you should exercise caution in [removing others' comments], and normally stop if there is any objection."  Several editors have now objected, in part, because deleting comments makes it hard to follow the discussion.  Second, you yourself describe the comments in question as "potentially defamatory".  In my opinion, these comments are not overtly defamatory. Third, you claim to be an IP administrator, but you offer absolutely no proof.  Why should we take your word?   If you still think that these comments should be deleted, the proper course of action is to file a confidential WP:OTRS request providing proof that you are in fact an IP administrator of TPG Internet Pty Ltd and why you believe the statements are defamatory.  If you have a legitimate case, a Wikipedia administrator can discretely perform the deletion. Arguing your case here is not the right way to proceed and could have unintended consequences (see the Streisand effect). Boghog (talk) 14:57, 14 April 2013 (UTC)

Dear BogHog TPG is the internet service provider. Each organisation is provided with a fixed IP. Even if you choose not to accept that this is the IP Admin then even as the "own comments" users, under this forum's guidelines, we are entitled to remove comments from this IP. -IP Admin- — Preceding unsigned comment added by 220.244.41.132 (talk) 15:04, 14 April 2013 (UTC)

Thank you for pointing to the dispute resolution section. We will follow this protocol. We request that the deleted comments remain deleted until such time as when the Wikipedia administrator has made a determination. -IP Admin- −		 −	If BogHog and RexxS are agreeable, this above section can also be deleted as it is off-topic.As per above, once Wikipedia administrator has made a determination, these can be reinstated if necessary.-IP Admin- −		 −		 −	This issue is already been raised with Wikipedia Admin.The complainant will also send an email to info-en-c@wikimedia.org −	on the grounds of: −	"Removing prohibited material such as libel, personal details, or violations of copyright, living persons or banning policies." −	and −	"http://en.wikipedia.org/wiki/Wikipedia:Copyright_violations"

>>See comments and legal issues to Wikipedia Admin before reverting.-IP Admin- >>Wikipedia Admin has also stated that deleting "own" comments [from this IP] is acceptable until further review and clarification -IPAdmin- SmartSe: See clarification and response elsewhere -IP Admin_ — Preceding unsigned comment added by 220.244.41.132 (talk) 17:43, 14 April 2013 (UTC)

Speculation on identities
Can I remind everyone, politely, of the policy on outing and BLP. Namely, speculating on who anonymous editors might be is inappropriate, especially without firm proof: this is because if you associate inflammatory comments with an individuals name it is then public. Please continue your discussions without further speculation. --Errant (chat!) 11:26, 15 April 2013 (UTC)
 * Thanks for the reminder. Unfortunately, when an anonymous editor claims to be the representative of an unnamed company in order to assert a right to remove other users' contributions, they must expect that claim to come under scrutiny. I have suggested that the editor register an account, which would no longer expose his IP address, and I have requested him to email OTRS so that his concerns can be dealt with privately - see User talk:220.244.41.132. Nevertheless, it is unacceptable for anyone to disrupt the normal use of this page in the way that the editor has done. If you happen to be dealing with the OTRS request, then hopefully we can either find a way of meeting legitimate concerns or dismiss the claims as groundless. In either case, the editors of this article will need to know that a resolution has occurred in order to inform future interactions. Cheers --RexxS (talk) 17:39, 15 April 2013 (UTC)