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Pharmacology NA‑class

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generic name

Is using the generic name for a drug as the title of the article perhaps a standard and universally followed WP convention? If so, then this article is properly titled, though I'm trying to figure out how to make the generally known name a little more prominent in the first sentence) . If it's not the universal or almost universal convention, I'm going to argue the point. I did change the cryptic section heading "PML" DGG 23:06, 4 October 2006 (UTC)

Yes, it is – see Naming of drug pages. Anyway, Tysabri redirects here, so anyone typing "Tysabri" in the search box will be brough to this article. Fvasconcellos 15:55, 5 October 2006 (UTC)

Title should be the generic name -- Samir धर्म 02:21, 6 October 2006 (UTC)

The drug is not generic, and so does not have a generic name, and will not for many years to come. Tysabri is the brand name. —Preceding unsigned comment added by Io io editor (talk • contribs) 21:48, 20 January 2008 (UTC)

All drugs have a generic name, whether or not they are currently available as generics. —Preceding unsigned comment added by 63.125.124.226 (talk) 15:18, 22 January 2008 (UTC)

Jo!

Is this notable for the Tysabri topic?

http://mugglenet.com/app/news/show/689

Subsequently, and following an outcry from MS organisations and personalities such as Ms Rowling, in both England and Scotland the Governments decided to reimburse Tysabri in cases of "highly-active" RRMS. At the start of 2008, the funding was becoming available.io-io (talk) 00:44, 21 January 2008 (UTC)

Why is there such an odd balance in this article?

Anyone have an idea why the pharmacology of this drug gets so little emphasis, while a rare brain disease and return to market get such big play in the article? Dr. Holland, Kd4ttc 15:03, 24 July 2007 (UTC)

I'm a writer, not an MD, so I can't improve it much further. Hopefully some medical/pharmaceutical editor will flesh out the pharmacology. --CliffC 01:22, 26 July 2007 (UTC)

That's because news of the successful phase III trials don't make headlines, while case reports of something horrible tend to tickle the public imagination ("Frankenstein drugs"). JFW | T@lk 18:43, 2 December 2007 (UTC)

I have added mechanism-of-action text directly from the FDA labelio-io (talk) 00:45, 21 January 2008 (UTC)

HRQOL in Crohn's

Initial improvement in health-related quality of life (measured by SF-36) is sustained when the drug is continued for a total duration of 48 weeks: doi:10.1111/j.1572-0241.2007.01508.x JFW | T@lk 18:43, 2 December 2007 (UTC)

Removal of 3 whole Sections

Someone has removed whole sections, titled "Summary of Clinical Trial Results in MS" and "Summary of Clinical Trial Results in Crohns" - presumably this is VANDALISM in order to focus on the Drug's infamous HISTORY - which is f_ing irrelveant to MS Patients ?io-io (talk) 01:25, 2 March 2008 (UTC)

Have a look at WP:SOAP - we are here to report, not condemn or praise. I did re-write several sections a couple weeks ago, the 'brief summary' sections were far from brief, and contained information better kept in other sections. Relevant, sourced information has been kept and moved around, and the lengthy quotes removed as articles are expected to be written in a summary style which does not involve extensive quotations. WLU (talk) 20:30, 2 March 2008 (UTC)

If you look closely at the discussion page, you will see that above where a year ago, a certain Dr. Holland lamented: ......... "Why is there such an odd balance in this article?"........."Anyone have an idea why the pharmacology of this drug gets so little emphasis, while a rare brain disease and return to market get such big play in the article?" This led to my revisions, and to the revisions of others.

Well I certainly had no "Praise" nor "Condemnation" quoted, nor any Soap-Box material - maybe in some section (because then as now, the History paragraphs are inappropriate), someone else had. But you also removed a quotation that I had taken from the FDA-approved MS label (a public document, not copy-righted), which directly addressed Pharmacology which the good doctor sought - if you wanted to remove that, why didn't you at least keep shorter quotations, or paraphrase it, instead of entirely removing it ?

The result is that the page is now more or less back to where it was last July when the doctor regretted the distorted content - the page is now 50% devoted to its History, and reads more like a Media story.

Also, to answer my original question, please explain why you removed the sections titled "Summary of Clinical Trial Results in MS" and "Summary of Clinical Trial Results in Crohns" - these were in no way "Praise" nor "Condemnation" nor Quotations nor Soap-Box material but FACTS. You say that this material was "far from brief, and contained information better kept in other sections" - what other sections did you have in mind ? And what could be more relevant here ? These sections should be restored.

I also think it reasonable for you to explain why, in your edit descriptions, you appeared to have attempted to cover your tracks - as these descriptions (referrring to your removal of SPAM and failing to mention the removal of at least 3 whole Sections) in no way reflect what you were really doing.io-io (talk) 23:21, 2 March 2008 (UTC)

Have you seen the indications sections on the extant page? If you think the history section is over-long, you can certainly shorten it. Unfortunately that is where much of the information was placed for lack of a better location and I'm not certain it is the best portrayal. If you have expertise and can cite reliable sources to verify claims, then feel free to trim, expand or cite information. I had brought the page to the attention of two admins, TimVickers and Jfdwolff, a biochemist and doctor respectively, and they did not see fit to alter or revert my changes. But feel free to edit the page. One thing to note would be medical manual of style section on drugs. One of my larger edits was to re-work the page to conform with the style guidelines there. Substantial revisions to pages that are relatively new or underdeveloped are pretty normal, but regards the change in headings and locations, this should be relatively fixed. Contents, of course, are still fair game. Note that WP:MEDRS are also a guideline to keep in mind - best sources are peer-reviewed journals. I don't know bow comfortable I would be adding large amounts of information on efficacy, benefits, etc. direct from the company's page, I'd stick to pubmed journals were it I. WLU (talk) 23:31, 2 March 2008 (UTC)

I have certainly seen the Indications section. These clinical trial results were most interesting as there are avalable established if inferior to at best equally effective medicines available in both indications, and in particularily in MS the results are considered astonishing. You have not answered my question as to where the "information better kept in other sections" was intended to be placed. You ask me if I have expertise and can cite reliable sources to verify claims - yet I used multiple medical citations and I dont believe I made any "claims" ? And why not use your expertise (I assume you have some, to touch the page) to at least paraphrase the FDA citation, instead of the wholesale deletion ? In doing so you simply ignore the prior Discussion on this page. Also, this was not the "company information" which you ascribe my writing to - the FDA label is a public government source, the actual medical label.io-io (talk) 00:04, 3 March 2008 (UTC)

The major problem with the old version of this article was the long quotations, which are not a good way of referring to source material. Have a look at the articles on Anabolic steroid or Paracetamol to see the kind of format this article needs to aim for. Tim Vickers (talk) 00:18, 3 March 2008 (UTC)

The "long quotations" cited by WLU is a Red Herring. The removed whole sections, titled "Summary of Clinical Trial Results in MS" and "Summary of Clinical Trial Results in Crohns" had ZERO quotations. They did have medical citations however.

The Clinical Trial Results are also what has distinguished Natalizumab, nothing else, and "formatting needs" while important, should come in second to content. Such needs do not imply that whole sections of relevant material should be deleted. I repeat, these sections should be restored.

And these deletions were without no notice to the recent author(s), no advance entry on the Discussion page, and with completely inaccurate descriptions of the Edits in the Edit History. "SPAM" indeed......io-io (talk) 00:48, 3 March 2008 (UTC)

IO, please assume good faith. I have over 18 months on the project and nearly 20K worth of edits - I'm here to help wikipedia, not to piss you off. If I have removed references, then feel free to replace them in the appropriate section in a summary style. The page needed to be significantly re-worked. Which I did. You are a new editor, with only 86 edits at this point - assume that you are not familiar with the manual of style and the myriad other policies and guidelines which determine what wikipedia will look like to readers and how editors edit. By my reading of the page, I may have removed two reference to the Elan webpage, justifying the items "Natalizumab treatment significantly increases the proportion of disease-free patients with multiple sclerosis" and "As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurrence". I would say these statements are quite strong ones to be justified by the company's website, they seem to push the idea that N is a safe drug (tenuous, better stated by a peer-reviewed journal) and generally don't add much good information to the page. Regards the rest of the references in those two sections, I kept them, and in one case made it much better through a citation template with a pubmed number allowing access to the abstract. As for long quotations, consider here (five sentences of quotations, easily summarized) and here (two full paragraphs). Those are long quotations I rewrote as prose.

Please discuss contributions, not contributors, and if you really think I have a specific agenda, feel free to bring it up at WP:AN/I to see what the community's administrators think. WLU (talk) 11:42, 3 March 2008 (UTC)

WLU, you say that I discuss a contributor, but where? I have a lot to say, but think have you any idea how long it took to put all my work together, with all the research needed for those citations? When I first asked you, in good faith, if you had made these deletions, your very first response (see above) was to "Have a look at WP:SOAP" and to caution me about “praise”. AND - you refer me to Wiki's “myriad other policies”. But such policies include 1) Airing concerns on Discussion pages; 2) Reading the Discussions page to see prior concerns; 3) Glancing at the Edit History before deletions to reveal who has done what, and how recently; 4) Showing respect for the Wiki contributions and the opinions of others; 5) Accurately describing edits.

When you say that you “may have removed references to the Elan webpage”, those references are news releases from not 1 but 2 companies (Biogen also) - but more importantly describe brand new Presentations to major MS conferences (e.g. read the one you listed above, it was presented on “October 13, 2007 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic”). Such demonstrations will not be available in medical journals for perhaps a year or more, but are highly relevant TODAY because MS patients (and who else is this page for?) NOW have to ascertain the drug’s benefits amidst all the media “noise”, and it is time-critical for these patients.

As to the statement by both Elan and Biogen-Idec that 21,000+ patients are on drug without PML – how can they possibly lie ? There is a FDA-mandated registry of patients, there can be no lie. Furthermore, it is contemporary, and MS patients need to know - plus how could it possibly appear in any medical journal ? - only the first new case of PML case will ! ....As to the quoted FDA mechanism of action that you “summarized”, well you summarized so much as to eliminate the real content, and contrary to Dr. Holland’s prior lament on this page. I read Wiki policy on quotations, and it made an exception for public policy documents. If you really wanted to summarize material, then why did you create the enormous History section, over 50% of the page, and which leads off like a media piece on the PML scare ?

In the history of modern medicine, are you aware that there has only been one drug ever withdrawn and successfully returned to general availability? That drug is N. If you google for it, you will immediately see the PML shadow everywhere, a soap-opera darling of the media. An example – quotations (not placed by me) defining the FDA’s recommendations clarifying that N is actually NOT limited to 2nd-line use (following interferons, etc) – have been deleted. This was in fact highly relevant, as very few MS patients and even some doctors are not aware of it......In summary, instead of being informative to MS Patients and even to MS Doctors, this Wiki page has degenerated to something not much better than a media soap. The reader is immediately directed to the Drug’s History, due to it’s vast size, as if relevant - and all at the expense of useful contemporary information.....io-io (talk) 14:36, 4 March 2008 (UTC)

(redacted) Edit the page then, and forward future complaints to Wolff who is far better qualified to judge their merit. You do not need my approval to change the page so feel free to do so. WLU (talk) 15:18, 4 March 2008 (UTC)

WLU, please WP:CIVIL. I have explained to this editor on my talkpage that some of the content may be suitable for reinsertion but integrated with the present outline and with an emphasis on secondary sources and professional guidelines.

In the USA, it is now approvied for Crohn's - doi:10.1172/JCI35179 JFW | T@lk 15:20, 4 March 2008 (UTC)

The approval for Crohn's is on N's FDA label, previously cited.io-io (talk) 03:29, 5 March 2008 (UTC)

These were the changes I made. Tim Vickers (talk) 01:12, 5 March 2008 (UTC)

Because Dr. Holland had earlier asked for more pharmacology, I had introduced the long quotes from the FDA label, as obviously this is an unimpeachable source. I would propose to restore those quotes, and perhaps someone with specialized skills will properly summarize them. Good/Bad ?io-io (talk) 03:29, 5 March 2008 (UTC)

That depends on the quotes. If it's this set, I see no need as it's already summarized in the MS section, references 3, 4, 5 and 6. Two sentences I did remove I discuss above - in my mind they look like apologetic from the drug company, add little to the page beyond the promotion of the drug, and are better sourced to journals than a company web page. That being said, if other editors have no problem with it, I am willing to be over-ruled. If it's this section, the first reference is used again in the current pharmacokinetics section (possibly not the right place, I believe I put it there and if so, I did so because I wasn't sure where to put it). The second, much longer quotation appears to have been removed wholesale, but it could definitely be replaced (the reference is used again in history as reference 18). I see no need to replace the quotations, but the information contained does look valuable, but far above my ability to understand and summarize. Perhaps Io, Tim or Wolff could do so but I think me doing it significantly risks misrepresentation or errors. The sole remaining quotes are for reference 18 in the old page, now reference 8, and though it could be expanded with more detail, I don't see a reason to quote. Reference 23 old is now 18, and again I don't see a reason to quote as the summary covers the same information. I agree that the information should be restored, but as a summary rather than a quote. I may have a crack at it anyway, but I could miss out on significant details. WLU (talk) 18:53, 5 March 2008 (UTC)

Done. Someone (or several someones) please, please, please PLEASE review for accuracy! WLU (talk) 19:56, 5 March 2008 (UTC)

It is an improvement, and your summaries of the pharmacokinetics look very good. These are in fact the quotes I was referring to, along the lines the Dr. had asked. But I ask this philosophical question: this is "only" Misplaced Pages, and should we not realize that quotes taken directly from unimpeachable and authoritive sources carry more weight to those who need to know than para-phrases by mere mortals ? This is not one of the same situations which the Wiki policy on quotes was meant to address, and is particularily true here because of the media mill-stone the drug carries, and patients are looking for clarity, and fear obfuscation. For example, there is a black box label, the very existence of which which will tend to confirm the well-known fears, but when its text is actually read, it is far milder in it's content.

As to the this set, I disagree, as I explained earlier here, these are news releases that refer to posters/presentations made to the top specialized medical conferences. I do not see providing such useful information to curious patients as adding "little to the page beyond the promotion of the drug". Instead, go to the very top of the Wiki page, very first paragraph, describing how the drug has been, when used with another durg, "linked" to a rare disease - is that useful or even relevant, given that the program prevents use with any such drug? Also the words "appeared to" should not be used when it is clear that in the abstract/release that the p-values were convincing on secondary endpoints, given that primary endpoints were met. Instead "demonstrated" or similar is appropriate....I will look further at other edits later this week.....io-io (talk) 02:31, 6 March 2008 (UTC)

1) WP:SS

2) I see it as promotion and adding little of merit to the page. Ask other contributors what they think. The info in the lead about PML is definitely prominent enough to remain in my mind. The page is not a how to manual, it's meant to be an encyclopedia, so conveying notable information. Lots of reporting in peer reviewed journals means notable. WLU (talk) 12:54, 6 March 2008 (UTC)

As to WP:SS - I believe that content supercedes style, and I think that my philosphical question is a very good one, as an encylopedia should inform its likely readership. I did think your paraphrases were also very good, but I ask which is this the best approach....I would welcome independent answers to the question.

Also, by the same standard, the things you call promotion are, as I said, presentations to medical conferences on the pivotal trial secondary or tertiary endpoints. What is particularly relevant to RRMS patients is that after going on an Interferon or Copaxone they have no idea while they wait-and-see for 6 to 24 months whether their drug is helping them at all, while their QoL will quickly decline - due the very act of self-injections (up to daily), the almost ubiquitous side-effects of interferons, the inevitable steroids for flares, optical neuritus, etc. No MS therapy has succeeded in these sypmtomatic benefits the way that N has. I suggest a search on YouTube might be revealing.

I dont know about "Lots of reporting in peer reviewed journals" - if so, it was about the same tiny number of cases. You are applying Wiki standards selectively here. May I direct you to - http://en.wikipedia.org/List_of_bestselling_drugs - can you show me just ONE drug treating a serious progressive disease for which the Wiki, in its introductory words, has your standard of profiling potentially fatal AEs? Or choose from the PML page - http://en.wikipedia.org/Progressive_multifocal_leukoencephalopathy, which you yourself have editted to actually duplicate N's listing as a cause, and reveal application of the same standard? Based on this and your other edits, I really have to suggest that your thinking is conflicted as to this Wiki page, and I think achieving a balanced informative page is a long way off while this persists.io-io (talk) 00:52, 7 March 2008 (UTC)

I think I'm going to give my opinion. First of all I do think that wikipedia is an encyclopedia for any reader, and it should be writted according to it. In any encylopedia some entries would be visited more often by those interesested in it, such as people with the disease, however this page can also be visited by medical students, friends, other health workers, or simply a fourteen year old boy who has been asked to do a school project in MS, so information should be directed to the general reader as stated in WP:MOS. Secondly I do think that conferences refs are of course of less quality than peer-reviewed jounals, and the latter should be always preferred if possible, as in any peer-review jounal. However there are times where there are not yet any peer-review jounal and official conferences or workshops are the best reference possible at that time. In most peer-review articles you can find one or two refs of this kind. Finally regardig PML I agree that is important, but not as important as to center the main discussion of the lead. Its an important (even deathly) secondary effect, but an intoxication with most medical-drugs can also be if indications are not followed and its rarely given any importance. It clearly should be discussed in the article but at most it should only be mentioned in the lead when it is a clear summary of the whole article so it does not receive an excesive weight. --Garrondo (talk) 08:14, 7 March 2008 (UTC)

In reponse : 1) I would think that everyone down to the school students would be more interested in what N can do for MS itself. 2) As to the relevance of PML, the FDA's Black Box label states: "Although the cases of PML were limited to patients with recent or concomitant exposure to immunomodulators or immunosuppressants, there were too few cases to rule out the possibility that PML may occur with TYSABRI monotherapy" - hardly an indictment to merit mention in the opening words of either the History section or the Wiki Page itself. 3) As to "excessive weight" I submit that, in the Page, the words -

• "progressive multifocal leukoencephalopathy" are spelt out 3 times;
• "PML" is spelled out independently an additional 8 times

-while in terms of what N does for MS, in the entire Page, the words -

• "lesions" is mentioned Once (and only in the M-o-A section).
• "relapses" is mentioned Twice
• "disability" is mentioned Once

I ask - is this not gross imbalance? Shouldn't it be reversed???....io-io (talk) 22:46, 7 March 2008 (UTC)

Balance

Regarding the complaint that the present article overemphasizes the PML problems at the expense of reporting the clinical benefits of the drug against MS, I do have one suggestion. The paragraph at Natalizumab#Multiple_sclerosis is extremely short. It would not be out of line to explain for general readers what would be the impact of Natalizumab on MS treatment if the clinical results hold up. Even our longer account over at Multiple_sclerosis#Disease_modifying_treatments gives me the impression that Natalizumab and the similar drugs are disappointing and may not be worth the expense or trouble. Is this a reasonable conclusion?

I hope this doesn't re-ignite a general debate, I was just looking for a vague two- or three-sentence bottom line, one that is independent of the genuine uncertainties as to whether the benefits and side-effects are well-enough studied yet. All that I can tell from Natalizumab#Multiple sclerosis is that some measure is cut by 68% and some other measure is reduced by 50%. Is this significant? And I support the others above who prefer that this kind of conclusion not be drawn from drug company material. EdJohnston (talk) 23:51, 7 March 2008 (UTC)

In terms of clinical benefit, you are essentially echoing what I have been protesting here. Attempts to say more have been termed "promotional of the drug". The benefits are indeed well-studied, as the sum of clinical trials leading up to approval 2 years ago were in excess of 3,000 MS patients, easily the largest ever.

The reference to "drug company material" is actually a couple of news releases that report on posters and/or oral presentations at medical conferences of the pivotal trials' secondary and tertiary endpoints, and if you scroll up, you will see why these achievements are unique to N and relevant to MS patients.

Finally, to get back to clinical benefit, here are two opportunities - on the Talk page - http://en.wikipedia.org/Talk:Treatment_of_multiple_sclerosis#Relative_effectiveness - there is collaboration ongoing for a DMD relative efficacy table in MS; ....while in the Treatement of Crohn's page - http://en.wikipedia.org/Treatment_of_Crohn%27s_disease - Natalizumab is erroneously only mentioned under the "Medications in Research" section, and where its future seems in doubt due to the PML cloud (in fact it is now approved it for Crohns).....io-io (talk) 00:36, 8 March 2008 (UTC)

Isn't there some medical review article that might give perspective? Even if it were just an editorial in a medical journal, written by a practitioner, it might help. I took a look at the proposed table you mentioned, but didn't find it terribly convincing. The current summary paragraph over at Treatment of multiple sclerosis may be the best we can reasonably do:

All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, although they differ in their efficacy rate and studies of their long-term effects are still lacking. The percentage of non-responsive patients to each medication also varies; being around 30% with interferons. Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab. Mitoxantrone is probably the most effective of them all in the short term; however, its use is limited by severe cardiotoxicity, and it is not considered as a long-term therapy. This is the reason why it is mainly used to treat patients who have advanced relapsing-remitting or secondary progressive multiple sclerosis.

Unless we can find a medical review that has a nice two- to five-sentence summary of the clinical benefit, perhaps we need to stick with what we have now. EdJohnston (talk) 04:38, 9 March 2008 (UTC)

It is a complex area. It is complicated by the fact that within RRMS many patients have near-benign disease, whereas others progress very quickly. The older drugs did pass their trials, and do have milder benefits (relative to N - but even this is not definitively proven, as the PML issue abruptly terminated head-to-head trials), but in the summation of all RRMS trials, neither the Interferons ( http://www.ncbi.nlm.nih.gov/pubmed/12598138?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1 ) nor Copaxone ( http://www.ncbi.nlm.nih.gov/pubmed/14974077?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1 ) - look much good. Still, it is easier to look backwards at older drugs, as more is known about both efficacy and safety. For N, in terms of safety, probably for some doctors the jury is still out until 12 months from now. So that summary of benefits (and risk-reward) is not written yet. Doctors and patients simply need to know the real (as opposed to the celebrated) Risks and the real Rewards as best the data can tell. One indicator is that the FDA and EMEA still allow placebo-controlled trials in MS (unlike other very serious diseases, it is not considered unethical to give patients no DMD at all for 2 full years). That proposed table you mentioned is improving with the contributions of others, and I have found more data for insertion soon. Perhaps you can comment over there on what else could be done, before its insertion....io-io (talk) 05:15, 9 March 2008 (UTC)

Liver toxicity

In the tysabri pamphlet, the issue of liver toxicity is raised on page 7, section 5.5. It includes the words "In some patients, liver injury recurred upon rechallenge, providing evidence that TYSABRI caused the injury." Given that, I think the statement about liver injury occurring with placebo patients is not the best way to deal with liver toxicity. I also don't like the line "Furthermore, the rates of liver issues are higher in the interferon drugs, such as Avonex and Rebif, and have led to liver failure and transplantation." as it looks to me like it is saying 'natalizumab isn't as bad and should be used because the alternatives are worse.' The Tysabri pamphlet doesn't mention Avonex in combination with liver issues, or Rebif at all, making this WP:SYNTHy to me. The Primetherapeutics page doesn't discuss natalizumab at all, and in my opinion it is original research to make any judgment or comparison, explicitly or implicitly, between the three drugs without a reference. I've edited accordingly. WLU (talk) 00:22, 10 March 2008 (UTC)

I think your statement that "The removal, then reinstatement of natalizumab resulted in the disappearance, then reappearance of liver injury...." is one that will nver be understood. As to your references to WP:SYNTH and/or "comparison, explicitly or implicitly, between the three drugs without a reference", etc - well then -

(1) The The Primetherapeutics page - of course it doesn't discuss natalizumab at all because it specifically addresses very serious Liver damage requiring transplantions in both Avonex & Rebif, something that has never happend to natalizumab, even now, 3 years later

(2) Here is such a reference - on the top of page 8 of http://www.fda.gov/cder/foi/label/2003/ifnbser050203LB.pdf - you can read that in just 48 weeks hepatic function disorders occurred in 18% Rebif and 10% of Avonex patients. On the other hand, I had referred to the natalizumab label describing 5% vs 4% for the same issue - and occurring over a much longer period of 120 weeks.

(3) It is also well-known in the MS community that failure to interferons due to Liver toxicity is epidemic. I am not bothered to find a source....io-io (talk) 01:26, 10 March 2008 (UTC)

I've reworded to avoid a direct quote, but I believe the reword captures the original intent. WLU (talk) 12:00, 11 March 2008 (UTC)

I note that you are quite willing to use a direct quote when it aligns with your "original intent". The fact is that your treatement of this issue leaves a whole section whose size is out of all proportion to it's medical relevance, as I have explained above - the entire issue could be dropped to a foot-note....io-io (talk) 00:39, 12 March 2008 (UTC)

addendum - here is Wiki precedent, as it has been proven to you above it is far more common in interferons, and you can see in http://en.wikipedia.org/Interferon_beta-1a how it is handled....io-io (talk) 00:47, 12 March 2008 (UTC)

Refs 5 and 6

References 5 and 6 on the current page ( New Data on Natalizumab Demonstrate Significant Improvement in Cognitive Function in Patients With Multiple Sclerosis. Doctor's Guide and New Pharmacoeconomic Data On TYSABRI® Demonstrate Significant Reduction In Steroid Use And Hospitalizations In Patients With Multiple Sclerosis) are sourced to news services. I've looked a bit on pubmed but found nothing published in medically reliable sources that says the same thing, does anyone have citations for these statements? They justify the statements "maintained cognitive function, reduced the use of steroids and hospitalization"; the other statements in the paragraph I tracked down pubmed journals for, but these ones I'm either not looking in the right spot or haven't been reported yet. WLU (talk) 01:01, 10 March 2008 (UTC)

I note you are asking these questions, but also you seem to have already shortened the section, summarily removing the Oct'07 Report to ECTRIMS that N "significantly increases the proportion of disease-free patients with MS". However, this Discussion has received input from others, including Garrondo who has contributed hugely to the Treatment of multiple sclerosis page, recently honored as a Wiki feature, and he has described the fact that sometimes you cannot find a better source. We will have to see if can find better citations for you, so that these secondary clinical trial results in MS symptoms can reach a wider audience, but you have to repect the Discussion. And please don't label a news release as "drug company material" when it clearly describes a poster or presentation at a leading Neurology conference....io-io (talk) 01:59, 10 March 2008 (UTC)

I have found and inserted an additional 4 abstract citations from the AAN (American Association of Neorolgy) annual meeting. On this basis I have restored at least 1 of the proven benfits that you had unilaterally deleted. Also, as no-one has contradicted my previous position stated above that this Wiki Page needs to have some balance restored, I have added bold-face paragraph headings in order to direct the reader to these proven claims of what N definitively prevents and achieves...io-io (talk) 02:53, 10 March 2008 (UTC)

Bold claims are addressed below - balance should be found by expanding sections, not SHOUTING at the reader. WP:MOSBOLD has more information. The lead could also be expanded to place more emphasis on benefits - I have done so, but only for a limited number of improvements (basically the ones I remember, but probably the most significant; though the lead should not enumerate every single benefit the most significant should be there). IO, please note that I am trying to do what I think is best for wikipedia, based on my experience on the project. I am not trying to smear or worsen the name of natalizumab. Please assume good faith that I am doing the best I can. I understand parity of sources; lacking a pubmed journal a conference presentation or publication from the drug's producer is adequate. But if such a journal is available, it is a superior source that I would prefer to cite, per WP:MEDRS. WLU (talk) 11:58, 11 March 2008 (UTC)

OK, I will assume good faith. I would point you to the WP:PILLARS and where it says that "Perfection is not required". Also WP:LOP states: "Every policy, guideline or any other rule may be ignored if it hinders improving Misplaced Pages." Take for example Bupropion, note how it's page departs rigid formatting into various conditions (perceived/symptomatic, and not diseases per se), some for which it is not approved. Also, the issue of how to present these trial results has been "Talked" for a week now, and two other informal WP:3O have come down on the side of more information about what N does, than what was presented hereto.....(separate issue: I believe now that, out of the 7 or 8 medical presentations, only 1 is uniquely sourced from a company news release)....io-io (talk) 00:20, 12 March 2008 (UTC)

addendum - earlier, I had proposed bullet-points below...would do later...io-io (talk) 00:23, 12 March 2008 (UTC)

Manual of style (further comments from WLU)

Acknowledging comments just received from WLU on my Talk page, and I believe the appropriate place for them is here as the Discussion is daily ongoing:

" Please review MOS:CAPS (in particular Misplaced Pages:Manual_of_Style_(capital_letters)#Section_headings) and WP:HEAD for restrictions and formatting of capital letters and section headings on wikipedia "

I will review and address later ....input welcome of course from others on all topics....io-io (talk) 23:41, 10 March 2008 (UTC)

Addressed the issue of capital letters in the sub-section headings...io-io (talk) 00:34, 11 March 2008 (UTC)

Per WP:ITALICS and WP:MOSBOLD, I've removed the use of italics and bold where not necessary. I've also collapsed the number of subheadings in the MS section to a single sentence listing the effects of N on MS patients (per WP:UNDUE, giving each its own section places excessive emphasis on each finding when there's no real need to have a sub-section for every single effect), re-wrote to avoid quotation, re-added the information on antibodies (as it's referenced in a peer-reviewed journal and a valid inclusion on the page), added the mechanism of action and the mention of its withdrawal and re-approval to the lead per WP:LEAD. The lead should summarize the main information in the body text below proportionate to the coverage in the body, and I think I've captured the sub-headings and contents appropriately. Please note that citation templates are used extensively in the referencing; {{cite web}} should be used when it is a web-based link only, there are also {{cite journal}} when published in a peer-reviewed journal and {{cite conference}} for conferences. I am not against information that supports the effectiveness of natalizumab, but the page should be encyclopedic - all information that can be included, should be included. Give me references about N being good or bad, I'll add both. Most of these changes are to standardize the page against other wikipages and primarily against the manual of style. Given this is a publicly editable encyclopedia, the only touchstones we have for uniform formatting are the MOS, policies and guidelines and that is what I try to edit by. Please let me know if I have made any errors per these guidelines. WLU (talk) 11:48, 11 March 2008 (UTC)

Others in the Discussion have pleaded that above all else, what the drug actually does, should be clear. That has been the problem. I have no time now, but propose bullet-points....io-io (talk) 18:53, 11 March 2008 (UTC)

What do you believe is missing? I have edited the lead twice (MS and CD) to show the benefits to those diseases, given a reference or specific suggestion, I could add more. WLU (talk) 18:56, 11 March 2008 (UTC)

What is missing is the clarity - these are the results that distinguish it in MS; these are what patients (and doctors, even from a technical sense, because symptom improvement is a reasonably reliably surrogate that the drug is working clinically) need to see, above all else, on the Page - this would be a Wiki improvement as I described in talk-section above, and that is why I propose bullet-points...io-io (talk) 00:27, 12 March 2008 (UTC)

Unpresented conference

The current reference 4, , is to a conference poster that has not yet happened (note the date is for April 15th, 2008). Is this normal? Is this kosher? I understand that research is done months in advance of publication and I've always been confused by the {{cite conference}} template and would love some informed opinions on this. WLU (talk) 15:50, 11 March 2008 (UTC)

"Is this normal? Is this kosher? " - Its normal that abstracts get published based in advance upon the paper. The asbtract is a fact now, the presentation is a scheduled fact, and nothing else is really relevant...io-io (talk) 18:56, 11 March 2008 (UTC)

Continued objection to arbitrary and selective "standards"

WLU has again added, in the introductory words, a slice of history about N's link with "death", despite that:

• Its just a putative link (as confirmed by the FDA Black Box wording)
• The fact that N is used in treatement conditions different to the fatal circumstances
• There is a separate sections on Page dealing with Adverse Events
• There is a separate sections on Page dealing with ContraIndications
• There is a separate sections on Page dealing with History

This is what I wrote previously, unanswered: "You are applying Wiki standards selectively here. May I direct you to - http://en.wikipedia.org/List_of_bestselling_drugs - can you show me just ONE drug treating a serious progressive disease for which the Wiki, in its introductory words, has your standard of profiling potentially fatal AEs?" For example, look at http://en.wikipedia.org/Trastuzumab, it is very hard even to spot the safety concern ANYWHERE on the page. "Or choose from the PML page - http://en.wikipedia.org/Progressive_multifocal_leukoencephalopathy, which you yourself have editted to actually duplicate N's listing as a cause, and reveal application of the same standard?" For example, look at http://en.wikipedia.org/Infliximab, which has a long list of safety concerns, many deadly, and none appear in the introduction.

Several months ago a doctor here decried the "Odd Imbalance" on this page. When will it achieve balance ? ........io-io (talk) 01:04, 12 March 2008 (UTC)

If the fatalities in infliximab were responsible for the drug being withdrawn, then replaced on the market, perhaps it should be in the lead. I will look into it tomorrow.

Why was natalizumab withdrawn from the market? Was it because of the association with death? Am I mis-representing the reason for withdrawal?

Please comment on edits, not the editor. WLU (talk) 01:15, 12 March 2008 (UTC)

I made ZERO comments about the editor above.

I did not say you were "mis-representing the reason for withdrawal", but I say you are consistently descerating the page by repeating safety issues in FOUR (4) different sections (introductory words, interactions, contraindications, and history) - all without precedent on Wiki - while at the same time minimizing the perception that this is a medical advance by subordinating the proven benfits to a difficult-to-read paragraph - and despite the WP:3O's offered on this Talk page...io-io (talk) 01:53, 12 March 2008 (UTC)

Note the title: Continued objection to WLU's arbitrary and selective "standards"

And the first line: WLU has again...

Compare with: "I believe the emphasis placed on PML-related deaths on the page is excessive." Or, instead of blaming everything on me, edit the page and suggest alternatives. The information should appear in the lead. The lead summarizes all information of note in the page below. Death or fatalities are mentioned as follows: in the lead (appropriate given the use below); in contraindications as a sequelae of poor liver function; in interactions in conjunction with PML; twice in history - once to say it was linked with PML, once to say no deaths have occurred when used as monotherapy. Which do you feel is inappropriate or excessive? WLU (talk) 10:27, 12 March 2008 (UTC)

Of course the fact that is you who is doing this is relevant, because you have been writing, reading, and ignoring on this Talk page for 10 days now.

I had already editted the page, in January and last weekend, but you have essentially reverted both edits.

It takes you 5 lines on this Talk page even to LIST where your you have added the fatality tags. I gave you links for comparable drugs - these prove your focus is "inappropriate" and "excessive", and yet these are the Wiki standards/precedents that apply here.......io-io (talk) 13:54, 12 March 2008 (UTC)

I'm generally not finding the talk page particularly useful. For instance, I don't really have much to say in response to your above comments as you seem to be complaining about me, rather than the page itself. In cases where I found value in your comments, I have edited accordingly. You thought insufficient weight was placed on the benefits of natalizumab to MS and CD. I altered the lead. You thought extensive quotes were necessary for the mechanism of action. I reviewed, paraphrased, wikilinked and referenced the section. Is there anything else you think requires a change? Are there any sources you think require beter representation? Every minute I take to read and reply on the talk page is time away from this main page, and other wikipedia pages I could be working on. Accordingly, I try to respond parsimoniously. With no new references or specific suggestions, I don't edit. And I think I'm doing a pretty fucking good job of holding back my temper considering you are consistently accusing me of having an agenda and being responsible for making the page worse, when all I am doing is attempting to improve the page in keeping with wikipedia's policies and guidelines. WLU (talk) 14:07, 12 March 2008 (UTC)

• NA-Class pharmacology pages
• NA-importance pharmacology pages
• WikiProject Pharmacology articles