This page is an archive of past discussions. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page. |
I have created an archive of the old discussions. I have copied back to this page the most recent conversations, in collapsible headers on the longer posts. Free free to read and reply to these conversations if you want; any text inside the {{hide}} template will be collapsible, and any text in the section after the }} will be displayed normally. Otherwise, reading involves clicking the header, and editing involves clicking the same edit button that you'd usually use.
In case anyone needs to know in the future, I used the Move Page method. WhatamIdoing ( talk) 22:29, 29 March 2008 (UTC)
Please add new topics for discussion to the bottom of the talk page. WhatamIdoing ( talk) 22:01, 29 March 2008 (UTC)
From an unimpeachable source, article analysing the other PML death (patient had life-long Crohn's Disease)...quote = "Furthermore, the treatments were, among other things, themselves linked directly with the development of PML!".... io_editor ( talk) 01:40, 2 April 2008 (UTC)
In MEDMOS WP guides how Drug pages be written - "For example, a long list of side effects is largely useless without some idea of which are common or serious. It can be illuminating to compare the drug with others in its class...." Last week I listed the DMD drugs in MS, Crohns and those implicated in [PML], and found no comparables close to this N page. Now its time to look at the other wiki-listed autoimmune disease DMD-class drugs. I used the shorter list on the autoimmune disease page; the longer list is very long with very rare conditions, some not treatable, and I doubt it would have a different result anyway. Accordingly:
Conclusion: on Wiki, the wp:weight of PML and death on the N page is hard to equal in comparable DMD drugs.... io_editor ( talk) 02:22, 2 April 2008 (UTC)
This list is irrelevant. This is a product article, not a disease article. If you want to compare Multiple sclerosis to Coeliac disease, then that's fine -- but please do that at the MS article, not here. WhatamIdoing ( talk) 22:41, 2 April 2008 (UTC)
I've been looking for citations to justify the 'approved in Europe' aspect of natalizumab, and the two I've come up with seem to support that it is not approved for use in Europe (possibly just for Crohn's disease - I think it's approved for use with MS). I'm not a drug wonk, so I'm not sure what all the terminology actually means. The two cites I've found are [1] and [2], but I've only scanned and they may just imply that they're not for use with Crohn's disease. Io, could you link to the European Union's approval? Is there a better, second or more lay-summary of it's approval for use in Europe (i.e. a news release from EU medical agencies that state what it's indicated/contraindicated for)? I'll do the citation template if you'd like. I was surprised to see that it wasn't sourced on the main page, and have been trying to track it down. WLU ( talk) 18:10, 2 April 2008 (UTC)
<undent>The reason I placed the word 'suggested' rather than 'demonstrated' is because of the non-approval in Europe. In one of the citations I placed I remember one of the reasons for non-approval for CD was because the reviewers felt it was not adequately demonstrated as effective against CD. I'll try to track it down later today. Of course, you could have assumed I had a reason and asked politely, since I don't believe I have ever edited the page without a good reason. But whatever. Keep pitching them, I'll keep knocking them out of the park. Thanks to WhatamIdoing and Antelan for proofreading and correcting my contributions. WLU ( talk) 11:38, 3 April 2008 (UTC)
Once again, starting what I hope will be a Science (only?) based section, and prompted by the edit here in which WhatamIdoing asks "to expand the more important adverse effect for patients, which is liver damage" and then here where he means "the potentially deadly adverse effect that is much more likely to happen to real patients, and that all regulatory agencies and the pharmaceutical companies agree is caused by natalizumab." Supported by concensus (Antelan, WLU), but it is completely wrong.
This is an issue that should be taken up with the FDA. Until then, and unless something comes out that casts serious doubt on the FDA's own claims, I don't see how this information could reasonably be removed from this article. Antelan talk 00:35, 7 April 2008 (UTC)
(Undent) Io-io editor, it's WP:PROVEIT time, not "insult the other editors" time. If you want to challenge the inclusion of the hepatotoxicity info, then bring us a reliable source that actually says there's no liver toxicity. I found one that says that the liver toxicity is no worse than any other drug, so that information has been included. If you want to say that it doesn't happen at all, then you need to provide a reliable source that states exactly that in plain, unambiguous language. And finally, if no such reliable source exists, then you need to make your own peace with that situation, by which I mean quit hassling everyone else for including verifiable information. If further research proves you right eventually, then I give you permission to say "I told you so" at that time (but not before then). Between now and then, please consider reading the WP:CIVIL policy. WhatamIdoing ( talk) 06:46, 8 April 2008 (UTC)
(undent)WhatamIdoing made his comment, Io, because without a reliable source there is no reason to adjust the page based on your comments. Seeking a reliable source is the next step when there is uncertainty or disagreement about a potential edit as mere assertions are not sufficient to support a contested edit. If you have an issue in the archive which you do not think was addressed, feel free to pull it out - archives only means the page is long, not that the issue is dead. Though if it's the undue weight placed on liver damage or PML, there's not much point. Crohnie, it's not necessary to read through the entire archive, WP:BDR means even if you make an edit we do not agree with, we can always revert and discuss. WLU ( talk) 22:39, 11 April 2008 (UTC)
Thoughts on removing the NPOV tag? I just read the article from beginning to end, and given the level of citation, which verifies almost all of the text (one {{ cn}} referring to liver damage), I think that the page is neutral enough. Natalizumab is portrayed as an effective drug in the treatment of two diseases, with side effects and interactions that are recognized by the FDA, the EMEA and the drug's manufacturer. To date, User:Io io editor is the only person who feels the page has a neutrality problem. I, User:WhatamIdoing and User:Antelan seem convinced the page is NPOV, while some of the past editors ( User:Fvasconcellos, User:MastCell, User:EdJohnston) were faced with the same issue I believe, and didn't see a problem. Can we remove the tag, or is a post on Wikipedia:Neutral point of view/Noticeboard warranted as the last place to bury the issue? WLU ( talk) 15:36, 9 April 2008 (UTC)
Sure thing. I've done so here. Hopefully, being terse there will avoid poisoning the well for or against any given "side". Antelan talk 23:07, 9 April 2008 (UTC)
I'm in agreement that this is a neutral article. OrangeMarlin Talk• Contributions 01:25, 10 April 2008 (UTC)
Review article I found trolling through the archives. pmid = 17122725 WLU ( talk) 15:50, 10 April 2008 (UTC)
(undent)Other pages do not matter so I won't bother. Which policy or guideline do you think is violated? Certainly not WP:UNDUE. UNDUE is meant to discount parts of articles which do not represent the mainstream, either because sources that support the section are unreliable, or they represent a minority position. PML is discussed by no less than seventeen references out of thirty nine, all either pubmed journals, the most reliable of sources, publications by a major regulating agency or the manufacturer themselves. The view that PML is a large part of the history of natalizumab is obviously the mainstream. PML and natalizumab is the majority position, according to extant references. If it's not, produce a source. Any other policies you think are violated? Does everyone else think that we should seek a WP:RFC on either Io's ongoing conduct or the issue of PML? Your ongoing tendentious editing is aggravating and unproductive. You seem to think that we are the problem, despite having much more experience on wikipedia and absolutely no other editors seeing the merits of your positon. I'm willing to put up with a lot crap because of your knowledge base, but your complete failure to grasp wikiquette, good faith and civility, as well as your continued accusations against me is really, really aggravating. WLU ( talk) 00:39, 12 April 2008 (UTC)
I had intended to describe the corrollary earlier; did not get to it. On the N page the recent "Liver-scare" edits include these very flawed lines among others:
Liver damage occurs in about 1 in 1,000 (0.1%), which may be similar to other immune-suppressing drugs used to treat MS (ref this). At least 29 cases are known (ref this). The liver damage appears to be reversible. citation needed
Putting aside the last sentence (odd, no serious outcomes reported) and the almost unprecedented standard for medical references on WikiPedia, I want to focus on the false statement that the incidence may be similar to other "immune-suppressing drugs used to treat MS". Those drugs consist almost entirely of the interferons. Yet, on the top of page 8 of the label you can read that in just 48 weeks hepatic function disorders occurred in 18% of Rebif and 10% of Avonex patients. Compare this to the natalizumab controlled trials, running out almost 3 times the duration - it was far, far less frequent.
And we had this summary before - addressing very serious Liver damage requiring transplantions in both Avonex & Rebif, something that has never happened to natalizumab. All of the above is clearly more wp:weight. io_editor ( talk) 00:25, 12 April 2008 (UTC)
Just give us a reliable source that says natalizumab does not cause liver damage, or that it causes less liver damage than other drugs. That's all we need here: something reasonably reliable that actually makes your claim. If it's true, then I'm sure you'll have no trouble at all finding a source. Until then, please don't bother complaining about this. WhatamIdoing ( talk) 04:43, 12 April 2008 (UTC)
Hepatotoxic-signs of liver injury including marked elevated serum hepatic enzymes and elevated total bilirubin has occurred as early 6 days of the first dosing and even after multiple dosing.
From my point of view as important as liver damage is I feel that all the second paragraph is not needed, not becouse it is not important, but because most of it is superflous or already said.: (Liver damage occurs in about 1 in 1,000 (0.1%), which may be similar to other immune-suppressing drugs used to treat MS.[26] At least 29 cases are known.[27] The liver damage appears to be reversible.[citation needed] Challenge-dechallenge-rechallenge indicates that the liver damage is due to natalizumab rather than being a coincidental occurence.[23] Liver damage may appear at any point, including among patients who have taken multiple doses previously without demonstrating illness or hepatotoxicity.[23] The symptoms produced by natalizumab are recognized as predictors of serious liver damage, possibly resulting in liver damage, need for a liver transplant or death.[23] If not diagnosed promptly, affected patients may die or require a liver transplant.[28] As of March 2008, no natalizumab patient had needed a liver transplant.[26]) It could simply be eliminated
-- Garrondo ( talk) 14:41, 18 April 2008 (UTC)
Garrondo,
Here's my perspective: #1 was included because of the fussing of one editor about the potential for liver damage not being sufficiently "proven" because it wasn't determined in a randomized controlled trial. Fine: we never claimed that it was. CDR also matters because it suggests that going back to the drug in the same patient has a higher likelihood fo recreating the same problem for that individual (whereas something like an infection due to immunosuppression probably wouldn't). #2 is the still-unsupported belief of said editor. Consider it another failed invitation to provide the source to support this belief. #3 and #4 are purposefully redundant to improve readability: general concept in small words, repeated in big words. From the perspective of patient advocacy, this is also valuable because it explains why you have to keep getting a liver panel. #6 explains why liver damage matters, in practical terms, to non-experts. I already know that, you already know that, but it's unreasonable to assume that all, or even most, average readers already know that. #7 was included to provide proper context for this adverse effect. I'm not trying to make the drug sound any worse (or any better) than it actually is, after all.
Basically, I'd restore most of the deleted information, but the outcome is not critically important to me. I appreciate your comments. WhatamIdoing ( talk) 18:55, 18 April 2008 (UTC)
Let's bury the undue weight issue once and for all. It comes up a lot, and it's kinda ridiculous. Wikipedia:Neutral_point_of_view#Undue_weight, if you actually read the section, is about minority views and how much text to give the minority position within a main article that is supposed to place the most emphasis on the majority position. So on a page about medical treatment of condition X, most of the text goes to drugs, surgery and other pubmed sources discussing mainstream treatment options, with a small amount of text discussion acupuncture, prayer, ear candling and other minority and alternative treatments. On a page about evolution, most of the text discusses the change in morphology, genes and fossils, with only a tiny bit of text discussing creationism and the US-based political and educational clash. On a page about Hitler, the majority discusses his political, military and personal biography, with only a short section on his vegetarianism and sexual proclivities. So, undue weight is found if large portions of the article deals with views which are not held by the mainstream. Since the mainstream is pretty much defined by that reported in reliable sources, a page gives undue weight if the text deals more with concerns expressed in unreliable sources than it does in reliable ones. Given the gross preponderance of sources that are from medical journals, regulating agency and manufacturer publications, I'm of the very strong opinion that the page gives due weight to the opinions of mainstream sources. Pending reliable sources that either through explicit discussion or pure volume of discussion, demonstrate that the risks of PML and liver damage are minor or of no consequence and represent a minority position on the impact of natalizumab on MS and the market in general, I think any further citation of WP:UNDUE as a reason to change the page is bollocks. Henceforth, I boldly suggest that such statements by Io Io editor, the sole individual who seems to think that there is any merit to the discussion of undue weight placed on natalizumab's side effects, should immediately be userfied to his talk page as tendentious and disruptive editing.
To summarize, the criteria for undue weight is undue emphasis on unreliable sources or viewpoints held only by the minority. Io, if you wish to adjust the page per WP:UNDUE, you must present reliable sources that explicitly support your point and not argue using original research. WLU ( talk) 14:23, 15 April 2008 (UTC)
When I suggested a "Corrollary" of "liver injury leading to N" - what I meant was that, because liver injury is generally much higher in the other DMDs for MS and Crohns, it is certain that a fair percentage of patients in both disease classes, failing the respective DMDs due to liver issues that wont go away, will find - and today are finding - in N a haven. Now, indeed MEDMOS / drugs, guiding how Drug pages be written, writes "For example, a long list of side effects is largely useless without some idea of which are common or serious. It can be illuminating to compare the drug with others in its class...." Accordingly:
damage; hepatitis; eructation; cirrhosis of the liver".
- What all the Wiki pages for these drugs have in common is that the liver issue is consistently relegated to just a single line, usually "rare reports of serious liver injury". This submitted here for new light on the dozen+ lines on “liver injury” on the N page - none of which have had ANY serious patient outcomes reported. io_editor ( talk) 14:13, 18 April 2008 (UTC)
--1. NSAIDs, consisting of aspirin, advil, phenylbutazone, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.
--2. Glucocorticoids consisting of Hydrocortisone, Prednisone, Prednisolone, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Beclometasone, Fludrocortisone, Aldosterone]].
--3. Natural products (mushrooms!) and
--4. Herbal and alternative remedies
I really don't know if this has been discussed so I thought I would go ahead and bring it to everyone's attentions just in case it hasn't been (too lazy to read through everything to check!) http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-6201.htm I forgot to say, if someone here with the medical knowledge could explain what this actually means I would appreciate it since a couple of my meds are on the list. -- CrohnieGal Talk 16:42, 19 April 2008 (UTC)
I am not happy with the current state of the "Legal status" section. It's a bit of a timeline-style mix of historical, pharmacological, and legal aspects, and I think it could be better focused. I know there will probably be some opposition, but what do other folks think of collating most of the PML info under a subsection of Adverse effects? I think the fact that this information is currently strewn across several sections may be adding to perception that PML is overrepresented in the article. Fvasconcellos ( t· c) 17:53, 19 April 2008 (UTC)
(undent)The number of places PML is mentioned is irrelevant. The relevant issue is if the mentions are justified in each section, if removing PML makes the section less informative, not gross number. The lead must mention PML because it is such an important aspect of it's history. The question to ask is 'is the page better with these changes?' Not 'does this make PML more prominent or not'. That kind of question is wholly inappropriate as it points to a significant bias and WP:NPOV issue. WLU ( talk) 01:06, 20 April 2008 (UTC)
Re-reading the adverse events section and PML, I've a thought. PML only occurred when combined with interferon, does it make sense to put the PML information into adverse effects? What about moving the whole section on PML in AE into interactions? A source says that the 3 events occurred only when combined with interferon, that suggests interaction, not an effect of Natalizumab alone. Thoughts? It would also reduce the mention of PML on the page, but in an appropriate way and contain the same volume and detail of text. My concern is that it buries the very important PML issue too far down the page, and I don't think there's consensus (yet?) for a reorder.
Another option is PML having its own separate heading, and putting all PML-related information in that section. Legal status would retain approval perhaps. PML is important enough to the history of the drug that it should be prominent, but it bridges a variety of otherwise separate sections. Did someone else already suggest this? WLU ( talk) 14:35, 20 April 2008 (UTC)
Seeing no further details of WLU's suggestion, and as the page got some Admin interest now, I am going to propose the following:
So, just say Yes or No. I don’t really like it, as the only common thread page on the page is PML, being still in 3 separate sections plus the Lead (which I think in 6 months time will odder and odder, because patients cannot get N+Avonex, and they sure are not getting PML) ….. io_editor ( talk) 17:02, 21 April 2008 (UTC)
To be brief, you have closed the Indications/MS sub-section with this:
"Natalizumab offers a limited improvement in efficacy compared to other treatments for MS, but due to the lack of information about long-term use, as well as potentially fatal adverse events, reservations have been expressed over the use of the drug outside of comparative research with existing medications, with ref name="pmid18354844".
But the full paper is free, and its conclusion is totally different:
"Uniquely, among the trials of DMTs, significant efficacy was seen in nearly all primary, secondary, and tertiary endpoints, including the quality of life measurements. Although direct head-to-head comparisons have not been performed, the preponderance of data strongly supports the notion that natalizumab offers greater efficacy than existing DMTs. Clearly, since MS is a life-long illness, it is important to recognize that the benefits found on relatively short-term measures seen in clinical trials may not translate into long-term effects in the prevention of disability progression. Natalizumab is not a cure for RRMS but it is a significant improvement on current therapy and given its efficacy and tolerability, natalizumab fulfills an unmet medical need in the treatment of MS." io_editor ( talk) 02:24, 22 April 2008 (UTC)
The page has a single image of a generic antibody. What do people think about adding this image? It'll add a bit more to the page and I believe N is infused via injection. Could it be placed in the infobox or is that reserved for chemical structure alone? I couldn't figure it out from the template page. WLU ( talk) 18:38, 28 April 2008 (UTC)
This page is an archive of past discussions. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page. |
This page is an archive of past discussions. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page. |
I have created an archive of the old discussions. I have copied back to this page the most recent conversations, in collapsible headers on the longer posts. Free free to read and reply to these conversations if you want; any text inside the {{hide}} template will be collapsible, and any text in the section after the }} will be displayed normally. Otherwise, reading involves clicking the header, and editing involves clicking the same edit button that you'd usually use.
In case anyone needs to know in the future, I used the Move Page method. WhatamIdoing ( talk) 22:29, 29 March 2008 (UTC)
Please add new topics for discussion to the bottom of the talk page. WhatamIdoing ( talk) 22:01, 29 March 2008 (UTC)
From an unimpeachable source, article analysing the other PML death (patient had life-long Crohn's Disease)...quote = "Furthermore, the treatments were, among other things, themselves linked directly with the development of PML!".... io_editor ( talk) 01:40, 2 April 2008 (UTC)
In MEDMOS WP guides how Drug pages be written - "For example, a long list of side effects is largely useless without some idea of which are common or serious. It can be illuminating to compare the drug with others in its class...." Last week I listed the DMD drugs in MS, Crohns and those implicated in [PML], and found no comparables close to this N page. Now its time to look at the other wiki-listed autoimmune disease DMD-class drugs. I used the shorter list on the autoimmune disease page; the longer list is very long with very rare conditions, some not treatable, and I doubt it would have a different result anyway. Accordingly:
Conclusion: on Wiki, the wp:weight of PML and death on the N page is hard to equal in comparable DMD drugs.... io_editor ( talk) 02:22, 2 April 2008 (UTC)
This list is irrelevant. This is a product article, not a disease article. If you want to compare Multiple sclerosis to Coeliac disease, then that's fine -- but please do that at the MS article, not here. WhatamIdoing ( talk) 22:41, 2 April 2008 (UTC)
I've been looking for citations to justify the 'approved in Europe' aspect of natalizumab, and the two I've come up with seem to support that it is not approved for use in Europe (possibly just for Crohn's disease - I think it's approved for use with MS). I'm not a drug wonk, so I'm not sure what all the terminology actually means. The two cites I've found are [1] and [2], but I've only scanned and they may just imply that they're not for use with Crohn's disease. Io, could you link to the European Union's approval? Is there a better, second or more lay-summary of it's approval for use in Europe (i.e. a news release from EU medical agencies that state what it's indicated/contraindicated for)? I'll do the citation template if you'd like. I was surprised to see that it wasn't sourced on the main page, and have been trying to track it down. WLU ( talk) 18:10, 2 April 2008 (UTC)
<undent>The reason I placed the word 'suggested' rather than 'demonstrated' is because of the non-approval in Europe. In one of the citations I placed I remember one of the reasons for non-approval for CD was because the reviewers felt it was not adequately demonstrated as effective against CD. I'll try to track it down later today. Of course, you could have assumed I had a reason and asked politely, since I don't believe I have ever edited the page without a good reason. But whatever. Keep pitching them, I'll keep knocking them out of the park. Thanks to WhatamIdoing and Antelan for proofreading and correcting my contributions. WLU ( talk) 11:38, 3 April 2008 (UTC)
Once again, starting what I hope will be a Science (only?) based section, and prompted by the edit here in which WhatamIdoing asks "to expand the more important adverse effect for patients, which is liver damage" and then here where he means "the potentially deadly adverse effect that is much more likely to happen to real patients, and that all regulatory agencies and the pharmaceutical companies agree is caused by natalizumab." Supported by concensus (Antelan, WLU), but it is completely wrong.
This is an issue that should be taken up with the FDA. Until then, and unless something comes out that casts serious doubt on the FDA's own claims, I don't see how this information could reasonably be removed from this article. Antelan talk 00:35, 7 April 2008 (UTC)
(Undent) Io-io editor, it's WP:PROVEIT time, not "insult the other editors" time. If you want to challenge the inclusion of the hepatotoxicity info, then bring us a reliable source that actually says there's no liver toxicity. I found one that says that the liver toxicity is no worse than any other drug, so that information has been included. If you want to say that it doesn't happen at all, then you need to provide a reliable source that states exactly that in plain, unambiguous language. And finally, if no such reliable source exists, then you need to make your own peace with that situation, by which I mean quit hassling everyone else for including verifiable information. If further research proves you right eventually, then I give you permission to say "I told you so" at that time (but not before then). Between now and then, please consider reading the WP:CIVIL policy. WhatamIdoing ( talk) 06:46, 8 April 2008 (UTC)
(undent)WhatamIdoing made his comment, Io, because without a reliable source there is no reason to adjust the page based on your comments. Seeking a reliable source is the next step when there is uncertainty or disagreement about a potential edit as mere assertions are not sufficient to support a contested edit. If you have an issue in the archive which you do not think was addressed, feel free to pull it out - archives only means the page is long, not that the issue is dead. Though if it's the undue weight placed on liver damage or PML, there's not much point. Crohnie, it's not necessary to read through the entire archive, WP:BDR means even if you make an edit we do not agree with, we can always revert and discuss. WLU ( talk) 22:39, 11 April 2008 (UTC)
Thoughts on removing the NPOV tag? I just read the article from beginning to end, and given the level of citation, which verifies almost all of the text (one {{ cn}} referring to liver damage), I think that the page is neutral enough. Natalizumab is portrayed as an effective drug in the treatment of two diseases, with side effects and interactions that are recognized by the FDA, the EMEA and the drug's manufacturer. To date, User:Io io editor is the only person who feels the page has a neutrality problem. I, User:WhatamIdoing and User:Antelan seem convinced the page is NPOV, while some of the past editors ( User:Fvasconcellos, User:MastCell, User:EdJohnston) were faced with the same issue I believe, and didn't see a problem. Can we remove the tag, or is a post on Wikipedia:Neutral point of view/Noticeboard warranted as the last place to bury the issue? WLU ( talk) 15:36, 9 April 2008 (UTC)
Sure thing. I've done so here. Hopefully, being terse there will avoid poisoning the well for or against any given "side". Antelan talk 23:07, 9 April 2008 (UTC)
I'm in agreement that this is a neutral article. OrangeMarlin Talk• Contributions 01:25, 10 April 2008 (UTC)
Review article I found trolling through the archives. pmid = 17122725 WLU ( talk) 15:50, 10 April 2008 (UTC)
(undent)Other pages do not matter so I won't bother. Which policy or guideline do you think is violated? Certainly not WP:UNDUE. UNDUE is meant to discount parts of articles which do not represent the mainstream, either because sources that support the section are unreliable, or they represent a minority position. PML is discussed by no less than seventeen references out of thirty nine, all either pubmed journals, the most reliable of sources, publications by a major regulating agency or the manufacturer themselves. The view that PML is a large part of the history of natalizumab is obviously the mainstream. PML and natalizumab is the majority position, according to extant references. If it's not, produce a source. Any other policies you think are violated? Does everyone else think that we should seek a WP:RFC on either Io's ongoing conduct or the issue of PML? Your ongoing tendentious editing is aggravating and unproductive. You seem to think that we are the problem, despite having much more experience on wikipedia and absolutely no other editors seeing the merits of your positon. I'm willing to put up with a lot crap because of your knowledge base, but your complete failure to grasp wikiquette, good faith and civility, as well as your continued accusations against me is really, really aggravating. WLU ( talk) 00:39, 12 April 2008 (UTC)
I had intended to describe the corrollary earlier; did not get to it. On the N page the recent "Liver-scare" edits include these very flawed lines among others:
Liver damage occurs in about 1 in 1,000 (0.1%), which may be similar to other immune-suppressing drugs used to treat MS (ref this). At least 29 cases are known (ref this). The liver damage appears to be reversible. citation needed
Putting aside the last sentence (odd, no serious outcomes reported) and the almost unprecedented standard for medical references on WikiPedia, I want to focus on the false statement that the incidence may be similar to other "immune-suppressing drugs used to treat MS". Those drugs consist almost entirely of the interferons. Yet, on the top of page 8 of the label you can read that in just 48 weeks hepatic function disorders occurred in 18% of Rebif and 10% of Avonex patients. Compare this to the natalizumab controlled trials, running out almost 3 times the duration - it was far, far less frequent.
And we had this summary before - addressing very serious Liver damage requiring transplantions in both Avonex & Rebif, something that has never happened to natalizumab. All of the above is clearly more wp:weight. io_editor ( talk) 00:25, 12 April 2008 (UTC)
Just give us a reliable source that says natalizumab does not cause liver damage, or that it causes less liver damage than other drugs. That's all we need here: something reasonably reliable that actually makes your claim. If it's true, then I'm sure you'll have no trouble at all finding a source. Until then, please don't bother complaining about this. WhatamIdoing ( talk) 04:43, 12 April 2008 (UTC)
Hepatotoxic-signs of liver injury including marked elevated serum hepatic enzymes and elevated total bilirubin has occurred as early 6 days of the first dosing and even after multiple dosing.
From my point of view as important as liver damage is I feel that all the second paragraph is not needed, not becouse it is not important, but because most of it is superflous or already said.: (Liver damage occurs in about 1 in 1,000 (0.1%), which may be similar to other immune-suppressing drugs used to treat MS.[26] At least 29 cases are known.[27] The liver damage appears to be reversible.[citation needed] Challenge-dechallenge-rechallenge indicates that the liver damage is due to natalizumab rather than being a coincidental occurence.[23] Liver damage may appear at any point, including among patients who have taken multiple doses previously without demonstrating illness or hepatotoxicity.[23] The symptoms produced by natalizumab are recognized as predictors of serious liver damage, possibly resulting in liver damage, need for a liver transplant or death.[23] If not diagnosed promptly, affected patients may die or require a liver transplant.[28] As of March 2008, no natalizumab patient had needed a liver transplant.[26]) It could simply be eliminated
-- Garrondo ( talk) 14:41, 18 April 2008 (UTC)
Garrondo,
Here's my perspective: #1 was included because of the fussing of one editor about the potential for liver damage not being sufficiently "proven" because it wasn't determined in a randomized controlled trial. Fine: we never claimed that it was. CDR also matters because it suggests that going back to the drug in the same patient has a higher likelihood fo recreating the same problem for that individual (whereas something like an infection due to immunosuppression probably wouldn't). #2 is the still-unsupported belief of said editor. Consider it another failed invitation to provide the source to support this belief. #3 and #4 are purposefully redundant to improve readability: general concept in small words, repeated in big words. From the perspective of patient advocacy, this is also valuable because it explains why you have to keep getting a liver panel. #6 explains why liver damage matters, in practical terms, to non-experts. I already know that, you already know that, but it's unreasonable to assume that all, or even most, average readers already know that. #7 was included to provide proper context for this adverse effect. I'm not trying to make the drug sound any worse (or any better) than it actually is, after all.
Basically, I'd restore most of the deleted information, but the outcome is not critically important to me. I appreciate your comments. WhatamIdoing ( talk) 18:55, 18 April 2008 (UTC)
Let's bury the undue weight issue once and for all. It comes up a lot, and it's kinda ridiculous. Wikipedia:Neutral_point_of_view#Undue_weight, if you actually read the section, is about minority views and how much text to give the minority position within a main article that is supposed to place the most emphasis on the majority position. So on a page about medical treatment of condition X, most of the text goes to drugs, surgery and other pubmed sources discussing mainstream treatment options, with a small amount of text discussion acupuncture, prayer, ear candling and other minority and alternative treatments. On a page about evolution, most of the text discusses the change in morphology, genes and fossils, with only a tiny bit of text discussing creationism and the US-based political and educational clash. On a page about Hitler, the majority discusses his political, military and personal biography, with only a short section on his vegetarianism and sexual proclivities. So, undue weight is found if large portions of the article deals with views which are not held by the mainstream. Since the mainstream is pretty much defined by that reported in reliable sources, a page gives undue weight if the text deals more with concerns expressed in unreliable sources than it does in reliable ones. Given the gross preponderance of sources that are from medical journals, regulating agency and manufacturer publications, I'm of the very strong opinion that the page gives due weight to the opinions of mainstream sources. Pending reliable sources that either through explicit discussion or pure volume of discussion, demonstrate that the risks of PML and liver damage are minor or of no consequence and represent a minority position on the impact of natalizumab on MS and the market in general, I think any further citation of WP:UNDUE as a reason to change the page is bollocks. Henceforth, I boldly suggest that such statements by Io Io editor, the sole individual who seems to think that there is any merit to the discussion of undue weight placed on natalizumab's side effects, should immediately be userfied to his talk page as tendentious and disruptive editing.
To summarize, the criteria for undue weight is undue emphasis on unreliable sources or viewpoints held only by the minority. Io, if you wish to adjust the page per WP:UNDUE, you must present reliable sources that explicitly support your point and not argue using original research. WLU ( talk) 14:23, 15 April 2008 (UTC)
When I suggested a "Corrollary" of "liver injury leading to N" - what I meant was that, because liver injury is generally much higher in the other DMDs for MS and Crohns, it is certain that a fair percentage of patients in both disease classes, failing the respective DMDs due to liver issues that wont go away, will find - and today are finding - in N a haven. Now, indeed MEDMOS / drugs, guiding how Drug pages be written, writes "For example, a long list of side effects is largely useless without some idea of which are common or serious. It can be illuminating to compare the drug with others in its class...." Accordingly:
damage; hepatitis; eructation; cirrhosis of the liver".
- What all the Wiki pages for these drugs have in common is that the liver issue is consistently relegated to just a single line, usually "rare reports of serious liver injury". This submitted here for new light on the dozen+ lines on “liver injury” on the N page - none of which have had ANY serious patient outcomes reported. io_editor ( talk) 14:13, 18 April 2008 (UTC)
--1. NSAIDs, consisting of aspirin, advil, phenylbutazone, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.
--2. Glucocorticoids consisting of Hydrocortisone, Prednisone, Prednisolone, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Beclometasone, Fludrocortisone, Aldosterone]].
--3. Natural products (mushrooms!) and
--4. Herbal and alternative remedies
I really don't know if this has been discussed so I thought I would go ahead and bring it to everyone's attentions just in case it hasn't been (too lazy to read through everything to check!) http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-6201.htm I forgot to say, if someone here with the medical knowledge could explain what this actually means I would appreciate it since a couple of my meds are on the list. -- CrohnieGal Talk 16:42, 19 April 2008 (UTC)
I am not happy with the current state of the "Legal status" section. It's a bit of a timeline-style mix of historical, pharmacological, and legal aspects, and I think it could be better focused. I know there will probably be some opposition, but what do other folks think of collating most of the PML info under a subsection of Adverse effects? I think the fact that this information is currently strewn across several sections may be adding to perception that PML is overrepresented in the article. Fvasconcellos ( t· c) 17:53, 19 April 2008 (UTC)
(undent)The number of places PML is mentioned is irrelevant. The relevant issue is if the mentions are justified in each section, if removing PML makes the section less informative, not gross number. The lead must mention PML because it is such an important aspect of it's history. The question to ask is 'is the page better with these changes?' Not 'does this make PML more prominent or not'. That kind of question is wholly inappropriate as it points to a significant bias and WP:NPOV issue. WLU ( talk) 01:06, 20 April 2008 (UTC)
Re-reading the adverse events section and PML, I've a thought. PML only occurred when combined with interferon, does it make sense to put the PML information into adverse effects? What about moving the whole section on PML in AE into interactions? A source says that the 3 events occurred only when combined with interferon, that suggests interaction, not an effect of Natalizumab alone. Thoughts? It would also reduce the mention of PML on the page, but in an appropriate way and contain the same volume and detail of text. My concern is that it buries the very important PML issue too far down the page, and I don't think there's consensus (yet?) for a reorder.
Another option is PML having its own separate heading, and putting all PML-related information in that section. Legal status would retain approval perhaps. PML is important enough to the history of the drug that it should be prominent, but it bridges a variety of otherwise separate sections. Did someone else already suggest this? WLU ( talk) 14:35, 20 April 2008 (UTC)
Seeing no further details of WLU's suggestion, and as the page got some Admin interest now, I am going to propose the following:
So, just say Yes or No. I don’t really like it, as the only common thread page on the page is PML, being still in 3 separate sections plus the Lead (which I think in 6 months time will odder and odder, because patients cannot get N+Avonex, and they sure are not getting PML) ….. io_editor ( talk) 17:02, 21 April 2008 (UTC)
To be brief, you have closed the Indications/MS sub-section with this:
"Natalizumab offers a limited improvement in efficacy compared to other treatments for MS, but due to the lack of information about long-term use, as well as potentially fatal adverse events, reservations have been expressed over the use of the drug outside of comparative research with existing medications, with ref name="pmid18354844".
But the full paper is free, and its conclusion is totally different:
"Uniquely, among the trials of DMTs, significant efficacy was seen in nearly all primary, secondary, and tertiary endpoints, including the quality of life measurements. Although direct head-to-head comparisons have not been performed, the preponderance of data strongly supports the notion that natalizumab offers greater efficacy than existing DMTs. Clearly, since MS is a life-long illness, it is important to recognize that the benefits found on relatively short-term measures seen in clinical trials may not translate into long-term effects in the prevention of disability progression. Natalizumab is not a cure for RRMS but it is a significant improvement on current therapy and given its efficacy and tolerability, natalizumab fulfills an unmet medical need in the treatment of MS." io_editor ( talk) 02:24, 22 April 2008 (UTC)
The page has a single image of a generic antibody. What do people think about adding this image? It'll add a bit more to the page and I believe N is infused via injection. Could it be placed in the infobox or is that reserved for chemical structure alone? I couldn't figure it out from the template page. WLU ( talk) 18:38, 28 April 2008 (UTC)
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