Talk:Oseltamivir/Archive 2

Archive 1

Archive 2

Archive 3

Lede

Good to have your input here Doc.

I realize this is not a great drug, but I'd like to make 3 main points on why I think the article is unbalanced, particularly after your most recent edit.

• The Cochrane group reviewed the same data that was reviewed by the FDA and the EMA. The head of the Medicines evaluation group at EMA has stated this, and Cochrane states that their new info came from Clinical Study Reports, which are regulatory documents submitted to these same organizations. So we have secondary evaluations of the same dataset by three groups. It's not clear to me why the Cochrane group's interpretation of this data should completely dominate that of EMA and FDA.

• The CDC is a fourth party that has evaluated the available data for this drug. They also reached a different conclusion than Cochrane. I'm not understanding why you believe that the Cochrane viewpoint belo7ngs in the lede but not that of the CDC.

• There are problems with the Cochrane analysis. For example, the "dose-response" relationship they reported for psychiatric side effects is driven entirely by an increase in events in patients who recieved an unapproved dose. But this is a minor point I think compared to the first two bullets above, which I would appreciate your thoughts on Formerly 98 (talk) 13:59, 16 April 2014 (UTC)

My concerns are 1) copy and pasting 2) expanding the lead to 7 paragraphs rather than 3 or 4 (read WP:LEAD). I never stated "that I believe that the Cochrane viewpoint belongs in the lede but not that of the CDC" Doc James (talk · contribs · email) (if I write on your page reply on mine) 14:04, 16 April 2014 (UTC)

Sorry for the lack of clarity, I was referring to the deletion of several paragraphs from the lede, which included not only NBC News as a citation as you noted in the edit summary, (the article contained quotes from several experts in the field) but also cited the CDC website and a meta analysis of observational studies in hospitalized patients. I realize observational studies are a little crappy from an EBM POV, but its ethically difficult to do an RCT trial in severely ill pts when you have an approved drug that might help.Formerly 98 (talk) 14:21, 16 April 2014 (UTC)

Certainly. Will look at putting it back in an summarizing. Doc James (talk · contribs · email) (if I write on your page reply on mine) 17:16, 16 April 2014 (UTC)

Thanks. You've seen all the arguments on both sides, and I'm sure that whatever you decide will be fine by me.Formerly 98 (talk) 17:40, 16 April 2014 (UTC)

Issues

Why did the lead expand to 7 paragraphs and why is NBC news being used to refute meta analysis? Doc James (talk · contribs · email) (if I write on your page reply on mine) 13:32, 16 April 2014 (UTC)

A bunch of the stuff added to "medical uses" is society and culture such as "The US has spent more than $1.3 billion buying a strategic reserve of antivirals, while in the UK the government has spent almost £424 million for a stockpile of about 40 million doses" Doc James (talk · contribs · email) (if I write on your page reply on mine) 13:33, 16 April 2014 (UTC)

Gah this is a copyright violation from [1] Doc James (talk · contribs · email) (if I write on your page reply on mine) 13:36, 16 April 2014 (UTC)

Have thus reverted all recent edits by User:Truebreath Doc James (talk · contribs · email) (if I write on your page reply on mine) 13:57, 16 April 2014 (UTC)

I didn't ad anything about NBC news that refuted a meta analysis. What do you mean? I only added the new cochrane systematic review to the lead, which you removed. So now for each addition i will ask if you agree and why. So i can learn the wiki rules. In the lead i added :No benefit on treatment, on hospitalization and mortality has been found in randomized trials in those with other health problems: the elderly and at-risk groups Do you agree? --Truebreath (talk) 15:28, 16 April 2014 (UTC) --Truebreath (talk) 20:30, 16 April 2014 (UTC)

One big concern was the copy and pasting of the text in this edit [2]. You must reword. You can never use text word for work from a source. We do not get a fair use exemption. Even large quotes are not allowed.

Yes I know it was not True who added the NBC news ref.Doc James (talk · contribs · email) (if I write on your page reply on mine) 03:14, 17 April 2014 (UTC)

Cochrane 2014 and the CDC

I tried to strike a balance here between my previous edit, which balanced too far toward the CDC view, and the most recent version of the article, which contained a lengthy paragraph that seemed intended to invalidate the CDC position. There is more criticism of the Cochrane paper in the CDC press release as well, but I think the high level summary here is that there is a controversy, and that controversy arises in part in the difficulty of doing RCTs in the population of interest to CDC.

The issue seems to me to be a complex one. The newspapers are full of the BMJ editor's comment about money wasted on the stockpiling of flu drugs, but I don't think that issue was really addressed by the Cochrane study, which mostly examined clinical trials performed under non-pandemic conditions with relatively non-virulent strains of the flu. There is excellent precedent for differential effects of treatment in severe vs mild disease. Statins, for example, reduce mortality in patients with prior major cardiovascular events, but have no beneficial effect in primary prevention.

The database for severe and/or pandemic flu is pretty lousy, consisting of observational studies only, but this is often the case for pandemic disease planning. For example, the FDA is currently approving drugs for ebola, anthrax, and other biowarefare agents based on animal studies of efficacy plus pharmacokinetic studies in humans. In some situations there are just ethical issues that force reliance on observational trials. There are, incidently, observational trials in severely ill patients that involve strains other than the 2009 swine flu that reached similar conclusions to the meta analysis that CDC cited.

Lastly (though I won't argue for including this in the article), I'm concerned that Cochrane had a major COI in performing this study, as they have made Tamiflu the poster child of their AllTrials campaign. Their position on full data release would have arguably been undercut if they had gotten all this primary data from Roche, and written a paper concluding that all was exactly as Roche claimed it was. The journal that published the Cochrane review is also working closely with Cochrane in the AllTrials movement, and was active with Cochrane in the campaign to get Roche to release the data. So I'm not sure this paper received a truly independent peer review either, but again I won't argue for including this observation in the article, as it is OR.

Let me know what you think. Formerly 98 (talk) 12:15, 15 April 2014 (UTC)

Not related to this tread exactly, but rather than start a new thread I'll ask here. Does anyone suggest that this drug be used prophylactically other than the maker? Gandydancer (talk) 21:41, 15 April 2014 (UTC)

Its approved in both the US and the EU for prophylaxis. On reviewing this a second time, it appears that I mis-spoke in the article by saying that the FDA reached conclusions similar to Cochrane. The FDA and EMA apparently concluded that it prevents infection, but Cochrane concluded it only prevents symptomatic infection. Being approved for prophylaxis, I'm sure that Roche promotes it for that purpose. Formerly 98 (talk) 21:51, 15 April 2014 (UTC)

Cochrane is independent which is important. The manufacturer of the medication has a huge potential to gain financially if the results are positive or if negative are portrayed as positive. Cochrane has little to gain in comparison. If people wish to repeat Cochrane's analysis they can now that the individual patient data is available. If a second systematic review of this data was published in a reputable journal we would also state the conclusions. The CDC is free to get another group such as the USPSTF to do one if they think the methods of Cochrane are poor. We however will still state the CDC's position as it is notable. That it is based on observational data though means that the position is not very evidence based. Doc James (talk · contribs · email) (if I write on your page reply on mine) 07:42, 17 April 2014 (UTC)

This text

We had "Several studies have suggested that it does change the rate of complications from influenza, such as the risk of hospitalization or pneumonia" supported by this ref [3] which states "There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and sinusitis in the ITT population." Not sure how that makes sense? Doc James (talk · contribs · email) (if I write on your page reply on mine) 18:04, 16 April 2014 (UTC)

Looks bad, presumably a cut and paste error of some sort. (I very much hope that wasn't my edit but I'm afraid to look). I'm going over the literature on this to try to pull up what I think are the best supporting references for the utility of this drug in the severely ill, as posited by CDC. I'm doing so with an open mind to the possibility that I put too much confidence in the CDC statement. I'll post again later today with what I find. Thanks for your help, and I apologize if I've steered this whole discussion off course.Formerly 98 (talk) 19:24, 16 April 2014 (UTC)

I searched Pubmed for "oseltamivir influenza hospitalized" and identified no additional high quality secondary references other than the one cited by CDC in their press release (https://www.ncbi.nlm.nih.gov/pubmed/24034489). There were approximately 23 (I did not read every abstract, some had titles that looked irrelevant) primary research papers of which approximately 20 reported higher survivial or earlier discharge among hospitalized pts treated with Oseltamivir within 48 hour of symptom onset relative to those not treated or treated outside this window. These are clearly not appropriate sources for Wikipedia, but I found the trend interesting, especially as one would expect the bias to be that sicker patients would be more likely to receive drug.

I remain a little concerned about the objectivity of the Cochrane review. The BMJ and the Cochrane group worked as a team on this in many ways, including the political battle to gain access to the trial data and the use of the Tamiflu issue as a poster child for the AllTrials campaign. This, combined with the frequency with which BMJ publishes both editorials and review articles critical of Tamiflu, (30 articles in the last 28 months), leave me skeptical that there was any meaningful peer review of this study, leaving it dangerously close to being a self-published study. I say this realizing that the Cochrane group is highly respected and in general does outstanding work, and that most will disagree with my perceptions on this issue. I have no expectations that the article will incorporate any of these concerns, which I recognize put me well outside the mainstream, and which MEDRS would not allow in any case.

Please consider the descriptions of scientific articles as "industry funded" from the article. These industry ties have been considered both by those who wrote the reviews and/or performed the meta analysis, as well as by the referees and editors responsible for publishing the secondary articles. It seems to go outside the spirit of MEDRS for us to decide that we are better qualified than these editors and peer reviewers to decide these matters.

Thank you for your assistance, which has brought a lot of value to the article. I apologize for my own errors and an effort that in retrospect fell short of my personal standards of careful and objective analysis. I think I was seeing everything through the lens of my great respect for the scientists at CDC. More thought, less typing. Formerly 98 (talk) 20:51, 16 April 2014 (UTC)

We have run into a number of situations were a summary of the RCTs say one thing and lower quality evidence / large national organizations come to other conclusions.

I thing the best thing to say in the lead is Cochrane states X based on the RCTs. The CDC states Y. We can provide a more indepth discussion of the issues in the body of the article.

RCTs are the only way to show that something works / doesn't work conclusively. Observational trials are full of confounders that cannot be separated out and thus cannot be used to show mortality benefit. If we are going to go into the concerns around RCTs made by this meta analysis of observational trials than IMO the fact that it was funded by the manufacturer becomes notable.

It is very well supported that funding affects the conclusions people reach. This is why Cochrane is so exceedingly important. If we are not going to base our text on RCTs we need to state this in simple terms. Doc James (talk · contribs · email) (if I write on your page reply on mine) 04:45, 17 April 2014 (UTC)

I will look at this further in a few days when I have a proper computer and Internet. Doc James (talk · contribs · email) (if I write on your page reply on mine) 04:45, 17 April 2014 (UTC)

I agree with the viewpoints of mister Doc; but in the text it must be clair for the reader that the evidence from CDC is prospective cohort evidence and meta analysis from cohort studies, and so al kind of bias is possible and the conclusions can only be hypothesis forming. I did ad this but is was removed in the great clean-up from yesterday. --Truebreath (talk) 08:29, 17 April 2014 (UTC)

Well, I'd say that the standard of evidence will vary according to the decision being made. In some cases (clearly not this one) the effect size is so large that a historical control is sufficient. I'm not sure anyone has ever run a clinical trial comparing antibiotic treatment to non-treatment of pneumonia. We "know" it works without the need for a careful comparison because the introduction of antibiotics led to an 80% survival rate in a disease that historically killed the majority of those infected.

A second such situation would be when the harms of doing the trial are likely to outwiegh the harms of making a bad decision as a result of not having performed one. The FDA is now authorized to approve drugs for Ebola, anthrax, Marburg virus, and other very high fatality bioterrorism pathogens based on the Animal Rule, which requires only evidence of efficacy in animals and studies showing that the pharmacokinetics in humans are similar to those of the efficay species. In these cases you really can't ethically do a treatment trial, but it may make sense to do what you can to develop a drug and collect the best evidence that you can regarding its likely efficacy.

In the 2 years prior the the Tamiflu stockpiling decisions by various governments, there were multiple outbreaks of avian flus in China in which the fatality rate among those infected was >25%. Everyone at the time knew the drug was of marginal effiacy (which you can confirm by reading the FDA approval summary doc), but the idea was that if a similar flu went pandemic, having something would be much much better than having nothing.

Also, as I've said before, at least two other groups (EMA and FDA) have considered this exact same dataset and reached conclusions different from those of Cochrane. I don't understand why Cochrane's interpreation of the data is suddenly the only one that matters. I believe the situation we are discussing is actually very similar to one of the examples in the WP:MEDRS article.

"While the most-recent reviews include later research results, do not automatically give more weight to the review that happens to have been published most recently, as this is recentism."

Formerly 98 (talk) 10:23, 17 April 2014 (UTC)

Thanks Doc, I appreciate your thoughts. I looked over your edits, and though I am not 100% in agreement, I think you've done quite a nice job with it overall. Formerly 98 (talk) 05:25, 17 April 2014 (UTC)

It is unclear how indepth a review the EMA and FDA did. They sometimes come to conclusions without extensively reviewing all the evidence in depth. They may have just gone on the conclusions of the manufacturer and I would need to see evidence that they reviewed the same evidence as Cochrane.

I agree that one does not need a study that parachutes work and there are some situations like this in medicine. They are however few and as you say this is not one of them.

I am hesistant to state that at this point it is better to do something just because we as physicians and patients like doing stuff. Epecially that now we have a couple of reviews that do not find benefit. One must also take into account the amount of time spent and the amount of money spent when one says doing none effective treatments is not harmful. Anyway still travelling and will look further. Doc James (talk · contribs · email) (if I write on your page reply on mine) 12:48, 17 April 2014 (UTC)

OK, I'm going to drop this because I supsect that I'm being a pain in the a** over some relatively minor points and I shouldn't waste your time this way. But just as a general comment for future discussion, the FDA does its own statistical analysis, and these days at least they are pretty thorough. The Tamiflu ones are much less rigorous than one usually sees today. The core medical portion of the review of the original NDA for Tamiflu in the treatment of influenza runs to 245 pages. There is a separate review of the sNDA for prophylaxis. Thanks for everything and I'm going to go away now so as not to be such a nuisance. Formerly 98 (talk) 16:30, 17 April 2014 (UTC)

I have not looked at things fully. Will look at the sources further. Feel free to continue. Doc James (talk · contribs · email) (if I write on your page reply on mine) 19:09, 17 April 2014 (UTC)

Perhaps someone can clarify apparent discrepancy

@Eugene Kwan, or another knowledgable and active here: I was at the oseltamivir TS page and noted that it presents the commercial production method based on a 2007 Chemia review from the Roche team. Was surprised to come back here, at the broader article, to see that the synthesis presented is not the actual commercial production method, but a Roche JOC paper (primary source), for their discovery-stage work toward an improved procedure. Bottom line, should not this article have the commercial route, and the TS article have all others? Why single out an interesting (and, granted, nicely presented) laboratory synthesis at the drug article, rather than the actual commercial route? Esp. when the commercial is, by WP:VERIFY, the better sourced? The correction is simple (a ten second image swap, and a few minutes to adjust text and citations)— but I am not a regular here, and want the community to have their say. Am I missing something? RSVP here, thanks. Le Prof Leprof 7272 (talk) 09:15, 14 June 2014 (UTC)

Being a synthetic chemist myself, I find it difficult to believe that most readers are interested in the synthetic routes to these compounds, or that in most cases there is any reliable way to identify the method actually used in production. My preference would be to delete the synthetic route, but at a minimum swapping it out for the commercial process if it is known. Formerly 98 (talk) 12:59, 14 June 2014 (UTC)

CDC

I've tweaked the language in the section describing the CDC's postion a bit. My concern is with the phrase: "In particular, the CDC analysis relies on a large meta analysis ...funded by the manufacturer."

In particular, this language is at variance with the text of the CDC release, which states "CDC considers all of the published evidence available from Randomized Control Trials (RCT) conducted among outpatients and observational studies conducted among hospitalized patients, including benefits and risks from safety data, when issuing recommendations on antiviral treatment of influenza" and in referring to the study in question "This confirms findings from previous observational studies in hospitalized influenza patients that the clinical benefit of neuraminidase inhibitor antiviral treatment is greatest when started within two days of influenza illness onset. "

More broadly, I feel that this language flies in the face of the basic principle of Wikipedia's philosophy of presenting expert opinion and not that of the editors. What the former language seems to suggest is that the United States CDC naively made a policy decision based mainly on a single COI-tainted study (which would be a pretty extraordinary claim in its own right, even if not contradicted directly by the press release), but we the editors at Wikipedia are wisely pointing out the flaws in their reasoning for the benefit of the reader. Certainly my understanding is that we report the opinion of experts. When we start deconstructing it we have wandered into WP:OR. Formerly 98 (talk) 13:07, 12 June 2014 (UTC)

Yes agree. Feel free to adjust. Doc James (talk · contribs · email) (if I write on your page reply on mine) 23:51, 16 June 2014 (UTC)

Another issue

Thanks.

If I could offer one or two more more points...

We currently have the following text in the lede:

"No benefit of treatment, on hospitalization or risk of death has been found in randomized trials in those people at high risk for complications or the elderly.[8][9] The United States Centers for Disease Control continues to recommend the use of oseltamavir treatment for people at high risk for complications and the elderly..."

Which certainly leaves one to wonder what the CDC could possibly be thinking. Digging into the cited references:

• Reference 8 is a meta analysis of published trials. Since the studies performed in the elderly and frail were unpublished, the article simply states "No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality.". I am uncomfortable with this reference being used in support of a sentence that states that the question has been looked at and no effect was found.
• Reference 9 found no effect against a variety of endpoints in the ITT population, but found a 1% absolute reduction in risk in the the ITTI population (intent to treat-infected) for pneumonia.

The ITT population is most relevent to the a priori likelihood of benefit in those presenting with symptoms. But since hospitalized patients are likely almost all infected, the ITTI population is arguably more relevant to validity of the observational study results. I'd further argue that the relative risk and not the absolute risk difference is more relevant when translating into a hospitalized population from an outpatient population, but that number (which looks like its about 0.35 as a point estimate) is not well defined by this underpowered study.

Based on the above, I'd like to see the language "No benefit of treatment, on hospitalization or risk of death has been found in randomized trials in those people at high risk for complications or the elderly" should be toned down a bit. I propose removing reference 8 and summarizing reference 9 as "Randomized clinical trials failed to find a statistically significant benefit of treatment among people seeking care for flu-like symptoms. When the analysis was restricted to people with confirmed infection, a small reduction in the risk of developing pneumonia was observed".

One final point that I'm sure will not be very popular: The pharmaceutical industry is not the source of all possible conflicts of interest. We note that several studies cited in the paper were industry funded in spite of the authors' statement that the funder had no role in the analysis of the data, but the meta analysis in Reference 9 was funded by the state run health insurance program of Belgium and this fact is not noted. This organization is clearly subject to a variety of political pressures in addition to a pure dedication to patient outcomes as described here. Presumably one of these is limiting expenditures on pharmaceuticals. Furthermore, we note that the "Roche commissioned" meta analysis looked at endpoints not prespecified in the trial, but meta analysis cited in reference 9 clearly does so as well, and it is not noted here. I believe the Cochrane analysis did as well, though the text is not completely clear on this point. Goose/gander? Formerly 98 (talk) 16:56, 17 June 2014 (UTC)

Sorry I missed this earlier. Per "Reference 8 is a meta analysis of published trials. Since the studies performed in the elderly and frail were unpublished, the article simply states "No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality.". I am uncomfortable with this reference being used in support of a sentence that states that the question has been looked at and no effect was found."

I disgree. If you look at all the avaliable RCTs than you can say "not benefit" found. If the company decides not to release the RCT trials for review there is an exceedingly good chance that these trials do not show benefit.

We have a 2014 review that addresses the issue of pneumonia better [4] Doc James (talk · contribs · email) (if I write on your page reply on mine) 03:58, 22 June 2014 (UTC)

With respect to hospitalization we have have "two large unpublished studies in the elderly and in adults with chronic disease did not find a significant reduction in the symptom duration. There was no difference in the likelihood of hospitalization in the ITT population (33/2633 patients for oseltamivir versus 20/1694 for placebo)." [5] and "No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality" [6]. So IMO we can say "does not appear to be a change in the risk of hospitalization" in those at high risk. And evidence for mortality is unclear. Doc James (talk · contribs · email) (if I write on your page reply on mine) 04:14, 22 June 2014 (UTC)

Fair enough Doc. But my central point is that reference 9 found a reduction in pneumonia in the intent-to-treat-infected population, which is likely more representative of the hospitalized population seen in the observational trials. If the difference in conclusions between reference 9 and Cochrane was that Cochrane considered more data, I would agree that Cochrane would trump reference 9. But in this case, the difference was a matter of investigator judgment: The Cochrane group but not the University of Georgia group decided that the ITTI analysis was unusable due to bias. (The Cochrane group's decision to eschew ITTI analysis was also a central criticism of the IDSA, which is usually considered a very respectable source). That's a judgment call, and I don't see why the judgment call of a group with a long history of conflict with Roche would so completely trump that of a group without such history such that the former is not even mentioned. I think both are worthy of inclusion.

Overall, the tone of the article to some extent still has the issue I raised in the section above. We all but flat out state that the drug does not work, and then we juxtapose that with a statement that the CDC still supports its use. I don't see how it is possible that we could have such a juxtaposition unless we are violating NPOV as I have understood it. We describe controversies rather than take sides in them. And here is Wikipedia nearly flat out saying that the CDC is wrong. Isn't it better to simply present the different points of view of the antagonists in this debate and avoid a Wikipedia as Expert Authority judgment that Cochrane is right and the CDC and the IDSA are wrong? The article is clearly taking sides in this fight among 3 very respected organizations.

Formerly 98 (talk) 06:39, 22 June 2014 (UTC)

Added other review. Doc James (talk · contribs · email) (if I write on your page reply on mine) 14:37, 22 June 2014 (UTC)

Phosphorus?

The chemical data section lists the composition as C16H28N2O8P which includes Phosphorus. I really really don't know what I am talking about on this subject but the structural diagram does not seem to indicate the presence of that element (again, please consider me an idiot on this topic). I'd just like somebody who knows that they are talking about to double check. — Preceding unsigned comment added by 146.115.66.18 (talk) 22:30, 22 June 2014 (UTC)

Controversy

All smighthtces more or less agree that their is no important benefit in those who are otherwise healthy. The controversy is in those who are not as their is simply not good data. Doc James (talk · contribs · email) 17:56, 2 November 2014 (UTC)

My memory was some generically recommended for those presenting in first 48 h, but feel free to correct anything you are sure about. (Not being flippant, its just that I'm out and on my phone today)Formerly 98 (talk) 18:33, 2 November 2014 (UTC)

Badly Unbalanced; needs rewrite

At the risk of jumping in on an edit war that has apparently died down, I have put back the "Undue" and "Quality" tags on this article. (I'd originally thought about putting "NPOV" on, but I think "Undue" is a little more accurate here). This is a badly written article. Perhaps it is, indeed, unbiased-- but it reads like a biased article, and should be rewritten to have a more balance. The lede has one sentence about what the drug is and how it works, and then jumps to a long paragraph summarizing studies suggesting it's not effective (without mentioning any studies suggesting the opposite.) This shouldn't even be in the lede-- the lede should simply say "The efficacy of oseltamivir and its overall risk-benefit ratio are controversial." Although that paragraph is inaccurate according to the article: nothing in the article suggests any controversy; the "controversy" is entirely one-sided. The very first sentence--before even discussing the drug itself-- states it doesn't have any benefits. Rewrite desperately needed. Geoffrey.landis (talk) 16:51, 5 December 2014 (UTC)

Evidence for benefit is lacking. The medication; however is still recommended. I am not seeing the issue?

The issue is that this is a badly-written article: poorly balanced in both senses of the word. If it is not in fact biased, then please make at least an attempt to make it read like an article that is not biased. Geoffrey.landis (talk) 17:02, 5 December 2014 (UTC)

Any refs to support your claims? The article appears to have lots. Doc James (talk · contribs · email) 16:56, 5 December 2014 (UTC)

Let look at the VERY FIRST SENTENCE "Oseltamivir marketed under the trade name Tamiflu, is anantiviral licensed to prevent or slow the spread of influenza A and influenza B (flu) virus between cells in the body by stopping the virus from chemically cutting ties with its host cell." Appears Geof is mistaken. Doc James (talk · contribs · email) 17:01, 5 December 2014 (UTC)

My claim was that the lede has a single sentence devoted to what the drug is and how it works. That's the sentence. Your point is? Geoffrey.landis (talk) 17:02, 5 December 2014 (UTC)

You state "The very first sentence--before even discussing the drug itself--" which appears to be wrong. Doc James (talk · contribs · email) 17:03, 5 December 2014 (UTC)

Good lord, you're trying to nit pick-fine details of phraseology on a talk page? Why don't you spend that energy actually writing the article so that it is well written?

Let me explain some terminology in Wikipedia. The lede is the stuff at the beginning of the article. It is, basically, a precis of what will be found in the article. Following the lede is the contents. Following the contents is the body of the article. The sentence you quote-- of which I said "the lede has a single sentence devoted to what the drug is and how it works" is in the lede. The first sentence of the body of the article is the one of which I stated "The very first sentence--before even discussing the drug itself-- states it doesn't have any benefits". Geoffrey.landis (talk) 17:13, 5 December 2014 (UTC)

Good point. Fixed that section. Doc James (talk · contribs · email) 17:41, 5 December 2014 (UTC)

Feedback please

According to the Tamiflu website, "Tamiflu is a prescription medicine used to treat the flu (influenza) in people 2 weeks of age and older who have had flu symptoms for no more than 2 days. Tamiflu can also reduce the chance of getting the flu in people 1 year and older." Is there an objection to adding this information to the article even though our article states, "There is low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1% to 12% in those exposed.[8]"? Gandydancer (talk) 17:40, 5 December 2014 (UTC)'

By the Tamiflu website you mean this one [7] It is not a reliable source per WP:MEDRS. Doc James (talk · contribs · email) 17:42, 5 December 2014 (UTC)

Yes, that's it - they have been running that ad in the US. Thanks Doc. Gandydancer (talk) 17:44, 5 December 2014 (UTC)

Yes that is how the ad people re interpret the evidence. Doc James (talk · contribs · email) 17:49, 5 December 2014 (UTC)

Mass changes to lede without discussion

I disagree with the changes to the lede. The lede can summarise the body. If there is text in the lede that is not in the body it may also be included in the body. I do see any reason for the tags. The change to the lede also restored the tags. The tags were added to the body instead of the lede this time. QuackGuru (talk) 18:58, 5 December 2014 (UTC)

Thanks, yes a very controversial topic. And this user feels they should be able to edit war in changes. Doc James (talk · contribs · email) 19:04, 5 December 2014 (UTC)

To the contrary, it was not "without discussion." The discussion-- which User:Doc James participated in, and hence presumably knows about-- had the following statement: "The lede has one sentence about what the drug is and how it works, and then jumps to a long paragraph summarizing studies suggesting it's not effective (without mentioning any studies suggesting the opposite.) This shouldn't even be in the lede-- the lede should simply say "The efficacy of oseltamivir and its overall risk-benefit ratio are controversial.""

There were no comments nor objections made to this proposed change. Moving the material (note: not deleting it, just moving it to the appropriate section) goes a long way toward dealing with the (undue) and (quality) problems with the article that User:Doc James believes should not be mentioned. Geoffrey.landis (talk) 19:43, 5 December 2014 (UTC)

Should have been obvious but to clarify I oppose. Doc James (talk · contribs · email) 19:51, 5 December 2014 (UTC)

revision of article - was overly WP:TECHNICAL and clear product of battles among editors

I just took a shot at revising and simplifying this. It was written by smarty pants for smarty pants and had completely lost track of our mission to give people straightforward information per WP:MEDMOS.

I moved a ton of detail that was only in the lead into the body and condensed the lead. I put advice of major medical bodies first (consensus of the field about how to actually use the drug), followed by evidence expressed in reviews, per discussions at WT:MEDRS on consensus vs evidence (again, we are not here to WP:ADVOCATE for evidence-based medicine) I renamed cochrane2014 & coch2012 & CDC refs to make them easier to find. I also removed a bunch of the blow-blow as time unfolded from the Efficacy subsection. We just need to provide the current understanding, not the geeked-out history of how we got here. Jytdog (talk) 20:01, 7 December 2014 (UTC)

Doc James please provide a citation for the organization or individuals who actually say they are contesting the recommendations of the world's major medical bodies on use of this drug. Thanks. Jytdog (talk) 20:30, 7 December 2014 (UTC)

For what article content are you wanting a ref? Doc James (talk · contribs · email) 20:34, 7 December 2014 (UTC)

thanks for talking. it is very clear that you see a controversy. I am asking for a source that says there is a controversy. Also, what major medical body opposes the CDC, ECDC, IDSA, etc etc? What justifies giving cochrane WP:WEIGHT over all these major medical bodies? Jytdog (talk) 20:52, 7 December 2014 (UTC)

You are requesting evidence that their is a controversy? We have this review that states "Oseltamivir is now on the list of World Health Organization essential drugs,4 5 but we could not clarify on what basis WHO or the Centers for Disease Control and Prevention recommend its use" [8] published in the BMJ

We have news sources from 2014 that state "Researchers, regulators and Roche row over stockpiled drug Tamiflu [9]

And a news report in nature [10] Doc James (talk · contribs · email) 21:05, 7 December 2014 (UTC)

I appreciate everyone's work on this today (and especially that my edits were not all reverted :>)). But I'd have to agree withh what I think Doc is saying, the material in the text provides prima facie evidence of a controversy. No ref needed. There are a number of articles out there that support the Cochrane position, and they are not all from BMJ. But I don't think this is something we need to document. Formerly 98 (talk) 21:18, 7 December 2014 (UTC)

Yup thanks Formerly. Documentation can be provided that it is controversial as lot of press describes the controversy. Have provided three systematic reviews and one systematic review of systematic reviews from the last two years above. A reuters states their is a disagreement between regulators and researchers. Doc James (talk · contribs · email) 21:25, 7 December 2014 (UTC)

Both the Nature news article and Reuters article are the typical kind of science news that comes out when articles are published. The reuters source is decent for saying that Carl Heneghan is arguing with pretty much every major medical body on the planet - and makes it clear that the EMA thinks he is just dead wrong on this. And Nature News says "But a dozen experts contacted by Nature’s News team said that the clinical-study reports, although they allow more detailed analyses, offer no substantial fresh findings." So the "controversy" appears to be all hype - which you and I assiduously avoid when we edit. Jytdog (talk) 21:24, 7 December 2014 (UTC)

While I guess we disagree that the controversy is all hype. BMJ, Cochrane and PLoS One do not just publish hype. Doc James (talk · contribs · email) 21:26, 7 December 2014 (UTC)

I am OK with either of those as a source for the "controversy" per se - although I see that Everymorning jumped in with a ref (thanks for that!). But this is a side show. The thing I am really looking for and that we should discuss if there is not agreement to let the article stand as it is, is -- what is the basis in policy or guideline for giving EBM/Cochrane more WEIGHT than the views of pretty much every major infectious disease body on the planet? Doc James please do reply to that, if you don't agree with the current state of the article. If you agree, we can just let this go. thx. Jytdog (talk) 21:32, 7 December 2014 (UTC)

This sort of preface should not occur "The world's leading medical bodies for infectious disease." We do not state "published by the prestigious Cochrane Collaboration" or leading medical journal PLoS One. Doc James (talk · contribs · email) 21:43, 7 December 2014 (UTC)

As much as Doc and I have disagreed about this article, we're on the same page today. Agree "leading" does not belong here. Overkill. Formerly 98 (talk)`

• Cochrane is not the only reputable publication objecting to Oseltamivir recommendations. A1candidate (talk) 21:45, 7 December 2014 (UTC)

ok i admit that was my own bullshit piece of WP:ADVOCACY - WP:POINT-y even, over against the kooky elevation of Cochrane that was going on here. Removing it. Jytdog (talk) 21:57, 7 December 2014 (UTC)

Edits of Dec 27 2014

As someone with a long history of carping about this article, I think this version https://wiki.riteme.site/w/index.php?title=Oseltamivir&oldid=637069978 looks pretty good, and would like to express my appreciation to everyone who worked on it today. Formerly 98 (talk) 21:07, 7 December 2014 (UTC)

Agree that it is much similar and to the point. Doc James (talk · contribs · email) 21:47, 7 December 2014 (UTC)

I think we changed it from "fraudulent drug known to be worthless", or something leaning heavily that way, to "controversial in part because the developer did an irresponsible job of designing and performing the clinical trials". I think the latter is probably a fair characterization. Formerly 98 (talk) 22:00, 7 December 2014 (UTC)

Neuropsychiatric side effects.

I have some concerns about the appropriateness of the following sentence and would just like to ping to see if anyone else agrees with me

"A survey conducted in 2009 by the Health Protection Agency and the European Centre for Disease Prevention and Control found that out of 85 children treated with the drug 18% reported a neuropsychiatric side effect (defined as one or more of the following symptoms: poor concentration or unable to think clearly, problems sleeping, feeling dazed or confused, bad dreams or nightmares, behaving strangely"

My concerns are as follows:

• The suggesting that Tamiflu is causing an 18% incidence of AEs seems extraordinary given 1) the drug was approved four use in children on two continents without a label warning for psychiatric events, and 2) the NNH in adults is 94
• Its unclear exactly what the number means in the absence of a control group - how many of these events were drug-related and how many flu-related. "Trouble sleeping", "feeling dazed", "problems with concentration or unable to think clearly" are very reminiscent of my last bout with the flu, and I wasn't taking any Tamiflu.
• We usually require secondary sources for this sort of information, e.g. a review or meta analysis. In this case the source is a "investigative report" by BMJ that is not a peer reviewed scientific publication.

— Preceding unsigned comment added by Formerly 98 (talk • contribs) 13:25, 25 April 2014‎

As you say in your second bullet, before worrying about an 18% incidence of poor concentration, problems sleeping, and other symptoms, you'd have to know what the likelihood of those symptoms are for people who have the flu anyway. I don't think I've ever heard anyone say that they feel like they're mentally at their best when they have the flu. It could well be that 18% is a lower rate of problems than people with untreated influenza, in which case this "harm" is actually a "benefit". WhatamIdoing (talk) 01:51, 8 December 2014 (UTC)

Disagreement over pregnancy category content

Will look at it further tomorrow. But here [11] you removed the plain language summary? Why. And you changed the refs? Also why? Doc James (talk · contribs · email) 03:55, 8 December 2014 (UTC)

With regard to this edit by Doc James. Per WP:LEAD, nothing should be in the lead that is not in the body. Also, one of the refs was for a different drug and the other ref was a general description of what the Australian pregancy categories are; neither was a source for the information about this drug. I made this edit, where i moved the content to the body and provided proper sourcing, and Doc James gave me an edit warring warning. Unclear to me what the problem is. Do we generally put pregnancy categorization only in the lead, or even usually put it in the lead? Please explain! Please don't tell me that providing actual sources is a problem.... :) Thanks. Jytdog (talk) 04:18, 8 December 2014 (UTC)

Yes ref should have been "It is pregnancy category C in the United States and category B in Australia meaning that it has been taken by a small number of women without signs of problems and in animal studies it looks safe."

The second ref for Au all you need to do is scroll to the bottom and click on accept pull up oseltamivir and it gives you a plain language description plus the category. This is the most official source of this information. And yes we sometime put this information in the lead. Doc James (talk · contribs · email) 04:25, 8 December 2014 (UTC)

the ref I provided is definitely better for the US (no big deal that you goofed, everybody does) and the australian one is reasonable-to-disagree. and i am not aware of many (not any, actually) articles where we cite pregnancy information only in the lead; and few where we mention it at all int the lead. nor do we often (ever?) explain what the pregnancy categories mean. what do you want to do - what is really at stake for you here? this seems kind of mountain-out-of-molehill. i'll add the australian database source and the plain language meaning in the body Jytdog (talk) 04:32, 8 December 2014 (UTC)

A few more items to tidy up

I'd say the lede is too long. I support reducing it in an NPOV way.

I'll preface my other remarks by noting that I've gone back and forth with Doc James for quite a while on this article. He has generally been very open to my concerns, but I still think the article somewhat over-emphasizes the Cochrane-BMJ PR juggernaut over the opinions of just about every other medical organization that has commented on the data. Cochrane had a huge COI here, in that they had made Tamiflu the poster child for their AllTrials campaign. If successful, that campaign sets up Cochrane as a "shadow FDA" with extraordinary influence over public policy. The AllTrials campaign would be strengthened in direct proportion to the extent that Cochrane's meta analysis "proved" that Roche had used data secrecy to perpetuate a huge fraud upon the public.

A couple of suggested aspects of the article that I think need to be further tweaked.

• "Randomized clinical trials have failed to find a benefit of treatment among people seeking care for flu-like symptoms,[9] that treatment does not change the risk of hospitalization in the elderly or other high risk populations, and that it is unclear if it affects rates of death.[8][9]" Here we present Cochrane's conclusions in Wikipedia's voice, in spite of the fact that the design of the Cochrane review has been contested by important healthcare groups

• According to Public Health England, "The Cochrane review has been reported as suggesting that antivirals are not effective for influenza. This is not the case because of the following aspects of the review... [LIST]", "It [the Cochrane Review] has limitations in understanding hospitalisations, complications, and the prevention of complications occurring in cases of severe infection, and mortality", and "There is good evidence that antivirals can reduce the risk of death in patients hospitalised with influenza".
• According to the ECDC, "They [the Cochrane review results] do not give reasons for changing the current approach to public health use of antivirals, including prophylaxis, pandemic preparedness, stockpiling or use in outbreaks. While their publication represents a ‘signal event’ we clearly have a long way to go in this field."
• The IDSA refers to the Cochrane review as "causing confusion", and states " the Cochrane analysis included both influenza virus-infected and non-infected persons with influenza-like illness. Given the specific antiviral activity against influenza viruses of NAIs, this analytic approach underestimates NAI treatment efficacy."
• And so on. There are too many disputes of the Cochrane methodology and conclusions for us to state Cochrane's conclusions in Wikipedia's voice. Doing so implies the existence of a scientific consensus that has not yet been reached.

• We further state that "A survey conducted in 2009 by the Health Protection Agency and the European Centre for Disease Prevention and Control found that out of 85 children treated with the drug 18% reported a neuropsychiatric side effect (defined as one or more of the following symptoms: poor concentration or unable to think clearly, problems sleeping, feeling dazed or confused, bad dreams or nightmares, behaving strangely.[32]" The source is a news article written by BMJ staff, and given BMJ's advocacy role in this affair, this should be deleted or supported by a MEDRS-compliant, WP:THIRDPARTY source.
• "Rare ADRs include: liver inflammation and elevated liver enzymes, rash, allergic reactions including anaphylaxis, and Stevens–Johnson syndrome.[30][31] Various other ADRs have been reported in postmarketing surveillance, including: toxic epidermal necrolysis, cardiac arrhythmia, seizure, confusion, aggravation of diabetes, and haemorrhagic colitis.[30]" - According to the cited source, these are not ADRs but AEs, "causation has not been established".
• "Regulatory reports examining harms in the prophylaxis trials, were analysed while participants were receiving treatment only and not after they stopped taking it, although this information was available in the full clinical study reports.[32]" - The source is not MEDRS compliant, and the statement itself seems dubious. Formerly 98 (talk) 10:24, 7 December 2014 (UTC)
• "From about 2004 there were concerns that oseltamivir caused dangerous psychological, neuropsychiatric side-effects including self-harm in some users. These dangerous side-effects occurred more commonly in children than in adults.[33]" - this provocative language indirectly references the package insert, which says "the contribution of TAMIFLU to these events has not been established." We have 5 paragraphs on this AE of unestablished causation, reminscent of the sort of endless discussion of the "history" of FDA commentary on rare AEs of unknown causation in the FQ articles of several years ago. Formerly 98 (talk) 13:15, 7 December 2014 (UTC)

Ah "their AllTrials campaign" It is not their campaign. Yes they are involved with it but other supportive organizations include NICE, the Medical Research Council and Wellcome Trust.

That this represents a meaningful COI I do not agree.

Agree this "A survey conducted in 2009 by" is poor and trimmed

Change the heading to "side effects". We can discuss both confirmed and potential side effects in this section. The section heading does not need to fully describe the sectionDoc James (talk · contribs · email) 18:34, 7 December 2014 (UTC)

The Cochrane reviews are typically the most authoritative sources to be used on Wikipedia. They usually represent the scientific consensus. Some of the wording can be tightened or reworded. Current wording "A 2012 Cochrane review maintained that...". I would change it to "A 2012 Cochrane review stated that...". QuackGuru (talk) 20:05, 7 December 2014 (UTC)

There was no consensus to delete Cochrane review from the lede. QuackGuru (talk) 20:47, 7 December 2014 (UTC)

While Cochrane often represents the medical consensus, this is one case where it does not (see the other guidelines by WHO, IDSA, CDC, etc). It's conclusions are controversial and I would not place their conclusion in the lead, especially without the caveats that their conclusions have been largely rejected by the wider medical community. Yobol (talk) 20:51, 7 December 2014 (UTC)

You are absolutely correct if it was just Cochrane. But there are other sources that show a disagreement. QuackGuru (talk) 05:52, 8 December 2014 (UTC)

It is not just Cochrane

• 2013 PLoS One "The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established." [12]
• 2013 Family Practice "There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and sinusitis in the ITT population." [13]
• 2014 Cochrane "The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza." [14]
• 2014 BMJ "The trade-off between benefits and harms should be borne in mind when making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling." [15]

Doc James (talk · contribs · email) 21:22, 7 December 2014 (UTC)

• Yep. For the sake of neutrality we should include the disagreement in the body and the lede. QuackGuru (talk) 05:52, 8 December 2014 (UTC)

I object to this edit. QG you are putting WP:WEIGHT of individual authors against every major medical authority on this issue. This is definitely WP:UNDUE. QG, or Doc James, please provide just one - one major medical authority that has sided with the nay-sayers here. Thanks. You guys are behaving exactly the pro-alt med people here. Even Mark Crislip is opposed to this position, that there is no value to the drug. This is crazy WP:ADVOCACY. Jytdog (talk) 06:36, 8 December 2014 (UTC)

No, there is a disagreement and other sources have commented. You added nonsense to the article with including a blog and undue weight. Did you add that to counteract my recent edit? QuackGuru (talk) 06:41, 8 December 2014 (UTC)

no i did not. i actually had an edit conflict with you. are you really calling Crislip "nonsense"? Jytdog (talk) 06:48, 8 December 2014 (UTC)

and please reply to my request for a major medical authority that agrees that Oseltamivir is worthless. Thank you. Jytdog (talk) 06:49, 8 December 2014 (UTC)

actual recommendations

• CDC recommends use of tamiflu to "treat influenza or to prevent influenza" - no restrictions.
• IDSA recommends for treatment of anyone (doesn't mention prevention). notes that its recommendation goes beyond the label
• APA recommends for treatment and prevention in kids.
• ECDC recommends use to treat and prevent in observed risk groups (old, young, sick, pregnant, etc)

Curent text says "recommend the use of oseltamavir for people at high risk for complications and those at lower risk who present within 48 hours of first symptoms of infection" which is not accurate. Fixing. Jytdog (talk) 21:47, 7 December 2014 (UTC)

Ah. Slow down User:Jytdog Doc James (talk · contribs · email) 21:53, 7 December 2014 (UTC)

what's wrong? Jytdog (talk) 21:54, 7 December 2014 (UTC)

While you agreed to discuss and are not. Doc James (talk · contribs · email) 21:55, 7 December 2014 (UTC)

I self-reverted. here is the change i made. what is wrong with it? thx. Jytdog (talk) 21:56, 7 December 2014 (UTC)

Lets look at the CDC "Antiviral treatment is recommended for any patient with confirmed or suspected influenza who: is hospitalized; has severe, complicated, or progressive illness; or is at higher risk for influenza complications. Persons at higher risk for influenza complications"

This could be summarized as "any one who has or is at high risk for complications"

"Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset"

Can be summarized as "and those at lower risk who present within 48 hours of first symptoms of infection" Thus there was nothing wrong with waht was there fore. Doc James (talk · contribs · email) 21:58, 7 December 2014 (UTC)

doc james that bit you quote is prefaced by as early as possible (bolding from the original) - you are applying an urgent warning for a special case, to the overall use of the drug. That is even POINTier than my use of "world's leading medical bodies for infectious disease".  :) The very first bullet in the bottom section is the general one: "Clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of complications from influenza" and per the table above it, this applies to everybody. hence my suggested content: "recommends for treatment and prevention (as a second line, after vaccination) of influenza" Jytdog (talk) 22:07, 7 December 2014 (UTC)

you've got your big Efficacy section clearly explaining the Cochrane perspective. You must allow the voice of the major medical bodies to speak clearly. Thanks. Jytdog (talk) 22:14, 7 December 2014 (UTC)

The CDC does not recommend it for everyone. They recommend it for those with complications or at high risk of complications. They do not recommend it in those who are otherwise healthy, have no complications and are not at high risk. It can be considered for some in that group but it is not recommended "Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset." Doc James (talk · contribs · email) 22:21, 7 December 2014 (UTC)

I see what you mean. I will let the current language stand. Jytdog (talk) 22:32, 7 December 2014 (UTC)

I hesitate to suggest any further changes at this point, as the article basically looks good and the discussion seems to be close to consensus. But didn't this article formerly contain reference to a meta analysis of observational studies in hospitalized patients that many of the aforementioned medical groups refer to in defending their treatment guidelines? These obviously are not RCTs, but given the crappy job that Roche did on looking at these issues in their clinical development program, and the reference to them by the groups above, they seem to be a significant contributor to the overall evidence base. Or at least many view them that way. Formerly 98 (talk) 22:46, 7 December 2014 (UTC)

do you mean this PMID 12885681? Jytdog (talk) 03:31, 8 December 2014 (UTC)

it would be bad to counter more recent reviews with an older one, tho...Jytdog (talk) 03:31, 8 December 2014 (UTC)

The CDC quoted an industry supported meta analysis of observational trials.http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(14)70041-4/abstract But there are also some other meta analyses of observational data that are less positive that come up in a pubmed search.

This German guideline lines up with Cochrane. But not a real well known group. http://www.aerzteblatt.de/int/archive/article/159698 Formerly 98 (talk) 13:11, 8 December 2014 (UTC)

Science-based medicine

OK, just came across this. What shall we do with this? Mark Crislip for Science-based Medicine. May 2, 2014 Cochrane Reviews: The Food Babe of Medicine? Quote: "There was a lot of good information in the article, but the bias and FUD rendered it, like much of the Cochrane influenza reviews, more infomercial than a nuanced discussion of a complicated topic. And while I didn’t go through all the supplementary material, I did not see that they suggested oseltamivir is used in the manufacture of yoga mats. But not for a lack of trying." There are many WP articles where we rely on this blog. Note. that article also says, "Not only is the press not bothering to read the article with more critical thinking than Food Babe, the Wikipedia editors fell for it hook, line and stinker." Jytdog (talk) 03:51, 8 December 2014 (UTC)

i went ahead and added content based on this to body and to lead in this dif. Jytdog (talk) 06:27, 8 December 2014 (UTC)

Are you sure about adding a blog to this particular article? QuackGuru (talk) 06:31, 8 December 2014 (UTC)

absolutely. Please tell me why we shouldn't - please tell me how this blog is not reliable for calling bullshit, bullshit. Jytdog (talk) 06:40, 8 December 2014 (UTC)

and if you really stay to true to your usual reliance on SBM and Crislip, you have to acknowledge that there is some serious ax-grinding going on with the Cochrane reviews of this drug, and likewise the 2014 BMJ review and the 2013 PLoS review. Jytdog (talk) 06:52, 8 December 2014 (UTC)

I don't like this. I don't think the addition of Science Based Medicine to a list including the IDSA and the CDC adds anything in terms of giving the reader a picture of the balance of viewpoints out there. One can always find that someone, somewhere has offered caustic criticism of a given person or organization, and it tends to be more difficult to find positive quotes. I cut these kinds of quotes out of articles all the time, and I don't think this one is helpful either. Formerly 98 (talk) 11:28, 8 December 2014 (UTC)

The source is 100% solid and we use it all the time in situations where the regular scientific literature won't normally discuss something. QG uses it this way all the time, as the scientific literature generally doesn't discuss alt-med kookiness in any reasonable depth and doesn't come out and call bullshit, bullshit. In this case, we have somebody with an ax to grind running the anti-infective arm of one of the one most important EBM groups in the world. It needs to be said, and Crislip says it. That said, I am willing to take the quote out of the main text, which I will do now. Jytdog (talk) 12:11, 8 December 2014 (UTC)

and btw Formerly, Crislip makes exactly the point that you have made a few times - namely that the biases of authors of meta-analyses can really frustrate and even pervert the goals of EBM, namely to see what the evidence says and state it clearly, so that the field can be guided by it. Something has got to be amiss when Cochrane is so utterly at odds with the entire medical establishment. I wasn't looking for dirt; I found this looking for the origins of the controversy for the history section, and this popped up in my searching. I was truly dismayed by what Crislip says of this guy.... and what it says about Cochrane that somebody like this has a key role there and has kept it so long. But it makes sense of this terrible situation. Jytdog (talk) 12:40, 8 December 2014 (UTC)

I see your point. Its just that there is a lot of room for abuse of this sort of quote. Somebody somewhere responds to anything that Merck does with the comment "this is the most morally reprehensible thing I've ever seen, comparable to the Holocaust", and of course there is never a balancing quote where someone other than the company says "Oh come on, get life you moron. We're talking about a price increase, not 6 million dead". In general quotes tend to be used on Wikipedia to introduce POV remarks by proxy. If we add this we open the door for lots additiona of editorializing by Fiona whats-her-name of BMJ, Goldstein, and all those folks. The article then becomes a battle of competing POV remarks that were made by third parties.

Also I think the article looked fine before this material was added, and by adding material that there may not be broad support for, I worry you are risking a backlash that takes us back to "Evil Roche and it's Fraudulent Drug". The article really is about Tamiflu and not about Cochrane. Formerly 98 (talk) 12:52, 8 December 2014 (UTC)

I hear your concern about backlash. But really, SBM (and Quackwatch) play a special role in WP. They are not like other blogs. As to the broader picture... the article is now on very solid ground asserting the (astounding to me) consensus among actual medical authorities on this drug. That cannot be buried as it was - that was a very clear violation of NPOV. And there was also violation of NPOV by our article not stating clearly in the lead that the critics have themselves been roundly criticized and dismissed; both the body and the lead probably aren't clear enough yet about how non-mainstream the view is, that tamiflu is worthless or even just harmful. I have been debating whether we should go so far as to call it WP:FRINGE. (and it is in dealing with FRINGE that SBM and Quackwatch are especially useful). This Jefferson guy is almost like Seralini with regard to his conclusions getting rejected by literally every major medical authority. The strength of the consensus I have seen so far is really amazing - I didn't understand that before yesterday. Jytdog (talk) 13:06, 8 December 2014 (UTC)

Well, there are a few more statements that have come out or been added over time. The ACP is lined up too. But on the other side of the coin, the observational studies of tami in hospitalized patients have not been uniformly positive. I have somewhat mixed feelings here. The article was clearly over the top before, and I'd surely take this drug in an epidemic of 15% mortality bird flu. But it doesnt strike me as clearly a great drug, and Roche didn't do a great job of developing it. Formerly 98 (talk) 13:14, 8 December 2014 (UTC)

It is not a great drug and no one is saying it is; this is very parallel to the psych drug situation, where the recommendation is to actually use the best drugs we have (and poor as it is, there are still not better anti-influenza drugs out there). But the Cochrane perspective has no room from grey - as Crislip writes it is "more infomercial than a nuanced discussion of a complicated topic" And so the mainstream view is that you absolutely should give it to at-risk patients in the first 48 hours. The CDC even has that in bold. What is the source for the ACP position? Thanks. Jytdog (talk) 13:25, 8 December 2014 (UTC)

http://smartmedicine.acponline.org/content.aspx?gbosId=139&resultClick=3&ClientActionType=SOLR%20Direct%20to%20Content&ClientActionData=Module%20link%20Click Formerly 98 (talk) 13:51, 8 December 2014 (UTC)

thank you but oh :( that site says "The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP." Jytdog (talk) 23:49, 8 December 2014 (UTC)

• Science-based medicine is a non-peer reviewed, self-published blog that has no impact factor and is not indexed in any scientific databases. It is, by all measures, a pseudoscientific source. -A1candidate (talk) 18:35, 8 December 2014 (UTC)

funny. per the discussion at project medicine that you just left, please drop the stick. thx. Jytdog (talk)

Please stop throwing tantrums and try to actually address my points. If Dr. Crislip wants his criticisms of Cochrane to be appreciated by the scientific community, he needs to publish them in a respectable scientific journal. It's as simple as that. -A1candidate (talk) 18:46, 8 December 2014 (UTC)

No tantrums, there is no traction in Project Med for your perspective on QuackWatch and SBM. Jytdog (talk) 19:05, 8 December 2014 (UTC)

See what WAID said. -A1candidate (talk) 19:39, 8 December 2014 (UTC)

I did see that. You have one voice on your side, on that issue in that other article. yes. Jytdog (talk) 20:28, 8 December 2014 (UTC)

And see what QG and Formerly said above. -A1candidate (talk) 21:07, 8 December 2014 (UTC)

you seem to think I haven't read the thread that I started. before you parachute into a discussion maybe you should explore what it is actually about? Jytdog (talk) 21:25, 8 December 2014 (UTC)

Let me actually bring some guideline to bear here. First of all, it is not clear that it is accurate to call it a "blog". Check out its about page. It has an editorial board, and it says that "SBM’s authors are all medically trained and have spent years writing for the public about science and medicine, tirelessly advocating for high scientific standards in health care." It has an (informal) peer review process. It is somewhere between a journal and a professional blog. Even if you want to treat it as an SPS, WP:SPS says: "Self-published expert sources may be considered reliable when produced by an established expert on the topic of the article, whose work in the relevant field ha[[s previously been published by reliable third-party publications" I don't see on what basis you can exclude it. It fills an important niche. Much like Quackwatch does. We can certainly bring this to WP:MEDRS or project medicine and get feedback for how it used here. Jytdog (talk) 21:46, 8 December 2014 (UTC)

According to WP:SELFPUB, these blogs cannot be used for exceptional claims. -A1candidate (talk) 22:23, 8 December 2014 (UTC)

no extraordinary claim is being made in the content of this article - and here is where you show that you are not even plugged into the issues concerning this article and instead are just here to piss on a source you don't like. I am not interested in that discussion. So am pretty much done here. Jytdog (talk) 22:29, 8 December 2014 (UTC)

Before you leave, do us all a favor and remove the citations to SBM. -A1candidate (talk) 22:35, 8 December 2014 (UTC)

I was just talking to you. I'm not going anywhere. You are the only one objecting here. Formerly just expressed some discomfort but gets it (I am a bit uncomfortable too); QG said IDONTLIKEIT but isn't going to push this. And that leaves just you. And 99% of what you have written here is just IDONTLIKEIT too. Jytdog (talk) 22:43, 8 December 2014 (UTC)

there are other editors here, A1 - you don't have any support to remove that on the basis that it is a bad source. Jytdog (talk) 22:54, 8 December 2014 (UTC)

No this does not qualify per WP:MEDRS. Wikipedia has an informal peer review process aswell. Doc James (talk · contribs · email) 00:01, 9 December 2014 (UTC)

ok, so A1 deleted it, I reverted it, and Doc James just deleted it with a typical funny misspelling, "You must be jocking". :) Doc James can you please say more - we use that source all the time to deal with content that goes strongly against the view of mainstream medical institutions and practice. The guy is an infectious disease doctor. In my view, it is a great source to show that criticism of Cochrane has itself been criticized, which is an important piece of the story that was left out before. and ... Are you really taking down that source? Do it here and now, and you do it everywhere in similar contexts. Thanks. Jytdog (talk) 00:03, 9 December 2014 (UTC)

Yup. We use the best available sources. In some situations sciencebasedmedicine is. In this one it isn't. Doc James (talk · contribs · email) 00:08, 9 December 2014 (UTC)

please explain why. as of today, the view of some (not all) EBM reviewers, that tamiflu is ineffective and harmful, is completely (and so far unanimously) rejected by our mainstream institutions. how is that different from say, the claim that acupuncture is effective to treat flu? it is strange to me that you are taking a stance similar to the purveyors of woo here. Jytdog (talk) 00:10, 9 December 2014 (UTC)

I think Jytdog has a point. IF sciencebasedmedicine.org is a reliable source in one context, it doesn't suddenly become unreliable because it expresses a POV that someone does not like. It has been quoted by the US Preventative Services Task Force, for example. On the other hand the quote seems to me to go overboard. Per WP:IMPARTIAL we are encouraged to avoid direct quotes from participates in hotly contested debates. I think something along the line of "Mark Crislip expressed the opinion that conclusions of the cochrane review were more expansive than what could be supported by the evidence" would easily suffice. Formerly 98 (talk) 00:37, 9 December 2014 (UTC)

Formerly, I took the quote of the article content early this morning. The only quotes that were left, were inside the refs. Jytdog (talk) 01:01, 9 December 2014 (UTC)

Doc James you just trimmed the bot-replaced text you are still around. please do respond to my question above. thx. Jytdog (talk) 01:02, 9 December 2014 (UTC)

That was not what I said. One uses the best available sources. Thus we sometimes use primary sources when their are no high quality reviews available. Doc James (talk · contribs · email) 01:52, 9 December 2014 (UTC)

It is interesting how some appear to be referring to the Lancet,[16] BMJ [17], Cochrane [18] and PLoS[19] as fringe. The recent RfC did not support this position. Doc James (talk · contribs · email) 01:57, 9 December 2014 (UTC)

I am sorry but it is bullshit to say that I or any of the other reasonable participants here are calling entire medical journals FRINGE. We can discuss without making each other out to be morons. Please strike. Jytdog (talk) 02:08, 9 December 2014 (UTC)

That said, I appreciate that your edits to the article are an effort be responsive to what we've been trying to say. Thanks for that! But let's see how the RfC turns out. We may be reducing WEIGHT of the reviews yet further. Jytdog (talk) 02:11, 9 December 2014 (UTC)

Yup this is getting rather confrontational. Would advise that you tone it down a bit. Doc James (talk · contribs · email) 02:18, 9 December 2014 (UTC)

Again, please strike. No one here called entire journals FRINGE. Jytdog (talk) 02:20, 9 December 2014 (UTC)

You state "both the body and the lead probably aren't clear enough yet about how non-mainstream the view is" So you are stating that these journals are publishing non-mainstream / fringe articles which would imply that the journals are non-mainstream / fringe for publishing them. Especially as it is not just a one off but they have published multiple Doc James (talk · contribs · email) 02:28, 9 December 2014 (UTC)

saying that an article takes a FRINGE view is very very different from calling a whole journal fringe. We get bullshit like the from woo pitchers all the time ("NEJM says X"!) and you and I are both way more sophisticated than to make crap claims like that ourselves, much less make them about each other. Jytdog (talk) 02:46, 9 December 2014 (UTC)

you said we use the best sources. so what is the best for showing that Jefferson has an ax to grind that twists his recommendations (did you read the showboating "Implications for practice" in the 2014 Cochrane Review? oy.) That is what Crislip shows with careful detail. Jytdog (talk) 03:33, 9 December 2014 (UTC)

Readability

Readability at this point needs work. Eight of the first eleven statements in the article are attributed, making the article read a little like a joint Republican-Democrat report on ObamaCare. And we now use Tamiflu to treat "High Risk" (according to the United States Centers for Disease Control (CDC), European Centers for Disease Control (ECDC), Public Health England, IDSA and American Academy of Pediatrics, though we shouldn't according to a Cochrane Review and a meta analysis of meta analyses). Important to think about the readers and what serves their needs. Formerly 98 (talk) 13:47, 9 December 2014 (UTC)

While I think it is currently decent and better than it was previously. We reflect the major positions with respect to this medication.

We clearly describe where the disagreements occur and where they do not now that we have the medical uses split into three sections for its three uses.

What suggestions do you have for improving it? It is hard to make controversy simple. Doc James (talk · contribs · email) 20:27, 9 December 2014 (UTC)

Same sentence repeated twice

"The medical establishment rejected the recommendations of the 2014 Cochrane review to urgently change treatment guidelines and drug labels.[4][6][7][8][21][23]" This is overkill to repeat the same sentence twice. QuackGuru (talk) 04:28, 9 December 2014 (UTC)

Yup agree. We should mention it once under medical uses. Doc James (talk · contribs · email) 04:42, 9 December 2014 (UTC)

The part "the medical establishment rejected" the recommendations of the 2014 Cochrane review might be a SYN violation. Does each individual source represent the "medical establishment"? Both sentences might have to be deleted. QuackGuru (talk) 04:46, 9 December 2014 (UTC)

as i wrote in my edit note and above, am trying to deal with the tripartite structure and the rejection of Cochrane 2014's recommendation to "urgently change guidelines". and am trying to be concise and not repeat the laundry list of initials. But yes in my view they represent the medical infectious establishment pretty darn thoroughly - and together they make a powerful statement. I checked before and each one that I originally had there explicitly refered to the publication of the Cochrane study. I know that the CDC one does (it is a press release about it... "did you hear?"); i know the IDSA one does, and the reuters EMA/Roche one for sure does. The ECDC one is also a piece put out directly to deal with the Jefferson flurry... and the Peds one also explictly addresses it. Jytdog (talk) 04:50, 9 December 2014 (UTC)

this is what i have been trying to say to you guys. the medical establishment for the most part just spit it out. the implications section was way too strong. Jytdog (talk) 04:51, 9 December 2014 (UTC)

Yup issues with "the medical establishment" But right know we have students handing in their assignments so other things to deal with. Doc James (talk · contribs · email) 04:56, 9 December 2014 (UTC)

I could not find one source that does say it is the "medical establishment". I'm not finding it. Can we remove the duplication for now? QuackGuru (talk) 04:59, 9 December 2014 (UTC)

'll fix it. ugly. Jytdog (talk) 05:04, 9 December 2014 (UTC)

QG what is your solution for dealing with global rebuttal and the tripartite structure. Please try to deal with the problem.Jytdog (talk) 05:05, 9 December 2014 (UTC)

The problem is the repetitive text. Both sentences are repetitive. QuackGuru (talk) 05:11, 9 December 2014 (UTC)

Current text: "The United States and European Centers for Disease Control (CDC), Public Health England, Infectious Disease Society of America, and the American Academy of Pediatrics, and Roche (the originator) reject the conclusions of the Cochrane review, arguing in part that the analysis inappropriately forms conclusions about outcomes in people who are seriously ill based on results obtained primarily in healthy populations, and that the analysis inappropriately included results from people not infected with influenza.[4][6][7][8][21]" See Oseltamivir#High risk.

Repetitive text: "The United States and European Centers for Disease Control (CDC), Public Health England, Infectious Disease Society of America, and the American Academy of Pediatrics, and Roche (the originator) rejected the recommendations of the 2014 Cochrane review to urgently change treatment guidelines and drug labels.[4][6][7][8][21][23]"

Even more repetitive text: "The United States and European Centers for Disease Control (CDC), Public Health England, Infectious Disease Society of America, and the American Academy of Pediatrics, and Roche (the originator) rejected the recommendations of the 2014 Cochrane review to urgently change treatment guidelines and drug labels.[4][6][7][8][21][23]"

There is way too much repetitive text in the article. Now the article states the same WP:POINT three different times. QuackGuru (talk) 05:11, 9 December 2014 (UTC)

Quack, I have said what problem I was trying to address - please suggest a different way to fix it. Thanks. Jytdog (talk) 12:13, 9 December 2014 (UTC)

Part of the problem here is that the Cochrane review does two things: a) presents results of meta-analysis; b) makes recommendations on changing treatment guidelines.. In our "use in healthy people" section, the recommendation (b) is reported: "They recommended that guidance should be revised to take account of the evidence of small benefit and increased risk of harms. Moreover, the authors stated that their conclusions are similar to those reached by the U.S. FDA at the time of approval; that randomized clinical trial data supported the use of oseltamivir for the prevention and treatment of flu symptoms only, and did not support claims of prevention of infection, transmission, or complications". That recommendation was heard by the medical institutions and was responded to with near unanimity with rejection, and so we need the iteration of that rejection here. . note - I removed the text about "the authors stated that their conclusions are similar to those reached by the U.S. FDA at the time of approval; that randomized clinical trial data supported the use of oseltamivir for the prevention and treatment of flu symptoms only, and did not support claims of prevention of infection, transmission, or complications" as this is just argumentation for their recommendation, not their recommendation itself.Jytdog (talk) 13:22, 9 December 2014 (UTC)

i looked at this more closely and felt OK taking out the iteration of the medical consensus view in the prevention section, as a) we don't pass on Jefferson's assertions about changing treatment guidelines in this arena and b) what we express about the medical consensus and the reviews is close enough for horseshoes. Jytdog (talk) 13:22, 9 December 2014 (UTC)

I think it would be better to find one source that summarises the medical bodies. That way the clunky sentence can be shortened. I'm not sure about repeating similar statements twice. QuackGuru (talk) 20:31, 9 December 2014 (UTC)

Done edit warring for the night

Have other stuff to do. I recommend others do the same, as any changes made now are likely temporary and contingent upon the results of the RFc. Formerly 98 (talk) 03:19, 9 December 2014 (UTC)

Ah, not separating the three uses of oseltamivir out to discuss them such as your revert did was highly unproductive. Doc James (talk · contribs · email) 03:45, 9 December 2014 (UTC)

Put in a request for full protection given our inability to behave like adults. Formerly 98 (talk) 03:47, 9 December 2014 (UTC)

If you like. Doc James (talk · contribs · email) 03:47, 9 December 2014 (UTC)

The RFc is vague and not relevant to any specific sentence. QuackGuru (talk) 03:48, 9 December 2014 (UTC)

"Highly unproductive"? It was an attempt to restore the last version that was apparently acceptable to all parties that took 2 minutes and which was reverted with an additional 10 seconds consideration and 10 seconds of effort. In contrast, last night's 7 hour edit war (conducted in the middle of an RFc) gave us introduced errors, scrambled references, and an arguably less readable article. I'll stand by the productivity of my efforts here. What will be done about the readability issue? Or do we need to spend another week hashing over whether it is 3 or 4 organizations that recommend prophylaxis in nursing home residents? Formerly 98 (talk) 13:53, 9 December 2014 (UTC)

With respect to "spend another week hashing over whether it is 3 or 4 organizations that recommend prophylaxis in nursing home residents".

That was the reason for the revert? Seems fairly easy to address. Has it not already been addressed? Mashing all uses together in one paragraph / section does not improve readability. Doc James (talk · contribs · email) 20:35, 9 December 2014 (UTC)