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Cochrane Reviews: The Food Babe of Medicine?

There are two topics about which I know a fair amount. The first is Infectious Disease. I am expert in ID, Board Certified and certified bored, by the ABIM. The other, although to a lesser extent, is SCAMs.

When I read the literature on these topics, I do so with extensive knowledge and, in the case of ID, 30 years of clinical experience. The extensive knowledge, and, one hopes, understanding, has led me to read meta-analyses with a grain of salt substitute. They average meta-analysis and systematic review is good for gaining a general understanding of the topic within, as well as, and here is the key phrase, the limitations of the included studies.

And like all the published literature, when writing a meta-analysis, those with an axe to grind will grind it. Even, or perhaps especially, the Cochrane reviews.

Just because something is labelled as a systematic review does not mean it is any good. We have to be just as vigilant now as ever. Even a review with a Cochrane label does not make its true. Four out of 12 Cochrane reviews on acupuncture were wrong. Caveat lector rules, OK?

Randomized placebo-controlled trials can be definitive if done well. But all too often they are done on a well-defined population and how widely applicable the results are, is always a question. When I was a resident it seemed all the cardiovascular intervention studies were done on a VA population and we wondered how applicable outcomes on old, white, male, smokers were to other populations.

All clinical trials are part of a context of the medical literature and Xigris was a classic example of how a single study may not be definitive or even right. Even in a field as binary as ID, it is not always clear cut what the right intervention is from individual clinical trials and you have to try and synthesize a conclusion from the preponderance of the data.

As I have mentioned before, the theory behind meta-analyses is that if you gather all the cow pies into one big pile you get clinical gold. I think they are often better as an overview on a topic rather than as a tool for coming to a conclusion as to the benefit of a particular intervention, especially since meta-analysis do a poor job of predicting the results of a (perhaps) definitive (ha) clinical trial.

GIGO is perhaps the more common result of a meta-analysis. Reading the Cochrane review of late, I am less certain that their output is gold, but a larger pile of the original material.

Take oseltamivir (aka Tamiflu). Please.

As mentioned, I am an Infectious Disease doctor and this year was the second-worst influenza outbreak of my career. One of the hospitals in our system is a level-one trauma center and we offer ECMO, so we see those who are the most ill from influenza. I will say, on balance, I was glad we have oseltamivir during outbreaks.

How (or perhaps do) ID docs think? Infections are caused by germs. Duh. But not everyone thinks so. Germs come in a wide variety of forms: viruses, bacteria, fungi, parasites and more. I once did a rough count and, if you are splitter, there are about 1,200 common germs I need to know to do my job. See. ID isn’t that hard.

We treat these germs with antibiotics. Antibiotics usually interfere with one biochemical pathway or another to kill or disable the germ. Antiseptics, like alcohol, kill non-specifically. Some antibiotics are cidal (they kill germs) and some are static (they stop the germ from functioning, but once the antibiotics is removed they get back to business as usual). For many infections, but not all, static is good enough. Stop the bug from dividing and the host immune system, if there is one, will have time to catch up and take care of the infection.

Viruses are not alive (the debate as to what is alive can go on in comments), so they can’t be killed. It is part of reason antivirals are just OK as a therapeutic intervention. It would be nice if our drugs against viruses were as good as our drugs against S. pyogenes, eradicating them. But they don’t.

As a clinician what you expect with an antiviral is to take the edge off the illness. If you have genital herpes, you will get fewer attacks with less severity. For HIV it took the use of three antivirals to have a significant effect of the virus and they are still not a cure. And for influenza you would expect a mild amelioration of the disease given that the drugs are usually given late into a process of robust viral replication.

Of course not all viruses are the same and not all infections are the same. Outcomes depend on a complex integration of pathogen life cycle, pathogenicity, the host’s immune function and the ability of the medication to affect the organism. And sometimes, for some patients, the difference between doing well and doing poorly may be due to relatively small shifts in favor of the infection.

Oseltamivir is an OK drug for the treatment of influenza. By the time most patients get to a doctor, get the medication filled and then get steady state with drug, the virus has had several days to run rampant and I would not expect that oseltamivir would, in normal people, do much more than take the edge off. And, as the recent meta-analysis in the BMJ demonstrates, that is what oseltamivir does in relatively normal people in the outpatient setting.

Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

As we have known for a while, oseltamivir shortens illness by about a day. In relatively normal outpatients. It may reduce pneumonia and it modestly reduces the risk of symptomatic flu in individuals and households. And there are side effects. There always are. The results of the meta-analysis confirm what was known. Oseltamivir is a drug of modest efficacy in treating influenza in a mostly normal outpatient population.

The authors did a tremendous amount of work and the basic results are sound. Then the editorializing slips in, ground to the fineness of the atomic axe.

Two of the authors have a strong bias against the treatment and prevention of influenza by the current methodologies. I have discussed Jefferson’s semi-coherent arguments concerning influenza in another post and it is safe to say that Doshi and I are not on the same planet about influenza since he considers that:

For the vast majority, influenza is unpleasant but self-limiting.

It is a characteristic of those who are against the current treatments and prevention of infections to directly, or indirectly, minimize those who suffer and die from infections. They usually use the word ‘only’ in front of morbidity and mortality statistics.

It is certainly true that I see the minority of influenza patients: those trying to die. The 18,000 who died in 2009 in the US of H1N1 were a minority of the 60.8 million cases. As a physician I tend to side with John Donne in my approach to the ill and dying:

No man is an island,
Entire of itself,
Every man is a piece of the continent,
A part of the main.
If a clod be washed away by the sea,
Europe is the less.
As well as if a promontory were.
As well as if a manor of thy friend’s
Or of thine own were:
Any man’s death diminishes me,
Because I am involved in mankind,
And therefore never send to know for whom the bell tolls;
It tolls for thee.

If the patient is sick enough to be hospitalized, prompt therapy with oseltamivir probably decreases the odds of needing ICU care and if you are in the ICU or pregnant, probably decreases your chances of dying. Note “decreases the chance”. The data is not great, but consistent: in hospitalized patients, oseltamivir decreases the chance of death. When thinking about treating populations during a pandemic, having sufficient medication available will be a good thing for those ill enough to require hospitalization.

The problem if you are deciding to stockpile drug for an infection like influenza is virus’s variability. This century we have had influenza with high mortality but low infectivity and low mortality and high infectivity. When, not if, we get a strain of influenza with both high infectivity and mortality, we will probably be thankful that we have oseltamivir and given the data it will probably prevent some from dying of the disease.

Of course, those in public health are screwed no matter what they do. If they prepare and the pandemic does not occur, they have wasted money. And if there is an event that is the ID-equivalent of Katrina, no preparation will ever be enough. The scariest thing in my career was the 2009 H1N1, when in Portland every bed in the ICU and every ventilator we had was being used. If another patient came in with flu and needed ICU support we had nothing to offer them. And, by total luck, we peaked exactly at our surge capacity. And, thanks to the ICU, ECMO and maybe oseltamivir, some people that should have died, did not.

Whether we should stockpile anti-influenza medications, spend the money and time, is an interesting political questions. Of course we never have honest conversations about health care in the US, so let’s make a decision based on a good study with flawed and misleading propaganda in the discussion and conclusion. Sounds about right for a county that got all wiggens about death panels.

However, I do not think the data on the efficacy for treating influenza in relatively healthy outpatient populations during influenza seasons of relatively low mortality really informs decisions as to the appropriateness of stockpiling drugs for a repeat of the pandemic of 1919 (an estimated 675,000 Americans among the dead) or if one of the bird influenzas becomes more contagious.

They allude to this exact issue in their conclusion:

Given that oseltamivir is now recommended as an essential medicine for the treatment of seriously ill patients or those in higher risk groups with pandemic influenza, the issues of mode of action, lack of sizeable benefits, and toxicity are of concern. This is made worse by the record and stated intentions of governments to distribute oseltamivir to healthy people to prevent complications and interrupt transmission on the basis of a published evidence base that has been affected by reporting bias, ghost authorship, and poor methods.

We believe these findings provide reason to question the stockpiling of oseltamivir, its inclusion on the WHO list of essential drugs, and its use in clinical practice as an anti-influenza drug.

Note: seriously ill patients or those in higher risk groups. Those not covered in this meta-analysis. Those who may die and, at least from observational studies, get benefit from oseltamivir. I like how they analyzes one patient population then tries to apply it to another population where the preponderance of data suggests benefit. And if you are dying of flu, those side effects are of a little less importance. I would take a bit of a headache and kidney dysfunction to avoid being buried 6 feet under.

Not that it stopped anyone from reporting the conclusions of the study without a modicum of critical thought. Most of the secondary reporting repeated the no stockpiling message and that oseltamivir therapy wasn’t good. The anti-Tamiflu propaganda component seems to have far exceeded the actual results of the paper.

I would lean towards the stockpile. I like to keep the bell from tolling. But to use the BMJ as evidence against stockpiling for a more virulent pandemic is, to my mind, inappropriate. Like I have often said, a meta-analysis is useful if you can use it to confirm your pre-existing bias and ignored if it does not.

That bias can lead to some really Food Babian discussion, as is evident in the BMJ article. They suggest in the conclusion that there are

the issues of mode of action

for oseltamivir. The paper says

Oseltamivir may have anti-inflammatory properties that make people with influenza-like illness feel better by shortening the duration of symptoms and reducing the occurrence of symptoms

and

Sufficient plasma concentrations of oseltamivir carboxylate from orally administered oseltamivir phosphate may act directly on the host’s endogenous neuraminidase to reduce (or suppress) the immune response. The potential hypothermic or antipyretic effect of free oseltamivir as a central nervous system depressant may also contribute to the apparent reduction of symptoms.

As Mr. Doo says, “Huh?” Both of these paragraphs are not referenced. Residents at my hospitals know I am enamored of the immunomodulatory effects of antibiotics. I had never heard of either of these effects with oseltamivir so I went looking.

In mice, oseltamivir given at 30 to 1,000 times the human dose causes hypothermia. In another mouse model oseltamivir led to a decrease in a variety of pulmonary cytokines. Color me unimpressed, and if you are going to use the mouse model, might as well include all the animal studies that show increased survival with oseltamivir. No wait. Only including statements that support your contention is the Food Babian way.

Oseltamivir is a neuraminidase inhibitor, serving as a competitive inhibitor of the activity of the viral neuraminidase (NA) enzyme upon sialic acid, found on glycoproteins on the surface of normal host cells. By blocking the activity of the enzyme, oseltamivir prevents new viral particles from being released by infected cells.

As a rule when you inhibit viral replication you give the immune system a chance to catch up and you slow down the disease. I can find no data that the immunomodulatory effects of oseltamivir are relevant in human disease at standard dosing and the data in humans and animals all point to the usual mechanism by which an antimicrobial works.

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 [sic].

Oseltamivir might induce a low immune response with low levels of pro-inflammatory cytokines. This may reduce symptoms of influenza, but is not related to inhibition of virus replication. There is also a potential temperature lowering effect that can contribute to symptom reduction. The influenza virus specific mechanism of action proposed by the producers does not fit the clinical evidence. Evidence rather suggests a multi-system and central action.

Not. It is amazing how easily and rapidly cow pies get spread on the internet. I suppose a meta-analysis gets halfway around the web before the truth has a chance to get its shoes on.

As best I call tell, these two ideas are more for the purpose of FUD. It is of Food Babian proportions to suggest the primary mode of an antiviral is due to immunomodulatory effects instead of messing with viral replication, considering the nature of the data supporting the idea. All the data suggests benefit by slowing down the virus.

They continue

Oseltamivir relieves symptoms in otherwise healthy children but has no effect on children with asthma who have influenza-like illness, a population that should most benefit from its intake.

Should it? I don’t know. That is why we do studies. I would expect valacyclovir suppression to help with recurrent herpes meningitis. It doesn’t. It makes the disease worse. That doesn’t mean that valacyclovir is ineffective for other manifestations of the disease or in other patient populations.

An explanation for this finding is in the nature of the young asthmatic population, which is well cared for and used to a regular intake of powerful drugs and close follow-up. The incremental benefit of oseltamivir assumption is thus likely to be undetectable in such a population.

On the other hand, once lung inflammation started because influenza I would expect cough and SOB to be hard to control as the asthma kicked in, and inhaled steroids, known to increase the risk of pneumonia and TB, may suppress local inflammation to decrease the local immune response in favor of the infection and prolong illness.

The oseltamivir trials did not detect any influenza related mortality events, a reflection of the benign nature of influenza and influenza-like illness and perhaps trial design.

Or it could have been healthier populations with prior immunity from prior disease exposure and vaccinations. Outpatient antibiotic studies are usually done in patients with little risk for mortality and until the 2009 H1N1 flu seasons have been relatively mild, except to those who died. The mortality from flu leading up to the release of oseltamivir in 1996 were comparatively low. Test a drug during a benign flu season and you will not see mortality.

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 other goofy Cochrane reviews that leave we wondering about their standards. They evidently operate on the assumption that every intervention, no matter how ridiculous, should be subject to a meta-analysis. When all you have is a hammer, everything is a nail. So we get acupuncture for mumps.

We could not reach any confident conclusions about the efficacy and safety of acupuncture based on one study. More high-quality research is needed.

No it isn’t.

Or Homeopathic Oscillococcinum(®) for preventing and treating influenza and influenza-like illness..

Our findings do not rule out the possibility that Oscillococcinum(®) could have a clinically useful treatment effect [although reality does ed.] but, given the low quality of the eligible studies, the evidence is not compelling.

They think a meta-analysis on magic is going to have compelling results. It is a tough job but someone has to see if magic is effective. But if you want the ultimate in goofy, you have to turn to “Vitamin C for preventing and treating the common cold” which contains what may be the most dumbass statement in the medical literature of 2014. Here goes:

Authors’ conclusions .The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out.

Fine so far. The literature shows vitamin C is of minimal benefit, and probably none, for cold treatment and prevention. As the main conclusions say

Thirty one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration.
Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials.

Here it comes. Ready? It is really muttonheaded. Do not say I did not warn you, because, as my favorite box of blinking lights likes to say, it has napalm levels of burning stupid.

Nevertheless, given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety,

Here it comes, the apex of idiocy.

it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them.

A more pathetic example of what’s-the-harm shrugery I cannot imagine.

As if there is any way a patient can really know if vitamin C does anything. Cochrane, please, give me a framework I can suggest to my patients that they can apply to help determine if vitamin C is effective. I am waiting. Godot will arrive sooner.

The uselessness of personal experience in determining efficacy of medical interventions is why we do clinical trials. For crying out loud, I though it the raison d’être of the whole Cochrane Collaborative: relying on evidence instead of anecdotes. Wrong.

The biases alone render such an endeavor useless. It is why the words “In my experience” are the most dangerous in medicine for determining if an intervention is effective. And it is what they suggest. Why even bother with the analysis in the first place?

If there is a worse statement in all the published evidenced-based medicine, let me know.

There was a time when I was under the impression that the conclusions of a Cochrane review were of value. No more. Now I see one and a roll my eyes. What kind of Food Babian nonsense is this one going to have?

Posted in: Basic Science, Clinical Trials, Critical Thinking, Pharmaceuticals, Science and Medicine

Leave a Comment (86) ↓

86 thoughts on “Cochrane Reviews: The Food Babe of Medicine?

  1. R.w.Foster says:

    So, you dismiss the entirety of the review system based on a couple reviews you didn’t like? What, then, would you suggest to replace them? And, how are we to know the replacement will be any better?

    1. MadisonMD says:

      And, how are we to know the replacement will be any better?

      My criteria for an improved replacement are:
      (a) That it would consider prior plausibility; and
      (b) It would avoid inviting homeopaths, soothsayers, or voodoo priestesses from authoring reviews on these subjects.

      If the replacement met these criteria, I would conclude it is better than Cochrane.

  2. Darwy says:

    Influenza is unpleasant but self-limiting?

    Really? What planet is he living on, that influenza is just ‘unpleasant’? And self-limiting – yeah, you either survive it, or you don’t.

    I’ve had influenza. I don’t actually have any *memory* of having it, because I was so sick for two weeks my parents thought I was dying. Febrile seizures, etc – you name it, I had it.

    1. Calli Arcale says:

      Re: self-limiting.

      You make a good point, there, as to the uselessness of this phrase. It’s like the old dictum that “all bleeding stops eventually”. And it does, one way or another. So whether or not it’s self-limiting isn’t the point. The point is whether or not we can make it end faster and with a better outcome or at least make the duration less unpleasant.

      I’m recovering from some kind of upper respiratory tract infection, and I’m pretty sure it was not influenza. But it sucked all the same, with three days off work (and it probably should have been four, given how useless I was on the day I tried to come back to work too soon; the commute alone wiped me out and I got nothing accomplished). Yeah, I didn’t die, I didn’t need ER care, I didn’t need the ICU. But damn, I hate having a cold.

    2. Max says:

      “For the vast majority, influenza is unpleasant but self-limiting.”
      For the vast majority. I mean, it’s nothing to sneeze at, but argue with the actual claim, not a strawman.

  3. Motherofmultitudes says:

    I read this article with great interest this morning. I have an asplenic, immune-compromised 1 year old with “multiple congenital anomalies and complex past medical history” (as they like to tell it on rounds). In her short little life, of dealing with multiple bouts of sepsis, cellulitis, endocarditis, muktipke UTIs leading to urosepsis, the flu is not something I think is “no big deal” for her. We have a large family and all my children including my 1 year old were vaccinated against the flu.

    Unfortunately, my 4 yo son had battled several respiratory illnesses this winter, and one night got sick again with a really high fever. I treated him at home with supportive measures. My youngest had no fever but started to look unwell, so I took her to the ER. We actually thought she likely had another UTI. Imagine our shock next morning when she turned up positive for H1N1 that in retrospect she likely caught from her older brother. We started her on tamiflu right away, before symptoms had fully started. And thankfully, tamiflu started less than 24 hours of oresentation helped *tremendously* with drastically mitigating the symptoms of the flu.

    Unfortunately, taxing her poor little immune system with having to fight the flu, even with help from tamiflu, meant that she wide open to other opportunistic pathogens. Septic shock ensued and the cascade of the domino effect where illness worsens her endocrine disorders, worsens her cardiac function, throws her GI system into chais, which in turns worsens her endocrine issues and round and round we go,mtrying desperately to roll the rock back hill. She got the flu in February and we are still inpatient today, dealing with the ramifications of H1N1. She has almost died several times.

    And maybe she is a “rare” case. But the thing that confounds me is listening to anti-vaccination groups is how much they harp on on the serious complications of vaccines that are also very rare. Yet, that doesn’t stop them from acting like vaccines are the worst thing in the world.

    My child can’t have live vaccines; it isn’t medically safe. Which means she is unprotected against things like the measles outbreak in my area, from parents who are so afraid of the rare side effects of an MMR vaccine they don’t mind potentially killing *my* child with the measles all while they talk about how measles itself “isn’t a big deal.”

    Dont get me started. I will never understand.

    1. Calli Arcale says:

      *HUGGLES*

      Thank you for sharing your story, and I hope your daughter gets better soon and can come home. People need to hear stories like yours, to know that yes, it *can* be terrible, and not just uncomfortable, so they know the real cost.

    2. Young CC Prof says:

      Thank you for sharing your story. It grinds my gears when people claim that these diseases are “only dangerous in the immunocompromised.”

      1) Not necessarily true, occasionally perfectly healthy children or working-age adults get dangerously ill from flu.

      2) So, immunocompromised people don’t MATTER? What kind of horrible person says something like that?

    3. Chris says:

      Thank you for sharing. Lots of hugs. While my oldest has put me through the wringer with his medical issues, they pale compared to your challenges.

      And maybe she is a “rare” case.

      Oddly enough, it is not rare when it is your own child.

      But the thing that confounds me is listening to anti-vaccination groups is how much they harp on on the serious complications of vaccines that are also very rare. Yet, that doesn’t stop them from acting like vaccines are the worst thing in the world.

      They really hate it when I tell them that my kid had seizures and ended up at the hospital from one of “mild” diseases before there was a vaccine. They also get upset when I ask them if the vaccine affects their child so much, why would they fair better with the actual disease.

      On a side note: I am very glad that the hospital where my son had open heart surgery does require influenza vaccines from its employees.

    4. lilady says:

      Dear Motherofmultitiudes,

      Thank you for sharing your story about your youngster. I’ve “been there” and “done that” with my own multiply handicapped son who was born with congenital anomalies and who was immune compromised (pancytopenia) and medically fragile.

      Your precious daughter and other children with similar disorders…and infants who are too young to have received the primary series of the Recommended Childhood Vaccines, are the reason why (the Science Based Medicine bloggers, parents and child advocates), fight for parents to get accurate information about vaccines and the serious, oftentimes deadly, diseases they prevent.

      My very best wishes to you, your little girl and your family,

      Warmly, lilady

    5. Max says:

      So the flu shot didn’t work for your 4-year-old son either, even though it was supposed to cover H1N1.

      1. Chris says:

        Where does it say the vaccine is 100% perfect? And if one child has an immune problem, there might be a reason for the older child to also have a milder form. This is perhaps the reason for this sentence: “Unfortunately, my 4 yo son had battled several respiratory illnesses this winter, and one night got sick again with a really high fever.”

        Her story shows the importance for strengthening community immunity by making show all that can get immunized get vaccinated for influenza.

      2. Max says:

        Doesn’t sound like Tamiflu helped tremendously either, what with septic shock ensuing and the child almost dying several times. Maybe it did save her life, or maybe this is the placebo effect in the parent.

        1. Chris says:

          This is what she said: “We started her on tamiflu right away, before symptoms had fully started. And thankfully, tamiflu started less than 24 hours of oresentation helped *tremendously* with drastically mitigating the symptoms of the flu.”

          What exactly is your point?

          Do you need to be reminded that this is a child with an immune disorder? Again, it is an argument for more community immunity. So, please help by by getting your annual flu shot, it could help another person like her.

          Again, to repeat the mother: “And maybe she is a “rare” case. But the thing that confounds me is listening to anti-vaccination groups is how much they harp on on the serious complications of vaccines that are also very rare. Yet, that doesn’t stop them from acting like vaccines are the worst thing in the world.”

          If you have no medical condition that prevents you from getting an annual flu shot, make sure you get one. And make sure that your next tetanus booster is a Tdap if you have not already had the one with added pertussis protection.

          1. Max says:

            If the anecdote was supposed to demonstrate the efficacy of the flu vaccine and Tamiflu, it wasn’t very convincing. If the point was that flu is dangerous to immunocompromised children, then no shit.
            Anti-vaccination groups think vaccines are not effective, and this anecdote only reinforced that.
            I think the flu shot didn’t work for me either this year.

            1. Chris says:

              Then you need to work on increasing your reading, biology and logic comprehension.

              Especially when applying the Nirvana Fallacy to those whose codons don’t exactly align with adequate immune function.

            2. Chris says:

              Some extra reading for you:
              http://www.sciencebasedmedicine.org/protect-yourself/

              You seem to be perfectly described in Bullet Point #15.

              1. Max says:

                Is that the one about people who didn’t get the flu shot that I got?

                When you learn that something didn’t work for someone, that doesn’t mean it doesn’t work at all for anyone, but it is a small bit of evidence against the thing’s efficacy, not in favor of it.

              2. Chris says:

                Why don’t you just read it? All you have to do is click on the blue text and it will take you to the page. If it helps just search for the word “budget.”

      3. Motherofmultitudes says:

        Max, we are a family of 10. I have 8 children. We all received the flu shot. My 4 year old is otherwise a healthy child but has had a bad winter with upper respiratory viruses and had been in a “sick leads to more sick” cycle for a while. That is the reason the medical team believes he got the flu and then my immuno compromised daughter after him. No one else in our family got the flu, despite the obvious close contact and exposure.

        Because my daughter received tamiflu so rapidly, she never showed any major symptoms of the flu itself. Her lungs looked fantastic. She didnt even cough. Considering her underlying cardiac and pulmonary issues, that was a pretty incredible win. What fighting the flu did do, even with antivirals on board, was tax her body enough winning the war against the flu that she was further immune-suppressed with a more severe pan-cytopenia than is normal for her and she picked up a bacterial infection that caused the septic shock. Tamiflu, as you know, isn’t anti-bacterial.

        Because her complex medical issues are all interconnected, it is a domino affect either down the spiral or up the up the spiral. Tamiflu was effective at mitigating the symptoms of the virus it was prescribed for. Yet the flu itself was enough to trigger us down the downward spiral we are still inpatient trying to correct.

        No vaccine is 100% effective. My daughter clearly had an insufficient response to the flu vaccine. And she can’t get vaccines like the MMR at all. I know I certainly can’t force anyone else to vaccinate their children, nor would I want to. But the more people vaccinate the more it lessens the risk of exposure for my child. There is a measles outbreak in my area. There is no “tami-measles” we can give her if she contracts measles, to mitigate symptoms and complications. My daughter could very likely die from measles or its complications and there is nothing I can do about it except limit her contact with the outside world and ensure all of those in contact with her are appropriately immunized. . That is a terrifying fact I get to live with.

        I apologize if I come across as a poor communicator of my larger point.

  4. David Gorski says:

    I really do think the reliability of Cochrane Reviews strongly depends on the section from which they’re coming. The Acute Respiratory Infections Group (ARI) run is run by Tom Jefferson, whose bias and anti-flu vaccine bias have been dissected here and elsewhere many times. That he apparently enlisted someone like Peter Doshi, who is well known in the antivaccine whackosphere as a sympathetic voice and is a signatory on a prominent HIV/AIDS denialist statement:

    http://thepoxesblog.wordpress.com/2013/10/07/science-and-reality-and-aids-denialism/

    http://aras.ab.ca/rethinkers.php

    Clearly, the ARI section is biased against the flu vaccine, and it’s got at least two reviewers whose ability to evaluate epidemiological data is at best questionable. I sometimes fear that the mammography section is heading down that road.

    It’s all because Cochrane is infused with a cognitive blind spot that I’ve heard described as “methodolatry,” namely the obscene worship of the randomized clinical trial as the only valid means of clinical investigation:

    http://scienceblogs.com/effectmeasure/2009/10/24/journalists-sink-in-the-atlant/
    http://www.sciencebasedmedicine.org/methodolatry_my_new_favorite_term/
    http://www.sciencebasedmedicine.org/blatant-pro-alternative-medicine-propaganda/

    Oh, and Tom Jefferson has appeared on Gary Null’s radio show:

    http://scienceblogs.com/insolence/2013/01/25/cochranes-tom-jefferson-on-gary-null-show/

    1. Sawyer says:

      Tom Jefferson, not Tom Cochrane. I spotted that because I have made the same mistake. :)

      Although I would love to hear the remix “Tamiflu Is Highway, I Wanna Deride It”.

  5. jpmd says:

    Many of the meta-analylsis reviews suffer from the garbage in- garbage out problem. That is also why I get frustrated with the AAFP’s American Family Physician, which is big on referring to Cockrane.

  6. Ed Whitney says:

    What exactly is the axe that Jefferson is grinding? There is a back story which begins in 2006 with his Cochrane review of neuraminidase inhibitors which supported conclusions that it reduced the risk of complications in adults. However, a Japanese pediatrician pointed out to Cochrane that their analysis was based on incomplete evidence, since 8 of the 10 studies included in that analysis had not been published. Trial data that goes unpublished seems to me to be the issue that got Jefferson and Doshi on the warpath and led to their criticism of Roche and its handling of that data.

    No criticism of the Cochrane review of Tamiflu is complete without some discussion of this issue.

    1. David Gorski says:

      Trial data that goes unpublished seems to me to be the issue that got Jefferson and Doshi on the warpath and led to their criticism of Roche and its handling of that data.

      Citation, please. I’d love to know if this is true.

      I also don’t buy that that’s what got Doshi on the warpath. He’s shown antivaccine (at least, anti-flu vaccine) proclivities for a long time now, having shared a stage with Andrew Wakefield at least twice, once at the NVIC conference in 2009 and once in Jamaica a couple of years ago. I predict it won’t be long before Doshi is appearing at AutismOne.

      1. DJ Nrrd says:

        Ben Goldacre summarises in the Guardian

        It names Jefferson but not Doshi

      2. Ed Whitney says:

        Reference was http://www.cochrane.org/features/neuraminidase-inhibitors-preventing-and-treating-influenza-healthy-adults-and-children which has a link to a Jefferson/Doshi NY Times editorial in which they decry the Tamiflu unpublished trial data and outline what they saw as a struggle with Roche for data which was being treated as if it were a legitimate secret of the drug manufacturer. (I tried to embed this lengthy URL as a hyperlink earlier; I wrote my linked comment in Word but the hyperlink did not carry over when I pasted it into the comment section. Can you point me to any user-friendly tutorials on how to embed URLs in making comments? I would like to be able to use the HTML tags and attributes but need a practical lesson on how to accomplish same. )

        Also http://www.ncbi.nlm.nih.gov/pubmed/24721793 appeared in the same issue of the BMJ which published the Cochrane review of Tamiflu a few weeks ago. It repeats Jefferson’s and Doshi’s complaints about the same problems with getting Roche to share its data.

        Doshi’s comments about vaccines appear to be worth pursuing. If he is an HIV denier that is worth knowing about.

        Ben Goldacre published Bad Pharma a couple of years ago and has some discussion of the incomplete Tamiflu data in the “Missing Data” chapter of that book.

        1. Andrey Pavlov says:

          Hi Ed:

          This should help

          1. Ed Whitney says:

            Thanks, Andrey!

            Ben Goldacre summarizes his reasons for writing about missing trial data.

            Hope that works; here goes!

        2. David Gorski says:

          Doshi’s comments about vaccines appear to be worth pursuing. If he is an HIV denier that is worth knowing about.

          Um, no. They’re really not. The dude is about as reliable as Christopher Shaw; i.e., not very.

          http://thepoxesblog.wordpress.com/2013/07/25/non-epidemiologist-tries-to-do-epidemiology-feeds-anti-vaccine-activists/

          http://effectmeasure.blogspot.com/2006/03/unhelpful-commentary.html

          http://www.skepticalraptor.com/skepticalraptorblog.php/vaccine-deniers-abuse-appeal-authority/

          OK, so there’s missing Tamiflu data; that doesn’t explain the anti-flu vaccine rhetoric. That was more what I was wondering about.

  7. goodnightirene says:

    Sarah Palin/Food Babe
    Food Babe/Sarah Palin

    Hmmmmmm………….

  8. Joel A Harrison, PhD, MPH says:

    Even the best randomized trials have limits, among them is the simple fact that randomization does not guarantee equal distribution of all the potential variables that could explain an outcome which is why replication is essential. Simply, randomization means that the risk of differences caused by other factors can be estimated if one “assumes” a particular probability distribution. And, of course, ones assume probability distribution may not be right.

    The Cochrane reliance on randomized clinical trials is a problem as other research designs can arrive at valid conclusions. For instance, Kenneth J. Rothman has shown that one can draw equally valid conclusions from well-done case-control studies (Kenneth J. Rothman & Sander Greenland, “Modern Epidemiology, 2nd Ed.”, Lippincott Williams & Wilkins, 1998). In addition, randomized trials usually take quite some time and are very expensive, so we have come up with other approaches to base decisions on, including systematic reviews and evidence-based clinical practice guidelines. Their strengths are that the “better” ones include the search criteria, a complete references list, often tables summarizing the key variables from each study, and a clear decision process. If any of the steps are omitted or unclear then we have a problem; but this problem exists for randomized clinical trials, case-control studies, observational studies, etc. I have had occasion to wonder how research papers I have read arrived at a conclusion since I couldn’t follow the methodology. A well-done paper, whether direct research or a review, should allow the reader to clearly follow what was done, thus allowing for replication and/or criticism. The fact that sometimes people go on talk shows or in some other format draw unwarranted conclusions does not change the basics.

    Dr. Crisplig would throw the baby out with the bathwater. Are some of the Cochrane reviews biased? Yes, of course, as Dr. Gorski writes in his comment. Humans conducted them. Are some clinical trials biased, was only a select subset of the data from the study presented, backing the researchers’ biases, of course; but as I wrote, if the paper gives a detailed methods section, then the reader can try to replicate and/or criticize it.

    One last thought. I am a retired epidemiologist, a PhD, not an MD, so I have never treated a critically-ill patient or any patient, nor am I an expert on influenza; but a CBS report from 2000 found that Dr. Michael Elsashoff and others at the FDA did not believe Relenza, a neuraminidase inhibitor, should be approved; but, as has happened several times, pressure from the manufacture led to its approval (CBS News. “Controversial Flu Drug Approved Despite Scientist’s Protest”, November 7, 2000, http://www.cbc.ca/consumers/market/files/health/relenza/ ) While I would not rely on one news report, it does give one reason to question a bit more.

    1. Mark Crislip says:

      baby and bathwater again.

      At issue is not the results of the anaylsis, but the interpretation, application and speculation beyond the results by folks who apparently have a stong bias against the current approach to the treatment and prevention of flu.

    2. Windriven says:

      “While I would not rely on one news report, it does give one reason to question a bit more.”

      Apparently you have at a minimum been moved by one news report. On just what basis? In the case you cite the source was either CBS or CBC – it isn’t quite clear. What if the report was Fox News? MSNBC? The National Enquirer? The popular media is saturated with spin, opinion, and shockingly flawed analysis. Was your time as an epidemiologist marked by this casual approach to rigor?

  9. Thor says:

    I do not when, how or why research authors became so non-commital to just saying flat out what the results are. Why say “further research is warranted”, “might be efficacious”, “finding were moderatley consistant”. Just call a duck a duck. for example our findings demonstated this drug does not work or this drug works, then list the possible side effects found and move on. Why be so PC about everything. Shell shock is just that and not combat fatigue syndrome.

  10. Laurens says:

    Some of these Cochrane Reviews are just downright silly. How about “Therapeutic touch for healing acute wounds” (http://www.ncbi.nlm.nih.gov/pubmed/22696330). The review reached the spectacular conclusion that “there is no robust evidence that TT promotes healing of acute wounds”. Who’d have thought it! This review was actually an update from a 2003 review that concluded that “there is insufficient evidence that TT promotes healing of acute wounds”. So we go from “insufficient evidence” to “no robust evidence”. Let’s put out some flags.

    And how about “Therapeutic touch for anxiety disorders” (http://www.ncbi.nlm.nih.gov/pubmed/17636838), which stressed that “given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders”.

    So we should compare real air massage with placebo air massage to investigate whether real air massage is in fact placebo air massage? I don’t think so.

    That ocsilo… iscollio…. oscillonicco…. occiloniso…. ah Duck Liver And Duck Heart Diluted Endlessly Review is actually interesting for many reasons. First of all, the authors actually found side-effects!

    “One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum”

    I get headaches from reading Oscillococcinum reviews. In fact, there have been reviews of this ‘natural product’ in 2000, 2004, 2006, 2009 and 2012. The 2009 review has apparently been withdrawn. These reviews do seem to draw the finest and most open-minded researchers available. The latest Oscillococcinum review was in fact co-authored by Peter Fisher, editor-in-chief of Homeopathy and the Queen of England’s homeopath, who did the unthinkable and removed Edzard Ernst from the editorial board of his magazine (http://edzardernst.com/2013/03/ive-been-fired/).

  11. Harriet Hall says:

    I think Cochrane reviews are useful as long as you read them with awareness of prior probability, GIGO, and bias. I find them most helpful when they say a treatment DOESN’T work; in that case they are very likely to be right. If they say a treatment does work, they could be wrong, and it warrants a closer look, not just blind acceptance. If they say a treatment with a prior probability close to zero like therapeutic touch or homeopathy works, we can (and should) disregard them.

    1. Ed Whitney says:

      Cochrane has a musculoskeletal group which rarely comes to any clear conclusions about its interventions. “There is little overall evidence to guide treatment” and “Most trials were of low quality” are so common in these reviews that that Cochrane group may as well have macros that they can paste in just to save time. This is the Cochrane group that I personally use the most, and that seems to be their mode of operation.

      One big problem with meta-analyses (not just Cochrane) is outlined above by Dr. Crislip; the patient populations for which the interventions are tested may be a mix of differing subtypes. This happened with the SSRIs for depression, for example; the drugs’ effectiveness in severe depression is different from that in mild to moderate depression. Or, to look at a different musculoskeletal issue, http://www.ncbi.nlm.nih.gov/pubmed/23362516 was a meta-analysis of epidural steroid injections for sciatica. There was insufficient information to distinguish between herniated discs and spinal stenosis. A hot disc may benefit from an epidural injection and this may work well enough for the problem to resolve and avoid the need for surgery. Narrow spinal stenosis is probably better served with decompression surgery; injections do not have the same benefit in a condition with a different pathology and different clinical course. The meta-analysis combined different conditions in the same pooled data summary. As with Tamiflu, treatment effects in different patient populations are likely to be missed if their data are combined.

      I must put in a good word for downloading the RevMan software from Cochrane; it is free and can be used to allow the reader of a meta-analysis to interact with the published data. In my book, the main value of meta-analysis is not so much proving things through statistical significance but rather in offering opportunities for exploration and understanding. With RevMan, you can update published meta-analyses with more recent trials (you have to determine that these trials would meet the inclusion criteria) and can see whether new trial data influences the estimate of pooled effect size. It is awfully decent of Cochrane to give this software away.

      1. David Gorski says:

        Cochrane has a musculoskeletal group which rarely comes to any clear conclusions about its interventions. “There is little overall evidence to guide treatment” and “Most trials were of low quality” are so common in these reviews that that Cochrane group may as well have macros that they can paste in just to save time. This is the Cochrane group that I personally use the most, and that seems to be their mode of operation.

        Heh. That sounds like the Cochrane Breast Cancer Group, at least whenever Cochrane does a meta-analysis about screening mammography. :-)

  12. Mike says:

    There is a popular web site called Examine.com which markets itself as an unbiased independent source of reviews of supplements and nutrition. The goal, like Cochrane, is to aggregate scientific papers and summaries thereof in one central place.

    Examine used to have affiliate links but removed them to reduce the appearance of impropriety. The site is funded by selling a reference guide.

    This site also suffers from Garbage-In, Garbage-Out issues because they do not attempt to evaluate how good the studies are. Thus, they added a page on Chinese medicine and have many reviews on Chinese herbs that may exaggerate their efficacy.

    1. Sol Orwell says:

      > Garbage-In, Garbage-Out … that may exaggerate their efficacy

      If we have included such studies, let us know. We do keep an eye on quality/data/methodology/funding/etc, but we’re obviously not infallible. If we missed/messed up, let us know.

  13. thor says:

    My comments got deleted..my apologies if I made offence

    1. thor says:

      now they are back, disregard

  14. Rectofossal says:

    I think the BMJ / Cochrane paper has two intrinsic flaws in addition to those listed by Dr Crislip. Principally the selection criteria for the systematic review seem to be designed to exclude any cohort that might benefit from neuraminidase inhibitors (for example anyone in hospital with lab-confirmed flu). In addition the BMJ / Jefferson / Doshi / Cochrane all have ‘a dog in the fight’ given their public antipathy to Roche and oseltamvir.
    I wrote about this at the time and had a response from one of the Cochrane Collaboration that others have characterised as what one might expect from a stroppy teenager – at http://www.rectofossal.com/tamiflu.
    Interesting that the obs study published in the same BMJ issue was ignored. If only journalists read beyond the press release or the abstract occasionally…

    1. David Gorski says:

      Nice review. Doshi’s and Jefferson’s reply is quite amusing. So, then, not only are they highly biased, but they’re tools, too.

      1. lilady says:

        There was some push-back about the BMJ Cochrane Collaboration meta analysis authored by Jefferson and Doshi, from a U.K. physician, Dr. Dunning, who actually cared for patients hospitalized with H1N1 influenza

        http://www.bmj.com/content/348/bmj.g2263?tab=responses

        “The latest Cochrane review of neuraminidase inhibitors for influenza[4] was an impressive undertaking but unfortunately addressed the wrong question. It is unable to provide the answers we need. Consistent with their previous findings[5] the authors found that, in a randomised controlled trial (RCT) setting, oseltamivir and zanamivir modestly reduced the duration of symptoms in previously healthy individuals with uncomplicated illness caused by non-pandemic, seasonal influenza viruses. Importantly, their findings do not address antiviral effectiveness in severe influenza, or in illness caused by pH1N1, or in patients with risk factors for severe illness. Therefore, these new findings cannot guide decisions about future antiviral stockpiling or the treatment of severe flu.[6] ”

        Peter Doshi’s reply, IMO, was less than satisfactory:

        “Dunning questions the relevance of our systematic review, suggesting that any research data – no matter its quality — that tests the effect of neuraminidase inhibitors on non-pandemic influenza answers the wrong question. As all randomized trial evidence is on non-pandemic influenza, he argues we must look elsewhere and highlights non-randomized observational studies which conclude the drugs provide great benefit, contrary to the conclusions which can be drawn from randomized trials.”

        and….

        “First, Dunning’s description of the 2009 H1N1 influenza as “severe influenza, or in illness caused by pH1N1″ assumes that so-called pandemic H1N1 influenza is by definition severe and non-pandemic influenza is not. Certainly seasons classed as “pandemic” get more media attention than non-pandemics, and certainly the 1918 influenza was severe, but all other so-called pandemics (1957, 1968, and 2009) had mortality comparable with non-pandemic influenza (3, 4) The randomized trial evidence does answer important questions.

        Second, we are unconvinced we were wrong to exclude observational studies. We published our methodology in 2010, stating that we would focus on randomized trials. Since 2010 no experts or peer-reviewers questioned this approach.”

        There are a slew of “experts” who have questioned their approach and a boatload of observational studies to justify the use of antivirals for hospitalized patients, patients in nursing homes and groups of patients who are at profound risk in terms of morbidity and mortality associated with influenza infections:

        http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm

        1. Rectofossal says:

          Doshi and Jefferson have also suggested RCTs of neuraminidase inhibitors during a pandemic would be appropriate. One wonders on which planet one might find an IRB who would permit the sacrifice of the seriously ill on the altar of methodolatry…

    2. simba says:

      Love your blog, rectofossal- I just encountered it recently for the first time and had an archive binge.

      1. Rectofossal says:

        Simba,
        I only do it to save my poor wife and co-workers from my ranting. That anyone else would take the time to read the ravings of a semi-housetrained microbiologist with no redeeming features astonishes me.
        Thank you.

  15. PMoran says:

    Harriet: “I think Cochrane reviews are useful as long as you read them with awareness of prior probability, GIGO, and bias. I find them most helpful when they say a treatment DOESN’T work; in that case they are very likely to be right. If they say a treatment does work, they could be wrong, and it warrants a closer look, not just blind acceptance. If they say a treatment with a prior probability close to zero like therapeutic touch or homeopathy works, we can (and should) disregard them. ”

    Yes, someone needed to say this.

    I think the EBM movement, of which Cochrane is part, began during a period where we were still a little naïve about all the potential failings of our supposed “Golden Standard of evidence” — the RCT.

  16. Ed Whitney says:

    Perhaps GIGO is relevant to some meta-analyses, but basically they are best seen as blunt instruments which are poorly designed for doing a fine dissection of reality. Dr. Crislip started out by making a distinction between critically ill hospitalized adult patients and adult outpatients. Meta-analyses pool data from populations which bear a basic resemblance to one another, but they are often mixing Jonathan and McIntosh apples. There may be enough statistical homogeneity to allow for a fixed effect model to work, but, as George W. Bush said to Joe Biden on the eve of the Iraq war, they don’t necessarily do nuance. That is why guideline committees need content matter experts on their panels, to help the methodologists with issues of external validity when threats to internal validity have been controlled.

  17. Stephen H says:

    You haven’t fixed the Wikipedia article yet, Dr Crislip?

  18. Max says:

    You should explain who Food Babe is for those who don’t know.
    By the way, she doesn’t just write about food. In 2011, she wrote about all the nasty ingredients in –you guessed it– flu shots.

  19. Max says:

    Do the patients have to be hospitalized within the first 48 hours of illness to get Tamiflu?

    1. Mark Crislip says:

      Im not too picky as the hour of onset it hard to exactly know and there is a suggestions that it may be of some benefit after 48 hours. But sooner is better.

      http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70267-6/abstract

      1. Sawyer says:

        I think the time of diagnosis/treatment brings up an interesting question that I haven’t yet seen addressed. If Tamiflu is marginally effective right now, is it likely to be more effective with new advances in technology? In 20 years if everyone had the Super Duper F-U-Flu diagnostic kit (trademark pending) and we could determine whether someone had a cold or the flu on day one, neuraminidase inhibitors would almost certainly be an effective treatment. Is it reasonable to gamble current public decisions on suspected future advancements? I’m assuming the legalese answer would be a resounding “NO” but it’s fun to think about.

        Of course in any near-future pandemic I suspect that overworked hospitals would mean worse diagnostics rather than better, which would be more points against Tamiflu.

        And of course I’m curious if any of the review authors have bothered discussing these sorts of dilemmas, either to Roche or at least to themselves.

      2. Calli Arcale says:

        The 48 window is the thing that bugs me the most about Tamiflu. Usual advice is to treat fevers at home for at least 24 hours before calling the doctor. My daughter has been diagnosed with influenza before, but it was days after the symptoms started so there was no point in retrovirals. By then, however, she had pneumonia as well and a high white blood cell count so they started her on antibiotics. I’ve never been to the doctor for a respiratory infection quickly enough for Tamiflu to matter, so to me, the drug is sort of “meh”.

        1. Max says:

          Guidelines say to call the doctor if fever lasts longer than three days, or when symptoms improve but then return with fever and worse cough. By that point it’s too late for Tamiflu.
          So the only ways to get Tamiflu in the first 48 hours is to either have an underlying condition and see the doctor right away, or to develop the worst symptoms like shortness of breath and severe vomiting that send you to the hospital in the first two days.

  20. Lee says:

    For more in a similar vein, with a dash of intelligent humor, one might enjoy today’s audio offerings from radio program On The Media:

    http://www.onthemedia.org/story/on-the-media-2014-05-02/

    Transcripts generally available by the following Monday.

    1. Sawyer says:

      I was initially annoyed to see a repeat this week, but considering that episode was responsible for me subscribing to the OTM podcast feed, I’m happy to hear it again.

  21. Joel A. Harrison, PhD, MPH says:

    Mark Crislip writes: “At issue is not the results of the anaylsis, but the interpretation, application and speculation beyond the results by folks who apparently have a stong bias against the current approach to the treatment and prevention of flu.”

    Isn’t that exactly what I wrote when I said: “The fact that sometimes people go on talk shows or in some other format draw unwarranted conclusions does not change the basics.” People can say whatever they want. They can draw the most absurd conclusions. I look at the original document, its methodology, its sampling scheme, and even its reference list. Whether an evidence-based clinical practice guideline, a randomized clinical trials, whatever methodology, that is what counts. If the original document gives the appropriate information, then it is subject to critique and/or replication.

    Windriven writes: “Apparently you have at a minimum been moved by one news report. On just what basis? In the case you cite the source was either CBS or CBC – it isn’t quite clear. What if the report was Fox News? MSNBC? The National Enquirer? The popular media is saturated with spin, opinion, and shockingly flawed analysis. Was your time as an epidemiologist marked by this casual approach to rigor?

    No, if you read what I wrote, I rely on methodology, replication, etc. I simply mentioned one CBS report. I have a half dozen or more medical articles and FDA reports that I could have summarized; but am not interested in writing a treatise just to comment on a blog. Seems you are ready to pounce on every little detail. Are you an anti-vaccinationist? This is their approach. They read through a paper, find one minor thing and blow it out of proportion.

    Laurens writes: “Some of these Cochrane Reviews are just downright silly. How about “Therapeutic touch for healing acute wounds” (http://www.ncbi.nlm.nih.gov/pubmed/22696330). The review reached the spectacular conclusion that “there is no robust evidence that TT promotes healing of acute wounds”.”

    While personally I do not even remotely subscribe to any form of naturopathy or alternative medicine, many people do and if a Cochrane Review chooses to give them the “facts” in a systematic and coherent manner, fine by me. It may seem silly to you; but people who avail themselves of alternative medicine can be intelligent; but desperate. While once committed, many will refuse to even remotely admit they are wrong. The only hope is clear rigorous systematic information.

    Ed Whitney writes: “Cochrane has a musculoskeletal group which rarely comes to any clear conclusions about its interventions. “There is little overall evidence to guide treatment” and “Most trials were of low quality” are so common in these reviews that that Cochrane group may as well have macros that they can paste in just to save time. This is the Cochrane group that I personally use the most, and that seems to be their mode of operation.”

    ‘”Their mode of operation”? Do you want a conclusion from inconclusive data? Knowing that the evidence is inconclusive is a valid contribution. At the least it can lead to actual research or people questioning. The question is not whether they found the evidence to be inconclusive, a valid “conclusion:” but how thorough the review was.

    My main problem with Cochrane Reviews, some of them that are excellent (which is the exact same thing I could say about any type of publication) is the use mainly or solely of randomized clinical trials and, secondly, what Robert Rosenthal called the File Drawer Problem, that non-significant studies are seldom published. And, finally, replications are also seldom published.

    Evidence-based clinical practice guidelines use similar methodologies, that is systematic reviews, meta-analysis, etc. Many years ago, Brent James, MD, MS, head of the seven non-profit hospital chain Intermountain decided to try to improve health care. He chose a number of conditions to develop evidence-based clinical practice guidelines. A review at the time of Acute Respiratory Distress Syndrome found a survival rate of 10%. A review was carried out of each case together with a review of the research. It was found that different drugs, different dosages, different procedures were practiced by different doctors and even the same doctor changed treatments. A preliminary clinical practice guideline was developed. Doctors were free to deviate from it; but they had to be able to explain why, not just “based on their experience.” Remember their experience resulted in only 10% survival. I’ll just make up something to make a point. Imagine a doctor’s patient had, say, diabetes, and he/she knew that a certain drug interacted with insulin, so he/she substituted the number two choice. At the next meeting, he/she would explain this and the outcome. In any case, the end result was 40% survival and also a 25% reduction in overall costs. Forty percent is still not great; but certainly a significant improvement. What was the alternative? Randomized clinical trials? How often does one hospital get ARDS cases? Probably not often. To develop protocols, get enough hospitals on board, make sure they adhered to the protocols, etc. would have been a herculean effort and taken years. A systematic review of the literature and several iterations to a clinical practice guideline worked.

    Randomized clinical trials may be considered the gold standard; but they need to be replicated and all such trials need to be reported, even those that did not reach statistical significance; but there are other legitimate designs and systematic reviews/meta-analysis, evidence-based clinical practice guidelines, when done well, when the methodology is transparent, can be quite valid.

    If anyone wants a sample of how I approach things, I recently got an article published in an online peer-reviewed open-source medical journals, an article that tore to shreds Andrew Wakefield’s book “Callous Disregard.” I did this by juxtaposing accurate quotes from the book with accurate quotes from peer-reviewed articles and government documents. What’s more, where possible, if the articles or government documents were available on the internet, I gave hyperlinks to them. You can find my article and a supporting letter at:

    Joel A. Harrison, PhD, MPH. “Wrong About Vaccine Safety: A Review of Andrew Wakefield’s ‘Callous Disregard.” The Open Vaccine Journal, Vol. 6, 2013, pp. 9 – 25. Available at:
    http://www.benthamscience.com/open/tovacj/articles/V006/TOVACJ20131126002.pdf

    Brith Christenson, MD, PhD. “Letter to the Editor: Comment on Dr. Joel A. Harrison’s ‘Wrong About Vaccine Safety.’” The Open Vaccine Journal, Vol. 6, 2013, p. 26. Available at:
    http://www.benthamscience.com/open/tovacj/articles/V006/26TOVACJ.pdf

    In case the hyperlinks don’t work, you can find the two papers:
    Google:
    The Open Vaccine Journal
    then click on “View Journal Articles”
    then under “Volume 6, 2013” click on “[General Articles]”

    1. Andrey Pavlov says:

      Laurens writes: “Some of these Cochrane Reviews are just downright silly. How about “Therapeutic touch for healing acute wounds” (http://www.ncbi.nlm.nih.gov/pubmed/22696330). The review reached the spectacular conclusion that “there is no robust evidence that TT promotes healing of acute wounds”.”

      While personally I do not even remotely subscribe to any form of naturopathy or alternative medicine, many people do and if a Cochrane Review chooses to give them the “facts” in a systematic and coherent manner, fine by me.

      No, what Laurens was referring to is the conclusion – it is based on a conclusion drawn from methodolatry. We do have sufficient evidence to conclude that TT does not and cannot promote the healing of acute wounds. To couch a conclusion in such wishy washy language as “no robust evidence to support” implies that there is less robust evidence in support. It is also to ignore an incredibly huge swath of evidence.

      The “more research is needed” conclusion is what Laurens, myself, and others are against when it comes to modalities that do not and cannot work, such as homeopathy.

      ”Their mode of operation”? Do you want a conclusion from inconclusive data? Knowing that the evidence is inconclusive is a valid contribution.

      Agreed, but in these cases the conclusions are not inconclusive. They are only inconclusive if you choose to ignore evidence and find Bayes too complicated to fathom.

      1. Joel A. Harrison, PhD, MPH says:

        Andrey Pavlov writes: “but in these cases the conclusions are not inconclusive. They are only inconclusive if you choose to ignore evidence and find Bayes too complicated to fathom.”

        Having studied Bayes, I have NO problem “fathoming” it; however, Bayes has its own problems and is not universally accepted as any type of gold standard. I suggest you start with a book edited by Kenneth J. Rothman. “Causal Inference” published by Epidemiological Resources Inc, 1988. I won’t bother summarizing the book for you; but you might find it worthwhile.

        Just one point. Anyone who thinks that one approach forms a gold standard demonstrates a poor understanding of the multitude of problems involved in drawing any “causal” conclusions.

        1. Andrey Pavlov says:

          Just one point. Anyone who thinks that one approach forms a gold standard demonstrates a poor understanding of the multitude of problems involved in drawing any “causal” conclusions.

          When did I even imply that only one approach forms “the” gold standard? I even explicitly commented on the idea of methodolatry which is precisely contra to that assertion.

          The fact that there are problem with Bayesian statistics (there are problems with everything and all approaches will have failures and limitations) is not a refutation of my point. In fact, nowhere in your response did you even come close to addressing the actual point.

          I did not say, nor imply, that a Bayesian framework is always applicable nor always entirely sufficient. I very specifically picked a part of your comment to respond to, as you had evidently missed the point being made. And in the specific instances I referenced yes, a Bayesian approach plus the inclusion of other relevant forms of evidence typically excluded in Cochrane reviews would be sufficient for a firmly negative conclusion.

          Which is a long winded way of saying you are attacking a straw man.

    2. Windriven says:

      No, if you read what I wrote, I rely on methodology, replication, etc.I simply mentioned one CBS report. I have a half dozen or more medical articles and FDA reports that I could have summarized; but am not interested in writing a treatise just to comment on a blog. ”

      Emphasis mine.

      Then why didn’t you cite one of the FDA reports? Is it irrational to expect someone to use their strongest evidence when making a point? Whenever a writer cites a soft resource to demonstrate what a regulator did or did not support – or any other action that should have its own paper trail – my bullcrap alarm sounds. Then I start to wonder about the accuracy of other assertions the writer has made. The less known to me the writer is, the louder the alarm sounds.

  22. Joel A. Harrison, PhD, MPH says:

    Windriven writes: “Then why didn’t you cite one of the FDA reports? Is it irrational to expect someone to use their strongest evidence when making a point? Whenever a writer cites a soft resource to demonstrate what a regulator did or did not support – or any other action that should have its own paper trail – my bullcrap alarm sounds. Then I start to wonder about the accuracy of other assertions the writer has made. The less known to me the writer is, the louder the alarm sounds.”

    So, find one thing you don’t like and you “start to wonder about the accuracy of other assertions the writer has made.” Each assertion should stand by itself. You obviously subscribe to the same mentality that anti-vaccinationists and others do; that is, find one thing that bothers you and immediately use it to filter everything else. Years ago I read a book about Psychological Projective Tests. I don’t subscribe to psychoanalysis or any other so-called “dynamic psychology;” but find it fascinating. In the chapter on the Rorschach Inkblot an example was given of a patient who described one of the inkblots as showing a man’s head in a lion’s mouth. The therapist asked how he arrived at the conclusion and the patient pointed to a very short line in the corner of the inkblot. To him it was a tail and if there was a tail then it went to a lion, etc. The book called this fabulization or confabulation. Can’t remember which; but basically SICK!

    At the very end of my comment I threw out something just as an example, not as an argument. I have been a member of Public Citizen, a consumer group, for more than 25 years. One division is the Health Research Group, headed until recently by Dr. Sidney Wolff. During that time, approximately 25 drugs approved by the FDA were later withdrawn. In most, if not all cases, Dr. Wolff, based on initial reports from the FDA, fought against approval. In most cases, one or more of the original FDA officers had either said the drug should not be approved or that additional data was required. Pressure from the company on members of Congress led to pressure on the FDA. As for the neurominidase inhibitors, the Health Research Group maintains a list of drugs, often with extensive bibliographies. Access to the list requires a separate yearly fee which I haven’t pay recently since I have had no need to use the list. I guess I should pay it for this year to get the bibliography on neurominidase inhibitors which I read several years ago; but it isn’t worth my while just to satisfy someone who thinks like an anti-vaccinationist. I’d love to get someone to give you a Rorschach Test.

    You can read the paper I wrote which is available online and decide if I have any credibility or not; but your opinion doesn’t really concern me. However, in a quick search of Google I did find an extensive interview with Dr. Michael Elashoff on PBS Frontline which you can find at:

    http://www.pbs.org/wgbh/pages/frontline/shows/prescription/interviews/elashoff.html

    In addition, I did a quick search on PubMed for Dr. Elashoff and he has an extensive list of peer-reviewed publications.

    Give it a rest!

    1. Windriven says:

      “Each assertion should stand by itself.”

      No, then you run into the blind squirrel and acorn problem. Look, we have commenters here who spray a cloud of stupidity every time they hit the ‘Send’ button. So what if they periodically get something right? It is incidental to their body of commentary and the thrust of their argument. Citing the fact that water is wet doesn’t add weight to the argument that homeopathy is useful for anything.

      In the larger sense Dr. Harrison, life is short and one’s interests are varied. None of us has the time or patience (or technical expertise in particularly arcane areas) to carefully vet every assertion. Speaking for myself, I read comments skeptically. As I develop confidence in a writer I spend more time carefully examining her arguments. If they bear up – or at least are defensible – my confidence increases and so does my scrutiny – not because I don’t believe them but because there is high likelihood that I will learn something by persuing the subject.

      And it works in the other direction as well. Everyone here knows Steve Rodrigues and his thoughts on science and on acupuncture. I actually like the guy in an odd kind of way and I am impressed with his professed passion for his patients. But I don’t respect him because I find his thinking deeply flawed and his citations meaningless. Dr. Rodrigues occasionally says something true and incontrovertible. But again, so what? I no longer follow his citations because they have led to too many empty wells.

      In the instance of your comment, you made an important point (in my view) that RCTs can be difficult, expensive, time-consuming, and not necessarily settle an issue of efficacy or/or safety. You went on to say that case-control studies can draw valid conclusions. I would have liked to hear more about that.

      But then you went off on ‘this doctor didn’t want to approve this drug* but the pharmaceutical company forced FDA to do it’ and cited a TV news report. Sorry, but I rolled my eyes and stuck you in the ‘probably a crank’ column. But then I’m just one reader and occasional commenter.

      *I’m too stupid to remember the doctor or the drug and too lazy to go back and look. These are incidental to my point.

  23. Joel A. Harrison, PhD, MPH says:

    To Windriven: Do you write to actually make a point or . . .? Do you really want me to give references to the recent history of drugs withdrawn by the FDA? Are you totally oblivious to this fact? Did you even bother to read either the CBS report or, especially the PBS Frontline interview? In fact, have you even glanced at the recent Cochrane review on neurominidase inhibitors? I did. As it is over 500 pages, I have NO desire to read it page by page; but discovered that they had included non-published randomized clinical trials , that there is extensive discussion of FDA reports, and at the end of the report is included a number of criticisms from various researchers who read it. In addition, they list in their reference section (pages 53-54 of the document, see below). And I found a recent paper by Dr. Ben Goldacre on the subject: “What the Tamiflu Saga Tells Us About Drug Trials and Big Pharma,” April 9, 2014, which can be found at:
    http://www.theguardian.com/business/2014/apr/10/tamiflu-saga-drug-trials-big-pharma/print

    I would suggest before you mouth off again that you actually take the time to read some or all of the above. You have wasted enough of my time already. I am long retired and it is enough to deal with the irrationalities of the anti-vaccinationists.

    FDA 1999a
    Food, Drug Administration. Administrative/
    correspondence documents part 2. Relenza (Zanamivir).
    Application No.: 21036. http://www.accessdata.fda.gov/
    drugsatfda˙docs/nda/99/021036-admin2.pdf 2009
    (accessed 26 August 2009).

    FDA 1999b
    Food, Drug Administration. Medical review part 6.
    Relenza (zanamivir). Application No.: 21036. http://
    http://www.accessdata.fda.gov/drugsatfda˙docs/nda/99/021036-
    medreview6.pdf 2009 (accessed 26 August 2009).
    FDA 1999c

    Food, Drug Administration. Tamiflu (Oseltamivir
    Phosphate) Capsule. Medical Review Part 2 (Application
    No.: 021087). http://www.accessdata.fda.gov/
    drugsatfda˙docs/nda/99/21087˙Tamiflu˙medr˙P1.pdf 1999
    (accessed 26 August 2009).

    FDA 2000a
    Food, Drug Administration. Letter from FDA to Hoffman-
    La Roche Inc. re ”NDA 21-087 TAMIFLU (oseltamivir
    phosphate) MACMIS ID#8675. http://www.fda.gov/
    downloads/Drugs/GuidanceComplianceRegulatoryInformation/
    EnforcementActivitiesbyFDA/WarningLettersand-
    NoticeofViolationLetterstoPharmaceuticalCompanies/
    UCM166329.pdf 2000 (accessed 14 April 2000).

    FDA 2000b
    Food, Drug Administration. Drug approval package.
    Relenza (zanamivir). Application No.: 021036S001. Label.
    http://www.accessdata.fda.gov/drugsatfda˙docs/label/2000/
    21036S1LBL.PDF 2000 (accessed 26 August 2009).

    FDA 2000c
    Food, Drug Administration. Drug approval package.
    Tamiflu (oseltamivir). Application No.: 021087-SE1-
    002. http://www.accessdata.fda.gov/drugsatfda˙docs/nda/
    2000/21-087SE1-002˙review.pdf 2000 (accessed 27 August
    2009).

    FDA 2000d
    Food, Drug Administration. Review. Tamiflu
    (oseltamivir). NDA 021087 Supplement 002. http://
    http://www.accessdata.fda.gov/drugsatfda˙docs/nda/2000/21-
    087SE1-002˙review.pdf 2000 (accessed 26 August 2009).

    FDA 2000e
    Food, Drug Administration. Site inspection report in
    Review. Tamiflu (oseltamivir). NDA 021087 Supplement
    002. http://www.accessdata.fda.gov/drugsatfda˙docs/nda/
    2000/21-087SE1-002˙review.pdf 2000 (accessed 26 August
    2009):177.

    FDA 2000f
    Food, Drug Administration. Faxed letter to Roche (file
    UCM166329) [NDA 21–087TAMIFLU (oseltamivir
    phosphate) MACMIS ID#8675]. http://www.fda.gov/
    downloads/Drugs/GuidanceComplianceRegulatoryInformation/
    EnforcementActivitiesbyFDA/WarningLettersand-
    NoticeofViolationLetterstoPharmaceuticalCompanies/
    UCM166329.pdf 2000 (accessed 19 October 2010).

    FDA 2011a
    F. Hoffman-La Roche. Tamiflu label (for FDA NDA no.
    021087). http://www.accessdata.fda.gov/drugsatfda˙docs/
    label/2011/021087s057lbl.pdf 2011 (accessed 7 February
    2011).

    FDA 2011b
    Food, Drug Administration. Drugs@FDA. http://
    http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ 2011
    (accessed 5 July 2011).

    FDA 2011c
    Food, Drug Administration. Warning letters. http://
    http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/
    default.htm 2011 (accessed 5 July 2011).

    1. Windriven says:

      “Do you write to actually make a point or . . .?”

      Absolutely.

      “Do you really want me to give references to the recent history of drugs withdrawn by the FDA?”

      Nope. The assertion that made me roll my eyes was:
      “pressure from the manufacture (sic) led to its approval”
      There are many factors that come into play in the approval of drugs and devices. If “pressure from the manufacturer” was enough there wouldn’t be many drugs or devices that didn’t get approved. Every manufacturer pushes as hard as they can for approval of their product. If you are making a specific charge that GSK did something illegal to get Relenza approved, lay out the case. I’ll help you build the fire on which we burn the bastards. But don’t just wave a stink bomb at them. That’s coals to Newcastle.

      “Did you even bother to read either the CBS report or, especially the PBS Frontline interview?”

      Nope. Well, I did read a bit of the PBS telling us all what we already know.

      “You have wasted enough of my time already.”

      And I have to ask myself: why? I had a simple and straightforward 100 word question about your citation of a mass media source in a comment you made about scientific studies and, parenthetically, the approval of a single drug. I’ve no idea why you have engaged me beyond linking something meaningful regarding the approval. That doesn’t mean a PBS interview, at least not for me, unless the interview is with a prosecutor trying GSK. Beyond that I don’t care if PBS interviews Jesus Christ on the subject.

      1. Joel A Harrison, PhD, MPH says:

        Windriven writes: “Every manufacturer pushes as hard as they can for approval of their product. If you are making a specific charge that GSK did something illegal to get Relenza approved, lay out the case. I’ll help you build the fire on which we burn the bastards. But don’t just wave a stink bomb at them.”

        Of course “every manufacturer pushes as hard as they can.” That is a given; but the 25 or more drugs that were approved and later withdrawn have resulted in investigations that clearly in several cases indicated that members of Congress intervened and that the same members of Congress were both lobbied and received contributions from the manufacturers involved. Are you completely oblivious to this? And, if you read the article by Ben Goldacre and the actual review by the Cochrane Collaboration you will understand that the manufacturer of one of the neuraminidase inhibitors intentionally withheld lots of data and studies, only presenting data that backed their drug.

        Unfortunately, lobbying and contributing to politicians is not against the law and withholding data and studies from the FDA apparently isn’t either. Whether they did something illegal or not, the result is a drug that was approved when major pieces of the data and studies were withheld. The fact that this is legal certainly doesn’t make me any happier about whether any drug I receive really works as promised and has only the adverse events as listed.

        As for your simple question, it really was not simple because you clearly stated that what I threw in at the end was all you needed to decide that anything I wrote lacked credibility. I made it clear that I only mentioned the CBS report and did not by any means believe it was anything more than something to arouse interest. I’ve now given references to FDA reports, an excellent article by Ben Goldacre and mention that the excellent Cochrane Review dealt extensively with the FDA reports. Excellent doesn’t mean it is the end all. It is excellent in that it explains clearly every step in its methodology, gives an extensive reference list, etc. Someone else may conduct another review, equally well-done, using a different search strategy, and may come up with different conclusions; but the negative attacks on the Cochrane Collaboration in both Dr. Crisplip’s original paper and following comments are and were unwarranted. And that Dr. Crisplip believes his use of neuraminidase inhibitors is warranted from his own personal experience vs reviews such as Cochrane’s bother me. I would remind you if you read my description of the development of an evidence-based clinical practice guideline for Acute Respiratory Distress Syndrome that every one of the doctors involved were conscientious highly skilled; but they relied on their clinical judgment. Crisplip may be right; but then again he may not be. And the fact that you choose not to actually read any other articles I refer to just shows how closed minded you are.

        Seen any lions with a man’s head in their mouths lately?

        Now, I am a senior citizen and don’t wish to waste my time. My dog needs walking, a much more worthwhile endeavor that dealing with the likes of you.

        1. Windriven says:

          “Unfortunately, lobbying and contributing to politicians is not against the law and withholding data and studies from the FDA apparently isn’t either.”

          But bribery is. Didn’t you say this just a few lines earlier:

          “That is a given; but the 25 or more drugs that were approved and later withdrawn have resulted in investigations that clearly in several cases indicated that members of Congress intervened and that the same members of Congress were both lobbied and received contributions from the manufacturers involved.”

          ” it really was not simple because you clearly stated that what I threw in at the end was all you needed to decide that anything I wrote lacked credibility.”

          Look, I explained already that I don’t know you from Adam’s housecat. You said some interesting things early in your post. At the end you executed a maneuver very like one used all the time in these pages: make a broad allegation and back it with a weak citation.

          The only way people build credibility in these pages is with a history of largely solid commentary. I hope you stick around a earn that credibility because you might well add real depth to the discussion. But don’t be a pansy when you say something weak and somebody jumps in your stuff. Fix it and move on. You’ll be respected for that a lot more than whining that a weak argument should be allowed to pass because you have to walk your dog.

          “And the fact that you choose not to actually read any other articles I refer to just shows how closed minded you are.And the fact that you choose not to actually read any other articles I refer to just shows how closed minded you are.”

          I tried to read some of the FDA links – but the three that I tried were all broken links (to say nothing of the fact that the links were incompletely built in the href tags). Try them yourself. I’m not making that up.

          I’m not much impressed with Cochrane and their constant refrain that idiocy like homeopathy needs further study. If you think I’m full of crap in that regard, marshal up a compelling argument. But wheezing that we’re throwing the baby out with the bathwater only seems accurate if it is a kingcake baby* and a whole lot of bathwater.

          *Kingcake is a Mardi Gras specialty, an iced sweetbread often laced with cinnamon and sometimes cream cheese. A small plastic baby (originally a bean) is baked into the kingcake. Tradition holds that whoever gets the slice with the baby has to host the next day’s kingcake party.

          1. Mark Crislip says:

            “The dog needs walking” gambit.

            I have seen that many times over the years in the comments of blogs to dismiss someone. We need to give it a formal name and get it in the wikipedia’s list of fallacies

            Argument from micturation?
            Argument from fire plug?

            Argumentum ab ambulans canem ?

            1. Andrey Pavlov says:

              Argumentum ab ambulans canem ?

              More latin = more better

              Latinorum multo magis semper quod melius est

            2. Windriven says:

              My vote is for ambulans canem if on no other grounds than the one Andrey cites.

        2. Mark Crislip says:

          And that Dr. Crisplip believes his use of neuraminidase inhibitors is warranted from his own personal experience vs reviews such as Cochrane’s bother me.

          I guess I was not clear enough when I said
          “If the patient is sick enough to be hospitalized, prompt therapy with oseltamivir probably decreases the odds of needing ICU care and if you are in the ICU or pregnant, probably decreases your chances of dying. Note “decreases the chance”. The data is not great, but consistent: in hospitalized patients, oseltamivir decreases the chance of death. When thinking about treating populations during a pandemic, having sufficient medication available will be a good thing for those ill enough to require hospitalization.”

          It is not my experience, but rather the observational studies in patients sick enough to be hospitalized who have a decreased chance of death if they received osletamiver. Studies such as this

          http://www.ncbi.nlm.nih.gov/pubmed/21415133
          and this
          http://www.ncbi.nlm.nih.gov/pubmed/20032319

          and there are others that are similar

          Which is my patient population; who I treat. And who may benefit in a pandemic from treatment

          Flu can be terrible in some as h1n1 demonstrated, but it was a minority of patients.
          http://jama.jamanetwork.com/article.aspx?articleid=184820
          “A striking percentage of hospitalized cases were severely ill, with more than 30% requiring intensive care; most adults and more than one-third of children required mechanical ventilation. Eleven percent died;”

          To repeat Dr. Goldacres calculations in a different context. If we have a flu that repeated the mortality of 1919, killing 3%, in the US that would be 9 million people dead. There are a lot of changes since 1919 that may or may not make that less likely (better nutrition, better infection control, vaccination etc) so could overestimate of death, but we probably have a far older, more chronically ill and a more at risk population than 1919 but even .3% would be a disaster. Hospitals do not have the surge capacity for such an epidemic and we maxed out capacity in 2009.

          If olsetamiver prevents 10% of people from dying, that would be 900,000 lives saved in a 1919 repeat and you would have to treat a huge number to save those lives. Hence the stock pile. And worth a whole lot of vomit in my calculus

          The analysis, despite the discussion, has little application to a pandemic for a worst case influenza like 1919. You may poo poo the idea of a repeat of 1919, but those who do not remember the past blah de blah de blah.

          1. Windriven says:

            And kindly note that Dr. Crislip arrived at his well-supported conclusion sans Cochrane and without wallowing in confirmation bias.

  24. Kiiri says:

    Thank you Dr. Crislip! As an Epi in local public health with H1N1 reared up in 2009 I can state that we in PH are definitely screwed. We can never prepare enough for the 1918 pandemic but if we are wrong then we ‘wasted’ too much ‘funding’ on a ‘minor’ issue. When the data clearly shows that if you are pregnant, obese, or have an underlying health condition pray you don’t get H1N1 because those were the folks who died. The elderly, who generally don’t do so well with flu, didn’t die. Everyone looks at the total numbers but that masks that the vast majority of those deaths were those who statistically shouldn’t have died! Being as how I hope to get pregnant again if I’m in the hospital with H1N1 I hope they dose me to the gills with Tamiflu as I want to live to see my children grow up.

    1. Joel A Harrison, PhD, MPH says:

      To Kiiri:

      Before being to grateful, I suggest you read Dr. Ben Goldacre on the subject: “What the Tamiflu Saga Tells Us About Drug Trials and Big Pharma,” April 9, 2014, which can be found at:
      http://www.theguardian.com/business/2014/apr/10/tamiflu-saga-drug-trials-big-pharma/print

      1. Ed Whitney says:

        This is the issue I raised the other day concerning what axe Jefferson and Doshi were grinding. The missing data issue did not seem to be of much concern to Dr. Crislip and Dr. Gorski. No one can say that Ben Goldacre is an antivaccine lunatic; his attack on the media for its role in enabling Wakefield to spread vaccine fear is proof of that.

        The major problem with meta-analyses arises when they pool data from populations which differ from those you are interested in. Adults with flu-like illness, much of which is due to viruses other than Influenza A, have a response profile different from that of hospitalized patients with proven Influenza A infection.

        Jefferson and Doshi were rightly provoked by the conduct of Roche, but their conclusions do not apply to a subset of patients with baseline risks which differ from those of the patients in most of the randomized trials.

  25. Yodel lady says:

    It frustrates me that articles on influenza mention death as the only down-side. I haven’t been able to find any statistics on the complication rates following the flu in either healthy or at-risk populations. Five years ago I had a pleural effusion and a collapsed lung which would not reinflate and needed to be decorticated. One possibility is that the lung shrank away from a pleural infection following the flu and then became trapped. If that’s what happened, it happened when I was a very healthy person, and that’s no small consequence for a “self-limiting” illness. The simplicity of judging people to be either healthy or dead enables many of the inane beliefs people fall into.

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