Effect Measure

This was an incident waiting to happen. Indonesia has signed a preliminary agreement with vaccine maker Baxter international an arrangement to supply with with viral vaccine seed in exchange for an unknown compensation. It is unclear whether the arrangement is exclusive to Baxter or not (see today’s New York Times, says not). Until the deal is completed they will not continue to send viral isolates to other scientists for research or other purposes. Sharing of sequence data is said to be unaffected. The deal with Big Pharma Baxter International puts viral seed strains from the world’s current bird flu hotspot and plausible origin of a future pandemic in the hands of a single manufacturer. Whether exclusive or not, it seems Indonesia has decided to get compensation for its viral isolates. The action underscored in dramatic fashion Indonesian displeasure over the production of a vaccine from a strain of H5N1 the Indonesians sent to WHO. WHO in turn sent it to Australian blood products company CSL to produce an H5N1 vaccine, using a model of non-exclusive seed strain sharing with vaccine makers now used for seasonal influenza. In this context, CSL did not notify or ask permission of the Indonesians:

[The] news this week that the Australian pharmaceuticals company CSL had developed a vaccine against the H5N1 bird flu virus was met with alarm by Indonesian Health Minister Siti Fadillah Supari.

She says Indonesia is seeking intellectual property rights over the Indonesian strain of the virus on which the vaccine is based.

But CSL spokeswoman, Dr Rachel David, says it is not possible to “own” strains of bird flu.

Dr David says the company received its stock of the virus from the World Health Organisation (WHO).

“To talk about strains of the flu as being something you can own is no a useful concept – it’s like trying to grasp smoke,” she said.

“It’s not a useful concept in dealing with this disease.” (Australian Broadcasting Corporation)

One sympathizes with both sides of this dispute. The Indonesians, like other developing countries are angry that viruses isolated on their territory from their citizens and provided voluntarily to the international community would be used by companies in rich countries to produce a vaccine they can’t afford and in any case would be far down the queue for available supplies.

A number of developing countries affected by H5N1, most notably Thailand and Indonesia, have been increasingly vocal in airing concerns that their people will not have access to vaccine made from viruses isolated in their countries if H5N1 goes on to become a pandemic.

“Developing countries in many instances would like to have their own stockpiles or would like to have some benefit from the viruses that they’ve given, seeing that there is not a great access to vaccines in the world,” Dr. David Heymann, the WHO’s influenza czar, said in a teleconference from Geneva on Tuesday.

A retired industry expert who follows pandemic vaccine production issues closely said there is little surprise that Indonesia has upped the ante in this way.

“One could view this as a hard-nosed negotiating tactic on the part of a developing country to gain access to the vaccines it will need for its population. And this is perfectly understandable,” said Dr. David Fedson, speaking from his home in France.

“This was inevitable and we should have seen it coming.”

In fact, Thailand served notice of these concerns at last month’s meeting of the WHO executive board, saying the current situation where pandemic vaccine would flow almost exclusively to developed countries with vaccine manufacturing plants is untenable.

“We are sending our virus (samples) to the rich countries to produce antivirals and vaccines. And when the pandemic occurs, they survive and we die,” Thailand’s representative Suwit Wibulpolprasert told the meeting.

“It is unfair to let the poor die and the rich survive. . . . We are not opposing the sharing of information and virus, but on the condition that every country will have equal opportunity to get access to vaccine and anti-virals if such a pandemic occurs.” (Branswell, Canadian Press)

The Indonesian action may or may not have been triggered by the CSL incident. WHO says they have been threatening to sign an exclusive license since last November and have sent no isolates to WHO since the first of the year. That means the new isolates from last month’s cases in Indonesia have not been shared. On the other hand, CSL’s David is also right that you shouldn’t be able to license a life form, especially the seed for a dangerous viral disease. Current Intellectual Property doctrines favor this, but it is a monstrosity that shouldn’t be allowed.

What’s the solution? Here’s one suggestion. Influenza vaccine is too important to be in private hands. This episode is a good example of what happens. WHO should set up a dozen or so geographically distributed international vaccine institutes whose task it is to manufacture and provide at cost seasonal and pandemic vaccines for their regions. The vaccine would be distributed according to need to countries in the region of the institute.

For years Big Pharma has explained its neglect of the vaccine business as the failure of the market where the profit was insufficient to justify investment. That’s fine. Those companies have a duty to their shareholders that trumps global health. They are profit making corporations. But if the market doesn’t work, then we shouldn’t distort market forces by subsidizing or guaranteeing profits from these same companies. Let’s take this vital commodity outside the market and manufacture it as a public good. Benefitting from the expertise of the regional vaccine institute would be contingent upon sharing viral isolates in a timely fashion. Meanwhile viral isolates should be in the public domain.

There may be other, better solutions than this, but this is better than what we have now. The Intellectual Property fascists have gone beyond suing elementary school students and grandmothers for downloading a few songs. Time to stop this nonsense before it kills us all.

Comments

  1. #1 crfullmoon
    February 7, 2007

    If Indonesia made it, they can pay for all the damages…

    or other nations could, if all the sequences are ever seen…

    (Monsanto should be stopped putting its patented monster plants outdoors, where they contaminate open-pollinated crops and damage biodiversity, rather than claim contaminated crops belong to them because their patented genes got in there… they are going to ruin small farmers who save “heirloom” seed, and, ruin our food crop biodiversity.)

  2. #2 anon
    February 7, 2007

    when they have the sequences, then they could produce the
    vaccine from it even without the samples, or not ?
    It’s just more expensive, takes longer, (how much ?)right ?

    This “jealousy” , rich countries having vaccine and
    poor ones not, I don’t understand.
    Poor countries should benefit from it too – just not so much.

    And let’s not forget, that Indonesia is “threatening” the world with a pandemic and now wants money for mitigating
    devices.

    Sure, we should help them to handle the problem.
    Sure, it’s not their fault that H5N1 migrated to Indo.
    Careless handling and failing to examine the hidden reservoir however is.
    I don’t think they have a point legally, else they would sue
    CSL for paying royalties. Instead they refuse to
    share samples with WHO.

    Just imagine panflu breaks out and there is no vaccine
    due to Indo-Baxter secrecy.
    Who will historians blame for the damage for centuries ?

    How much are we willing to pay to help them in handling BF ?
    How much do they require/want/need from Baxter or whoever ?

  3. #3 Karen
    February 7, 2007

    < >

    Now there’s something I’d be happy to pay increased taxes to fund.

  4. #4 bar
    February 7, 2007

    Could not agree more. Some sort of international co-operative (& why not WHO?) should manage vaccine production.

    I think that it is time big pharma was robbed of some of it’s monopolies. The banner on Murdoch’s Sydney “Telegraph” http://www.news.com.au/dailytelegraph/story/0,22049,21190558-5007132,00.html

    is:

    “PHARMACEUTICAL companies are deliberately creating shortages of generic medicines to force sick Australians to pay top dollar for identical brand-name medication.”

  5. #5 Victoria
    February 7, 2007

    I think this is just a case of – hand out – money now.

  6. #6 Tom DVM
    February 7, 2007

    If the World Health Organization had a brain…they would eat it.

  7. #7 M. Randolph Kruger
    February 7, 2007

    Well, Indon can just wait a bit and bird flu will spread and mutate as it goes. Then we will have the latest version in our backyards and then we will make a vaccine from that. When it happens, they get shit as far as I am concerned.

    I posted on this about a year ago. At some point in time this was going to become about money and not public health. This is state sponsored terrorism and we shouldnt send another dime in there. Several Chinese cruisers are in the area to supposedly the rights of Chinese nationals who are at work on Sumatera (Sumatra). They are nuclear tipped.

    A lot of what ifs are starting to come into being. Jimmy Buffets “Where you gonna go when the volcano blows? ” comes to mind.

  8. #8 M. Randolph Kruger
    February 7, 2007

    That should read to protect the rights of Chinese nationals. There have been incidents there in recent weeks where the workers were being beaten up by the locals because they would work for less than the Indons.

  9. #9 Greg
    February 8, 2007

    Baxter, too, plays the Intellectual Property card.

  10. #10 Patch
    February 8, 2007

    MRK – I’m not sure I’m right, but as closely as you follow things, you should know that Indonesia IS SHARING those sequences with a US manufacturer.

    It certainly is possible that when it’s in our backyard, it’ll change, but this is a start. I don’t know how the US company got the deal, but I would certainly trust a US company with information before any other.

    I guess I’m not sure, where you are from, but I thought Tennesee area, in the US?? While it would be ideal, to share sequences with everyone so we can all collaborate on a vaccine process, if only one company has exclusive rights, I’m sure glad it’s the US.

  11. #11 M. Randolph Kruger
    February 8, 2007

    Patch-Baxter Labs is a multinational and has offices in every major city on this globe. Indonesia is royally pissed that the Aussies came up with a 70% vaccine that was sent out for “research”. It was incredibly stupid of them to think that it wouldnt be used for that. But It clearly isnt intellectual property. It reminds me of the stories leading up to SABIN-SALK polio vaccine which might have been the origins of AIDS. Well informed means you try to get down to the lowest common denominator. Indon is full of shit. Baxter knows that this would be worth at least 1 trill if they develop it and the most that it does is keep someone alive.

    Revere posted that a 70% effective vaccine is about the same as what we get for protection from the seasonal flu and the Aussies have it. My fear is that they put some bullshit out there that mutates this crap further e.g. China’s vaunted vaccine program for poultry. I could care less who comes up with a vaccine that works, just as long as it does and in quantity. Fact is we are likely the only society that will be able to pay for it along with the EU and some of the developed world.

    Indon isnt SHARING anything. They are SELLING the bug. I guess therre is just a big void when the page turns in the dictionary to the word whore. Its this kind of stuff that starts wars. What would Russia pay if Indon/Baxter had a working vaccine that would keep its population alive? I dont think we would see the UN kissy-kissy stuff that goes on as it does now or the pussy footing about providing the vaccine to all for production. 6 months into an 8% pandemic that showed now signs of letting up they would be getting mighty antsy and desperate.

  12. #12 Tom DVM
    February 8, 2007

    Revere posted that a 70% effective vaccine is about the same as what we get for protection from the seasonal flu and the Aussies have it.

    If you wouldn’t mind sharing the references demonstrating that ‘any’ influenza vaccine is protective beyond anecdotal reports, I would appreciate it.

    Thanks

  13. #13 anon
    February 8, 2007

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15266445&query_hl=13&itool=pubmed_docsum

    …recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%)…

    [reduction in laboratory-confirmed cases]

  14. #14 Tom DVM
    February 8, 2007

    anon. Thank you for the reference. I have seen it before.

    See, the thing is that I would like to believe that seasonal influenza vaccines work; so would a lot of others. The problem is that like the study you quoted, the study is anecdotal and subjective rather than objective.

    My own observations and anecdotal circumstancial evidence indicates that seasonal influenza vaccines don’t work…

    …and pandemic vaccines against H5N1 are a whole other animal from seasonal vaccines…difficult to grow, low yields of antigen…poor immune response to vaccine in test subjects…

    …and we can add to that…uncertainly as to efficacy of seaonal vaccines.

    Why is this a problem.

    1)Well, since these vaccines will be given to essential workers, what if they don’t work and yet give a false sense of security which leaves recipients careless about other precautions such as hand washing.

    2) What if they mask clinical signs but allow for shedding. You could very well end up as front line health professionals dessiminating the infections to all others they come into contact with…while not becoming sick themselves.

    These are important issues to be answered proactively, especially when monies are hoarded for the two ‘magic pills’and unavaliable for sound treatment protocols that will make a real difference in lives saved in a pandemic.

    Thanks again.

  15. #15 anon
    February 9, 2007

    TomDVM, you have seen it before, yet you ignore it in your posts.
    I have seen that before. Why is it ?
    It’s a multy-study statistics. Why/how is it “anecdotal and subjective
    rather than objective” ?.
    That flu-vaccines work so poorly must be because so many other diseases
    misdiagnosed as flu falsify the statistics or the vaccine only
    prevents virus-detection but not symptoms, I don’t know.

    But we have tests for H5N1-vaccine, you can read the papers.
    I might work better than for seasonal flu, because H5N1 hasn’t yet
    learned how to escape immunity.

  16. #16 Tom DVM
    February 9, 2007

    anon. Thanks.

    Okay, you have to ask yourself a question…Why would these vaccines work under laboratory conditions and not under field conditions?

    While nature like time is fluid, in a laboratory, time is freeze-framed or stopped altogether. The researcher plucks a virus strain, cultures it, produces a vaccine with it…and then and most importantly, challenges the vaccinated laboratory animal with the exact same strain that was used for the vaccine…and under these conditions, influenza vaccines work reasonably well.

    …However, nature doesn’t work in this linear way!!

    I believe that influenza vaccines actually protect less than 5% of the recipients. One of the reasons is the lag period between concept and product…

    …In the time delay before seasonal and pandemic vaccines can be produced, this unstable family of viruses will have ‘shifted genetically’ to evade the vaccine.

    The very success of the influenza virus is based on the ability to turn it’s instability (which usually would bring about its rapid extinction)to an advantage in continually shifting antigenically and evading the immune system.

    On the second issue you mentioned, the scientific method and the advancement of science has been based on ‘double-blind’ studies whereby the observer does not know which group the subject he is recording fits into…therefore, the researcher cannot prejudge the results.

    Influenza researchers state that using a double-blind approach in influenza research is unethical because there is always the chance that even a mild influenza infection could cause permanent damage to the subject.

    I agree that there are ‘real’ risks infecting human subjects with influenza and certainly would not downplay them…but there are simple and more importantly known procedures to use a double blind experiment without the risk.

    Your first question should always be…Who is paying for the research?…

    …Because…”He who pays the piper…chooses the tune” and nowhere does this statement apply more than to the field of pharmaceuticals and regulatory medicine at the present time.

  17. #17 anon
    February 9, 2007

    TomDVM,
    that was a database search. They gave a negative conclusion about vaccination,
    hard to imagine that this was a big-pharma-paid bias ;-)

    “Analysis of vaccines matching the circulating strain gave higher estimates of efficacy”,
    so they didn’t assume matching in advance. The reason why vaccination only
    saves 0.16 working days – I don’t know. I only have the abstract.
    It’s unclear to me whether we would expect similar things with H5N1-vaccine.
    When 20% of the population is infected then things could be different.
    Apart from reducing symptoms, vaccination could also mitigate/stop
    the spread and thus protect others.

  18. #18 revere
    February 9, 2007

    Tom, anon: The vaccine efficacy problem isn’t clear. I have discussed it elsewhere here (in connection with the Simonsen paper), but there is a distinction to be made regarding benefit for the individual who is vaccinated and some measure of influenza in the population. These are different. It can still be effective for individuals but not be effective in a population. These things are measured differently. With respect to the current vaccines for H5N1 we know neither. The studies in humans that show it is “effective” are not studies that test protection but the development of neutralizing antibodies. To the extent that these things are the same, then it is a study of actual protection against disease but we don’t know that yet.

  19. #19 Tom DVM
    February 9, 2007

    Thanks anon Revere.

    Anon. I did not say that his study was paid for by big pharma or big food companies or big alcohol or big government etc….I suggested that it might be a good idea when you hear the next time that alcohol etc. is good for you, you might want to ask who is funding the study…and it also might be useful to know that a nice sounding group like Crop Life Canada is actually a group fully funded by Monsanto and the Agricultural Chemical Industry.

    The fact is that there are a lot of mercenaries…guns for hire in the epidemiology business at the moment…who will produce any data you want if you have the money. The way they do it is producing subjective analysis and sell it as objective science.

    An independent longterm (20yr) American study was reported in I think 2005. Revere might know the respected female researcher and her association and maybe the report itself. Anyway, they studied influenza in years when the vaccine matched to years when it didn’t match and found no significant difference. Ontario Canada has had free vaccines for more than five years and an independent study didn’t find a difference in that case either. Both of these studies could also be termed subjective…so my point in mentioning them is that for every one saying they work, there is one that says they don’t.

    “Apart from reducing symptoms, vaccination could also mitigate/stop the spread and thus protect others.”

    I would repectfully disagree. Vaccinations that work incompletely often create asymptomatic infections or carrier states which do more harm then good. Instead of mitigating, stopping the spread…they assist it

    “The studies in humans that show it is “effective” are not studies that test protection but the development of neutralizing antibodies. To the extent that these things are the same, then it is a study of actual protection against disease but we don’t know that yet.”

    It seems to me that you can produce a vaccine to any antigen but just because you can demonstrate antibiodies does not mean in the slightest, that the immune response is effective in preventing natural disease.

    An effective vaccine protects individuals and populations…I don’t quite understand how you can have one without the other.

    Thanks.

  20. #20 anon
    February 9, 2007

    but HHS wants to stockpile 20million doses.
    (8million or such so far)
    So they should know something.

  21. #21 Tom DVM
    February 9, 2007

    anon. There is more politics in this issue then science…I wouldn’t assume anything if I were you.

    Politicians put all their eggs in two baskets: antivirals and vaccines…

    …The resistance to Tamiflu plus the significant side effects were known before one dollar was ever spent on them by any Government…but that is not my point.

    My point is that no Government having wasted their time for three years and billions of dollars is not going to come back to their constituents now and say…

    ‘we were wrong…antivirals won’t work and vaccines even if they were effective cannot be produced and even if they could be produced, could not be for 6 months under ””ideal””’ conditions.

    Make no mistake…an H5N1 pandemic is coming and I expect it will occur in one wave with no mild predecessor to provide natural immunity as in 1918. The CFR is going up rather than down…

    …so how many deaths do you suppose will occur if the virus has a free ride for six or probably twelve months before a vaccine can even be produced.

    That is why they should ask scientists about these issues rather than famous non-scientist risk mediators or SPINNERS…no matter how nice they are in person.

  22. #22 Greg
    February 9, 2007

    Tom DVM, I said the other day, don’t believe CDC etc. I should have added don’t believe not-CDC, either.. and especially don’t believe yourself.

    Here’s the difference : If we stick Revere in a triage tent for three days, then the CDC Bull comes down, save Star-Bellied Sneeches, he’s going to think about the Sneeches whom he has seen, those who have stars and those who have none, and maybe check out the burial trenches. You, from what you have posted here, will blindly send those who have stars to the end nearest the trenches.

    “Don’t believe CDC” does not mean, “Assume everything they say is a lie”. It means _if_ you have any information or if Dick In The Next County has information, and _if_ it contraindicates CDC’s advice, then settle down, be honest about your motives, remember that you will kill people who trust you. Take responsibility for them.

    This isn’t a game over bragging rights or who goes to bed with whom. This is real-life where to help one is to hurt another. You get to live afterwards with the one you killed.

  23. #23 M. Randolph Kruger
    February 9, 2007

    The military considered doing away with the flu shots all together during the Clinton years because they really couldnt find any correlation between cost of the vaccine and the days off that someone was sick. They would spend millions on vaccines, then maybe a guy/girl would come back in still honking, coughing, maybe infectious or not and still have the supervisors send them back to the barracks because they were too sick to work.

    Toms point is well taken. If a vaccine simply allows you to survive and you spend months recovering, whats the difference? Sounds to me like the vaccines they could make might only do just that. If they arent able to work, feed themselves or be productive then we are going to have protracted problems afterwards.

    Anon-encirclement vaccination I think is what you are getting at when it pops out. Logistically speaking and I am part of that vaccine transport program I dont think you will get that much participation. This includes the drive thru flu idea because of personal logistics. They simply might not be able to get there. There are one hell of a lot of assumptions being made but the first one is based on a 5% event, a little time to prepare for people and that the infrastructure will hold. It would be a great thing if those assumptions are right. But more likely as Tom posits, it will be a lot worse.

    We would be into a six month or one year before vaccine became available position and by then the infrastructure would have collapsed or be near it. E.g. The Sabin Salk polio vaccinations with the sugar cubes in the sixties took weeks to get off the ground and polio was spreading slowly. We get a wild hair virus like this and they might have to walk thru the drive thru. Just getting people to take the shot is going to be fraught with problems if its available. I kind of lean towards Tom’s description of what is going to happen. They will drone on and on that vaccine is coming and they will be stacking up bodies like cordwood in the meantime from either starvation or the flu itself. Could be a slate wiper for us.

    I keep on coming up with the same conclusions and that the only way to survive it is via personal preparations and having a good recovery plan.

  24. #24 anon
    February 10, 2007

    looking at it again..
    that paper shows – as I understand- that “cases of clinical flu” decreased from 24% to 18%
    per year when vaccinating, and in those clinical cases the duration decreased
    by 0.16 workdays = 0.48 days in average. While cases of serologically confirmed
    influenza decreased by 70%. I assume the reason is, that many cases of
    “clinical influenza” couldn’t or just weren’t tried to be serologically confirmed.

    Well, much is still unclear about vaccine efficacy.
    But I’m not comfortable with that.
    We have to estimate it’s efficacy, how else can we
    decide whether/how much prepandemic vaccine to stockpile ?
    So, my guesstimate is, that in 2 otherwise equal communities
    the one with actual prepandemic vaccine will have 10% less
    deaths in a pandemic. (expectation value) What’s your estimates ?

  25. #25 revere
    February 10, 2007

    A recent entry into this controversey is this: Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population
    Lone Simonsen, Thomas A. Reichert, Cecile Viboud, William C. Blackwelder, Robert J. Taylor, and Mark A. Miller
    Archives of Internal Medicine. 2005;165:265-272

  26. #26 Lea
    February 10, 2007

    MRK: You said: I keep coming up with the same conclusions and that the only way to survive it is via personal preparations and having a good recovery plan.

    And not to put yourself “in the line of fire”.

  27. #27 anon
    February 10, 2007

    I remember another study, which showed a 2.7% probability
    for elderly people to die per year, 2.4% with 1st time vaccination and 2.0% with repeated vaccination.

  28. #28 Ari T
    February 14, 2007

    Some commenters, in their anger, are missing the point – Indonesia is not withholding the samples out of greed, nor is it doing so to maliciously extract future profits from other countries. It is trying to ensure that its population will have full access to the vaccine when it is developed. The current system does not guarantee that.

  29. #29 anon
    February 15, 2007

    … by withholding the samples which are needed
    to produce even that vaccine ?
    Makes more sense, if they would e.g. stop selling oil
    or threaten with war unless they would get vaccine.

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