Remember Dr. Sin Hang Lee?
If you don't remember Lee, maybe you remember a while back, when the antivaccine group SaneVax touted findings that it claimed were devastating to Gardasil. Specifically, they claimed that there was vaccine-derived human papilloma virus DNA in Gardasi. Ring any bells yet? And it turns out that the guy who made this apparently horrific "discovery" was—you guessed it!—Dr. Sin Hang Lee. Back in 2011, Lee, apparently either funded by or working with SaneVax, "discovered" that there was DNA in his Gardasil. As I explained at the time, there was a lot less to this claim that meets the eye. Basically, Lee used a very sensitive nested PCR assay to amplify and detect what he claimed to be vaccine-derived sequences from the human HPV strains used to make the vaccine. Specifically, his nested system, as I explained at the time, can radically ramp up the sensitivity of the PCR assay. Of course, it can also radically increase the chances of amplifying a nonspecific strand of DNA.
Given that, it wasn't too surprising that there might have been minuscule quantities of the recombinant plasmid used to make the protein antigens that go into the vaccine. At least, it wasn't too surprising to me or anyone with a modicum of knowledge about how sensitive PCR is and how easy it is to get false positives. Even if Lee did everything right and actually did detect a bit of recombinant DNA from the HPV DNA used to make the vaccine. Does this matter? My answer, of course, was no, as was the answer of anyone who knew anything about vaccines and biologics. One factor to consider is how much DNA was present, which was almost certainly very, very little, given that it took nested PCR to detect it.
In fact, even if Dr. Lee’s analysis was completely correct correct and his new, allegedly more sensitive methodology had actually picked up previously undetected traces of HPV DNA from the plasmids used to make the HPV vaccine, it is, as I described before on multiple occasions, incredibly unlikely that such tiny amounts of DNA could cause problems because, as I explained, it’s incredibly difficult to get naked DNA into cells and making the proteins it normally makes, and, even if Dr. Lee were 100% correct about there being undetected HPV DNA in Gardasil, the quantities involved are many orders of magnitude less than what would be needed to have even a whiff of a wisp of a hope of the DNA getting into cells and making its protein. That’s even assuming it could pass the blood-brain barrier or that the DNA fragments were large enough to contain whole coding regions of genes with a proper promoter in front of them to drive their expression. I mean, it's not as though whole plasmids are likely to have survived the vaccine manufacturing process, and that's not counting the fact that Gardasil uses a yeast expression system while the other HPV vaccine Cervarix uses a baculovirus (insect) expression system, neither of which would be likely to drive significant expression in human cells.
So what we had was a fear mongering campaign derived from a nonexistent understanding of molecular biology. This campaign reached utterly ridiculous levels when the not-so-dynamic duo of HPV vaccine quackery, Sin Hang Lee and Christopher Shaw (who seems dedicated to the idea that somehow HPV DNA bound to the aluminum adjuvant in the vaccine is deadly) descended like ghouls on the corpses of two young women whose untimely deaths antivaccinationists have been trying to blame on Gardasil ever since they happened. This campaign reached a ridiculous extreme when they actually testified in an inquest in New Zealand into one of these two deaths, a young woman named Jasmine Renata, and tried, in essence, to claim that the poor woman's body was riddled with HPV and that that HPV caused her death. It was an utterly despicable performance that Shaw, at least, followed up with an article in which he attempted to demonstrate that, in effect, Gardasil killed a young woman. It was not the least bit convincing.
And now Dr. Lee has taken his crack by publishing his paper related to the death of this same young woman in a paper published in an open-access journal I've never heard of entitled Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil® vaccination—A case report. Like Shaw's paper, it's a massive load of fetid dingo's kidneys, and it won't take that long to explain why.
First off, as I've always said before, you can tell what you're in for in a paper by its introduction, and Lee's introduction is a doozy. It's full of anti-HPV tropes that would be more at home on the antivaccine propaganda blog Age of Autism (or SaneVax, for that matter). He does, however, inadvertently reveal what I've always suspected to be true about this case:
The parents of a formerly healthy New Zealand young woman who suffered a sudden unexpected death in sleep 6 months after Gardasil® vaccination requested testing for the presence of HPV L1 gene DNA in the post-mortem samples of their deceased daughter collected at the time of autopsy. Some of the consultants to the parents suggested that if residual HPV L1 gene DNA which is known to be present in the Gardasil® vaccine [8,9] were present in the postmortem samples, there might be a potential link between the residual HPV DNA and the un- explained death of their daughter. This paper reports the experience in developing a method for the detection and validation of minute quantities of HPV-16 L1 gene DNA in the postmortem blood and spleen obtained at autopsy. The data reported in this paper were extracted from a full report which was submitted to the Wellington coronial court at a public inquest held on August 8-9, 2012.
Who were these "consultants"? One wonders. Were they perhaps Sin Hang Lee and Christopher Shaw, aided and abetted by SaneVax? One wonders, one does. In any case, I wrote about the ridiculousness of letting Shaw and Lee testify at this inquest. One hopes that the committee listened politely and then completely ignored the pseudoscience as embodied in this paper.
So let's take a look at what Lee did (or claims to have done). He took DNA isolated from these tissue samples and subjected him to his own new super-duper, super special, super sensitive nested PCR, looking for a 190 base pair sequence from the HPV L1 gene. As you might expect, given Lee's background, there were...problems with his methodology. Rather than critiquing the exact primers he chose and how he went about doing his PCR, let's step back and look at the experimental design from a bird's eye view. Basically, he tested DNA from tissue samples from one young woman. There are no controls. How many people in the general population would test positive using Sin Hang Lee's methodology? We don't know because he hasn't made an attempt to find negative controls, and without negative controls we don't know that every tissue sample would test positive when subjected to his methodology. In fact, the only negative controls I saw mentioned anywhere were negative water controls. That's perfectly fine to rule out nonspecific amplification that doesn't depend on DNA (such as artifacts like primer-dimer, but it doesn't tell you anything other than that.
Another issue is that troubles me is the way that Lee uses degenerate oligonucleotides. It's worth going back to images I've sued before to illustrate nested PCR:
And here's nested PCR:
Nested PCR can be very, very sensitive, even more sensitive than "simple" PCR, depending upon the number of amplification cycles used in each PCR step. It's that sensitivity that allows nested PCR to amplify very tiny amounts of target sequence. Now, Lee used a combination of degenerate primers and non-degenerate primers. A degenerate primer is a primer in which some of the positions in the sequence contain more than one base; i.e., there is a mixture of primers with different nucleotides at that place. The reason this is done, generally, is to amplify sequences for which we know there are variations in the sequence. Alternatively, it is done when trying to amplify sequences based on the protein sequence. Because of the degeneracy of the genetic code, most proteins can be coded for by more than one codon of three nucleotides. Usually, the variable base is the third base in the codon, but not always. To account for those nucleotides, degenerate primers are sometimes used as a way of putting a "wildcard" in the positions that can have more than one base in nature. However, such primers have a downside. The more "wild cards" a researcher puts in his primer sequences, the larger the number of potential sites to which those primers can bind. What one gains in sensitivity for potential coding sequences to be detected, one loses in specificity. It's a tricky balancing act that is not as straightforward as those without much experience in PCR realize.
That's why in general we avoid using degenerate primers except for this sort of purpose: Trying to isolate a sequence where we know that certain positions can have different bases. If the target sequence that a researcher is trying to amplify by PCR is known (and, make no mistake, the HPV-16 L1 gene sequence used to make HPV vaccine is known), it's usually a bad idea to use degenerate oligonucleotides, because doing so will decrease specificity and greatly increase the chance of amplifying what I like to call crap. Basically, I can't figure out why Lee would use the method he's using. Arguing that there is variability in the natural HPV-16 L1 sequence and he wants to pick that up won't wash. In fact, he is aiming to detect the vaccine strain sequence; so detecting any natural HPV that might have come from warts or other HPV infections would actually be counterproductive to what he's trying to accomplish: To detect the vaccine HPV-16 L1 sequence postmortem in Jasmine Renata. It's almost as though he's intentionally trying to muddy his findings. Maybe more than almost.
In any case, the same-nested procedure used by Lee, as far as I can tell, involved using degenerate primers for the first round of PCR, and then selecting one set of specific primers that make up the degenerate primer mixture and then using them to repeat the amplification. The idea is to start out less specific and then get more specific by removing the degenerate primers in the second round of PCR. The problem is, of course, garbage in, garbage out. The other problem is, as I said before, we don't have any negative controls from tissue samples from people who were not vaccinated with Gardasil. The reason this is important is inadvertently described in Lee's discussion:
Since the human genomic samples contain numerous DNA fragments which are substan- tially complementary to the base sequences of the HPV PCR primers, co-amplification of non-target DNAs of the human genome invariably occurs in the same-nested PCR settings when PCR amplicons are re-amplified with the same primer(s).
Of course, Lee did sequence several of his products. The first sequence was clearly not a pure sequence, but was contaminated with additional sequences, which prevented identification and validation of the PCR product. A couple of the PCR products that Lee sequenced (Figures 6 and 7) were in fact genomic DNA, and it took a lot of fiddling with different primers and conditions for Lee to get fragments that sequenced as HPV 190 base fragments. This suggests to me findings that aren't robust, which suggests to me that it's more likely that he's amplifying contamination than anything else, which, given the multiple rounds of PCR would be very easy to have happen if even a single prep of the plasmid containing HPV L1 were done in the same lab as the PCR of the DNA from tissue samples. That's yet another reason why controls from tissue samples derived from people who were not vaccinated would be important.
Here's another thing that would be important. Lee claims that vaccine-derived HPV L1 DNA is somehow hanging around in the body and that it, in essence, might have killed Jasmine Renata. It's not as if the sequence of the plasmid that is used to make the protein antigen used to make the vaccine isn't known. Lee only looks at HPV L1 sequence that is inserted in the plasmid. If fragments of the original plasmid used to make the vaccine were in fact still in the vaccine and somehow magically did continue to hang around in the body after vaccination at concentrations detectable by PCR, then it should more than just L1 there. There should be random fragments derived from the whole plasmid, not just the L1 insert. There should be readily identifiable plasmid and promoter sequences. In fact, the sequence I'd look for is a sequence containing overlapping the promoter used in the plasmid. That way, you'd detect HPV L1 sequence attached to the specific yeast promoter used in the manufacturing process connected to known plasmid sequence. It's the obvious thing to do, because, if that sequence were found, it would be very hard to explain any other way than coming from the plasmid used to make the vaccine. It would even be hard to explain by plasmid contamination because the plasmid containing the HPV-16 virus that Lee bought from ATCC to use as his positive control for PCR reactions because that virus is in Bluescript, which is an E. coli plasmid.
Lee didn't choose to do that. One wonders why. He even acknowledges that he knows about this issue:
The presence of HPV-16 L1 gene DNA fragments of a vaccine origin indicates possible co-existence of other companion microbial DNA, such as DNA fragments of the plasmid pGAL110 and yeast cells which are used in the vaccine production by the manufacturer [2]. A poten- tial consequence of these viral and microbial DNA frag-ments with their unmethylated CpG motifs in macro-phages [41-46] is to cause release of various cytokines, including tumor necrosis factor (TNF), a recognized myocardial depressant [47-51]. TNF-induced hypoten- sive shock is a documented observation among animals [52,53] and humans [54,55]. To answer the question whether the quantity of these persistent viral or microbial DNA fragments can stimulate the macrophages to release enough TNF to generate a significant pathophysiological impact following Gardasil® vaccination needs expanded research.
Uh, no. Lee should have done the research right in the first place if he wanted to convince anyone by actually looking for the sequences I described above, specifically an amplicon (the DNA target sequence to be amplified by PCR) that encompasses part of the L1 gene, the promoter region used, and pGAL110 sequence that is directly attached to the insert. He could also look for yeast genomic DNA sequences, as he himself suggested. The combination of finding HPV-16 L1 sequences from the plasmid used to make the HPV vaccine plus yeast genomic DNA would be very supportive of his hypothesis. Instead, Lee claims to have amplified L1 DNA fragments "of vaccine origin." Yet he hasn't proven that they are of vaccine origin. To do that, he would actually have to amplify some pGAL110 plasmid sequence as well as L1. Then at the end he concocts a handwaving explanation to justify why he had so much trouble amplifying L1 from Jasmine Renata's tissues when he can amplify HPV L1 DNA from the blood of women infected with HPV-16 in other studies, in which the HPV DNA isn't in the normal B conformation or is somehow stabilized by binding to aluminum adjuvants. It's utter nonsense.
Much like everything I've seen published by Lee on this topic. No wonder SaneVax and Age of Autism love it so. It's kind of sad, given that Lee clearly has some skill at PCR, that he chooses to use it for such a silly application in the service of antivaccine fear monger. As a physician with these mad PCR skillz, he really should know better. He should even know just how tiny the amount of HPV-16 L1 DNA there could possibly be in the vaccine, given that he could only detect it with a very sensitive nested PCR test and that that amount is so tiny that it is incredibly unlikely to hang around in the body for more than six months and be detectable in the tissues postmortem, much less cause harm.
Yet Lee chooses not to know.
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@JGC "non-B conformer, thank you for pointing out a second logical error that’s been pointed out to you, but you prefer to ignore..."
That's non-B conformation. The logic was clearly stated both here and in the case report. Since you bring up bimler, he still hasn't answered the key question in post #472. If you disagree with the logic explained in the paper, then please answer: How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair? Silence from everyone so far.
You see, you seem just like the others: Parroting some sciency sounding arguments from textbooks, groupies, or even unrelated PCR lab work, but unable to address the real meat of the problem. By now it should be obvious to even you that discussing the details requires some practical knowledge and real lab experience finding target HPV DNA mixed with human genomic DNA.
In addition to the question above, despite numerous pleadings that population studies are required to qualify the finding as unique, not a single person here has been able to articulate a scientifically plausible source (aside from the vaccine) for HPV-16 L1 DNA fragments in non-B conformation in the autopsy tissues. Nada.
That means those two arguments of false or missing logic are totally unsubstantiated by anything other than rhetoric so far.
Sorry, kid, show me the poll crashing. With feeling. Oh, and the "well-known" part. In detail.
Then you offer a splendid example of flawed logic because you should judge a paper you have access to based on the contents, not based on where or how it's published. Unless of course, you can't actually understand what they're talking about and need to defer to some other authority. That's a different flaw.
No, I won't answer, because when you have the details in front of you, it's not relevant. It only comes into play if you're using irrational flawed logic or deferring to authority. I prefer to avoid both of those things.
Opps, missed the blockquote in #504.
Detail? Do your own homework. Lilady validated it. For more evidence it's straight from the great leader's mouth: "If you can’t beat ‘em, join ‘em: Crash this poll" on December 31, 2008. No apology or thanks required, it's called Google old one.
Must suck to be a chickenshıt.
I think it sucks a lot worse to be illogical or wrong. Dishonest questions premised on false logic should not be answered. Don't take it too personally now.
Nope, fail. Perhaps you're thinking of Pharyngula. I don't need to do your homework, but apparently you don't grasp the underlying concept. Lilady voted on a poll, so "Orac’s groupies have been known to crash online polls"?
Do I get to be a "groupie" even though I don't give a rat's ass about online polls?
It sucks to be illogical or wrong. Dishonest questions premised on false logic should not be answered. Don't take it too personally now.
I gave you the OP title and the date and the blog (hint: this one, not Pharyngula). If you can't find the link, then the failure is clearly not on my end. The title says it all.
You're asking me? Why don't you ask lilady? She seems to know the entry criteria and proudly wears the badge.
There is no "dishonest question." I asked you a question, and you retreated to asking one instead, I answered yours, and now I would like you to get back to the original one. You have refused, and when challenged, have resorted to simple babbling. Answer the question.
Mr. Pink, you seem to be assuming I lack sufficient real knowledge and practical lab experience to be able to understand Lee's publication and identify the logical problems with his claims. That isn't the case.
But let's assume I was that ignorant of PCR amplification.. That ignorance wouldn't alter the fact that Lee's has failed to demonstrate the DNA he amplified was vaccine in origin or present in as a non-B. conformation.
Mr. Pink,
If so, why did Lee write this?
Taking an example from my own field, if I developed a method for measuring serum rhubarb using an enzyme-linked immunosorbent assay, I would still have to demonstrate its specificity and sensitivity, even though ELISA is an established methodology. I most certainly wouldn't use it to analyze post-mortem samples and suggest that the person died of a rhubarb overdose until others had replicated and validated my new method.
The important point here is that Lee is behaving in an irresponsible manner by publishing an alarmist paper that is clearly designed to frighten people away from HPV vaccines. His findings are even more implausible than the malarial Inuit you posited above, and his conclusions linking these findings with a young woman's death are extremely premature. Couching his conclusions with a lame disclaimer about further research being required doesn't excuse his behavior. He knows perfectly well he is being used as a propaganda tool by people whose beliefs about HPV vaccines are already fixed and who are only interested in evidence that supports them, no matter how reliable it is. I have little doubt that there are some people who will avoid Gardasil because of Lee's work, and that some of these will develop HPV and cancer and die as a result.
Well, this conversation devolved nicely. Marg was more fun as a chew toy, she had more pizazz.
Arguments from popularity are now apparently known as 'facts'. Even with her postmodernist views she never managed to pull that one out but would have done it with more style...
They are not. I won't put them at the top of the pile, but there are a lot of very bad bogus publishers and bogus journals. Some open access, some subscription and some "free" industry funded.
@Narad
I'll take your silence on Orac's OP, as a concession that you accept my assertion.
Blockquote fail again.
What a bizarre point to make: I must have been wrong in my assumption, but let's go with it anyways?
I didn't make an assumption, I made an observation. You made a strawman, because my observation was far more qualified than you lacking PCR experience in a lab. I observed that it seems like you lack lab experience detecting target HPV DNA mixed with human genomic DNA. I would be delighted to find out that was wrong, but you have provided nothing to indicate otherwise.
Non-Sequitur. If you are ignorant of PCR amplification and by corollary, DNA in non-B conformation, you could not practically dispute the claim of the HPV-16 L1 DNA fragment in non-B conformation as it requires an understanding of both topics.
But since you claim adequate expertise, stop assuming anything. If you insist the HPV-16 L1 DNA fragment is not in non-B conformation, then please provide a articulate description of the results from the case report. How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair?
Without answering that question, your criticism amounts to unsubstantiated claims, and that is the farthest thing from fact despite your pleadings.
Do I really need to describe the difference between "method" and "methodology"? The specificity of the results was well documented in the case report.
So elegantly stated as fact despite you having admitted non-expertise in the area covered by the report. Given that you can't articulate an issue with the science, your claim (not fact) of irresponsible behavior is unsubstantiated. As for your claims of "alarmist" paper, I think that is dubious as well. This was the conclusion:
A call for investigation is hardly alarmist. This is especially true in a scientific paper that can only be comprehended by those who have expertise in HPV genotyping which excludes 99.999% of the population. There are more than enough VAERS entries describing serious Gardasil reactions resulting in morbidity and mortality that this is barely a blip on the "alarmist" scale. The scientist doth protest too much, methinks.
The unique and unexpected findings in autopsy tissues are linked to her death by the fact they were done as part of a post mortem investigation. The real question is causation, and no definitive conclusions were claimed. However, plenty of evidence was given during the coronial hearing to justify further investigation, which is exactly what the case report recommended based on the findings.
Arg, You would think Wordpress would offer preview...
Such a definitive and confident prediction based on a faith in industry and HPV vaccine strategy. There isn't an ounce of quality evidence showing the vaccine has or will ever reduce the incidence of cervical cancer. That's why people should avoid Gardasil, not because of one linked death. Isn't this supposed to be the site of Science Based Medicine? I forgot, Orac dropped the evidence part.
How hypocritical. What do you think this blog is all about? You exposed your true colors with that gem of an argument Krebiozen.
No, in fact I do not. You stated the following:
You have, as your lone example (and please try to learn what "OP" means), this, which of course immediately invokes PZ. And Lilady stating that she voted in a some online poll somewhere. So who's been "known" to do what? Who are the "groupies"? Where's the evidence?
Where's the non-B conformation DNA?
@Krebiozen,
Good comparison.
@Mr Pink,
So you continued to put words in others' mouths, offer twisted, distorted, versions of what others have written, slurring the writer each time with cheap shots?
Great way to show everyone you're trolling. (See also comment #478.)
In your latest, you repeatedly made inaccurate claims about me (to be polite). I can't be bothered with your silliness, really, but it's perhaps worth illustrating for other readers the extent you mess up others' words (for whatever reason) with one example that they might find easy to follow.
(If for nothing but entertainment's sake, I suppose.)
I tried to point out to you the paper under question here is paid for by SaneVax, saying that was stated in the paper.
Ignoring the cheap shots, in comment #499 you said:
"The HPV genotyping methodology paper was not paid for by SaneVax"
My statement was about the current paper. (You know, the one being talked about.) You made my statement to be about some earlier paper. Goodness knows why, but clearly this twists, gets wrong or whatever, the meaning of what I wrote. So, QED. Then you compound this error or deception by going on to try "fit" a lot of other things I wrote under your strange re-interpretation.
The paper at hand is paid for by SaneVax, it says so in the paper:
"This study was commissioned and sponsored by SANE VAX, Inc."
It couldn't be clearer.*
Just a thought: some might say you are trying to deflect attention from a conflict of interest by arguing if some earlier paper is not paid for by SaneVax then Lee's recent work can't have a conflict of interest either (which is illogical). SaneVax state on their website that they recruited Lee to test patients. Others can verify this, but I believe SaneVax stated that before this coroner's inquiry. It would follow that Lee's involvement with the Renata samples has been entirely within his time of involvement with SaneVax.
I think it's clear to everyone that you seem unable to accurately note what has been written by others. (To be polite.)
I could speculate why you do that, but whatever the reason might be I think the way you treat others speaks for itself.
---
* This statement has SaneVax commissioning the study into the sample, as opposed to carrying it out on behalf of a third party.
I see, there's a pile. (Well, a pile of something, to be certain.) SCIRP has trotted out a stable of approximately 150 journals in the space of six years. Again, they have "published" articles from other journals to pretend that their inventions have submissions. They have accepted an article from a random text generator.
What does it take to get a retraction? Republishing something that has already been retracted for plagiarism, apparently.
They can't even set the HTML or PDF of a retraction competently. This stable is garbage. It is the putrefying corpse of a pregnant mouse that the cat brought in and left in your shoe. Strangely, you seem to wish simultaneously to argue that the journal is irrelevant but the publication in the journal lends credibility.
The best defense that SCIRP could possibly establish is that it might allow "third world" authors to get published in lieu of real journals that assess page charges. But this also appears to be a crock, as every society EIC I've encountered has had a fund specifically for this purpose. If you are doing sound work, even basic observational work, you don't need a vanity press.
But let's return to the orignial hierarchy that you've asserted. Clearly, you are reduced to trying to would like to try to drag in Elsevier's unseemly practice of having sold ghostwritten, bought-and-paid-for titles. This may surprise you, but they're not the only game in town. But anyway, tell me: who's lower on "the pile" than SCIRP? Does it rhyme with "eunuchs"?
Given your persistence with that line of argument, I'm beginning to think you're purposefully playing a dupe in some bizarre attempt to paint me as the troll. You also sound like you're going to run off again (post #329), without ever addressing the science. It's a shame that was a lie the first time (and that is being polite), since you've come back over and over and over, and still You refuse to discuss the case report. Your trolling obsession looks more like a projection but you're right on one count, you have been entertaining.
You need to learn to write what you mean. This is what you said: "It’s also possible, if not probable, that the high count is, in part, due to SaneVax groupies and others they have promoted this work to[sic]" [emphasis mine] "The high count" refers to the methodology paper and without another subject in the sentence "this work" appears to apply to the same unless otherwise qualified. Indeed, the whole paragraph opens by discussing reading "a paper" with high counts. To be polite, I'll assume you just weren't articulate enough, instead of trying to move the goalpost. Examining your modified argument reveals it doesn't make any sense, because the methodology paper isn't promoted by the blogs, or articles about the case report. Your explanation for the high read counts is non sequitur now. You continue to back yourself into lose/lose arguments. So which way will you have it: Shifting goal post or non sequitur?
Yes, it is illogical and lo and behold: You're the one who wrote it. It's even more illogical since I'm sure the $1 commission generated a ton of conflict. Unlike IMAC, I have no need to deflect anything about COI. Cognitive dissonance down under?
As I described above, what's quite clear is that you can't articulate a coherent argument (to be polite). I see you've wisely stopped holding up the IMAC paper as anything relevant to the case report in the OP. Perhaps you should examine the rest of your arguments here with the same rigor given that you still have not said anything about the science in the report being discussed by the OP. (to be polite) Or, perhaps you'll actually do what you said almost 200 posts ago, and go off and do other important things -- like convincing hippies to vaccinate their kids (to be really polite).
@Grant
Earth to Grant: One more time. It's post #520+ and You still haven't commented on the science in the report. (to be blunt)
Contratulations on finally getting the google query to work. Are you trying to shift the goalpost now by pointing out that he "invokes PZ" because you were pretty sure Orac didn't do it. You said: "Nope, fail. Perhaps you’re thinking of Pharyngula." The fail is clearly yours. I quote the OP I referenced:
As for groupies being involved, I'm guessing you forgot to read the comments old one.
You also complain about a lone example. As someone in the "publishing racket" your own research capabilities appear questionable. Try looking up "Another idiotic poll: Do you think vaccines are safe?" on August 29, 2010. I'll help you out by quoting the OP right away so you don't confuse the author again in disbelief:
Don't forget to read the comments this time. I want to know though, are you really new here, or do you just have a defective memory?
If you're done foaming about the mouth about OA journals who happen to be disrupting your decreasingly profitable publishing "racket", then you might realize that when you have a fully detailed case report -- with all the details to allow anyone to reproduce it -- you should probably read it. Instead of trying to tar papers based on the publisher or other similar arguments of authority, you might actually have to understand the science. Open access, the internet, and a raft of civil court cases, have allowed people to expose the crap in "the pile" for what it is coming from the new or old publishers. Whether the new problems cropping up are worse than the old ones is a good question, but it won't change the inevitable. Whether you, bimler, or others (like the defenders of monastic education) like it or not, the fallacy of authority defence long wielded by the old guard of the science establishment is crumbling. Enjoy the last vestiges of it while it lasts a few more years. Since you fixate on things like proper PDF publication, it seems logical that you would give Grant and that IMAC group (a purported NZ "authority" on vaccines) a hand since they appear to have some competency issues in that department as well.
By spending more time reading the paper instead of fixating on the name of the publisher, you might avoid asking questions which have already been answered in the report. Since you disagree with the assertion in the paper, answer the question: How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair?
Oh, the irony.
The vast majority of my experience is in nonprofit publishing. Societies, remember? I assure you that for-profit journals publishers such as Elsevier are doing just fine, because they have monolithic control over not just price but what's in the package. And the likes of SCIRP and OMICS represent a threat to absolutely no one.
Mr.Pink,
Disingenous nonsense (PDF). We have every reason to believe the vaccine will reduce the incidence of cervical cancer. It has been proven to reduce the risk of cervical changes that are known to be associated with cervical cancer in the short term, so it would be extraordinary if it isn't found to reduce the incidence of cervical cancer in the longer term.
Well, I take it that "quality evidence" means published in a vanity press and financed by a special-interest group.
I should probably also address this:
It wasn't an argument, I was expressing my opinion. Having looked at much of the available evidence, the benefits of HPV vaccines seem to me to greatly exceed any possible risks. That's not hypocritical, that's rationally weighing the evidence. I have no dog in this fight, I simply want to see people protected against HPV and the cancers it causes.
Are you seriously suggesting that all the safety and efficacy studies and post-marketing surveillance on HPV vaccines are faked by the industry? That HPV DNA (in amounts so tiny nested PCR is needed to even detect them) somehow migrated from a young woman's arm muscle to her brain and killed her 6 months after vaccination? As the old maxim goes, extraordinary claims require extraordinary evidence, and I need to see something a lot more robust than Lee's studies before I give this any credence at all.
Mr Pink @ 516 says -
Are you part of the population who have expertise in HPV genotyping?
If so, where and how did you come by this expertise? How do you use genotyping in your daily life?
I'm just going to do this piecemeal, as my attention is scattered between tasks today and, really, it doesn't merit anything more.
This nothing more nor less than an argument against genuine peer review itself, coupled with an argument for shoddy peer review in some sort of weird Levellers gambit. You are, in effect, advocating precisely this.
If the "establishment" is "crumbling," why did Lee bother to ape it using a vanity publisher?
Mr Pink stated earlier that
Now I wonder why/how he jumps to the conclusion that any events that follow vaccination are necessarily "serious gardasil reactions"? Has he not realized that anyone can report any event they like, and that such amazing "serious gardasil reactions" like a fatal car crash, or a death from congenital heart disease 6 months after the second gardasil shot have been recorded on VAERS? I guess not. Perhaps he should stop using VAERS for purposes it was not designed for, and look at other less malleable sources of information on gardasil safety/reactions.
Mild amusement may be derived from Googling "Sin Hang Lee" along with the name of his attorney, Anthony J. Musto.
Um, no, I didn't need "the google query," as I was around for that. Your second sentence is simply incoherent. PZ is known for encouraging "poll crashing" and was invoked at the very start of the item that you first cited. "Orac's groupies" are not particularly "known to crash online polls," perhaps because nobody much gives a damn about them in the first place.
You, on the other hand, advanced the strange position that download stats for Lee's article were somehow meaningful, which just seems to be a rehash in structure of the contradictory position that you have adopted regarding journals.
his attorney, Anthony J. Musto
Connecticut State Senator Anthony J. Musto is probably ex-attorney, I imagine.
Perhaps whoever is representing Sin Hang Lee in his suit against Milford Laboratories will have better luck. He does not have much luck with employers, does he?
Sin Hang Lee's suit against the FDA (with Musto representing HiFi DNA) was mentioned by lilady and Laura in a previous thread:
http://scienceblogs.com/insolence/2011/09/06/oh-no-theres-dna-in-my-gar…
@Krebiozen
LOL, denial in the face of contradicing evidence. Looks good on you just like the illogical ideas around tarring a paper based solely on who published it.
In #421 all you said was journal publishing was your racket and in #520 you encountered society EICs. Remember? Post the quote from this topic where you outlined the majority of your experience as the fully qualified nonprofit publishing industry.
A claim was made to the effect that no one reads Dr Lee's papers. The download statistics are meaningful with respect to showing interest in the paper. The rest is your strawman.
Nice dimwitted strawman. I didn't draw any conclusions about the validity of the reports. I described what is in VAERS because such entries -- regardless of their validity -- will cause way more alarm than this case report. Of course, that would have required you to read and understand all of what I wrote in context. Let me guess, you've been waiting to jump in, you saw VAERS, and your brain stopped working because you happen to know its limitations. You thought: that dumb Mr Pink really screwed up this time. ROTFL. Please, keep posting dingo199. You're dragging down the groupie score. Do you have a comment to make about the case report?
Do you have a point to make about the case report? The big outstanding question right now is: How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair? Many here say Dr Lee is wrong about his assertion in the report, but not one of them will answer the question. Funny that.
It is a veritable geyser of irony.
This is a blindly stupid remark to the extent that it's comprehensible at all. The default assumption is traditionally against preemption. You are, in effect, attempting to invoke Bruesewitz. The amicus brief is irrelevant to the decision. Levine turned on labeling.
(And was also a warning-defect claim, not a design-defect claim. I recommend that Pink stick to other things that he doesn't understand.)
@Narad
Let's not forget Mr Pink's argument started off with Lee being THE authority on PCR, having written the book on it, and is such an authority on the topic we should simply accept the paper without question.
@Narad “Are you or are you not willing to admit that SCIRP is the bottom of the barrel?”
They are not. I won’t put them at the top of the pile, but there are a lot of very bad bogus publishers and bogus journals
Mr Pink has us there, Narad. When I reflect on it, it is rash to describe the SCIRP journals as the absolute bottom of the barrel, when there are indeed even more egregious scams -- such as the people who fired up the random-text generator and constructed seven fictitious previous issues of their junkjournal, to give the rubes the impression of a publication history.
If you’re done foaming about the mouth about OA journals who happen to be disrupting your decreasingly profitable publishing “racket”
I believe this to be an example of what the young people call a "straw man, possibly large enough to burn Patrick McGoohan alive, since I can't recall anyone here criticising OA journals per se. Only the crooked ones. I wager that some of the commenters have published in or are on the peer-review panels of journals from Frontiers or PLoS or BioMed Central.
the fallacy of authority defence long wielded by the old guard of the science establishment is crumbling.
Just for clarification, is Sin Hang Lee -- "who has basically written the book on high sensitivity PCR testing" -- part of this Crumbling Old Guard Authority?
I've no need to comment on the case report, Mr Pinkie. You're screwing the narrative on that well enough on your own. I just thought it apposite to contrast your blind faith in VAERS with your decrial of other more reliable vaccine safety studies.
Mr Pink @472
That’s a major analogy fail at the most basic level.
The lack of effort you are putting into this thread is depressing. The analogy between reporting malaria in a "native Eskimo living near the North pole" [a North Dane, some of my colleagues would say] and reporting "HPV DNA in non-B conformation in human tissue" is yours (comment #452), so if it fails, don't blame me. I merely pointed out that in both cases, one would want validation of the method used to detect the unexpected condition "against people known to have [$CONDITION]" (comment #468).
Your response is that the reagent has been validated to Sin Hang Lee's satisfaction in a different test for a different purpose:
I can't see any mention in the Infect Agent Cancer. paper of non-B conformation. I've read it. Have you?
Did I miss Mr Pink's answer to Johnny's question?
Given that, per Mr Pink, the paper in question "can only be comprehended by those who have expertise in HPV genotyping which excludes 99.999% of the population", it's fair to wonder if Mr Pink is "part of the population who have expertise in HPV genotyping". Orac, of course, most certainly is part of that population.
Before Mr Pink jumps on me, let me add an omitted step: expertise in HPV genotyping specifically doesn't seem required, but expertise in using PCR and genotyping in general would be. Mr Pink has not offered evidence that HPV is so uniquely different from all other viruses in existence that expertise with other viruses cannot offer an understanding of HPV.
@Mr Pink:
I guess any possible confusion could not possibly be because Mr Pink was not being clear because Mr Pink is Always Right and Knows So Much More than anyone else.
JK. Mostly.
I don't have to paint you as a troll: you act like one (even in the paragraph you wrote that).
"I see you’ve wisely stopped holding up the IMAC paper as anything relevant to the case report in the OP."
Still trying to foist this particular twist and bait on me? Trying to make out that from not saying something that I have done some particular thing is illogical and, besides, here you, who keeps accusing others of using strawmen, is using a strawman.
You criticised everything but what the IMAC document said about Lee and his work. In particular, you tried to shoot the messenger - and still seem to want to. I pointed out that you at the time. There's not much more I can do than that.
I suppose could "demand" that you address the points made there in the way that you are "demanding" things of me, but really it's your choice not to engage with it if you don't want to.
"You still haven’t commented on the science in the report"
I guess you have forgotten that I have actually pointed out some issues with Lee's work from your mind, but never mind.
I choose to leave aside most of your statements about Lee's science because the paper has bigger issues, as I pointed out some time ago.
Like anyone here I don't "have" to reply to you, never mind address particular things that you would like others to. You don't get to dictate what others "must" do. Similarly, my not replying on any one thing doesn't mean a thing.
On the subject of the standing of the ABB journal: One simple way to judge if a journal in the bio-med area is up to a reasonable standard is to check if Medline has indexed it. It's not an infallible way of doing this, but Medline looks at the standard of peer review and the policies of the journal, etc. Medline indexes thousands of journals in the bio-med area. The journal the paper by Lee that Orac examined above (ABB) is not indexed by Medline.
Another way is to see if the journal falls in the list of vanity publishers (previously linked by others). As a SCRIP journal, ABB is on this list as others have pointed out.
There are also list of journal rankings you can inspect.
I could go on. The bottom line is that you can't really avoid that with or without the vanity element ABB is a bottom-end journal. It's just the way it is.
Regards my points: the points themselves stand - some might suggest you are trying to use tit-for-tat about who said what in what order to distract from from the points themselves. (I haven't time for the side-issue of the sequence of discussion: the sort of thing you're driving to seems more than a bit inane to me.)
You seem to be arguing that COIs can only about money (something I've seen anti-vaccine proponents say). SaneVax said they commissioned and sponsored the study: that is the issue.
(I have other concerns on this issue, but enough for now.)
Finally, it's worth reminding you that it was you that argued from authority from your first comment here, saying that His Word Will Rule And Will Be Right Because He Is The Grand Expert. (Sorry, but you get the point.) It's the basic fallacy you built this on. After you were shown up on that, and the standing of the journal, you moved to bluff and bluster about his work... and so on.
edit: omit "from your mind". (It's very late here; I'll be surprised if that's the only typo!)
Mr. Pink,
I think you have been snared by the Nirvana fallacy. By "every reason" I mean that the available evidence is consistent with our expectations that HPV vaccines will provide long term protection against cervical and other cancers. Scientific papers use careful language to avoid making any statements that cannot be directly supported by their contents, which sometimes provides wriggle room for people (like you) to claim that something is not proven when for all practical intents and purposes it is. In real life we have to look at all the available evidence and make decisions based on that evidence. In my opinion the evidence is more than adequate to support universal HPV vaccination.
Public health decisions like this are always a gamble to some extent. If we waited until clinical trials had gone on for decades to see what actual reduction in cervical and other cancers HPV vaccines deliver, that would also be a gamble, one that would likely result in numerous unnecessary cases of cancer and some deaths.
This is a blog, not a scientific paper, and I'm not running a clinical trial. The evidence shows beyond any reasonable doubt that HPV vaccines greatly reduce the incidence of precancerous cervical lesions. That's enough for me to happily use the word "proven" in the sense of "demonstrated by evidence or argument", not in the mathematical, absolute sense of the word. The evidence also shows beyond any reasonable doubt that the presence of precancerous cervical lesions is predictive of cervical cancer. It is not a large leap of faith or speculation to deduce that HPV vaccines will prevent cervical and other cancers.
There is a huge body of evidence, all of which is consistent with HPV causing cancer, and HPV vaccines preventing both HPV infection and cancer. That's what makes it a no-brainer. All I see from you is special pleading.
I grabbed that "narrow study" more or less at random; there are plenty of other studies that support my position. Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality.
Do you have any evidence to support that statement? I thought the latest idea is that persistent latent, not repeated, infection leads to cancer. Prevention of the initial infection by vaccination would prevent that.
You are making a series of leaps of faith here. Repeated infection? Immune system problem? As I understand it, natural infection does not induce long term immunity as reliably as the vaccine does. The reduction in precancerous changes seen after vaccination strongly suggests it will also prevent cancer.
We never have the luxury of certainty in the arena of public health. The evidence is always incomplete. If we waited for evidence of high enough quality to satisfy the antivaxxers we would still have thousands dying of smallpox, polio and measles. It's true this is a gamble, but it is a very safe one in my opinion.
I think it is quite obvious that this sentence, “He knows perfectly well he is being used as a propaganda tool by people whose beliefs about HPV vaccines are already fixed and who are only interested in evidence that supports them, no matter how reliable it is", is my opinion. I can't offer any citations to support what I wrote about Lee's motivations, I can only state what conclusions I have come to based on what I have read.
My true colors? If you mean I support the public health decisions taken in many countries around the world regarding HPV vaccination, then yes those are my true colors.
I disagree. There is plenty of post-marketing evidence to suggest HPV vaccines are remarkably safe and effective. When you consider that they are made using genetically engineered baker's yeast and they contain nothing that was ever part of a pathogen, their safety is to be expected.
Not Sergeant Howie?
No, I'm part of the 99.999%. My background isn't this field, or any other medical field. I'm not qualified to make points about this case report, or any other medical issue. I mostly sit in the corner and read. I doubt that in the 5 years or so I've been reading RI that I've commented as many times total as you have in this one thread. I'm here for my education and amusement only, not to discuss topics in which I only have a basic understanding.
I know that argument from authority isn't proof of anything. However, expert opinions are valid data points, and I do consider them. Our host has some experience in genotyping, and has stated why he believes Dr. Lee is using the wrong tool for the job, and incorrectly interpreting the results. You seem to take exception to this, and I was wondering what in your experience has led you to this conclusion.
Not Sergeant Howie?
Everything is better with Yakety-Sax!
So Mr Pink answered Johnny's question with a non-sequitor. How surprising (NOT).
Listen, Pink. If you're going to dismiss our criticisms of the paper on the basis that we don't have the expertise to interpret it, then we have the right to ask if you are an expert in the field of genotyping.
You can't have it both ways.
Only if you read a press release, otherwise you would see the direct link between drug warning labels, preemption, tort law, and FDA regulation regarding the safety of pharmaceuticals. Apparently, the FDA also didn't get your memo because their position over three decades and especially since 2006 was to insist on preemption. A ruling against preemption means the court did not place the FDA as the sole gatekeeper of public safety and allowed state tort to continue. From the ruling: "State tort law will sometimes help the Food and Drug Administration (FDA) “uncover unknown drug hazards and [encourage] drug manufacturers to disclose safety risks.”" The reasoning and impact of what was written in the ruling go far beyond labeling and are pertinent here contrary to your assertion. The briefs are completely pertinent here, especially the one from the NEJM. It contained a lot of well researched and referenced evidence regarding the inability of the FDA to effectively regulate and monitor drug safety because they rely so heavily on the manufacturer for information and expertise.
Your strawman again. I didn't put any faith in VAERS, let alone blind faith. I said the records would cause more alarm than this case report. If you want to contrast blind faith in VAERS with vaccine safety studies, then go ahead, but you will be arguing with yourself. You should check out post 547 though, because Krebiozen is holding up VAERS as quality post marketing evidence. Go go go.
That pretty much says it all dingo199.
Why don't you actually discuss the point being made there then? If you think a greater percentage of the population will find and think they comprehend the case report, tell me what that percentage is. Why don't you give me a better number than 0.001%? Is it 0.01% or 0.0154%, or even 1%? Then you can tell me how that compares to the percentage of the population that will read and be alarmed by VAERs entries. Then, and only if there is a substantial difference from the number I gave compared to VAERS will you have a pertinent point to make. So what are better percentages in your mind?
How appropriate that you're talking about non sequitor assertions. Last time you were here #403 insisting in some convoluted argument that Dr Lee didn't even find HPV DNA fragments ("There is NO PROOF that what Sin Hang Lee found was HPV DNA"). Why don't you explain to everyone here how one can get a full 184 bp HPV L1 gene DNA sequence which was a 100% match for the HPV-16 sequence stored in GenBank. and somehow not have found HPV DNA? I'm sure we would all love to hear your logical explanation for that one.
I'll use Narads words here "It is a veritable geyser of irony." @472 is the post where I asked you the last question you ran away from, not a discussion of analogies. That "lack of effort" that's depressing you must be your own or Krebiozen's shoddy evidence. Since you so conveniently brought it up again, why don't we go back to that critical question before we open up another tangent of yours: How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair?
You forget so quickly that you're the one who foisted it upon yourself... twice. (comments 410 and 447) As for taking bait, you've done that many times according to your own line of argument which you insist on maintaining. This would be another example in your world.
You are the one who provided a document "published" (certainly not by Narad's standards) prior to the case report and then claimed it is relevant. And yet, you refuse or can't quote a single section from it that is relevant to the case report. You can't even explain why these "experts" were absent from the investigation when something could have been put on the official record. Your attempts to make it relevant have been a spectacular failure.
And here I thought this was a kangaroo court of sorts and you would be forced to answer. I guess you can wax poetic all day and night without addressing anything real. That's a real bonus for you.
No, those are your words. Why don't you articulate why commissioning studies is an issue? Are you proposing that all commissioned studies should be casually dismissed without ever evaluating the content? As for other issues, I have no doubt you have many more but they must be secret or really dumb because you vaguely allude to them but say nothing of substance. You seem to have an endless list of issues external to the science itself that are problematic for you. Doesn't it seem even a little strange to you that still refuse to talk in any detail about the report itself? Finally, it's worth reminding you that the major bone of contention here still seems to be the assertion about non-B conformation. Since you've expressed confidence about your knowledge of such things, it should be a trivial thing for you to take a run at the question: How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair?
@Krebiozen
That's a vast over simplification. You also have to consider the quality of the evidence, and identify what evidence is missing. Public health should only play when the odds are heavily weighted in its favor and there is a good prospect for a positive ROI and that requires serious high quality evidence. Making long term public health decisions based on only on weak evidence is foolish and generally leads to wasted money, just like this initiative has already started doing.
I disagree. To use the words "beyond any reasonable doubt" requires results from a systematic review. There are also pockets of problematic results showing up in both the original and later trials. I can only guess you might be referring to the regulatory FUTURE I and II trials which only demonstrated significant efficacy for grade 2 cervical intraepithelial neoplasia. Unfortunately, grade 3 cervical intraepithelial neoplasia is the one that has the strongest potential to be invasive and no efficacy was demonstrated by the vaccine (Sawaya et al. "HPV Vaccination — More Answers, More Questions", NEJM May 10, 2007). To quote:
To put your confidence in even more perspective, this is the first "cancer" vaccine ever trialed. No scientist worth their salt pronounces success before the first clinical trial generates any data. Your words do not come even close to accurately representing the state of the evidence.
Did your analysis include the costs of ADRs and the increased risk among certain groups? From earlier, 129 vaccinations are required to prevent one case of the surrogate outcome. That's not a great ratio to start with. Please reference your financial model. Extraordinary statements require at least a shred of evidence no?
That's a great explanation for why you're using inappropriate and inaccurate language. It doesn't change the fact that it's wrong and inappropriate.
Pointing out that you only have evidence for surrogate outcomes is not pleading. Neither is pointing to a lack of evidence to validate the assumptions inherent in the choice of surrogate outcomes.
I quote Ian Frazer, one of the pioneers of the vaccine.
Immune system problems related to HPV infection is clearly not a faith based assertion.
From Spinosa JP, Riva C, Biollaz J, "Cancer Letters", doi:10.1016/j.canlet.2011.01.024
Here they are discussing data showing viral replacement problems and issues of increased risk among pockets of vaccinated individuals. Apparently, it's not faith based either.
Have you read the results of the 2012 ATHENA HPV study? (Wright T, "The ATHENA human papillomavirus study: design, methods, and baseline results) This real life evidence shows a remarkably low vaccine efficacy rate against HPV-16 and HPV-18 let alone very concerning signs of increased risk for hrHPV (high risk HPV) in the vaccinated group. Why don't you plug those numbers into your cost/benefit model and tell us all how it comes out? I highly suspect it will be a negative ROI.
Bimler was complaining about a depressing lack of effort in arguments. He must have been referring to you. Randomly grabbing low quality evidence to support your point is either trolling or shooting yourself in the foot. You have now successfully backpedalled to an evidence free position.
You missed the point. You can't use definitive statements of success while the clinical trial is still running and the data hasn't even started coming in yet. You're just making excuses for bad decisions by public health. They've already botched the delivery of the vaccine which makes the whole program cost ineffective. That's usually considered a failure for public health.
But it was worded as a statement of fact and as such it was justifiable for me to treat it like an argument.
No. I meant by swallowing whole the bias, propaganda, and misinformation being distributed here.
Can I introduce you to dingo199? Hey Dingo, here is someone who is actually pointing to VAERS as evidence of effective post marketing surveillance. What do you have to say about that? I'm sure you can tell us the number of reactions that actually get reported to passive post marketing surveillance systems right?
As for pointing to a CDC website as evidence? The CDC used to say ~30,000 people in the US died every year from the flu which turned out to be very wrong. When H1N1 came along that number suddenly dropped to a fraction of that. Their websites are not a reliable reference or evidence of anything in particular. Until you produce some actual evidence your words are empty. I'll even read it if it's from a SCIRP journal although Narad might go ape on you if it is.
Hi Johnny. Experience genotyping with PCR does not readily convert into expertise for finding HPV DNA mixed with human genomic DNA. You can find basic instructions for PCR on a web site like this: https://www.roche-applied-science.com/sis/amplification/pcr_amplificati…. You will find no such instructions to help you sort through the noise of human genomic DNA and find a small amount in post mortem samples.
Our host did not provide any references to back up his assertion that nested PCR was an inappropriate tool. I already provided a reference to show that it was used in the industry as a valid tool for HPV genotyping. Our host complains about the high risk of nested PCR generating junk, but Dr Lee was able to sequence a full 184 bp HPV L1 gene DNA sequence which was a 100% match for the HPV-16 sequence stored in GenBank. You won't ever get that from junk so that argument goes out the window.
Our host specifically says he doesn't understand the approach, which leads me to believe he does not have experience genotyping HPV DNA fragments mixed with human genomic DNA. He complains about "fiddling" with primers but that is hardly a good reason to disregard the results. It's true, you won't "fiddle" if you're doing basic genotyping but that is why the specific expertise matters. After all that though, the "fiddling" did not generate junk because as I noted above, it generated a sequence that matched 100% and the reasons for the fiddling were described in the case report.
Our host wants a population study, which is a good thing and a logical next step, but it doesn't invalidate the results of a case study especially one with such a unique finding. This HPV-16 L1 DNA fragment in non-B conformation has no plausible explanation for existing in the general population or existing at all unless you consider the vaccine manufacturing process.
Several posters here disagree with the assertion that the fragment was in non-B conformation. However, none of them will answer the question to provide an alternate characterization that explains the test results. Several posters here think that the lack of a population study invalidates the claim of uniqueness. However, none of them -- including the host -- has proposed a plausible explanation for how a unique DNA fragment in non-B conformation would have gotten into the autopsy tissue let alone the general population without having been discovered by the many HPV researchers. Dr Lee, provides a very plausible explanation for the conformational change because aluminum is known to cause this sort of thing. (the explanation and references are in the case report)
Our host complains that Dr Lee should have looked for a more vaccine specific sequence. Our host's suggestion to find a DNA "that encompasses part of the L1 gene, the promoter region used, and pGAL110 sequence that is directly attached to the insert." is based on a whole host of assumptions. For instance, it assumes the entire circle of the L1 gene, the promoter region and the pGAL110 that were inserted into the yeast as one piece are still freely floating in the patient's spleen cells. Frankly, that's an armchair researcher assumption. Even the FDA was smart enought to say "HPV L1 gene DNA fragments" were in the vaccine, not the L1 gene attached to other parts.
When the original findings of DNA fragments in the vaccine were announced, our host went on about many of the same things. He expressed extreme skepticism about the methodology of nested PCR (it produces junk), he expressed doubt that the fragments existed and he wanted published details on the methods. To quote the host: "Maybe Dr. Lee should be come a homeopath. He seems to think that the more the HPV DNA is diluted, the stronger it becomes."
More than a year later he has confirmation from the FDA about the findings and he has the methods clearly published for all to read. (It's worth noting that the FDA confirmed the finding a while after Dr Lee announced his findings, which means it's likely they had to do some testing themselves) Even still, our host he complains about the methodology again, and about most of the same things, except now he expects a population study instead of a case report. It seems pretty clear to me, that any potential issue with this vaccine will be met with outright hostility by our host.
I am very interested which specific argument of his you find compelling that hasn't yet been addressed somewhere in these comments.
@Mr Pink
Like changing a policy on giving the HPV vaccine on one non-replicated paper by one scientist for instance?
Ah darn it... there should be a 'based' between 'vaccine' and 'on'.
Like changing a policy on giving the HPV vaccine *based* on one non-replicated paper by one scientist for instance?
You are a buffoon. As I already told you, Levine turned on warning defect. Courts do not "place" anybody as "gatekeeper" of anything. Go read Bruesewitz, come back, and explain why Scalia used a textual analysis. Or, whatever, explain the history of the Boiler Inspection Act and its relationship to the Price-Anderson Act and why Silkwood turned out the way it did.
Or just get your head around the fact that you said something really stupid and still don't understand why.
Hey, who am I?
Why on Earth does Mr. Pink even still bother to comment? Anyone reading here will see him contradicting himself left and right - first we should believe that the work has no flaws because it was published in a journal; then we should believe that the choice of a bottom-feeding journal from a known scam operation doesn't mean anything because it's the paper that matters. One minute, when it comes to criticizing Lee, one needs to be an expert in genotyping; the next minute, when it comes to defending Lee, it's suddenly so elitist to even think about the expertise of the person saying "Trust me, all the experts know this is bulletproof."
Hell, even if I had no idea who was who, all it would take reading this to sway me is Mr. Pink's comment where he claims that a simple arguendo argument is beyond his comprehension.
If Mr. Pink finds a hypothetical argument which posits a single counter-factual "bizarre," the best case explanation for why he cannot follow something so simple is that he is a Dunning-Kruger poster child, convinced that he has expertise only because he has insufficient expertise to even recognize expertise. Worst cases, of course, include that he's simply willing to lie. There is no case that gives Mr. Pink credibility for all the claims he makes.
Why does he still bother? He's lost. No matter what he says, he cannot change the facts: the burden of proof for Lee's methodology and results has not been met, and there is no reason, therefore, to give it any credence. Everything Mr. Pink says is an irrelevant distraction from that point. Don't know why he imagines it can still work.
This is precisely why I stopped responding. There's really no point in trying to debate with someone who refuses to accept the basic premise that the data, as reported, are not sufficient to draw the conclusions that Lee presents.
Mr. Pink,
Clearly you and I disagree on the strength and quality of the evidence for the safety and efficacy of HPV vaccines.
You mean like this systematic review? It looked at 44,000 subjects and concluded:
You mentioned the FUTURE trials:
No efficacy could possibly have been demonstrated because there was only one case of grade 3 neoplasia in the entire cohort of almost 12,000 women. Grade 3 cervical intraepithelial neoplasia is rare, so grade 2 is used as a surrogate endpoint, which seems perfectly reasonable since most cases of grade 2 progress to grade 3. As FUTURE II states:
You then claim that the vaccine is ineffective, quoting:
You didn't mention that these results were for sexually active women many of whom had already been exposed to HPV. As the paper you referred to states:
If you accept grade 2 cervical intraepithelial neoplasia as a surrogate endpoint for cervical cancer, it does seem very likely that vaccination before exposure to HPV will prevent both cervical intraepithelial neoplasia and cervical cancer if vaccination occurs before initial exposure.
As I pointed out, that ratio is in women who have already been exposed to HPV, which is why Gardasil is recommended in girls and boys before they become sexually active.
You don't seem to understand that different language and different standards of evidence are appropriate in different contexts. While not wishing to invoke an argument from authority, it does seem that public health authorities all around the world agree with my assessment of the evidence.
You then indirectly suggest, if I follow you, that it is possible that HPV only leads to cervical and other cancers in those with impaired immune systems, so that the vaccine might not protect them from cancer. I don't see any evidence that the vaccine would not prevent infection in this group, but for the sake of argument let's assume you are correct. Wouldn't universal vaccination of people before they are exposed to HPV still reduce the incidence of infection in this immunocompromised group through herd immunity? They can't become infected if there is no one already infected to give it to them.
You also refer to viral replacement. This is a real possibility, of course, and I don't doubt that further vaccine development will be necessary to address this. I don't see the fact that the vaccine mostly protects against the viruses it is designed to protect against as a problem with the vaccine. HPV is a moving target. That doesn't mean we should give up efforts to dramatically reduce its impact or even eliminate it.
The ATHENA study didn't look at vaccine efficacy, it looked at prevalence of different strains of HPV. Perhaps you are thinking of one of Merck's studies that showed enhanced risk factors for development of CIN 2/3 or worse in small subgroups that were PCR positive and/or seropositive for the relevant HPV. Subsequent studies have not confirmed that finding, and even if it were replicated it would support early vaccination before exposure to HPV.
Grabbing one piece of evidence from a huge pile that all supports what I am suggesting is hardly an evidence-free position. What I'm saying is that if you don't like that study, there are plenty more that point to the same conclusions.
You ignore the many clinical trials that have been run and results of which have been published. There is no doubt that the vaccine is highly effective at reducing the incidence of HPV-16 and HPV-18 in those not previously exposed to it. There is very little if any doubt that reducing the incidence of these viral infections will reduce the incidence of cervical and other cancers. Even if your suggested immunodeficiency hypothesis is correct, herd immunity will still reduce the chance of those immunodeficient being exposed to these viruses and will reduce the incidence of cancer.
That depends on what factors you consider and what time scale. I don't think it is a bad decision, and I don't know what you are referring to when you write, "They’ve already botched the delivery of the vaccine".
The only bias, propaganda and misinformation I see here is coming from you.
No one has suggested that VAERS isn't a part of effective post-marketing surveillance, of course it is, but it is only a small part, acting as an early warning system. Assuming that any adverse events reported to VAERS are caused by the vaccine is the error Dingo199 was referring to. The CDC link also discusses VSD which includes rapid cycle analysis, active surveillance which has followed over 600,000 people given HPV vaccines.
I was pointing to the CDC as evidence that a great deal of post marketing surveillance supports the safety and efficacy of HPV vaccines. Since the CDC run the active surveillance I was referring to I don't see what better source I could point to. Dismissing the CDC entirely as a reliable source of information does your credibility little good.
Maybe you could start with the systematic review I linked to above.
@Antaeus Feldspar
Because he knows that he's been called out on his lies and deceit, knows he's lost the argument, and the only way he can attempt to cover it up is to state more lies and ad hominems?
On a different note, I admire all of those who have constantly called mr pink out on his lies and pseudoscience. That takes a lot of patience to deal with such a dishonest and persistent person as he/she/it.
Indeed, I think the question is more pertinent for you. You seem to keep coming back, but the closest thing you were able to articulate about the case report was a strawman about novel methodologies. Do you have any points to make about the case report yet?
Did you cut and paste random words from Orac's posts during the last month or something? My 5 year old could have come up with better rhetorical insults.
Flip, you shouldn't worry about the typos, it's the strawman you should be focused on. Who recommended changing any policies based on the case report? My objection to the policy of mass vaccination is based on a glaring lack of evidence of efficacy in real life situations, not the case report. Even you should be able to keep up with that.
@Krebiozen
Evidence fail #1. Making a very broad statement and supporting it with a narrow study doesn't sound like the smartest way to support your argument. Just sayin.
Evidence fail #2. Those are surrogate outcomes again. I was talking about cervical cancer remember? I also highly doubt that study would even come close to meeting the Cochrane definition of systematic review because all the studies were funded by the manufacturer (all but one from Merck) and thus they all have a risk of bias of the exact same type.
Evidence fail #3. You said: (comment 547) "There is plenty of post-marketing evidence..." and referenced a website which only contains a single study based on VAERS data. Oops. If you want to claim there is "plenty of post-marketing evidence" of remarkable safety and efficacy, then you must provide a reference to at least a few studies, and they better not all be from VAERS as we know from studies that it will only contain a tiny fraction of the actual adverse events.
Evidence fail #4. Did you read your own evidence or did you just pick one from Narad's barrel at random again? You do understand why that so-called systematic review can't count as evidence of post marketing surveillance right?
Definition fail. It appears you have redefined the term "most" (let me guess, this is a blog right?) because according to this paper the CIN2 progression rate was 15% (in 3 years) and the regression rate was 70%. (Moscicki AB et al, "Rate of and Risks for Regression of CIN-2 in adolescents and young women", Obstet Gynecol, March 15, 2011). It looks like "most" CIN2 regresses. Given that there is ongoing debate as to the validity of CIN2 as a reliable surrogate, the term "Perfectly reasonable" is also grossly misleading. http://jnci.oxfordjournals.org/content/96/4/250.long
By now you should also be asking why one spends so much money on mass vaccination when the best surrogate outcome is so rare and the disease only manifests in a fraction of those cases.
Comprehension fail. I never claimed it was ineffective, I quoted the efficacy rate from the letter.
From Merck's own website: "GARDASIL is a vaccine indicated in females 9 through 26 years of age ..." "GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL." No mention of sexual activity there. Age 26 is pretty old to assume virginity unless you're living on a different planet. You can't have it both ways, if you want to exclude the results, then you better make prior sexual activity a contraindication or do HPV testing prior to vaccination. Until then, those results are completely pertinent.
Given the long term nature of this disease, if the viral replacement happens too quickly the vaccine will be useless. That would at least double the cost or worse. I notice you totally avoided bringing any evidence outlining your extraordinary cost calculation to the table. Your claim was that half the estimated efficacy rate is still easily cost effective. Without seeing your evidence, I counter that any pharmaceutical company that prices their product to leave 50% of their potential revenue on the table is some dumb. Think about it.
No, I was looking at the Athena 2012 study data. They break down HPV genotype prevalence and show the difference between vaccinated and unvaccinated groups. The marginal or non-existent difference in HPV-16 or HPV-18 rates between vaccinated and unvaccinated groups is pretty indicative of vaccine failure unless you have some other definition. The increased prevalence of hrHPV in vaccinated individuals doesn't bode well for your surrogate outcomes, since as you noted yourself, the success of the program is predicated on preventing HPV infection in the first place.
I didn't ignore them. I pointed out that they all use surrogate outcomes and that the trial which will actually measure the endpoint (real usage) is still running with no data to report yet.
Cervical cancer is primarily a disease of the poor. In the US, the cervical cancer mortality rates in the poor states can be double that of the wealthy ones. The cost justification of the program assumes that the poor get the vaccine. (Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med 2008; 359: 821–32.)
Unfortunately health care distribution in the US is skewed to the wealthy and the vaccine distribution is the same making calling into question the cost justification.
Bach P, "Gardasil: from bench, to bedside, to blunder", The Lancet, Vol 375 March 20, 2010; 963
PS: The evidence in there also blows your prior assertion that half the efficacy easily cost justifies the program.
"Dismissing the CDC entirely as a reliable source of information does your credibility little good."
Your strawman about the CDC doesn't do your credibility any good. I didn't state the CDC was an unqualified unreliable source of information. I stated that the CDC websites are not considered evidence. Big difference.
You can stop whining now because look what showed up here: http://www.scirp.org/journal/abc/
Perhaps those crafty editors of SCIRP purposely published the two closely related articles by the same auther in two sister journals to generate more publicity among people who actually want to read new science.
Find the article: Lee SH. Topological conformational changes of human papillomavirus (HPV) DNA bound to an insoluble aluminum salt – a study by low temperature PCR. Advances in Biological Chemistry 2013; 3: 76-85.
You insist that Dr Lee is wrong in his conclusion, based merely on your assertion. Yet, you refuse to provide your own explanation for the test results. How do you characterize an HPV-16 L1 gene DNA fragment matched by sequencing after PCR amplification, that is not amplifiable by the commonly used degenerate consensus GP5/MY09 or GP6/MY11 PCR primer pair?
If you want to question Dr Lee's expertise, then I suggest you first read the two reports very carefully. Then compare Dr. Lee's PCR and the PCR you might get from your sales rep at Roche (I posted a link in comment 555). Could that sales rep teach you to perform a 1.3 x 10(exp36) fold amplification of a template for Sanger sequencing like Dr Lee did? Just do the math. If you don't get it, then you aren't really in the field. And he didn't get junk because he sequenced a full 184bp HPV L1 Gene DNA that matched HPV-16 in GenBank 100%.
Oh, the irony. Publishing in journals that don't even have impact factors sure is a great way to generate publicity!
From the conclusions section of the new article:
If you truly believe that this paper presents sufficient evidence to justify this conclusion, I have no interest in discussing this further.
Also, do you really think this is some kind of 'gotcha' question that proves your point? Dude, it's called a Bioanalyzer.
@mr pink
Hi. Try again with your petty insults, you really are entertaining but it does get lost in your wall of irrelevant text, you know.
Of course, I have to make my posts as simple for you to read, since it seems that you have major problems in basic logic and all it seems is that you cannot grasp a basic argument, instead relying on insults, putting words in people's mouths, and generally spewing nonsense.
Besides, why should we listen to you, who seems to be impervious to all logical and rational thinking. Your lack of logic in your posts is quite frightening if you really claim to be a scientist.
I mean, who would want to trust someone with such an astonishing lack of basic logic.
But of course, I'll be waiting for you to attempt another pathetic attempt at insult. It should be amusing to see what comes from your infantile mind. I should get at least a little chuckle from your nonsense.
This may well be the most stupid thing you've put on offer yet.
(And just to be clear, it represents an immediate leap to the well-known antivax morbidity–mortality conflation.)
Perhaps they (or somebody) should be notified that the listed affiliation is fraudulent. Note the received date. I suppose it's time to check whether he self-plagiarized.
I suggest a very close look at Figure 7 in the ABC entry.
Heh.
Out of general curiousity... is there any record of anyone other than Lee using his LoTemp™ PCR technology? His press releases document his attempts to shake down the FDA and his allegations against the NEJM as part of the conspiracy to suppress him -- the litigation also being covered on his News Page -- but the absence of customer testimonials is surprising.
Mr. Pink,
As I have already explained, surrogate endpoints have to be used as it would be unethical to use invasive cancer as an endpoint, and in any case cervical cancer is rare. This means that a clinical trial would require either impractically large numbers or be run for an impractically long period to have sufficient statistical power if it used invasive cervical cancer as an endpoint. That leaves us with a choice. We can run larger studies for longer and leave millions vulnerable to cancer, or we can trust the studies using surrogate markers for cervical cancer and assume that if the vaccine prevents HPV infection and reduces the incidence of these surrogate markers it will also reduce the incidence of cervical cancer. Both the WHO and the FDA consider CIN-2 and CIN-3 to be valid surrogate endpoints to assess the effectiveness of HPV vaccines.
Public health authorities in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Iceland, Israel, Ireland, Italy, Kenya, Latvia, Luxembourg, Macedonia, Mexico, Netherlands, New Zealand, Norway, Panama, Portugal, Romania, Slovenia, South Korea, Spain, Sweden, Switzerland and the United Kingdom as well as the United States have approved the vaccine with the great majority providing public funding, which suggests that public health authorities in these countries regard the vaccine as economically viable. If you are really unaware of the body of evidence that these decisions are based on, or are prepared to dismiss it because it is based on surrogate markers or suffers from bias because some of the studies are sponsored by vaccine manufacturers, there isn't much left to discuss.
You ignore the VSD and rapid cycle analysis referred to on the CDC page I linked to that has actively surveilled over 600,000 vaccine recipients and the large body of evidence that supports the efficacy and safety of the vaccines.
I did make an error about CIN-2 progression - I read this "The annual regression rate of CIN-2 in adult women is estimated to range from 15 to 23%, with up to 55% regressing by 4–6 years." and misinterpreted it. Even so, all cervical cancer passes through stages 1 through 3, making it a reasonable assumption that if you reduce the incidence of stage 1 that will also reduce the incidence of cervical cancer, either directly through preventing initial infection, through herd immunity or both.
It is you who is being misleading here, since the paper you link to debates whether CIN-2 is a useful surrogate for cervical cancer in making treatment decisions, not whether it is a useful surrogate in looking at vaccine efficacy.
Are you really suggesting that a disease that kills hundreds of thousands of women globally every year is not worth attempting to control? The vaccine appears to be safe and effective and can be expected to save a great deal of anxiety (as any woman who has had a positive pap screen can tell you), suffering, and several deaths over the next few decades. There is an argument about cost benefit ratios to be made here, as there always is in public health. I disagree with your implication that it is not cost effective, as do public health authorities in the countries I listed above. You are the one with the dissenting opinion here.
You quoted the efficacy rate in women who are sexually active and had already been exposed to HPV. Not surprisingly the vaccine isn't as good at preventing infection in those who have already been infected as it is in those who have not.
You do have a interesting habit of distorting information. Why does something have to be either contraindicated or recommended? Why does "9 through 26 years of age" automatically mean 26 years of age? Clearly the vaccine is more effective in people who have not been exposed to the virus, though it is still useful in those who have not. The vaccine is a component of the US Recommended Pediatric and Adolescent Immunization Schedule. As the CDC website states:
On viral replacement:
In strict economic terms that may be true, but this completely ignores any costs of human suffering. The vaccine is almost 100% effective at preventing HPV-16 and HPV-18 in those not previously exposed, and vaccines that protect against other strains are being developed. I think this is a public health goal well worth pursuing. In the long term it might even be possible to eliminate HPV entirely. There are several papers that discuss the pharmacoeconomics of the vaccine if anyone is interested for example here.
Do you have a link? ATHENA was not designed to assess vaccine efficacy and I can only find references to a sub-group analysis looking at vaccinated and unvaccinated but not the data itself.
The only place I can find these results is in women already exposed to HPV in one of Merck's trials which has not been replicated.
That's not true. You claimed that because the CDC got influenza mortality wrong we can't believe what they have to say about HPV vaccine safety and efficacy. If that's not stating that the CDC is an unqualified unreliable source I don't know what is.
I love 10^36 fold amplification. That gives you what, a billion tons from a single 10k DNA fragment?
Cervical cancer is primarily a disease of the poor. In the US, the cervical cancer mortality rates in the poor states can be double that of the wealthy ones.
No...cervical cancer does not recognize socioeconomic barriers. That mortality rates are higher among the poor in the US is an indicator of access to treatment, something that should be apparent to anyone who monitors health trends in this country.
@Mr Pink
So you'd agree with me that Lee's paper is pretty useless until it's replicated then? - Even assuming the contents of it are valid.
the two closely related articles by the same auther in two sister journals...
Find the article: Lee SH. .... Advances in Biological Chemistry 2013; 3: 76-85.
I saw no evidential value when Lee reported his claims on a no-peer-review, no-editorial-standards website, but now that he has paid again to have basically the same article appear a second time on another of the network's websites, I am totally convinced!
Then compare Dr. Lee’s PCR and the PCR you might get from your sales rep at Roche (I posted a link in comment 555). Could that sales rep teach you to perform a 1.3 x 10(exp36) fold amplification of a template for Sanger sequencing like Dr Lee did?
This is certainly a change from the original argument, that we shouldn't question Lee's claims because he is the accepted authority in the field. Now we shouldn't question Lee's claims because he's a brilliant outsider, reporting amplification rates orders of magnitude better than anyone else.
Between extravagant claims like this, and the history of litigation described on the HiFiDNA website, I don't understand why Lee is not finding any customers for his LoTemp™ technology.
This bit is hysterically funny if one knows what the CSE actually is:
Vis-a-vis Lee's history of litigation, I momentarily forgot his earlier battle with the FDA over his treat-cancer-with-green-tea scam.
Readers of previous threads will recall that the FDA insisted on Lee ceasing to advertise the magical green tea as preventing cancer, and modifying his claims with appropriate caveats:
http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthCl…
Lee's response was to spin his product as FDA-approved: "the Only Green Tea with FDA Qualified Health Claim".
(I think I put their style manual in the recycling when I came across "H π region" [yes, pi] under the putative astronomical notation. [For those unfamiliar, "H ɪɪ" is the notation for the spectrum of ionized hydrogen. Note to editors—photons, not baryons! It's not always unambiguous.])
It would be like making points against a report that claimed to prove a case of vaccine injury through palmistry, or phrenology, or oneiromancy. The burden of proof is on the person making such a claim to prove their methods are sound, not on everyone else to prove the opposite.
You claim that the methods are already proven to be sound science, but that claim rests on your credibility, and if you had any credibility before, it's been torpedoed by your conduct here.
@Krebiozen
HRT was a population study and looked at breast cancer as an endpoint. Your point applies to pre-approval RCTs, not to post approval population study. As for rarity, that is exactly why you should be questioning full population based vaccination, especially since it doesn't eliminate the need for screening that already occurs.
I love the circular reasoning. You can't gather the proper evidence to see if it works, because if you assume it works, people will be at risk while you gather the evidence.
You botched the argument based on the fact that most CIN-2 does not progress to CIN-3, so now you resort to an argument of authority.
This is getting better, now you go for an argument of popularity -- where is that flip guy when he would actually be right?
Sorry, reposting after blockquote fail:
Herd immunity for HPV is a pipe dream. Vaccination does not eliminate all infections so unless you identify the real risk factors for the small number of cases that progress, measuring the outcome based on a weak surrogate does not give you a whole lot of useful information about your endpoint.
The same logic applies. If you're not treating it because the risk of progression is low, why would it be a valid surrogate for measuring future cancer diagnosis?
I think you meant 3,900 every year in US (compared to 32,000 gun deaths, or 44,000 deaths from medical error). Are you really suggesting we base a public health decision on data from the developing world?
No, that is your distortion. I'll repeat the part you avoided quoting: You can’t have it both ways, if you want to exclude the results [people with prior HPV exposure], then you better make prior sexual activity a contraindication or do HPV testing prior to vaccination. Since the vaccine program does not exclude people with risk of prior exposure, you can't exclude that extremely inconvenient data from the analysis or discussion. If 100% efficacy assuming no prior HPV exposure is the premise of your economic model, it's a fail right out of the gate.
[facepalm] You still haven't learned to read your own references. That paper you linked uses the economic data from Kim et al which is the study I referenced in comment #565. It isn't cost effective if you only vaccinate the wealthy population with access to health care. Please note your evidence does not support your prior assertion that half the efficacy is still cost effective. "Vaccination against HPV-16 and HPV-18 is expected to be economically attractive (i.e., <$50,000 per QALY) if high coverage can be achieved in the primary target group of 12-year-old girls and if vaccine-induced immunity is lifelong." Clearly your statements on cost (like many of your other statements so far) were not even close to being evidence based.
It is not studying vaccine efficacy, but HPV strain prevalence. It certainly blows away any theories of 100% efficacy through prevention of HPV infection. Table 3. (Wright TC, Stoler MH, Behrens CM, et al. The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol 2012;206:46.e1-11.)
I didn't ignore them at all. You didn't provide any references documenting a safety analysis of Gardasil from these systems?
No I did not. Read my comment again very carefully: "Their websites are not a reliable reference or evidence of anything in particular." If they produce raw data or conclusions fully referenced by real published evidence, that is a acceptable since we can see the source of the data and judge the conclusions ourselves.
You need some serious training on how to write better insults. Orac has been regurgitating the same stuff for quite a while now so I would look elsewhere for good examples. Here is a lesson for you -- and I know, this will be a shocker to someone who is craving for my attention -- having you read my posts isn't even in the top 1000 reasons I'm posting here. However, for some incomprehensible reason, you read them anyways. What does that make you? Ask Grant.
Per my reference in the same post.
Mississippi -- Median Annual Household income: US$36,674 -- Age adjusted cervical cancer mortality rate: 3.6/100,000
Rhode Island -- Median Annual Household income: US$55,980 -- Age adjusted cervical cancer mortality rate: 1.8/100,000
Last time I checked 3.6 was double 1.8.
Quoting Ian Frazer: "Cervical Cancer is predominantly a disease of the developing world, with >250,000 deaths per annum. (Frazer I, "God's Gift to Women: The Human Papillomavirus Vaccine, Immunity 25, 179-184)
Read above. Access to healthcare is one of many reasons poor people suffer disproportionately from infectious diseases. If you think access to health care is the only one, you have some more research to do. Diet and smoking are among other factors implicated in cervical cancer and these also have correlations to socioeconomic conditions. If you had read the reference I provided, it points out that the people who will actually benefit from the vaccine are those that do not have access to healthcare. Unfortunately, these are the same people who do not get the vaccine. I will spell out the point since it apparently wasn't obvious enough: It's a waste of money to vaccinate the people with good access to health care but that's exactly what you're doing in the US. You are not actually vaccinating the people who the vaccine was designed to help.
No I'd not agree with you. I think it is quite useful in pointing out an avenue for investigating some of the more serious reports of reactions. Replication is one of the steps. I'm sure Dr Lee would love to see his work replicated. That DNA fragment isn't supposed to be in the vaccine and it certainly shouldn't persist in the human body for any length of time. There is other evidence supporting it's existence and unique properties as described in the new report I linked. Did you read it?
Gosh, you really do have reading comprehension problems. You left half a dozen arguments hanging. Still having trouble with the last question?
It should be trivial for you to ask the "listed affiliation" to issue a public statement and post it back here. I look forward to reading more than empty allegations.
I didn't think you could answer the hard questions or even make a logical comment about the case report. In the words of the infamous Narad, "it must suck being a chickensh.t"
You win the comment of the month award for that one while putting the wannabes to shame (Antaeus, Novolox, Bimler, Narad among others).
10^36 was a theoretical number if a nucleotide had been exponentially amplified 2^120 cycles non-stop in 4 same-nested PCRs. Similarly if you used the maximum 40 PCR rounds (from the Roche link) you would get a theoretical amplification of 1.09951 x 10^12 (2^40). This represents the maximum potential amplification in the system and reflects the fidelity of the low temperature PCR used in the study to prepare a template to perform an accurate DNA sequencing. If you are in the field, the PCR you use in your lab almost certainly can not accomplish that.
It is however correct to assume that if the E. coli in your colon is allowed to multiply 2^120 times exponentially non-stop, you would not live very long.
Here is a reference to others using the same technology for HPV genotyping: http://onlinelibrary.wiley.com/doi/10.1002/cam4.9/pdf
AdamG, Grant and ScienceMom: I guess Merck didn't get the memo from your labs regarding the superiority of that approach: "In this comparison study, neither assay was definitively considered a “gold standard” in HPV detection." (Else EA et al, "Comparison of Real-Time Multiplex Human Papillomavirus (HPV) PCR Assays with INNO-LiPA HPV Genotyping Extra Assay", JOURNAL OF CLINICAL MICROBIOLOGY, May 2011, p. 1907–1912)
What's the "empty allegation"? He doesn't work for Milford now and didn't in October 2012, when the paper was received. That's why he sued them, remember?
@mr pink
Nah, the only reason I read your posts are for the lulz I get from your sheer ignorance and stupidity. Your infantile excuses, insults, and non-answers say a lot about you. Try again, never-can-be.
But I like you, since you seem soo easy to poke around and make mad.
And thank you for admitting that you do not have an coherent answer to the questions posted to you, and that I am intellectually superior to you, since you have proven that you can only spew lies again and again. I'll take that as a compliment from a liar like you.
But please, keep entertaining us. I knew that you would come up with a piss-poor excuse for an insult, and I would like to see what pathetic excuse for an insult you can come up with next. I'll see your answer in two days I suppose. More time to get some popcorn ready for you.
PS: Ripping your name from a character from Reservoir Dogs doesn't improve your nonexistent argument at all
One might also note that Lee's contact E-mail points to an AT&T LEC that doesn't actually answer on port 25.
Or that the "Milford Molecular Laboratory" does not in fact seem to exist.
But let us return to Pink's original suggestion. The phone number for the Milford Hospital PR department is (+1) 203-876-4060, manned 8a–4:30; EST. I'm probably not going to be able to hit this window, as my sleep schedule has lately been torpedoed, but I mention it in case anyone wants to register an inquiry about the continued use of the affiliation. They do not have an E-mail address that I've been able to locate.
The Great Google reports:
If Lee has made up the b>name of the institution for which he works, then there is little reason to believe any of his assertions.
@Mr Pink
Probably off to the side laughing at your mix up over my gender. Boy, do I love using a gender-non-specific handle :)
And now we're off to the races... a nirvana fallacy to begin with.
Mr Pink doesn't live in Australia. For a certain age range, women were offered the vaccine for free via a government program. Fortunately in a country with universal health care, getting vaccinated is not so much a problem for poor folk. (I would have gotten it but had just missed the age cut-off. And yes, I need my government-subsidised health care otherwise I couldn't afford to see a doctor, much less pay for anything else)
Ding ding ding, we have a winner!
Thank you for playing Mr Pink. Here we quite clearly see that Mr Pink is not interested in confirming any analysis that agrees with his point of view, because one paper is enough; but if it disagrees with his point of view, be sure to call out for more research and argue that there is "weak evidence". But he knows it's silly, so he equivocates with "No I'd not agree with you" but yes "replication is one of the steps".
F*k but you walked into that one. Didn't you bother to pay attention to my questions? Or was I too subtle for you to see the punch line coming?
@Mr Pink:
Mr Pink misses the difference between mortality and morbidity.
As a thought experiment, suppose a hundred women in Rhode Island develop a certain form of cancer, all endure expensive and life-altering treatment (such as surgery, chemo, or radiation), and half of them survive. Meanwhile in Mississippi a hundred women develop the same form of cancer and all die without treatment. The mortality rate in Rhode Island is half that of Mississippi, but does that really mean that the problem in Rhode Island is half that in Mississippi?
Antivaxxers make the same mistake. If, thanks to modern medicine, antibiotics, ventilators, and so on, mortality from measles is much lower than it was in the Thirties, that means we don't need to vaccinate against measles, right? Only if you don't mind children ending up on ventilators or suffering permanent brain damage.
Mr. Pink,
Breast cancer is more than 10 times more common than cervical cancer. It is you who are suggesting that such RCTs should have been done before vaccine approval. With cervical cancer incidence at around 7 cases per 100,000 women per year in the US you would have to study a very large number of women for at least a year if you wanted to use invasive cancer as an endpoint and have enough statistical power. That's why a surrogate endpoint was used instead.
Prevention and early detection are two separate things. Using both should enable us to greatly reduce morbidity and mortality, and once incidence of cervical cancer is reduced enough no doubt screening protocols will be changed. If you really think that a condition that causes suffering and death in thousands of people every year is too rare for it to be worthwhile adopting measures to prevent it, then I can only disagree with you.
If you accept surrogate markers as viable, and you have presented no good reasons not to, then there is no circular reasoning. That's why the Data and Safety Monitoring Board terminated the FUTURE II trials in 2006, because it would have been unethical to deny the placebo group the vaccine because, I wearily repeat, the vaccine clearly reduces CIN and it is reasonable to assume that it will also prevent invasive cancer. You disagree with this assumption, I get that, but I don't really understand why.
Now you are claiming that an international scientific consensus that CIN is an adequate surrogate for cervical cancer in assessing vaccine efficacy, based on a large body of evidence is an argumentum ad populum? What part of "large body of evidence" is it that you don't understand?
Why? We have an effective quadrivalent vaccine that is safe and effective by all sensible measures. Why is it a pipe dream to suggest that in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated?
Unfortunately it is identifying the risk factors for progression that appears to be a pipe dream. If we knew in advance which cases of HPV will progress to cervical cancer, we wouldn't need to vaccinate against it or even treat it, except in those cases, would we? As I mentioned before, you seem to subscribe to the Nirvana fallacy, that if vaccination isn't 100% safe and effective, or if vaccine uptake is not 100% it isn't worth doing. I think that's foolish.
A low risk in a very large number of people results in a large number of people at risk. If vaccination prevents HPV, the risk of progression becomes essentially zero. Or to put it another way the risk/cost of treatment greatly exceeds any risks/costs of vaccination. CIN is used as a surrogate for an entirely different purpose in each case.
Use whatever figures you prefer, though gun deaths and medical errors are an irrelevant tu quoque here. HPV in general and cervical cancer in particular has a significant morbidity and mortality in both the developing and the developed world; that's the point I was making, and I think that's undeniable. Also, you may not be concerned about the health of those in the developing world, but I am.
I don't want to exclude any results. The results you have referred to that suggested that HPV vaccinations actually increase the risk of high risk strain infection in those previously infected have not been replicated in further studies. It seems to me it is you who wants it both ways. "Gardasil is recommended for 11- and 12 year-old girls, and also females 13 through 26-year-old who were not previously vaccinated", remember? If this recommendation is followed then most girls will be vaccinated before they are exposed. I don't have an economic model, I am suggesting that HPV infection leads to economic costs and also causes unquantifiable human suffering that I believe is worth tackling through vaccination. There is no citation I can provide to quantitate the cost of that suffering. As I wrote before, there is an argument to be had about the socioeconomic benefits of HPV vaccination, and I clearly disagree with you over this, as do the majority of experts internationally.
I didn't say that "half the efficacy is still cost effective", I talked about "worth" in which I would include non-economic factors. Economic attractiveness is a subjective measure, and QALYs are a controversial way of quantifying human well-being. The statement that “Vaccination against HPV-16 and HPV-18 is expected to be economically attractive (i.e., <$50,000 per QALY) if high coverage can be achieved in the primary target group of 12-year-old girls and if vaccine-induced immunity is lifelong." supports my arguments, does it not? If there was less misinformation about vaccine safety being disseminated perhaps it would be easier to achieve greater vaccine coverage and it would be even more economically viable. I don't think you are helping in this regard.
That vaccination data is for just over 1000 women aged 21-29 who could not possibly have been 12 years old when vaccinated when you consider when the vaccine was licensed. I don't expect 100% efficacy in the real world, but if vaccine uptake is kept high enough for long enough it will have a dramatic effect on the prevalence of HPV-16 and 18 infection and associated cancers. I expect future vaccine development to address other strains.
Regarding VSD and rapid cycle analysis:
Are you really incapable of clicking on the links in the list of 'Related Scientific Articles' at the bottom of the CDC webpage that I linked to? Here they are:
Gee J, Naleway A, Shui I, Baggs J, Yinc R, Lic R, Kulldorff, M, Lewis E, Fireman B, Daley, MF, Klein NP, Weintraub ES. Monitoring the safety of quadrivalent human papillomavirus vaccine: Findings from the Vaccine Safety Datalink, Vaccine 2011 Oct 26;Vol 29, Issue 46: 8279-8284 (PMID: 21907257).
Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua J, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 2009 Aug 10;302(7):750-7 (PMID: 19690307)
Centers for Disease Control and Prevention (CDC) and ACIP. Quadrivalent human papillomavirus vaccine. [PDF - 444 KB] MMWR 2007 Mar 23; 56(RR-2).
MMWR - FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from ACIP.
Everything on the CDC website is supported by real published evidence. There are several links there to further information and research that supports what I have been arguing.
That is perhaps a somewhat over-encompassing statement. Lest anyone misunderstand me, I was referring to the CDC's position on HPV vaccine safety and the utility of surrogate endpoints in assessing efficacy.
That's a lofty goal. You have a reservoir and latency to contend with. Quarantine is certainly out.
If cost effectiveness is all we're concerned about, why aren't we practicing horse track medicine?
Regards "Or that the “Milford Molecular Laboratory” does not in fact seem to exist." and the like.
Perhaps there is a company register that can supply details?
I suspect the best that can be said is that this laboratory has no web presence, at least outside of this SaneVax order form. (PDF file).
Perhaps the only work MML gets is via these SaneVax orders so Lee/MML and/or SaneVax feels there is no need for a web presence as such?
A list of Lee's papers shows the addresses on them have changed from "Department of Pathology, Milford Hospital" for his 2008-2010 papers (in one case giving 300 Seaside Avenue as the street address, which is the hospital address) to "Milford Hospital and Milford Molecular Laboratory, 2044 Bridgeport Avenue" for his 2012 papers, which is across the road from the hospital.
Searching for "2044 Bridgeport Avenue, CT" brings up Quest Diagnostics and a number of medics and medical services occupying that address. StreetView shows this as grey brick building which I guess has number of suites occupied by various independent workers in addition to Quest Diagnostics.
Lee might have listed both Milford Hospital and his new location as addresses if he felt the work was done in both places.
If Lee's was done without the hospital's approval, or in a way that the hospital did not approve, then perhaps the hospital would be less than happy with their name being on the papers. You'd have to ask them, really.
(Certainly I'd like to Lee to have said to the coroner's inquiry that the work was commissioned by SaneVax: you'd wish autopsy work to be done via players with no vested interests, but SaneVax has a vested interest.)
My previous comment (#602) should have been addressed to Narad.
"If Lee’s was" should read "If Lee’s work was".
Narad,
On the possibility of eradicating HPV:
A lofty goal perhaps, but I don't think it's an impossible one. There's no non-human reservoir as far as I am aware; the current human one will die off given enough time and people tend to have sex with those of a similar age, making vertical (in terms of age) transmission less common. It would require maintaining high rates of vaccination uptake for a long time, better means of detection and probably effective treatments in addition to vaccination.
I realize I am being (possibly unrealistically) optimistic about the future of medicine. I don't think antivaxxers realize the possibilities that vaccines offer, such as eradication of viruses that would ultimately eliminate the need for vaccines against them, so I like to throw the idea into the mix from time to time.
Indeed. Plug in business ID 0270302. The listed mailing address on the detail record, 300 Seaside Avenue, is that for the hospital, although the summary record has 2068 Bridgeport. This latter address finally gets one here.
No, "hard questions" is what your questions would be if the burden of proof wasn't still on Lee and his supporters to show the soundness of their work. Do you understand this?
Show us you understand this. "How can you deny the evidence obtained through oneiromancy that says this young woman was killed by a vaccine?" - in a world, such as ours, where oneiromancy has not been shown to produce reliable evidence, do you assert that a question such as this, founded on "evidence" produced through such unsupported methods, is still a "hard question"?
Since you're awfully fond of changing the subject and asking new questions, rather than answering the questions asked of you, we're going to make this an ultimatum question. If you make three comments, on this or any other RI post, without answering the question, it will be taken as an admission that questions relying on unproven methodologies aren't "hard questions" at all (no matter how convinced devotees of those methodologies are that they are sound and will someday be proven so.)
It is of course normal to list the primary affiliation as that where the work was done, but it's also normal to indicate (e.g., in a footnote) what the current affiliation is, even if it's just a home address. This whole presentation just smells fishy, and it goes without saying that SCIRP doesn't have a staff that minds such details.
Many ISP's have been blocking that port for years. The depths of igorance exposed by that inane observation is telling. Stick to your day job.
We were talking about real life and public health. Since there isn't enough money to go around, you fund the initiatives that give you the best return on money spent, which of course maximizes the reduction of pain, suffering and death. If you are aware of a better criteria, let's hear it.
Thought Experiment Fail: Access to health care reduces cervical cancer mortality not primarily due to the treatment of the disease, but because of access to screening (regular pap tests) helps avoid most of those expensive life altering treatments. And BTW, the cost analysis in the study I referenced uses QALY which factors in all those things you discussed. Vaccine bullies make the same mistake all the time, drawing false conclusions after making grossly invalid assumptions usually based on ignorance.
Antaeus, you're really off on some tagent comparing devining through dreams with nested PCR in a lab. I'm worried about you, get some help, please.
@Grant
You're back! You were secretly lurking here all along! Like a worm on a rainy day, the minute Narad starts a new track away from the science, you crawl right out the ground to try to swim in the puddle. All those non-science arguments must really interest you. BTW, the judge down under had no illusions who brought in the "foreign scientists" -- the ME sure looked to be a bit lacking in the science department -- because he complimented the family in going to get other opinions. Did you even know that?
@flip
Wow, you are perceptive. You're also right that the US vaccine delivery problems won't necessarily apply to other countries. Do you want a high five for that perceptive observation too? The only thing Australian public health has to do is keep the faith and hope really hard that the vaccine actually works based on the laughable assumption of 100% efficacy.
It wasn't me who proposed herd immunity or eradication of HPV. That's the nirvana fallacy.
Strawman #2:
I said "I think it is quite useful in pointing out an avenue for investigating some of the more serious reports of reactions." That doesn't even come close to meaning one paper is enough. Do they teach different english down under?
Strawman #3:
You said "So you’d agree with me that Lee’s paper is pretty useless until it’s replicated then?"
There is one key assertion in that statement --> Dr Lee's paper is pretty useless.
My response "I think it is quite useful in pointing out an avenue for investigating some of the more serious reports of reactions." That's a clear disagreement --> I stated the report was quite useful.
That's not equivocating and it's not ambiguous at all. Pointing out that replication is a natural next step does not weaken or change my position that you were completely wrong in your assertion.
Claiming that's equivocating is some dumb.
High fives to flip for beating the tar out of that strawman argument! There is a big crater in the ground and the straw stuffing flew 10 feet high in all directions. Hoo-rah.
Now that you've been supremely victorious and killed a whole series of strawmen (or were they strawwomen), do you want to get back to real life and bring a single substantial critique about the case report to the table?
@Krebiozen
I suggested no such thing. Do you want to beat the tar out of the strawwomen too, because you're just wasting time making up my arguments and then beating them down in a cloud of straw and dust. You and flip should take reading comprehension classes together.
Whine, whine, whine. HRT studies had 1 million women in the UK and the US based WHI study had 160,000 women. That should be more than enough to get good results on cervical cancer vaccination. Remember, the evidence part from evidence based medicine?
Screening is required because the vaccine only targets specific strains and other strains can cause cervical cancer. Screening already drastically reduces both the mortality and morbidity from cervical cancer. You saw the quote from Ian Frazer: the vaccine's most obvious use is the developing world, not where people have good access to healthcare.
Really, the pain and suffering gambit, from the same guy who stormed out here lecturing about public health needing to take gambles? What would happen if you applied that money to reduce medical error which causes way more suffering and death than cervical cancer and is one of the leading causes of death in the US? Which approach reduces more suffering and death? What causes more pain and suffering for others: an unnecessary death due to a mistake by the medical community, or death by disease?
Aye, but that's the point isn't it? This core argument is about the validity of the choice of surrogate outcome. I've produced good evidence to support that CIN-2 is not a very accurate surrogate at all and certainly is not universally accepted as such. You're the one bringing up the ethical argument to counter it. You can't counter a lack of efficacy argument with ethics because that creates the circular reasoning.
I am saying exactly that, we don't need to vaccinate against it where you have good access to healthcare. There are many well known risk factors associated with cervical cancer. The real problem is none of them involve pharmaceutical profit. That's the case with the most expensive chronic diseases as well in case you hadn't figured that out yet.
You are the one who brought public health into the argument at the beginning. High causes of death always involve public health (including guns, google it) so those stats are entirely relevant because the money you're wasting on the vaccine could save a lot more people if spent elsewhere. There was no fallacy there.
In the poor states, you aren't anywhere near 100% coverage. In the age range of 13-26 what percentage of girls and women have not been exposed to HPV?
You didn't read my reference from Bach did you? He uses the Kim et al study and points out that unless you vaccinate the populations at high risk in the US (i.e. the poor states without access to health care) the initiative is no longer cost effective (I pointed out Narad's foot-in-mouth by showing the large differences in cervical cancer mortality rates between wealthy and poor states). Unfortunately, you are not vaccinating the poor states properly, so the initiative is no longer cost effective. And since you clearly have problems with comphrehending this point I will spell it out for you: low rates of vaccination in poor populations in the US is due to lack of access to health care, NOT safety concerns so your false argument about misinformation is rhetorical musing, nothing more.
Slow down there fast one. QALY is the way public health quantifies the "worth" of a medical intervention. You invoked both public health and efficacy proving worth. You referenced the study that does the calculation using QALY!. You're trying to move the goalpost AGAIN, and now I suppose you would choose to retract that reference now right?
I missed the Gee study on VSD, the other one you linked was VAERS which I already addressed. Did you read the study? (I sense a pattern here) They only looked for pre-determined outcomes (pre-specified ICD-9 codes) which is very different from a thorough safety analysis. This is what the CDC says on their site: "This is because pre-licensure trials are often too small to detect rare events and special populations may not be adequately represented." So how does studying pre-determined outcomes help "detect rare adverse events that were not identified during pre-licensure clinical trials?"
One single study which was limited to pre-determined adverse events + one study on VAERS which gets a small fraction of unreliable reports "plenty of post-marketing evidence to suggest HPV vaccines are remarkably safe..."
Cognitive dissonance?
BTW, Did you ever figure out why that systematic review you posted doesn't count as post-marketing evidence?
@Krebiozen
OMG, you have really exposed your ignorance on vaccination with that one. Do you have any idea how smallpox was actually eradicated? Are you even aware that herd immunity for pertussis (one of the older vaccine preventable diseases) is a pipe dream? It is true irony that the same poster who erroneously quipped that I invoked the nirvana fallacy, turns around and suggests that HPV could be eradicated through vaccination. It is such a ridiculous suggestion that Narad (the self appointed referee) had to politely come by and tell you to back away from that one because you're making his side look really bad.
I see you've really shifted the goalpost now. Let's take a trip back to Post #547:
"Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality." --> Apparently now, you're claiming that this was a statement of opinion not based on any evidence at all.
Your arguments are all over the place. You invoked public health by storming into this argument with definitive statements of confidence in the vaccine program lecturing about taking gambles in public health: "Public health decisions like this are always a gamble to some extent. ... We never have the luxury of certainty in the arena of public health." When you invoke public health the term "worth" is well defined. I suppose by your new argument (i.e. shifted goalpost), public health should be gambling -- in an era with of scarce funding -- without evidence, or even an economic model.
Ignoring your over the top comments about safety, you assert that the vaccine is successful before a single shred of evidence has even been collected regarding the desired endpoint of cervical cancer.
"We have every reason to believe the vaccine will reduce the incidence of cervical cancer."
"The evidence also shows beyond any reasonable doubt that the presence of precancerous cervical lesions is predictive of cervical cancer."
You use inaccurate and completely definitive terms to characterize the state of evidence.
It has been proven to reduce the risk of cervical changes that are known to be associated with cervical cancer in the short term
When shown that your surrogate outcomes are far from a sure thing, you back off the unscientific language and you invoke:
False argument of authority --> The WHO and FDA says so, therefore it must be the right decision.
False argument of popularity --> Everyone else is doing it
Circular reasoning --> It must be effective because it's unethical to study the endpoint
None of these arguments are evidence based and they don't support your notion that CIN-2 is a credible surrogate for cervical cancer. The first preliminary real life evidence of HPV prevalence in the population blows the confident predictions right out of the water.
Now you're furiously backpedalling and invoking emotional arguments like "pain and suffering" and caring for the developing world. I'll take that as a concession because the program we've been discussing here isn't focused on the developing world and public health decisions shouldn't be based on emotional arguments. "Pain and suffering" will be reduced if public health spends it's money in the most effective way, but that requires cost models and quantitative measures.
I applaud your intentions on reducing morbidity and mortality, and I sincerely believe you have the right motives. The problem IMO, is that your faith ("We have every reason to believe the vaccine will reduce the incidence of cervical cancer.") is misplaced in a program that is based on seriously flawed assumptions for the developed world. Because of that, it has a high probability of being an enormous waste of money. Money that would be far better spent elsewhere reducing morbidity and mortality in your developed country.
Perhaps you don't grasp the point. Perhaps you would like to try dropping him a line using a normal sendmail client.
(For those unfamiliar with Pink's claim of "depths of ignorance," many ISPs block outbound port 25 to prevent their clueless customers from functioning as botnet nodes.)
I didn't tell K. to "back away from" anything, I said that eradication is a lofty goal, the practicalities of which he readily acknowledged.
CORRECTION in Post 610:
The parser ate my do not equal sign. It should read:
@krebiozen:
One single study which was limited to pre-determined adverse events
+ one study on VAERS which gets a small fraction of unreliable reports
DOES NOT EQUAL
“plenty of post-marketing evidence to suggest HPV vaccines are remarkably safe…”
Now that really is some dumb. Serious mail providers typically only accept traffic on port 25 from pre-approved MTAs, not personal mail servers. You should be originating your mail connecting through an MSA on port 587, unless you're trying to hide something or spam email that is.
Lofty goal? I said it was a polite warning. He didn't acknowledge the key missing ingredient of quarantine at all -- which indicates he doesn't understand how smallpox was really eradicated.
Narad,
re, #605: MML is "a subsidiary of Milford Hospital", then - so Lee has the work as being done entirely within Milford Hospital. OK, good that's sorted. Not what I was expecting though given, I thought, Milford had disemployed him at an earlier date, but it makes the outcome of the legals more interesting I suppose (?)
re, #607: "but it’s also normal to indicate (e.g., in a footnote) what the current affiliation is" - Originally wrote as much in my comment, but canned it.
A key difference between smallpox and HPV is that smallpox spreads through the air and HPV does not. Hence, one person with smallpox could infect an entire jumbo jet full of passengers during one trans-Atlantic flight, whereas it would be relatively uncommon for a person to infect an equivalent number of other people with HPV even over the course of a lifetime. Hence, the need for quarantine with smallpox does not necessarily imply an equivalent need for quarantine with HPV.
This betrays extreme stupidity. Do you even actually know what an MTA is? Don't try to teach your grandmother how to suck eggs.
True enough, but commensurately, tactics such as ring vaccination are out. This will be a long-term endeavor, as K. has noted. You just don't know where it "is."
You said no such thing. Your words were that I "had to politely come by and tell [Krebiozen] to back away from that one because you’re making his side look really bad."
I issued no "warning," and I did not tell K. to "back away from" anything.
/Users/narad> telnet gmail.com 25
Trying 74.125.142.83...
^C
/Users/narad> telnet gmail.com 80
Trying 74.125.142.83...
Connected to gmail.com.
Escape character is '^]'.
^C
/Users/narad> telnet gmail.com 587
Trying 74.125.142.83...
^C
Get it yet?
Allow me to clarify further.
/Users/narad> telnet smtp.gmail.com 25
Trying 74.125.133.108...
Connected to gmail-smtp-msa.l.google.com.
Escape character is '^]'.
220 mx.google.com ESMTP dy5sm4338538igc.1 - gsmtp
^]
telnet> close
Connection closed.
"True enough, but commensurately, tactics such as ring vaccination are out."
Oh, granted. Mr Pink was sneering at Krebiozen for not mentioning quarantine in connection with potential eradication of HPV. I was pointing out that quarantine isn't as relevant to HPV as it was to smallpox so there wasn't really any reason for Krebiozen to bring it up.
Also, Mr Pink doesn't grasp the meaning of "thought experiment."
To close the position,
/Users/narad> dig -t mx snet.net
; <> DiG 9.3.6-APPLE-P2 <> -t mx snet.net
;; global options: printcmd
;; Got answer:
;; ->>HEADER< telnet nb-mx-vip1.prodigy.net 25
Trying 207.115.36.20...
Connected to nb-mx-vip1.prodigy.net.
Escape character is '^]'.
220 nlpi167.prodigy.net ESMTP Sendmail 8.14.4 IN/8.14.4; Sat, 2 Mar 2013 16:28:34 -0600
^]
telnet> close
Connection closed.
See? I was wrong, but in kneejerk response, you were even wronger.
Hmph, that got oddly truncated midway. Anyway, the 'dig' yields the prodigy.net MXs that happily answer on port 25; it's easy enough to test for oneself.
I will reply to Mr. Pink anon, though I get the feeling we are going in ever diminishing circles. Meanwhile, I am not the only person to suggest it might be possible to eventually eliminate HPV and cervical cancer.
There's an interesting webcast on the subject here as well if anyone's interested.
Humph. Wordpress chewed up that URL. Try this page, 'Cervical cancer and vaccination- an overview'.
. I will spell out the point since it apparently wasn’t obvious enough: It’s a waste of money to vaccinate the people with good access to health care but that’s exactly what you’re doing in the US. You are not actually vaccinating the people who the vaccine was designed to help.
I don't know where to start...Adam, I feel your pain.
It's a waste of money to vaccinate people with access to health care? Holy steamin' pile o' stupid. Yes, my friends, let yourselves and your kids risk genital warts, RRP, and vulvar, vaginal, anal or oropharyngeal cancer because treating these is so much cheaper than a shot.
We're not actually vaccinating the people that the vaccine was designed to help? Per the CDC, HPV is now so common that all sexually active adults are at risk, not just the po' folks.
FYI, the vaccine is now offered by many health departments as part of the vaccination program for children from low-income families.
There are some interesting snippets in that webcast. For example a 50% reduction in genital warts has already been seen in younger (vaccinated) women in Melbourne, but not in older (unvaccinated) women, so it must be due to the vaccine. A similar reduction has been seen in genital warts in young heterosexual men (unvaccinated), presumably due to the herd immunity that Mr. Pink claims is a pipe dream. Also, you need to vaccinate 31 girls to prevent a case of CIN-2/3, 639 girls to save 1 life, and 14 girls to save 1 year of life, figures that are much lower than for other vaccines, which rather elegantly expresses what I have been trying to explain, perhaps somewhat inarticulately, about the value of the vaccine. Finally, polyvalent vaccines were in Phase 3 clinical trials in 2009 so presumably will be within a few years.
"presumably will be available within a few years"
Let it be noted that Mr. Pink definitely saw the ultimatum question, even quoted from it, but posted three comments without even attempting to answer. As warned, Pink's attempts to avoid the question will be taken as an admission that Lee's supposed "evidence" against Gardasil is utterly meaningless until and unless Lee's methodologies become accepted, verified science.
Of course, Pink will claim that Lee's methodologies already are accepted, verified science. This is false.
That's from Lee's own paper; Lee himself is admitting that his methodology is novel. Any fool who claims that Lee's results must be as solid as those obtained through standard techniques of nested PCR because Lee's newly developed method also employs nested PCR, doesn't understand Lee's own paper and has no credibility when assuring us how very convincing it is.
LW,
I would suggest that it is HPV antibody testing and the use of safe sex or abstention in those who test positive that will be analogous to the use quarantine in the eradication of smallpox. It wasn't that long ago I was trying in vain to explain to Th1Th2 that it was the use of surveillance, isolation and vaccination together that eliminated smallpox, with her insisting that the vaccination part was unnecessary.
I think you need to get the prevalence down via vaccination before antibody testing is practical. If something like half the adult population is exposed, you can't very well test everyone and urge safe sex or abstention just on the exposed. Anyway, everyone should be encouraged to act in ways that reduce the spread of HPV, as well as other such diseases.
LW,
I agree. Eradication in this way this would require a long-term strategy over the next 50 years or more.
True, but that's not entirely practical if you want to reproduce.
BTW I would add an effective treatment for HPV infection to my expectations (or perhaps utopian wish-list) for future medical developments.
If you read that graph carefully, each datapoint was 3 months, making it look like a much longer study than it was. I followed the reference. That data was from a clinic that treats a specific population. After they vaccinated the population starting in 2007, they saw a decrease in genital warts in 2008 (that's when the data ends). I would certainly hope to see some vaccine efficacy during in the period of one year! If you didn't see anything, the vaccine would immediately be declared a dismal failure. These results are hardly startling. It's long term efficacy that matters across a large population. Most of the rest of the slide deck regurgitates the data from the clinical trials which we've already covered to death. One thing that jumps out is the amount of ADRs from the Placebo. Do you think that it might just be because their "placebo" isn't really one?
You didn't factor in the cost. That's like saying I want to build and buy the safest car regardless of the cost. CDC Cost: Gardasil costs ~$300, DTaP ~$60, MMR ~40. That's almost an order of magnitude more expensive than MMR. Public health can't ignore cost as a criteria for deciding on initiatives.
I think the odds of success there are close to zero. People still engage in unsafe sex, even when the penalty is/was death from HIV/AIDS. Why would the fear of genital warts have a greater chance of success? People don't require proof of an AIDS test today, let alone an HPV test. Call me a sceptic, but I just can't see that flying unless you decided to create a police state where everyone had to carry around ID with test results on it.
If you disagree with the Bach reference, then post an alternate financial model which supports your rhetorical fury.
Do you have stats to show it's working? The state numbers from the CDC still don't look so good. The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money. Hopefully they can clean up their early failure.
You're now reduced to whining about the cost of the vaccine while simultaneously, in effect, advancing the "Pap smears are better" argument? The incremental lifetime cost is effectively nothing. What's the cost of treating cervical cancer?
You’re now reduced to whining about the cost of the vaccine while simultaneously, in effect, advancing the “Pap smears are better” argument?
If I understand correctly, the cost comparison is between (a) a vaccine of some form or (b) the SaneVax / Sin Hang Lee business model of "Pap smears plus regular payments from every woman regularly through her lifetime to SaneVax for a dodgy PCR test ".
@Mr Pink:
Seriously?!?! Have you never heard of the expression "Prevention is better than cure"? It can cost tens of thousands of dollars to treat just one case of cervical cancer. Even if the patient survives, there can still be lasting damage. I read that Brooke Shields's battle with cervical cancer permanently damaged her uterus and consequentially, her two daughters had to be delivered by C-Section. In addition, HPV has been implicated in cancers in males, and in cancers of the mouth and throat.
A $300-00 jab is looking like a very good, cost effective option.
don’t you think it’s a little disingenuous that Lee declares no conflicts of interest despite the fact the he has a clear financial interest in the LoTemp PCR system?
A thorough conflict-of-interest declaration would also include the direct competition between (a) vaccination campaigns that Lee and SaneVax have worked so hard to undermine, and (b) the program of regular PCR screening offered by Lee and SaneVax at $50 per person per test (possibly reimburseable).
http://www.businesswire.com/news/home/20100920005586/en/S.A.N.E.-Vax-Si…
If you disagree with the Bach reference, then post an alternate financial model which supports your rhetorical fury.
Which would you rather purchase -- a smoke detector or a brand-new house?
Prevention costs less than treatment. I have insurance and can afford to get treatment for diabetes and high cholesterol but I'd rather keep my weight under control; it's cheaper in the long run. However, if you can't be made to see how this makes sense from a medical standpoint, I'm not sure an argument from a business perspective is going to convince you.
You didn’t factor in the cost. CDC Cost: Gardasil costs ~$300…That’s almost an order of magnitude more expensive than MMR. Public health can’t ignore cost as a criteria for deciding on initiatives.
Are you seriously arguing that treatment for cervical or oropharyngeal cancer costs less than $300?
Two almost identical strawmen. Did you people not read the context of the discussion? Krebiozen was comparing various vaccines and the vaccination/prevention ratio compared to other vaccines. Do I really need to point out that cost and ROI is one of the most important criteria when choosing public health initiatives? Arguing that I am against preventative measures is a strawman.
The Bach reference clearly outlines that in order for the preventative measure to be cost effective (i.e. positive ROI) we need to vaccinate the populations without access to health care because they have a higher risk of cervical cancer.
Unlike far more targeted preventative measures -- like providing screening to high risk groups -- you are advocating we pay for an unnecessary procedure for the whole population, the vast majority of whom are not at risk of anything.
Of course, if you people want to continue living in a fantasyland where you assume infinite funding -- apparently you are in good company in America today -- go ahead and keep drinking the kool-aid corporate america is feeding you.
That would not work. From the CDC: "As HPV infection is confined to the epithelium and infected cells are shed before cell death, natural HPV infection results in minimal host immune response and not all those infected have detectable antibodies"
Any luck getting a public statement from the "affiliated party" yet? All those allegations of fraud sound like a lot of hot air.
I award you no points, and may G-d have mercy on your soul.
Mr Pink,
Regards "@Grant […] Any luck getting a public statement from the “affiliated party” yet? All those allegations of fraud sound like a lot of hot air."
I wasn't the person asking for a public statement. Nor did I make an "allegation of fraud". You need to read more carefully. (It's pretty rich how you accuse others of not reading carefully when you certainly aren't yourself!)
I would remind you—again—that accusing people writing here of things they haven't done and the various other silly put-downs you do with regularity won't make you or Lee right.
@Mr Pink:
How ironic. You accuse me and Shay of strawmanning and yet you yourself straw man. The ROI on the HPV vaccine is excellent. We accused you of miscalculating the ROI.
A higher risk of cervical cancer, or a higher risk of dying from it? Also, treating a case of cervical cancer costs a ton of money, whether or not the patient has access to health care. It's still cheaper to vaccinate.
A quick response to Mr. Pink as I am currently otherwise occupied:
Not all, but most do. I am suggesting this as part of a larger strategy to eradicate HPV. As I wrote before, it would require a long time, and quite probably technologies not yet developed. In theory all we have to do is reduce the average number of people each infected individual infects to less than one for long enough; there are several different and complementary ways of doing this. They have to be tailored to HPV and its modes of transmission just as the different complementary methods used to eradicate smallpox were.
@Pink
Nice dodge. I say again, are you seriously arguing that a $300 vaccination is more expensive than treatment for cancer?
Since not veryone infected with HPV will develope cancer as a results, I think he's arguing that $300 dollars per person to vaccinate enough people to prevent a case of crvical cancer costs more than treating that case of cancer.
I don't know if that's true--the cost of treating cancer can easily run into 6 figures--but even if it were that >isn't an argument against HPV vaccination: it's instead an argument in favor of reducing the per person cost of HPV vaccination.
All those allegations of fraud sound like a lot of hot air.
I don't know; Sin Hang Lee's activities as a cancer scammer are not in question.
I particularly liked the part of the story where he demanded that the FDA should shut down rival (non-medicinal) tea traders.
It's still a drop in the bucket amortized against the extant cost of screening.
herr doktor bimler,
Just to be clear, my previous objections (#645) were to Mr Pink getting confused about who wrote what again.
It wasn't my calculation, that came from the reference which you didn't read very carefully. It says: "Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective." That's disease, not death.
You appear clueless on how to measure the ROI of a public health measure. Read the post from JGC who gets it.
The model was just below the threshold of economically attractive (< 50K) if only 12 year olds were vaccinated. It's over 6 figures if you catch up to age 26. That's why Bach points out that ineffective delivery makes the program not economically attractive. Also, that number was based on the rosy assumption of lifelong immunity. The cost is well over 6 figures if immunity lasts only 10 years as they project only a marginal reduction of 2% over current screening in that scenario.
This is just a model based on a whole host of assumptions because there is no efficacy data available yet. I don't think there has been a single early vaccine cost model (i.e. prior to seeing actual efficacy in real life) that didn't grossly underestimate the cost. 1 shot of MMR was supposed to give immunity for life too. Even 2 shots still don't prevent a mumps outbreak today blowing the older cost calculations out of the water.
Given that Merck just lost patent protection on one of their biggest drugs (Singular @ 5.5B annual revenue in 2011), I doubt they will be dropping the price anytime soon.
LOL, most? Did you check the confidence interval on that 51% number? A more accurate term would have been half. The "technologies not yet developed" make this sound an awful lot like wishful or magical thinking. According to our host, that puts it right up there with homeopathy.
Tell us what the nudists do on port 587, Pink.
Oh, sorry, "LOL." I'd hate to appear not to have a measure of technological sophistication.
You didn't read the underlying reference, did you?
I suppose I should add, from the original (PDF),
@Mr Pink:
A pap smear detects the disease in the early stages where treatment is cheapest and most likely to be effective. However, it's still more expensive than the vaccination. The ROI still favours the vaccine.
Mr. Pink,
I'm starting to simply repeat myself, which is a waste of everyone's time. I think there is ample evidence to support the assumption that Gardasil will prevent cervical and other cancers, and that it will prove to be a safe, effective and cost-effective intervention in the long term. Perhaps we should reconvene here in a decade or two to assess how well it has done.
Anyway, I note that you appear to have changed your position from:
To:
Which is progress of sorts.
I will address this cheap shot:
I originally wrote, "in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated". I have stated that I might be being "unrealistically optimistic" and that this might require “technologies not yet developed” . We know that polyvalent HPV vaccines are currently undergoing RCTs, and that antiviral drugs targeting HPV are under development. As I pointed out above, I am not alone in thinking it might be possible to eradicate HPV eventually.
Wishful thinking? Perhaps.
Magical thinking? Certainly not .
One more thing - I was getting HPV testing confused with HPV antibody testing earlier. Testing for HPV is considerably more sensitive than cytology though less specific. There's a recent paper on the future of cervical cancer screening here if anyone's interested. It concludes:
I think that's worth pursuing.
Mr. pink, just for teh record I don't agree that the ROI for the vaccine is insufficient--quite the opposite. One doesn't have to prevent very many cases of cervical cancer to achieve cost effectiveness.
As for Bach's claims that ineffective delivery making the program economicallu unattractive, that's again not an argument against immunization--it's an argument in favor of optimizing the delivery program.
with regard to pap smears versus immunization, fail to see the relevance to this discussion. Regular pap screening is capable only of detecting cervical cancer once it arises, while immunization prevents its occurrence. Would you similarly argue that there's no need to expend resources preventing the sale of guns to convicted felons, long as we can accurately determine after the fact when a felon has purchased a firearm?
You appear clueless on how to measure the ROI of a public health measure. Read the post from JGC who gets it.
Yes, JCG gets it...you, on the other hand, don't.
Krebiozen, "I’m starting to simply repeat myself, which is a waste of everyone’s time." - similar for me. I felt sometime ago (what is it now, two weeks ago?) that it got to the point where all I could suggest was for him to re-read earlier comments as he clearly wasn't taking things in and was just pushing his own barrow.
You stopped reading after you found the quote you wanted. In the same paragraph: "Other studies have suggested that [b]race/ethnicity is likely not the primary mediator of disparities in cervical cancer screening rates[/b]... This is evidenced by the fact that the effect of race is significantly reduced or eliminated after controlling for these factors."
Further down in the study: "In a number of these studies, socio-economic position has been noted to explain differences in cervical cancer screening rates better than race/ethnicity."
Of course, the heart of the matter is put to rest further down: "Lack of access to health care has been correlated with reduced cervical cancer screening and treatment. In most studies, health care access is measured by insurance status or having a usual source of care. Having insurance, particularly private insurance, has been positively associated with cervical cancer screening, earlier stage at diagnosis, receipt of guideline-based therapy, and improved survival."
Or further: "An evaluation of three interventions to increase cervical cancer screening rates in a multi-ethnic sample found that having private insurance and/or a usual source of care were the strongest predictors of cervical cancer screening behavior."
Of course, the study starts out by saying: "Screening conducted every 3 years among women aged 20 to 64 reduces the cumulative incidence of ICC by 91% according to data from the U.S. Preventive Services Task Force."
This all fully supports the Bach quote that used the reference: "Those who are more affluent and have access to regular Pap testing are at low risk of the disease because the test, when properly done, is highly effective." Again, I'll repeat my original assertion, it reduces BOTH disease and mortality, NOT only mortality as Julian Frost suggested.
To keep insisting that in the face of evidence to the contrary is pretty illogical. I'm sure the authors of the financial model would be happy to address the concerns of Julian Frost based on the fact that "he says so".
Bach does make the argument for better delivery, but the argument for cancellation is also valid for consideration. In post #565 I raised this to point out how marginal the ROI was for the whole program, and that given the failure of distribution it was providing negative ROI.
Not true. Pap smears with proper followup is a preventative measure which reduces the incidence of ICC (invasive cervical cancer). "Screening conducted every 3 years among women aged 20 to 64 reduces
the cumulative incidence of ICC by 91% according to data from the U.S. Preventive Services Task Force."
(Akers AY, Newmann SJ, Smith JS. Factors underlying disparities in cervical cancer incidence, screening, and treatment in the United States. Curr Probl Cancer 2007; 31: 157–81.) That's why the ROI on the vaccine is so marginal and is also highly sensitive to several factors including efficacy and length of immunity.
That's ironic coming from the person who inferred that the cost of preventing a case of cervical cancer is $300 based on vaccination. You're only off by a couple of orders of magnitude on that one.
@Krebiozen
Thanks for pointing out my ommision: "The point is that the CDC has to actually deliver the vaccine properly, or they are wasting their money by their own calculations. Hopefully they can clean up their early failure."
All he did was say that it was theoretically possible but he doesn't express any confidence in it. He can't even forsee a future where screening is not required. You might note that he also confirms that screening requirements won't change based on the current vaccines. That borders on magical.
The expert you noted above was also quite vehement that screening was required to eliminate the incidence of cervical cancer.
I will point out now that Dr Lee's technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler's whining, your own references and quotes demonstrate quite clearly that he has competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination.
Thank you very much for making that point crystal clear for all to see.
One last thought for you: Since the vaccine will only prevent some of the incidence of cancer (certain strains), your quote above implies that the screening will be 100% effective for the rest. Why do you suppose that screening wouldn’t be as effective for vaccine strains? Cognitive dissonance anyone?
CORRECTION:
I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has NO competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination.
Pink, do you recall saying this?
Blockquote faiil. I take it that what's what is discernible.
Are you insane? You think that "community hospitals" are going to start performing some weird-ass nested PCR?
Moreover, what does this even have to do with HPV screening? As you may recall, Lee's "technology" is for detecting deadly Gardasil DNA brain residues.
Oh, right, I forgot that he's selling it by way of "SaneVax":
The point remains elusive.
@Mr Pink:
"A pap smear detects the disease in the early stages where treatment is cheapest and most likely to be effective. However, it’s still more expensive than the vaccination. The ROI still favours the vaccine."
To keep insisting that in the face of evidence to the contrary is pretty illogical. I’m sure the authors of the financial model would be happy to address the concerns of Julian Frost based on the fact that “he says so”.
It's not just I who says so.
Cost of treating early -stage cancer: $ 7,370.
Cost of the jab: $360.
Source (PDF): http://www.michigancancer.org/pdfs/mdchfactsheets/cervcainmichfact%20sh…
The maths says that 20 Gardasil vaccinations are cheaper than one early-stage treatment. But introduce the fact that HPV has been implicated in numerous other cancers and the ROI is even better.
It's still cheaper to vaccinate.
Please bring back the edit button.
Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has NO competition
This seems to be Mr Pink's response to my penultimate comment (#641) --a link to a press release from Lee and SaneVax in which they complain about the existence of competition.
@Narad
Dr Lee is awesomesauce, quite obviously.
If only they would glom onto fan death. (Yes, I know, wrong nationality, but still.)
Mr. Pink,
You have moved from suggesting that, "people should avoid Gardasil", to complaining that the problem is the CDCs failure to vaccinate enough people. Who was it that mentioned cognitive dissonance?
Did you read the article I linked to at #628?
That seems pretty confident to me, about an eventual end to screening too. How does expecting the polyvalent vaccines currently undergoing clinical trials and the antiviral treatment for HPV currently under development to be successful even border on "magical thinking"?
Where have I ever suggested that it would not be? If you are so concerned about the costs, look at them over the very long-term when HPV and cervical cancer have been eradicated and there is no longer any need for screening, treatment and, ultimately, vaccination. How much would smallpox have cost over the last 35 years if it hadn't been eradicated?
You appear to have an odd habit of rigid black and white thinking. I am suggesting that neither vaccination nor screening would be 100% effective on their own, but together with technologies currently being developed they could result in HPV eradication. Even if efforts to achieve this "pipe dream" fail, they can be expected to result in a dramatic fall in incidence of cervical cancer.
Missed an apostrophe in "CDC's". Better than a superfluous one, but I isn't illiterate, honest.
@Krebiozen:
I read somewhere (don't remember) that the elimination of smallpox pays for itself every 26 days. So, billions of dollars would be my guess.
Mr Pink's reasoning seems to be that poorer women are less likely to get regular screening for cervical cancer, therefore there is no reason for then to be vaccinated since that would only reduce the number of cancers that they aren't being screened for.
Do I have that right?
That’s ironic coming from the person who inferred that the cost of preventing a case of cervical cancer is $300 based on vaccination. You’re only off by a couple of orders of magnitude on that one.
That's ironic coming from someone who keeps using "ROI" and "orders of magnitude" with no indication you understand what they mean.
As has been pointed out already, you have shifted your argument from Gardasil doesn't work to other things work better and besides it's too expensive. Citations needed, as what you have provided so far doesn't support your argument.
(Pap smears as a cancer treatment. Hoo, boy).
Cookie please.
Still waiting for mr. or mrs Floyd in addition to mr. Pink.
@ LW:
I might argue the reverse: they need it more because they can't access screening.
But then, that's just me.
I don't understand the reasoning here - since pap smears & even testing doesn't actually prevent cervical cancer.........yet the vaccine does prevent the disease (so people who don't have access to screening or just don't screen, are less likely to get cervical cancer in the first place).
Mr. Pink - care to explain what the hell you're talking about? Because if there was a vaccine against breast cancer, it sounds like you'd be arguing that more mammograms would be better than prevention.......
@Denise Walter, "I might argue the reverse: they need it more because they can’t access screening. But then, that’s just me."
That's what you think. It's what I think too. But it doesn't seem to be what Mr Pink thinks.
While pondering this I found something interesting, from a 2008 article, 'The World Health Organization and global smallpox eradication'
The World Health Assembly Resolution WHA11.54, an undertaking to eradicate smallpox globally was accepted in 1959. The last case of wild smallpox was in 1977. I'm not saying that HPV can be eradicated in less than 20 years, but without the vision and determination shown by public health officials (and many others), we would still be seeing millions dying from smalllpox.
Another interesting (to me, anyway) snippet of history, from a review of 'Smallpox—The Death of a Disease: The Inside Story of Eradicating a Worldwide Killer' by D. A. Henderson, the sacrificial lamb described here:
I'd say the WHO DG shot himself in the foot.
Lawrence, this isn't my argument, it's the argument of the evidence I'm quoting. Read the Akers reference I provided in post #665. Screening (pap tests) and followup reduces the INCIDENCE of cancer by an average of 91%. Good screening is even more effective at reducing the incidence of the disease. The vaccine is projected (since it hasn't be shown to reduce any cancer yet) to reduce the incidence of cancer. Since the vaccine only covers several strains, the experts all recommend implementing the best screening available (which consists of HPV genotyping) to reduce the incidence of cancer caused by non vaccine strains. There is a huge overlap between pap tests and the vaccines, in that they both prevent the same types of cancer. The difference is that screening actually prevents cancer from all strains, while the vaccine is theoretically supposed to prevent a few more cases of vaccine strains only. But even this conclusion is dubious because the better screening which is available today (HPV genotyping) will further improve the rates of screening and prevention. At that point, the few extra cases vaccination might theoretically prevent, will only come true if the most optimisitic assumptions of efficacy and 100% lengevity are true. The early population data comparing vaccinated and unvaccinated populations in real life (2012 Athena study) gives us a hint that the vaccine prevents only a few percent of infections which is a huge deviation from the efficacy estimates.
If the strategy seems confusing -- confusing is a generous word IMO -- it's because it doesn't make a whole lot of sense unless you're the one selling the vaccine.
Just because you don't understand it doesn't mean it's weird or complicated. The heavily downloaded article describes both the methods and the efficacy show that there is quite a bit of interest and others get it even if you don't.
Are you dense? Re-read #665. Your graph is followed by the revelation that the correlation disappears when confounding factors are corrected. Bach's reference of Ackers et al is completely valid.
No you do not. Denice has it right. The vaccine was designed primarily for treatment of the developing world and people who do not have access to good screening and followup. Read Ian Frazer's quotes. He's the guy who kicked the whole thing off and he did it for the developing world (God's gift to women: The HPV vaccine). The Bach reference describes that the US program is inefficient (i.e. won't be cost effective) because it's vaccinating the women who need the vaccine the least (those with access to good screening and followup). There is a correlation between low average income and low vaccine uptake by state. That means that the people who need the vaccine the most (i.e. the ones for whom it is most cost effective) aren't getting it. That's the failure of the US vaccine program by it's own measured objectives. Read the Bach reference for more details. According to Bach, the failure is even more embarrassing because it was predicted prior to the start of the program.
I did not shift my argument. I made three independent ones. My first argument is that Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes. A second argument is that even using the most ROSY projections (from the reference I provided), the vaccine program in the United States has a negative ROI due to a failure in the delivery system (they have not vaccinated the highest risk populations). A third argument, is that even if the ROSY projections are all true, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.
I have provided references for those arguments. Your implication that it costs $300 to prevent a case of cervical cancer indicates that it is you who have no clue on the cost justification of the program. I'll also note that you have not provided a single reference for your fantastical claim. My references start in comment #565. You might actually learn something if you read them.
@Krebiozen
No, I have provided three independent arguments all of which are valid. My first argument is that Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes. A second argument is that even if we assume it works and use the most ROSY projections (from the reference I provided), the vaccine program in the United States has a negative ROI due to a failure in the delivery system (they have not vaccinated the highest risk populations). A third argument, is that even if we assume it works and the ROSY projections are all true and the delivery failure is corrected, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.
There is no conflict between those arguments.
Really? He says "IF they will be successful". He doesn't even indicate if he thinks they will be successful or not. In fact, he follows up with this: "Even for girls vaccinated before this age with the current vaccine, there will be a need for some screening to protect from cancers caused by HPV types not in the vaccine, so screening is here to stay for the foreseeable future."
He can't even foresee a future without screening! That doesn't sound too confident to me.
I didn't say you suggested it. That sentence led into the next paragraph: "I will point out now that Dr Lee’s technology provides the most accurate HPV screening which can be performed in community hospitals at low cost compared to the less accurate assays which are run by expensive labs. Contrary to Bimler’s whining, your own references and quotes demonstrate quite clearly that he has competition or conflict of interest with the vaccine since all of the experts are universally saying that effective screening is critical in reducing the incidence of the cancer regardless of vaccination."
Your analogy is invalid. Smallpox is not at all like HPV. If you want to use prior vaccination as evidence, it is far more likely HPV will NOT be eradicated given the vast number of vaccination programs and only 1 successful eradication. I don't accept an argument based on wishful thinking and no plausible mechanism for success, and neither should you.
You misread my argument -- now I'm repeating myself. I pointed out the quote from the reference YOU provided states that the combination of vaccination and screen could eliminate cervical cancer: "If vaccination were to be combined with HPV screening (which is much more sensitive than the currently used Pap smear test), then eventually the cancer would disappear in those countries that had successfully implemented national programmes." It seems you miss a lot of little important details in your own references. Don't accuse me of being black and white, when I'm actually reading the references you're providing.
#686, LW:
Objection? Assumes facts not in evidence (that Mr Pink actually thinks).
I'm a Bose condensate, baby. I am not ionized and I possess not valence. Nothing "disappears."
So vaccination doesn't get to the poorest women in America (even though it's provided by county health departments) but instead of implementing a better vaccination program what we should do is to provide *much* more screening, including piping plenty of work to Dr Lee.
Mr. Pink,
That's not an actual argument, is it? I agree that "Gardasil has no demonstrated efficacy against the target endpoint" for the reasons you list and that we have discussed ad nauseam. My argument is that it is perfectly reasonable to expect Gardasil to demonstrate efficacy against the target endpoint, invasive cervical cancer, in the long term because (i) Gardasil prevents HPV-16 and HPV-18 in those not already infected, (ii) HPV infection is a necessary precursor of all, or almost all, CIN (and AIS) and cervical cancer and (iii) treating those surrogate outcomes (CIN and AIS) prevents invasive cervical cancer (as you yourself have pointed out). There is a large body of evidence that supports all three of these assertions.
Again, I don't see an actual argument. The vaccine has a negative ROI due to poor delivery therefore what? We should throw up our hands in despair and abandon HPV vaccination entirely? Or should we make efforts to improve vaccine delivery to those who need it the most? Personally I am in the UK so the CDC's failings don't matter as much to me as the NHS's implementation of Gardasil (now replacing Cervarix) which is going very well.
The same goes for the fact that Gardasil protects mostly against 70% of the cancer-causing strains. That's an argument for polyvalent vaccines, not against vaccination.
At last an actual argument! I agree that you could argue that the money might be better spent elsewhere, though I (and public health authorities around the world) disagree with you. As I pointed out somewhere above, public health is fraught with uncertainty and is always a gamble to some extent; it is very rare, if it ever occurs, that you have hard evidence to definitively prove what the outcome of public health measures will be in the long term, and the unexpected does sometimes occur. That's one reason I find public health so interesting.
BTW, as I have also pointed out, there is more to preventing disease than ROI. The way you equate a case of CIN or AIS treated surgically with one prevented by vaccination suggests you don't quite appreciate this.
The only actual argument I can see there is about cost efficacy. You did initially suggest that "people should avoid Gardasil", and you do now appear to be suggesting that the problem with Gardasil is that too few, not too many, are getting it. Perhaps you would like to clarify your position..
There's that black and white thinking again. I originally wrote, "in the future we may be able to produce effective vaccines against all other high risk strains and eliminate HPV the same way smallpox has been eliminated". You claimed this is "a pipe dream" i.e. that it is impossible, equivalent to a drug-induced delusion. It is quite clear that Professor Cuzick agrees with me. What do you think he meant by, "That's the long-term future: vaccination and no screening"?
I see, so it was just a non sequitur you used as an excuse for plugging Dr Lee's products.
It wasn't intended as an analogy, it is an example of how public health measures can have very much greater ROI over the long term than they do in the short term. Clearly smallpox and HPV are very different and strategies to eradicate HPV will differ greatly from those that succeeded with smallpox. I don't see that as a reason not to attempt it, especially when the most likely outcome, even if we fail, is a large reduction in morbidity and mortality.
My argument was that "in the future we may be able to [...] eliminate HPV" (my emphasis). That is based on the development of polyvalent vaccines that already exist and are going through clinical trials, screening technologies that already exist and antiviral drugs that are under development. Those are extremely plausible mechanisms, not wishful thinking.
I don't follow your argument here. To clarify this, what you wrote was:
A minor niggle, the "quote above" you referred to was actually:
Not, “If vaccination were to be combined with HPV screening (which is much more sensitive than the currently used Pap smear test), then eventually the cancer would disappear in those countries that had successfully implemented national programmes.” The current vaccine doesn't cover all cancer-causing strains, but future vaccines will. Testing for HPV is considerably more sensitive than pap screening but it is less specific. Clearly eradication will require an ongoing and responsive strategy as progress against HPV is made.
It is possible I have missed some details, as I waded through most of the HPV vaccine literature a couple of years ago and have only skimmed through them to refresh my memory more recently. However, you do appear to have a habit of focusing on unimportant details while missing the bigger picture.
A third argument, is that even if the ROSY projections are all true, the ROI is so marginal that public health should spend the money elsewhere on a program with better ROI.
Taking into consideration that in the US, public health ROIs are outcome-based, not revenue-based, what other program offers a better ROI with regard to protection against HPV?
Don't take my word for it. The latest stats (at the CDC) show some improvement in overall coverage, but there is still a large disparity between the states. As for screening, just follow the expert recommendations. Krebiozen linked to one expert. Ackers et al says the same thing. Improved screening based on HPV genotyping is pretty much a unanimous recommendation. WRT Dr Lee, you don't seem to understand the technology or the motives. Dr Lee doesn't want the work, he wants it to be done at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more.
I'm not sure where you are getting your definitions. Check out slide 12. http://works.bepress.com/cgi/viewcontent.cgi?article=1083&context=glen_…
HPV screening (vs pap tests) is universally recommended and has a very high ROI.
@Krebiozen
It was originally stated in the context of your original assertion and you argued against it in post 525. "Disingenous nonsense (PDF)".
I have summarized the issues with your assumptions:
i) You are relying on historically unreliable regulatory studies AND the initial real population data differs significantly
ii) Most CIN2 (which is the only outcome they actually measured) regresses naturally. You don't know why some small number of cases progress so you can't assume those cases would have been vaccine preventable.
iii) Treatment of CIN2 has no bearing on your argument. Like I said in ii) it's not a good surrogate.
In post #547, you stated: "Even if the effectiveness of these vaccines was half that found in clinical trials, they would still be well worth using as a means of reducing morbidity and mortality." My response is an argument against that now proven ridiculous assumption from a public health perspective. However, I can also independently make the argument that Public Health is wasting money on the program and that is the supporting point.
You make the statement but bring no evidence to the table. Who is at greatest risk in the UK (i.e. those that aren't taking advantage or getting good screening and followup) and are they getting the vaccine? You own public health's decision to originally go with Ceravix is baffling -- unless you consider who was selling it of course -- to say the least so I hardly have confidence they're making any good decisions. I also understand that NHS has bungling some VERY expensive programs over the past few years, so trusting them to spend your money wisely is hardly a good choice.
Yes, you talked about gambles early on. You sound more like a wealth manager selling someone on an IPO of a new company that has no history or background. Even worse, your best case scenario is an outcome that is so narrowly positive that there is no contingency. That's a bad gamble in most books.
Your being the UK lends some insight into why you seem argue for public health decisions without consideration of cost. In the UK you have a heavily funded public programs and people often forget that it's coming out of your taxes. I won't even go into the money the NHS wastes.
I certainly do. You brought up the topic of public health, and they should be making decisions based on data, not emotion. One of the most important constraints in public health is money. To continually complain about it is baffling.
My position has not changed. On an individual basis, one should focus on screening since it is universally recommended. I would not recommend the vaccine because it has no demonstrated efficacy for cancer, and if you have good screening, the vaccine will at best theoretically reduce your risk a couple of percent and only if the regulatory data holds true in real life (which it never does). Public health should stay away since it's not cost effective and the money better spent elsewhere.
"Pipe dream" is not incongruent with "not in the foreseeable future" or "wishful thinking".
No, it was an observation based on your reference.
We already have a very effective way to reduce mortality and morbidity thanks to improved screening. In a way you're right, relying on a deux ex machina is reason enough not to attempt eradication so we don't have to bother talking about smallpox.
It's the quarantine part which requires the wishful thinking as you already acknowledged. Vaccination is only one half of the equation as you well know.
Neither statement was predicated on future vaccines. Screening is here to stay for the foreseeable future and still he thinks mortality can be eliminated with the technology we have today. That means that screening is expected to be highly effective and we already know it works for all strains.
If, treating cost as a key constraint in public health, basing decisions on real evidence of desired endpoints, and making assumptions based on known technology, is considered small thinking, then I guess we'll just have to leave the big stuff to wishful thinkers like you.
If you were in the US, I'd say enjoy your March break.
Have you ever been to the type of facility to which you refer? I sorely doubt that you're based in the U.S.
Are you fυcking kidding? This gruel, which has nothing whatever to do with HPV anywhere, is the best you can muster?
Mr. Pink,
There is a significant difference between, "There isn't an ounce of quality evidence showing the vaccine has or will ever reduce the incidence of cervical cancer" (my emphasis) which is what I was arguing against, and "Gardasil has no demonstrated efficacy against the target endpoint. That is a fact because the vaccine has not been around long enough to know if it works against cancer in a real population. All of the studies to date are based on surrogate outcomes."
So we can't believe the studies that show Gardasil is almost 100% effective at preventing HPV-16 and 18 in those not already exposed? Any particular reason why? There is barely any real population data yet - the study you mentioned above looked at 1000 women who were too old to have been given Gardasil at age 12 so we can't come to any conclusions based on that.
That's a strange reverse logic. HPV infection is recognized as the immediate and necessary precursor of all (or almost all) cases of invasive cancer, therefore preventing HPV infection must prevent invasive cancer. The fact that not all HPV infections progress to cancer doesn't mean that not all cervical cancer started as HPV infection.
So you are arguing that treating CIN2 surgically prevents cervical cancer, but preventing CIN2 occurring in the first place with a vaccine does not? That makes no sense at all. I could paraphrase what you wrote above to, "You don’t know why some small number of cases progress so you can’t assume those cases would have been treatment preventable" which would be equally nonsensical. As I have stated before, if there is some small group of women in whom vaccination is ineffective and in whom HPV is more likely to cause cancer, reducing the prevalence of HPV infection will reduce the chances of them becoming infected, and therefore their chances of getting cancer, through the herd efffect.
It's not a good surrogate for treatment, as you will end up treating too many women whose CIN would not have progressed to cancer, but if you prevent CIN you will prevent cancer.
It's not a "now proven ridiculous assumption" at all. It depends on what economic model you use, what time frame you look at, what assumptions you make and what you set as a threshold for cost effectiveness. This review of cost effectiveness found (ICER is incremental cost-effectiveness ratios and QALY is quality-adjusted life year):
If Gardasil costs less than $1,000 per QALY my "now proven ridiculous assumption" is definitely true, since even $2,000 per QALY would make Gardasil extraordinarily good value for money. If it costs more than $12 million per QALY, not so much. As I wrote before it's arguable. In every area of this arena there is a great deal of uncertainty, and very little is definitively proven at all.
You have made that argument and I, and apparently most of the world's public health authorities, disagree with you.
It isn't exactly difficult to find. Here's some data (PDF) that shows better than 80% average uptake of 3 doses of vaccine in 12-13 year-old girls in 2008/9. More recent data is similar.
Most younger girls are vaccinated in schools, so delivery is very effective. From the link above:
Uptake of cervical screening remains high with about 80% of women being screened every 3 or 5 years as appropriate - I won't link to the data as it will put this into moderation, but I'm sure you can find it easily enough. I agree with you about some poor decisions made by the NHS, but I don't think that introducing HPV vaccines is one of them.
I'm excited about HPV vaccines: I think the technology is extraordinary, the efficacy impressive and the safety record remarkable. For the first time ever we have a vaccine that looks very likely indeed to prevent a common cancer. Of course there will be many obstacles to overcome in reducing and ultimately eradicating HPV, but I find your (and others') negative attitude about such a powerful tool to pursue this goal incomprehensible.
My best case scenario is global eradication of HPV, cervical and other related cancers. That's "narrowly positive"?
Since I have spent several decades working for the NHS, and continually trying to do more with ever dwindling annual budgets, as well as paying taxes that pay for it, I am very well aware of how it works. You could argue that value for money is even more important here, as it is public money that will be saved on the treatment of CIN, AIS, cervical and other cancers if the vaccine program is successful. In the US it is mostly individuals and insurance companies who will have to foot the bill, or not.
You are the one complaining! I'm quite happy with the introduction of Gardasil and the pharmacoeconomic models that decision has been based on. It is you who seems to think that it is better for a woman to be treated for CIN or AIS than it is to prevent her from getting it in the first place.
There we agree, though that may change when HPV becomes less common.
You would seriously advise the parent of a 12-year-old girl (or boy) against her (or him) having Gardasil? You really think that preventing invasive cancer through surgery is just as good as never getting CIN at all? That's incomprehensible to me, unless you buy into the sort if misinformation SaneVax propagates, and you seem too well informed to swallow that nonsense.
You can play with semantics all you like, Prof. Cuzick still clearly agrees with me, not you.
CIN and AIS count as morbidity, even if successfully treated. Even the most improved screening does not prevent them. Which is better, the vaccine or cervical ablation/excision? If I were a woman I know which I would prefer, even at $120 a shot..
If vaccination uptake in 12-year-olds is high enough, we will have a generation in which HPV-16 and 18 will be rare. If polyvalent vaccines are introduced, other strains will also become rare. If antiviral drugs targeting HPV are successful they will become even rarer, and eradication will become a real possibility. As has been noted, because of its mode of transmission you don't really need quarantine for HPV, just some way of successfully treating it and/or preventing those infected from infecting others. There are lots of ifs there I grant you, but I still maintain it is a good bet that this gamble will pay off.
You're nitpicking, since he stated, "That's the long-term future: vaccination and no screening" so he clearly doesn't mean "never" by "the foreseeable future".
Don't forget those wishful thinking public health authorities in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Iceland, Israel, Ireland, Italy, Kenya, Latvia, Luxembourg, Macedonia, Mexico, Netherlands, New Zealand, Norway, Panama, Portugal, Romania, Slovenia, South Korea, Spain, Sweden, Switzerland, the United Kingdom and the United States ;-)
If you are in the US, consider it reciprocated.
Arguing that treatment is preferable to vaccine is heartless, and obviously comes from someone who has never had to experience a colposcopy, or the anguish of waiting years to be pronounced free of HPV displasia and its resulting risk of cervical cancer. The emotional cost is very different when it's your own body you're arguing about.
For the record, my son is getting the Gardasil jab when he turns eleven.
Dr Lee doesn’t want the work, he wants it to be done at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more.
Dr Lee doesn't want the work so much, he is trying to shut competitors out:
http://www.businesswire.com/news/home/20100920005586/en/S.A.N.E.-Vax-Si…
I particularly like the appeal to patriotism as the reason to shut out the competing laboratory : "NCI Pays a Foreign Laboratory for Similar Testing".
"at low cost in the local hospitals instead of leaving it to the big labs where they will charge you a lot more"
Apparently Milford's business model involves undercutting the large public hospitals.
While we're at it, one might note that Norma Erickson has flatly asserted that "the human papillomavirus does not cause cervical cancer."
You have no clue as to my medical history or that of my family. Arguing for universal experimental vaccination where the treatment holds little discernable benefit for the recipient, obviously comes from someone who has never had a child disabled by a vaccine. For the record, none of my boys will ever get any experimental vaccine.
Your density is showing, that slide talks about ROI measurements and includes a lot more than outcomes as Shay asserted. Why would I need a reference for the HPV screening recommendations, when K and I already discussed them at length?
Because the efficacy rates in real life are always lower than the rates observed during regulatory trials. Real life and large populations offer up a lot more complicated environments and individuals than controlled studies do. At the most basic level, regulatory studies for this type of pharmaceutical are designed to screen out anyone with any type of known health problem, and that is becoming less and less representative of the general population.
Not with the current vaccine it's not, which is the context from which you took the quote.
I would never recommend for anyone to participate in a medical experiment let alone a child. Until the outcomes are actually measured, it's still an experiment. I don't think there is enough data to confidently get a safety profile. It takes decades for problems with pharmaceuticals to be recognized and action taken to address them.
IMO, attempting to eliminate more and more pathogens through brute force strategies is bound for failure and will cause all sorts of unforeseen side effects. Cervical cancer is clearly caused by more than HPV, and those other factors are undoubtedly involved in other serious diseases. I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet, but there shouldn't be an expectation for everyone to accommodate or fund what amounts to a big experiment.
I agree and I believe your system is way more efficient, but the immense waste from several NHS debacles over the past few years is immensely disappointing. Our fundamental differences appear to be based on how we project the available data and how much faith we have in the system. The source of our bias' are obvious: You work in the system, whereas I work with it from the outside.
Oh, great, now we've gotten to both sexual and food ritual purity.
"Little discernable benefit?"... Yeah, we flat-out disagree.
"Experimental vaccine?" ...Yeah, we double-dog-disagree.
"I have no objection to people who want to protect themselves using HPV vaccination if they believe they need it because they live a high risk lifestyle or eat a high risk diet"... So, you think diet has something to do with cancer? Do tell us all about it, please.
Mr. Pink,
We are all participating in a medical experiment of sorts whether we like it or not. If Gardasil was not approved until its impact on invasive cervical cancer had been proven in RCTs the likely result would be that up to 30,000 women would die unnecessarily, and up to 4 million would require treatment for CIN or AIS that could have been prevented. Once an intervention like Gardasil is available, even opting out is an experiment, an experiment which in this case I think puts the child at far greater risk than opting in.
Most of the inflammatory diseases we suffer from are due to processes that are designed to protect us against pathogens. Once those pathogens are eliminated, by "brute force" or otherwise, we will inevitably see more diseases on the inflammatory end of the scale, such as cardiovascular diseases, autoimmune disorders, allergies and cancer. That doesn't mean that our brute force strategies cause the inflammatory problems, just that a century ago little Jimmy would have died of pneumonia but today he survives to get asthma and prostate cancer.
Now I'm bracing myself for Beauchamp or Pasteur's (bogus) deathbed recantation, "Terrain is everything!" I'm not sure I buy any of the kinds of ideas I think you are hinting at. "Eat, not too much, mostly plants" is about as far as I would go in that direction.
One thing I think we should have learned about vaccination is that it is an all or nothing venture. When rubella vaccination was introduced in Greece poor vaccine uptake meant that girls who contracted rubella tended to do so later than before vaccination, resulting in more of them getting it when pregnant and an increase in congenital rubella syndrome. That makes vaccines problematic when it comes to personal freedom, and I don't have any easy answers. When you consider being infected by a virus turns a person into a walking virus manufacture and distribution system, so I think it is reasonable to expect people to take measures to prevent this. How far we should go in coercing people into vaccination, I'm not sure.
I agree. I have personally felt extremely frustrated by problems in the NHS, such as the hospital I work for purchasing different incompatible computer systems in different departments, a half-assed internal market, and constantly being kept from doing useful work by being expected to attend pointless meetings. I once was asked to attend a meeting and realized when I got there that I hadn't the faintest idea what it was about, and spent half the meeting quietly trying to figure it out from what was being discussed (it turned out to be about developing a computerized staff record which was a total waste of my time). Large bureaucracies evolve organically over time into unwieldy and inefficient edifices that don't resemble anything anyone (except perhaps a committee) would design from scratch. The Peter Principle doesn't help matters - I have often seen a person good at their job get promoted into a management position that they were utterly incompetent at, where they stayed until they could swing early retirement. I could go on, but I won't.
I do both actually, as a healthcare worker and from time to time as a patient. A couple of times I have felt badly let down by the NHS, which was a very unpleasant experience since I support its principles passionately, and have worked for it for most of my life.
I meant to add that my statement, " up to 30,000 women would die unnecessarily, and up to 4 million would require treatment for CIN or AIS that could have been prevented" is based on an assumption that it would take 10 years to see if invasive cervical cancer is prevented by Gardasil, and refers to the US alone.
"I would never recommend for anyone to participate in a medical experiment let alone a child."
And if we all adopt this attitude, then there will never be any medical experiments at all.
[romantic story] Participating in a medical experiment was how I met the Frau Doktorin!
[/ romantic story]
[bladder pride story] Hey, participating in a medical experiment is how I set a record for largest urine sample the PET lab had ever encountered (seriously, this was around 1.3 liters). [/bladder pride story]
In an unrelated development, the fellow behind the absinthe FAQ caused the IRB to take a second look at the experiment (straight fenfluramine), so I was paid for my sessions despite not completing all five.
Did someone say bladder pride?
hdb - I was wondering when you'd link to that :-P
At least I didn't say rubber biscuit.*
* You don't want to know what was in the deleted footnote anyway.