Wednesday, August 29, 2007

HPV vaccine program

A pretty decent article in Macleans on the HPV vaccine. Gardasil is a human papilloma virus vaccine that is scheduled to be part of a massive vaccination program of young girls starting this September. The vaccine targets strains 16 & 18 which account for causing 70 percent of cervical cancer cases. It does a poor job of talking about the percentage of adverse events associated with inoculation (probably exceedingly low), however, it still makes one wonder about whether this is really the health priority that we are being led to believe. It also explains a bit of the politics that surround the approval of this vaccination program. I also hope that the makers of the vaccine, Merck & Co., have learned their lesson with Vioxx. On the scale of a vaccination program even rare problems could have serious financial consequences for the pharma giant.


17 comments:

Bayman said...

Nice article. It really highlights how unnecessary and probably useless the Gardasil vaccine is.

Regarding Rob's comments, I think it's clear that Merck have learned their lesson with Vioxx; this time, they've managed to convince our governments to cough up a down-payment of hundreds of millions of dollars for a massive public vaccination program based around an unproven product, before the shit can hit the fan. All this without investing any cash in serious clinical trials. Even if this vaccine ends up killing every 9-year kid our schools give it to, I'd say Merck will still come out making a profit. It's money in the bank.

What concerns me more than any losses Merck may or may not accrue is the millions of taxpayer dollars our government has agreed to fork over at this premature stage. You can kiss that cash goodbye forever, and that's cash that could've been spent on health care measures that we know will actually work.

This is probably the biggest pharma con-job in the history of medicine.

Pretty much any scientist who doesn't work for Merck is saying we are jumping the gun here, and even the journalists seem to get it, but our politicians are totally unconcerned. What's up with that? It's pretty obvious that Harper only listens to his own ethically bankrupt compulsions, but where are the opposition parties on this?

Even if adverse effects are "exceedingly rare", the risk of initiating a mass-vaccination program with a vaccine whose long term effects (postitive or negative) have never been investigated are absolutely unjustified.

Alfred Russel Wallace said...

Whoa... I thought the article was a bit sensational really. With the current aversion to vaccination this is the sort of stuff that reduces the uptake of all vaccines. Hope you guys don't get mumps from your neighbours' kids and have your nuts swell up and fall off....

As for clinical trials I believe the phase III involves 25,000 people. And to state that a vaccine that kills every recepient could still be profitable is just idiotic. Only cigarettes can do that...

Every year women die from cervical cancer caused by these viruses. In Canada. More women than have been killed by vaccines. Yes, behaviour modification could prevent virtually every case but should we stop spending money on an HIV vaccine as well?? And to say that getting rid of these two important strains may open the door for others could be said of every vaccine ever... it's a strawman.

Anonymous Coward said...

I agree ARW, I listened to a podcast with a panel of scientists and epidemiologist who helped to test this vaccine and they made quite a compelling argument. The chance of adverse effects is negligible and theopportunity to all but eradicate this particular cancer is a testament to modern science. If anything it's a shame that boys aren't vaccinated too, since they do transmit the virus. However ethicist felt that any risk however small was not acceptable since boys do not directly benefit from the vaccine. Anyways I would take one for the team. Better over-vaccination than having mumps outbreaks and the first death in decades in the UK because of the fear mongering media.

rob said...

I agree that the article was sensational, it's in Macleans, but I still think the argument that this vaccine program may be a bit rushed is valid. Also the fact that another vaccine that works against more strains is on the horizon is interesting. I was wondering also about the idea in the article that this vaccine would merely shift the dominant strains from the ones that are vaccinated against to resistant ones. I agree with the AC that if this vaccine is supposed to eradicate HPV then everyone should be vaccinated. But comparing the mumps vaccine to the HPV vaccine is not rational. Each vaccine must be evaluated independantly. Just because vaccination programs in the past have been successful it doesn't mean that they all will be.

Alfred Russel Wallace said...

Not comparing this one to the mumps vaccine... just saying that when your average Mom reads that a vaccine might be dangerous she just might avoid ALL vaccines. It's curious how vaccines get accused of safety issues when nearly any other mdedication you can think probably has more adverse events per dose (pretty hard to OD on Gardasil but try aspririn, Tylenol (can never spell acetominofen), iburprofen, Viagra etc... not at the same time though)

Bayman said...

ARW,

I agree that the safety of this vaccine is probably not the concern here, and that it can be damaging to public health when misplaced fears of useful vaccines are propagated amongst the public. Modern vaccinology is indeed a well established science; we are certainly quite capable of producing anti-viral vaccine formulations that, as you point out, are probably as safe as any drug out there.

It was not my intention to suggest that people will realistically be harmed or killed by this vaccine, but rather my concern is that our governments have committed large sums of health care dollars to a new mass vaccination program without allowing for any public discussion of the issue.

I guess my main reason for wanting to provoke discussion about this vaccine stems back to the way information has been conveyed to the public through the media. This CTV news story of typical of many I saw on TV and read in newspapers leading up to the time Gardasil was approved:

“Cervical cancer vaccine hailed as breakthrough –-

Researchers and the medical community alike are excited by a new cervical cancer vaccine. It's been found to be 100 per cent effective in clinical trials -- the first vaccine ever to prevent a cancer.”


A powerful message – we have the cure for cervical cancer – but misleading in two ways. First, this is obviously not a “cancer vaccine”, as the report states, but a vaccine against certain strains of a virus that sometimes cause cervical cancer. Second, with regards to the claim of preventing cancer, this has never been even studied. The reality is best stated by Merck scientists Eliav Barr and Gretchen Tamms in a recent review they published on Gardasil:

“phase III trials using a cervical cancer end point are not feasible, because the time from acquisition of infection to the development of cancer often exceeds 20 years, and the standard of care is to screen for and excise CIN 2 and 3 or AIS lesions prior to invasion. Instead, trials to evaluate the impact of HPV vaccines on cervical cancer risk must use surrogate markers”.

At best, Merck did not effectively communicate the limitations of their studies to the media. At worst, they used the media to intentionally misinform the public. The truth was packaged one way for the public and government policy-makers, but another way for the scientific community. Recent reports such as the Maclean's article cited above have thankfully pointed out many of the errors in the way the story was originally spun to the public, however they also may have gone too far in the opposite direction (ie exaggerating the prevalence of side effects, and suggesting that the soon-to-be released Cervavix is better than Gardasil because it's quadrivalent rather than bivalent - in reality Gardasil is also quadrivalent).

At any rate, I too hope that this vaccine will be effective, and you make a good point that since it is likely to be completely safe, we might as well be optimistic and give it a “shot”. I guess time will tell. Indeed early clinical reports do give reason for optimism. However, I find it pretty concerning that pharmaceutical companies don't seem to mind using disinformation to promote general ignorance of the biology related to public health issues and to sway government policy decisions in their favor. Maybe proper education and open discussion of medical issues are equally (if not more) important to human health as the administration of drugs and vaccines?

It's an interesting discussion though, and hopefully motivates people to think past the sensational headlines.

Bayman said...

Just to balance things out, here's an example of a pretty reasonable TV ad for Gardasil in terms of getting the biology straight. I assume this one aired in the US. I was couldn't find the example I was looking for online, but the Canadian TV ad I've seen is pretty wishy-washy. Again this might have to do with differences in drug advertising legislation between the US and Canada, as we've discussed in the past.

Dr. Edge said...

As a physician, it is very frustrating dealing with patients who are convinced various vaccines are harmful based on media sensationalism of limited and poor quality evidence. The best example which continues to come up repeatedly in my practice despite being disproved is that the MMR (measles, mumps, rubella) vaccine causes autism. People continue to believe this even though the physician who published this research is at risk of losing his license for behaving "unethically and dishonestly in conducting their research. The doctor was doing paid research for a group of parents of autistic children who were trying to mount a class action suit against the makers of the MMR vaccine. Later it was revealed {the doctor] had taken out a patent on a new vaccine while publicly challenging the safety of the existing one". There's a good summary of this issue at http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070716/vaccine_070716/20070716?hub=Health
With respect to the HPV vaccine, as with any new vaccine it is impossible to guarantee with certainty that it is risk free, but rigorous testing has shown it to be quite safe. Of course it is not perfect because there are so many strains of HPV. Women will have to continue to have pap tests but likely less frequently, especially with the advent of HPV serology testing. However, there are more cases or cervical cancer and genital warts than there ever was of hepatitis B and kids are now being vaccinated against that. This past year people who wanted the HPV vaccine have had to pay hundreds of dollars out of their pocket. Considering the costs of screening for and treating cervical CA as well as the morbidity and mortality associated with this disease (not to mention the grossness of genital warts), I think it's very worthwhile for the government to offer this vaccine.
As for the drug company, of course it's a big money grab...making money off drugs is what they do. With Vioxx, it still irks me that it was pulled of the market because it is a good drug that could still be used safely in appropriate situations and patients. It's risk profile is really not that much worse that other similar drugs that have been used for years.
One more thing, I thought the advertising campaign for guardisil was actually quite good because it encouraged females to inquire about women's health issues (HPV) and understand why they were getting yearly pap tests. I didn't find it wishy-washy and it didn't push the vaccine too hard but I certainly spoke to alot of women about HPV because of it.

Bayman said...

Dr. E,
Great to hear a clinician's perspective on the issue, and a lot of great points.

I think your point about the need for women to continue to be tested for cervical cancer underlines why it's especially important for media reports and drug ads to convey the potential limitations as well as benefits of this particular vaccine. As you point out, it's a great opportunity to educate the public on HPV and cervical cancer in general.

kamel said...

There are a lot of different issues being discussed here. I think we're mostly in agreement that the media is exaggerating the dangers of the vaccine. A scan of the literature will tell you that, and it will also tell you that it's highly effective at preventing cervical lesions associated with cancer. That the vaccine is full of potential can't really be argued.

I won't go too much into drug marketing since it's been discussed at length in this post and elsewhere (plus I haven't seen the Gardasil ads, but I assume they follow the typical Canadian script of "Gardasil, ask your doctor" without mentioning HPV - or vice versa). I can certainly understand Dr. Edge's frustration with patients who read a negative report and are scared off vaccines in general. But I would think it works the other way as well - a patient sees a Gardasil ad and gets it in their head that that's the solution for them, regardless of a doctor's advice. That's why I tend to think medical decisions should be made between patient and doctor and not patient and corporate interest (i.e. advertising). Drug marketing in Canada needs some sort of reform.

The issue of cost-effectiveness was raised. As far as I can tell, there's only one study on the cost-effectiveness of HPV vs. traditional screening/treatment and it was done by a Merck employee (and is riddled with numerous other conflicts of interest). Even then, the authors find it "may" be more cost-effective, but then hedge their bets with disclaimers about changes to screening, etc. (For those interested, the study is published here). Of course economics shouldn't be the primary concern when we're talking about disease prevention.

So all that rambling brings me to the main point, and I think the issue that Bayman was getting at originally (though I don't want to put words in his mouth), and that's the politics of the situation. The Globe and Mail had a good article about it a couple of weeks ago. A subscription is required, but the gist of it is this: The government vaccination program was fast-tracked without going through any of the usual debates/discussions/consultations with public health officials that are the norm. Even the logistical planning wasn't done, and what little discussion that was done before announcing government funding was apparantly done in secret.

The announcement wasn't made by a health official, it was made by the finance minister in a budget speech and blindsided a lot of people.

"Aside from the polio vaccine in the fifties, it was the first time that the federal government made a direct medical decision," said Noni MacDonald, an infectious disease specialist and professor of pediatrics at Dalhousie University in Halifax. "This has caused a lot of us in public health and medical circles to flinch ... Why are politicians making medical decisions? This is not how health-care delivery should be decided."

I could quote it at length, but if you can get your hands on the article (online access is available through the UOttawa library website), it's an interesting read. The bottom line is that Gardasil may be a Godsend, but it still should have gone through the checks and balances that any other new drug looking for funding has to go through. Instead it reeks of backroom deals and politicking - is it a coincidence that we have a provincial election this October?

Anonymous Coward said...

Yeah that's a strange way of making health decisions. I've actually been talking a lot to a cervical cancer specialist here in Japan. He shared some of his data with me, and showed me a surprising increase in new cases of cervical cytologic abnormalities that cannot be explained by increased screening. It seems the country could also be ripe for a vaccine program. Education is also important, if I got a penny for every person i heard saying that the vaccine is a cure, or that it protects for ovarian cancer, i would probably have enough to buy a bazooka joe, or something...

Bayman said...

(for the AC that's a lot of money)

kamel said...

Just to further comment on the HPV vaccine, there was an article in Tuesday's Globe and Mail claiming that one third of Canadian women belive that the new vaccines prevent ovarian cancer. (Just so I'm not just demonizing HPV vaccines, one quarter believed the same thing about Pap smears) Our institute's own Dr. Vanderhyden weighed in on the issue. From the article:

"It is critical that young women know that HV vaccine and Pap tests for cervical cancers are not catch-alls for diseases below the waist," [Dr. Vanderhyden] said.
Dr. Vanderhyden said her worry is that young women - many of whom will start receiving the HPV vaccine in school this fall - will grow up believing there is no need for gynecological exams.


Which of course isn't to say that's a basis for not having a vaccination program (we've already covered that area above), but it certainly demonstrates that educational programs should be happening simultaneously (and perhaps also that the Gardasil ads aren't as clear as they could be).

Bayman said...

So 1/3 of Canadian women basically don't know the difference between ovarian cancer and cervical cancer. That's kind of scary, but when I think about it, it's consistent with the general public level of understanding of most types of cancer. Whenever I hear of a family member with cancer of course my first question is "what kind?", and it's usually pretty rare that anyone knows. The most specific people will get is an organ - ie "brain cancer", which to a cancer researcher doesn't tell you much.

Maybe one reason for people's lack of ability to distinguish between cancer types is that in the past it has generally been the case that treatment options are the same - surgery, radiation and chemo - so people can get by thinking of all cancers as pretty much the same disease (although prognosis depends greatly on the specific type of cancer). However newer treatments are much more specific (ie Gardasil for HPV-associated cervical cancer, Gleevec for Chronic Myelogenous Leukemia) thus the need arises for a much more sophisticated public understanding of cancer as many different diseases.

I guess another potential issue is the information patients and families receive from their oncologists - I once read a disturbing study that showed patients were often given shockingly little information about their disease and prognosis upon diagnosis, particularly when their chance of favorable outcome was low.

Anyway whatever the reason, clearly public health education is lagging way behind technology. Not only is this counterproductive (ie producing drugs that people can't use properly) it also becomes really dangerous to society (ie vulnerability to manipulation through drug marketing, inadvertent misuse of drugs, or a false sense of protection from disease).

Perhaps this discrepancy shouldn't surprise us too much given that our system disproportionately rewards scientists for producing economically profitable technology rather than producing and disseminating economically worthless (but highly "humanity-valuable") knowledge.

These types of stats just emphasize that public education and technology development should be of equal priority to scientists, and right now, here in Canada, they are not.

Anonymous said...

Gardasil also protects against HPV strains 6 & 11

hydroxycut online said...

This program is very good, I think it has a pretty good logistics to begin with, the only thing is that we must analyze it to see if it is performed as stated in this blog

Anonymous said...

Most vaccines are live or killed virus. Cheap, easy to produce. The HPV vaccine is neither, it is a virus-like particle. It has the shell of a virus, but no genetic matter inside. Sounds pretty safe to me.