Thursday, May 10, 2007

Gardasil: Less Hype May Help

As reported in today's Wall Street Journal:
"An editorial published in the New England Journal of Medicine raises questions about the overall effectiveness of Merck & Co.'s cervical-cancer vaccine, Gardasil, and advises policymakers, doctors and parents to adopt "a cautious approach" toward vaccination. (See "Medical Journal Questions Gardasil Efficacy").
At issue is how effective Gardasil actually is. As always, it comes down to analysis of the data and which expert you believe.

Whereas Merck claims 98% efficacy against 2 types of HPV virus that cause cervical cancer, this drops to 17% when looking at data from another group and the authors of the NEJM editorial called the vaccine's overall efficacy against precancerous lesions of the cervix "modest."

This is not the message that Merck delivers through its DTC advertising, which leads viewers to believe that Gardasil is a cure for cervical cancer.

When Gardasil first came to market,like many other people, I was excited to see a pharmaceutical product that could actually save lives in a dramatic fashion by preventing disease, not just treating the symptoms.

Now it seems that I, and millions of others (including certain state governors and legislators) may have been duped or misled by the hype promulgated by the ads.

But, still, my main complaint isn't against the advertising -- after all, it's advertising job to hype the product (see "Is Pharmaceutical Marketing BS?").

The main issue I have of Merck's Gardasil campaign has to do with its lobbying efforts to pass mandatory vaccination laws in every state (see "Gardasil: To Be Mandatory or Not To Be Mandatory -- That is the Question").

It now appears that Merck was forced to unethically promote mandatory vaccination to milk the potential Gardasil profits before scientific evidence questioning the vaccine's efficacy hit the press and before more efficacious competing products are approved (see "Glaxo: HPV Vaccine Data Bests Merck").

I guess marketing and advertising alone cannot guarantee a drug's success these days. Merck's questionable lobbying practices, however, have also put its DTC advertising under the public microscope.

Perhaps it's time for Merck to change the Gardasil ads to be a little closer to the recent type of ad that Pfizer ran for Celebrex -- at least more transparent about the effectiveness of Gardasil and answering some of the questions that are now being raised, including:
  • How is Gradasil efficacy defined? (ie, more transparency about what the 98% efficacy number means)
  • How long does the protection conferred by the vaccine last?
  • Could the current recommendation of three vaccinations be lowered?
In other words, a little less BS in DTC advertising, please!

One other thing that may help Merck's cause: promote what it's doing to help free vaccination programs supported by some states. Free is better than mandatory, as long as education (see above) is part of the program.

10 comments:

  1. Mediavilla Jr10:10 AM

    When Gardasil first came to market,like many other people, I was excited to see a pharmaceutical product that could actually save lives in a dramatic fashion by preventing disease, not just treating the symptoms.

    ... that is why they call them "vaccines" fella...

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  2. Thanks for your comment.

    Well, yes, but vaccines are "cures" only in the sense that they help our defenses prevent the disease in the first place.

    Drugs, on the other hand, usually replace something that is missing or affect how a system operates.

    Why not dvelop drugs that "fix" the problem in the first place? If I produce too much cholesterol, what I need is a drug regimen (or vaccine if your wnat to call it that) that corrects the pathway that produces cholesterol -- when it's fixed, I no longer have to take the drug.

    yeah, I know... not profitable. But that's what they say about vaccines also.

    Just thinking out loud.

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  3. Anonymous1:48 PM

    Don't you think you're being a tad disingenuous here? This isn't about slicing and dicing data or deciding which expert to believe. The numbers are right there in black and white:

    The 98% efficacy is in the population not infected at baseline (remember THIS IS A VACCINE) and in whom the lesions were related to HPV-16 or HPV-18.

    It's not exactly shocking that efficacy is going to drop when you expand to a population infected at baseline or have lesions due to other strains given the quadrivalent nature of the vaccine. To fault the vaccine for not working on strains not included in the vaccine is absurd. (Hey, my MMR vaccine didn't prevent my chicken pox!) At least Merck reported the effects for all women and all strains.

    As mediavilla alluded to above, the point of the vaccine is to prevent, and in this case, the vaccine certainly lived up to that in terms of preventing disease in unexposed patients for the specific strains the vaccine is designed for. Hence, the recommendation that vaccination occur early (i.e., before infection).

    However, the efficacy against types 16 or 18 in women already infected with 16 or 18 was still pretty good at 44%.

    Also, Merck's lobbying and the whole TX thing notwithstanding, as noted in the perspective by Charo, the CDC ACIP unanimously recommended vaccination for girls 11-12. Did Merck buy off this committee to get their vaccine mandated? Doubtful, especially in this climate.

    As for claims of transparency, I haven't paid much attention to the details of the commercials or ads so I don't know if they specify the population criteria for the 98%. I think it would be great for Merck to be specific and say that in uninfected women, efficacy against the particular strains was 98%, and in the 44% women already infected with 16 or 18. What does the new Celebrex ad say?

    Look, it's easy to bash Pharma, and there's certainly plenty of fodder in general, but this doesn't strike me as an example where Merck was really out to hoodwink everyone. Save the bashing for instances of real wrongdoing.

    ReplyDelete
  4. Thanks for your comments.

    I think I was quoting experts about the numbers, but look, let's put the numbers aside. It's not going to win any arguments with consumers.

    I think my main point is that we agree that Merck should educate us about the numbers so that our expectations are not set too high.

    If you haven't seen the Gardasil commercials, then you are not qualified to judge how high you are after viewing it. It's like "Wow! A cure for cervical cancer!" I've even heard many smarter people than I call it a "no brainer!"

    Marketing, as always, sets the bar much higher than reality. For Pepsi, it's all well and good. Who cares if in reality Pepsi does or does not quench my thirst better than placebgo (ie, water) by independent taste tests. BS there is harmless, but BS in pharma marketing can be lethal as Purdue Pharma recently admitted.

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  5. Anonymous6:38 PM

    Can you be more specific about what Merck actually says in the Gardasil commercials? I vaguely remember something like effective against the strains that are most associated with cervical cancer. If I'm remembering correctly, I don't see a problem with that if they give the range for both infected and uninfected (i.e., 44 to 98%). If they say "up to 98%," they're pushing the line a bit, but still correct. If there's nothing like that, then I suppose there's a problem.

    Also, I'm not familiar with the Celebrex ad -- what are they doing to separate themselves in terms of transparency and expectations?

    It's definitely not a cure, and it may not be a total no-brainer, but let's add this up: 70% of cervical cancers are caused by strains 16 and 18. Gardasil was 98% effective in preventing lesions caused by these strains in uninfected women -- that's pretty darn close to a no-brainer for me in terms of vaccinating my 11-12 year old daughter! Seriously, tell me how that's NOT a no-brainer in that specific population. (Yes, long-term safety data are needed, but in this study alone you have 3 year follow-up on 6000 patients, not to mention the longer term follow-up from earlier studies.) And the 44% reduction in infected women is not a trivial reduction, either.

    ReplyDelete
  6. The problem is that the GARDASIL has not been proven safe or effective for its targeted population.

    There is no clinical evidence whatsoever that GARDASIL reduces the overall rates of type 3 dysplasias or adenocarcinomas among the general population of women aged 16 to 26.

    Even if you segregate out the women who hadn't been previously exposed to either HPV 16 or 18, we are talking about just a 17% decrease in all high grade dysplasias (266 out of 6080 vs. 219 out of 6087) -- many of which would spontaneously regress without treatment. So we would have vaccinate 129 women (at about $500 for the three shot regimen) to avoid a single dysplasia. That's about $60,000 per dysplasia prevented. And we currently have only 3 years of follow up to go on in terms of both GARDASIL's safety and efficacy, no data concerning its efficacy among 9 to 12 year olds and only 18 months of follow up on less than 600 total preteen girls in terms of safety data concerning GARDASIL within its targeted population.

    ReplyDelete
  7. I appreciate your analysis and the numbers you cite. The Gardasil ad ad is factual. I have no beef with that.

    The impression, however, is that any girl "can be one less" victim of cervical cancer, when, in fact only girls not already pre-infected with the virus. "can be" is factual but it leaves enough open for people to fill in the gaps with high expectations for the product -- higher than waranted by the facts.

    Advertising is best when low on facts and high on emotional impact. While you and I may be very fact/number oriented, the typical viewer reacts emotionaly to ads. This may be a topic for another discussion.

    If you look at my post about the new Celebrex ad and the little survey I did, many people did not remeber the facts correctly, but definitely came away with the impression that I am sure the ad wanted to convey above all else: ie, that Rx naproxen and ibuprofen DEFINITELY have CV risks, just like Celebrex.

    The ad was factual, however, and said "available evidence suggests." The impression far exceeds the facts. See http://pharmamkting.blogspot.com/2007/04/celebrex-ad-lets-dive-deeper.html

    ReplyDelete
  8. mhatrw1:46 PM

    To summarize this published medical journal article: http://content.nejm.org/cgi/content/full/356/19/1991

    1. In the FUTURE I trial, GARDASIL demonstrated no clinical efficacy among the general subject population for overall reduction in the rates of grade 2 and grade 3 cervical intraepithelial neoplasia and adenocarcinoma -- the only recognized precursors to cervical cancer.

    2. In the larger FUTURE II trial, GARDASIL demonstrated no clinical efficacy among the general subject population for overall reduction in the rates of grade 3 cervical intraepithelial neoplasia and adenocarcinoma -- the strongest (and many would argue only valid) precursors to cervical cancer.

    3. Extrapolating from GARDASIL's very limited clinical "success" (in the FUTURE II study only) against grade 2 cervical dysplasias (40% of which regress spontaneously), 129 women would be have to be vaccinated (at a cost of about $60,000) to prevent a single grade 2 cervical dysplasia.

    4. GARDASIL's protection against cancer associated HPV strains 16 and 18 appears to cause a disproportionate increase in of pre-cancerous dysplasias associated with other HPV strains associated with cervical cancer "raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18."

    5. Even if you segregate out the women who hadn't been previously exposed to either HPV 16 or 18, we are talking about just a 17% decrease in all high grade dysplasias (266 out of 6080 vs. 219 out of 6087) -- many of which would spontaneously regress without treatment. So we would have vaccinate 129 women (at about $500 for the three shot regimen) to avoid a single, eminently treatable dysplasia. That's about $60,000 per dysplasia prevented.

    This is all directly from the article: http://content.nejm.org/cgi/content/full/356/19/1991

    I myself would add that we currently have only 3 years of follow up to go on in terms of both GARDASIL's safety and efficacy among the 16 to 26 year female population, no data concerning its efficacy among 9 to 12 year old girls and only 18 months of follow up on less than 600 total preteen girls in terms of safety data about GARDASIL within its targeted population.

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  9. Gardasil Vaccine: So far 3 deaths and 1,637 Adverse Reaction Reports to FDA

    Opponents to Gardasil say things like:

    "This vaccine should not be mandated for 11-year-old girls.... It's not been tested in little girls for efficacy. At 11, these girls don't get cervical cancer—they won't know for 25 years if they will get cervical cancer. Giving it to 11-year-olds is a great big public health experiment." Dr. Diane Harper, lead researcher, HPV vaccine development

    Objections Listed:

    1. The vaccine is costly. ($360 for series of three shots)

    2. Lack of testing in 9–13 yr olds.

    3. Lack of evidence of duration of protection (estimated duration of 5 years).

    4. Efficacy has not been demonstrated and is unknown. In fact, there's already been talk of the need for booster shots.

    5. Benefit of Gardasil to 9–13 year olds is dubious. Cervical Cancer affects 45-55 year olds, 40 years later.

    6. Questionable Safety when used in conjunction with other vaccines (Hep B and Meningitis ).

    7. High rate of vaccine injury: the US Vaccine Adverse Event Reporting System is showing considerable serious injury from this vaccine, especially neurological and immune dysfunction. Included are reports of collapse, paralysis, Guillain-Barre syndrome, dizziness, vomiting, rash, syncope, seizures and headache.

    8. Gardasil may actually cause an increase in cervical cancer due to a false feeling of security in the females who receive it and decline PAP smears.

    9. Gardasil does not guarantee safety from HPV: Regular Pap screening tests with their incumbent costs will still be needed.

    10. The incidence of cervical cancer is low, and it would cost $360 million to pay for vaccine to prevent only 1–2 deaths.

    11. HPV is usually benign: The virus clears up on its own within 8–12 months.

    12. Pap screening already works and has been very effective in reducing cervical cancer rates.

    13. Gardasil gives the wrong message to kids about sex and may encourage promiscuity.

    For more information see my newsletter Guard Your Daughter from Gardasil

    Jeffrey Dach MD

    ReplyDelete
  10. Jeffrey,

    Thanks for your comments. I will have to read your newsletter.

    John

    ReplyDelete

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