Cynthia A. Janak
September 11, 2009
FDA - September 9, 2009: Vaccines and Related Biological Products Advisory Committee briefing information
An independent evaluation of the briefing documents
By Cynthia A. Janak

The first document I am going to reference is "Male indication for Gardasil" sponsored by Merck Research Laboratories.

The duration of this study is noted on page 6 of this document.

Sera were collected for immunogenicity at screening and at months 7, 24 and 36. Safety assessments were obtained at each visit and every 3 months after Month 6 by phone or email.

My focus is going to be on the safety section of this document which starts on page 11.

First, I am going to show you when these assessments were carried out.

Safety Assessments were performed at each vaccination visit and every 3 months post-dose 3.

All subjects were given a Vaccine Report Card (VRC) to record:

  • Oral temperatures out to 4 days

  • Injection-site adverse events (AE) out to 14 days

  • Systemic AE's out to 14 days

No routine laboratory tests were conducted within the context of the study.

Let us study these comments.

First you see that the study ran for 36 months. That in itself seems reasonable but what red flagged me here is that after the third immunization these people were contacted by phone or email. How can these individuals assess what could be signs of serious adverse events? They are not medical professionals and would not know what to look for. Therefore, the only real data available are the safety assessments that were performed at each vaccination visit. That leaves us with only 6 months of professionally evaluated data.

Next, we are going to look at the data that concerns the adverse events that were reported between the Gardasil group and the Alum placebo group. This starts at the bottom of page 11 of this document.

Adverse Events

The summary analysis of AE's was unremarkable. Similar percentages of subjects in Gardasil group compared to the placebo group experienced any AE during the study (69.2% vs. 64.2%, respectively), discontinued participation in the study due to an AE (0.3% vs. 0.7%, respectively), or reported a new medical condition (24.2% vs. 22.8%, respectively).

What I find laughable is the fact that the reviewer states, "The summary analysis of AE's was unremarkable." This reviewer does not see any concern over the fact that almost 70% of the participants of the Gardasil group had an adverse event of some type. I do not understand how 69.2% is unremarkable.

Let me use this analogy. If 69.2% of people who ate a certain brand of peanut butter got sick that peanut butter would be removed from the grocery store shelf immediately.

Let us go on to the section called "new medical condition." This reviewer sees no issue with the fact that almost 25% of the participants in the Gardasil group acquired a "new medical condition" during this study. They also did not feel it important enough to list what those new medical conditions were. Interesting.

At the bottom of page 13 there is a report about deaths that have occurred during the trial. This is what they report.


A total of 13 deaths occurred during the study 3 in the Gardasil group and 10 in the placebo group. In the Gardasil group, the fatalities resulted from a car accident, a motorcycle accident, and a gunshot wound. None of the deaths were assessed by the Investigator as being related to treatment.

Clinical Reviewer Note: The subject narratives from each of the SAE's and deaths were reviewed. Given the available information, the reviewer agreed that it was reasonable to conclude that in each case, the event was not likely related to treatment.

What we have learned since the approval of Gardasil on June 2006 is that a young woman can have a seizure or fainting episode minutes or weeks after immunization. What I find interesting here is that they do not itemize how many deaths were attributed to the alum placebo group. My interest would be in how many car accidents and motorcycle accidents there were and how long after immunization they occurred. I think that transparency in this regard should not only be necessary but required.

My other concern is if these accidents resulted in bodily harm of other people besides the participants of this study. To me that could be a significant factor.

Now on to page 17 were they start the combined analysis of the safety in Protocols 016, 018 and the present study 020. I find this analysis sends up all kinds of red flags because of omission. I would like to see all the adverse events reported not just injection site pain. Because of this statement by the reviewer makes me wonder what are they trying to hide. How about some transparency here or are we not allowed to make up our own minds with accurate information.

The results of the AE analyses in the combined males dataset led to overall safety conclusions that were similar to those for 16-26 year old males alone, so they are not repeated here in detail.

One exception is that the overall rate of AE's was slightly higher in the younger population. To a large degree, this was driven by a higher rate of injection site AE's in younger males. For example, in the 016 dataset, injection site pain was reported by 357 (71.4%) of the 10-15 year old boys, whereas 1113 (57.2%) reported injection site pain in the 16-26 year old 020 dataset. However, compared directly with 10-15 year old girls enrolled in 016, the 10-16 year old boys had proportionally lower injection site reactions, e.g. injection site pain was reported by 398 (79.4%) of girls.

Here you see that they are trying to justify the high percentage rate of 71.4% by referencing the girls in the study. This is like comparing apples and oranges. Why is this comparison flawed? In their own words; "Based on literature that indicates that male and female immune responses differ, including differences in reactogenicity to vaccines (Cook),"

To finish the Merck report, once again they are going to have to do a post marketing study called Phase IV. They are required to do this because of "limited number of participants." What this tells us is that just like the Gardasil girls we will now have Gardasil boys added to the ranks of VAERS (Vaccine Adverse Event Reporting System).


Based on literature that indicates that male and female immune responses differ, including differences in reactogenicity to vaccines (Cook), CBER has requested that the sponsor submit a plan for Phase IV studies and pharmacovigilance plans. There are no specific safety signals identified at this time; however, given
the limited number of participants in safety trials, CBER believes that post-marketing surveillance and studies will be essential. The sponsor has agreed to submit preliminary protocols by Friday, July 31. Thus CBER will not be able to include our review of the sponsor's proposal for post-marketing surveillance in this briefing document. The sponsor and CBER will present the post-licensure surveillance plan at the VRBPAC meeting.

The next document that we are going to evaluate is the one presented by GlaxoSmithKline Biologicals for Cervarix. My focus with this document is going to be on the safety just like with the Merck document.

So far I have found some very interesting facts in this 66 page report.

Right away red flags are flying all over the place with this document starting towards the bottom of page 4.

Safety data from pivotal study HPV-008 were reviewed in depth by CBER clinical and statistical reviewers. The overall rate of AE's was somewhat higher in the Cervarix group compared with the Havrix group: 85.4% versus 74.6%, respectively. This was driven largely by higher rates of injection-site symptoms in the Cervarix versus Havrix groups.

I want you to note the number of participants in study HPV 008 were 9319 for Cervarix and 9325 for Havrix (which was the control group).

When I saw these percentages I went right to the safety results for study HPV-008.

I found this on page 27.

Solicited local adverse events in 7 days after vaccination (Safety Diary Card Subset): Pain was the most frequently reported solicited local symptom in both groups. Overall, 90.5% and 78.0% of subjects reported pain at the injection site in the HPV and HAV groups.

Redness at the injection site was reported by 43.8% and 27.6% of subjects in the HPV and HAV groups, respectively. Swelling at the injection site was reported by 42.0% and 19.8% of subjects, respectively.

In the HPV group, the incidence of redness and swelling slightly increased from dose to dose (i.e., from 22.0% and 25.4% at Dose 1 to 30.8% and 32.4% at Dose 3, for redness and swelling, respectively).

Solicited general adverse events in 7 days after vaccination (Safety Diary Card Subset): Overall, the incidence of solicited general symptoms within 7 days after vaccination was slightly higher in the HPV group compared to the HAV group.

  • Fatigue was reported by 57.6% and 53.6% of subjects in the HPV and HAV groups, respectively.

  • Myalgia was reported by 52.2% and 44.9% of subjects in the HPV and HAV groups, respectively. Grade 3 myalgia was reported following 1.8% and 0.6% of doses, respectively. (95% CIs did not overlap).

  • Headache was reported by 54.1% and 51.3% of subjects in the HPV and HAV groups, respectively.

Unsolicited adverse events in 30 days after vaccination (Safety Diary Card Subset): During the 30-day post-vaccination period, 42.5% and 43.6% of subjects reported at least one unsolicited symptom in the HPV and HAV groups, respectively.

Before I comment I have to add what I found at the bottom of page 28.

Medically significant conditions prompting emergency room visits or physician visits (Total Vaccinated Cohort): The percentages of subjects reporting at least one medically significant AE prompting emergency room visits or physician visits within the 30-day follow-up period post-vaccination were similar in the two groups (31.8% HPV and 32.4% HAV).

The Cervarix vaccine really packs a punch with 90.5% reporting pain at the injection site. WOW! We can look at this two ways. Either the participants were real whimpy or they experienced something that was noticeably more intense than the standard needle prick. I am having a hard time fathoming 90.5%.

I want to bring your attention to the differences between Cervarix and the control group Havrix. This is huge.

  • Injection site pain 90.5% compared to 78.0%

  • Redness 43.8% compared to 27.6%

  • Swelling 42.0% compared to 19.8%

Then you see that over 50% of the participants were suffering from Fatigue, Myalgia and Headaches 7 days after the vaccinations. Besides this you have over 30% of the participants had at least "one medically significant" adverse event that caused them to go to the emergency room or to their physician within 30 days.

My question here is how can 30% and 50% be acceptable in regards to the pain and suffering that the participants experienced? I am having a very hard time with this.

Let me use this analogy. Your local high school had the flu virus affect over 50% of the students. That high school would be immediately closed and a pandemic would be announced. The students affected, 50%, would have to be quarantined at home or in an approved facility to stop the spread of the virus. This is a medical emergency.

But when 50% of the participants of a study such as this one for HPV report fatigue, myalgia and headaches, the only concern is whether they missed school or work. What is wrong with this picture?

I want to comment on this next paragraph but there are no words to express the disgust that I feel when I read this.

Adverse Events Leading to Premature Discontinuation of Study Vaccine and/or Study (total Vaccinated Cohort): In total, eleven subjects in the HPV group (spontaneous abortion 5 months after dose 1; skin infection day 1 day after dose 2; and 9 deaths) and nine subjects in the HAV group (road traffic accident 8 months after dose 3 and 8 deaths) withdrew due to an SAE, with none of these events reported as possibly related to vaccination according to the investigator. Five subjects in the HPV group (dry skin 9 days postdose 1; headache on days of dose 1 possibly related per investigator; acne 18 days after dose 1; nausaea 17 days after dose 1; ovarian cyst 1 month after dose 1) and three subjects in the HAV group (hypoaethesia 12 days after dose 1; facial pain day of dose 1 possibly related per investigator; gastroenteritis before vaccine) withdrew due to a non-serious adverse events.

I am going to stop here because I do not want to continue with this document. I did read the whole 66 page document and it made me ill with worry for the young people of this country. We will not only have an increased number of them becoming chronically ill from Gardasil but now we will see a marked increase of adverse events reported to VAERS by adding Cervarix to the mix.

My further concern is that because of the approval by the FDA panel of the extended use of Gardasil to boys and the addition of Cervarix our system is badly broken. Reason being, that peanut butter products were removed from consumption when some people got sick but when over 15,000 reports have already come into VAERS (Vaccine Adverse Event Reporting System) in regards to Gardasil, it gets passed over.

What will the FDA panel do when it comes time for the H1N1 immunizations? Will they approve those without proper safety studies or will they just use the same judgment that we see here?

In my opinion, what the FDA panel did today was legitimized "weapons of mass destruction, including chemical and biological weapons." This is even more horrendous than what Saddam Hussein did because this is legal and the companies are exempt from responsibility for their actions.

© Cynthia A. Janak


The views expressed by RenewAmerica columnists are their own and do not necessarily reflect the position of RenewAmerica or its affiliates.
(See RenewAmerica's publishing standards.)

Click to enlarge

Cynthia A. Janak

Cynthia Janak is a freelance journalist, mother of three, foster mother of one, grandmother of five, business owner, Chamber of Commerce member... (more)


Receive future articles by Cynthia A. Janak: Click here

More by this author