A. Janak: New Gardasil findings about clinical trials

[Guest guest]

A. Janak

<http://www.renewamerica.us/columns/janak/081208>New

Gardasil findings about clinical trials

A. Janak

December 8, 2008

<http://www.renewamerica.us/columns/janak/081208>http://www.renewamerica.us/colu\

mns/janak/081208

In my article Gardasil Clinical Trials ­ Placebo

that I wrote July 23, 2008 I showed you Table 7.

In that table it referenced Study 018 and that this study had a saline placebo.

Being the truthful person I am, I am going to

admit that this study, in fact, did not have a

saline placebo. I have finally had the chance to

sit down and read the whole 464 page report to

the FDA

(<http://www.fda.gov/cber/review/hpvmer060806r.pdf>http://www.fda.gov/cber/revie\

w/hpvmer060806r.pdf).

I have found starting on page 300, 8.1.6: Trial

#6, Protocol 018 Objectives, Design: bullet point

three that the saline placebo stated in Table 7

is false. In fact it was a non-aluminum containing placebo.

Design:

• Randomized, double-blind, placebo controlled,

multicenter study in 9-15 year old subjects.

• Enrollment was stratified by age and gender.

Subjects were to be enrolled into 2 age strata (9

to 12 years of age and 13 to 15 years of age) in approximately a 2:1 ratio.

• The ratio of enrolled boys to girls was to be

approximately 1:1. Approximately 1650 subjects

were to be randomized in a 2:1 ratio to receive

either quadrivalent HPV (Types 6, 11, 16, 18) L1

VLP vaccine or nonaluminum-containing placebo.

Randomization was stratified by study center only.

When I read this it brought back the memory of

the conversation that I had in September with one

of the lead scientists in the Brazilian study. I

asked this person why they did not use a saline

placebo in the studies. Their answer to me was,

" Why should we use a saline placebo? The only

side-effect from a saline placebo would be

injection side pain. " I had thought that this

person was only speaking of the study that they

were a part of, not the whole study. That is where my mistake happened.

So at this juncture I must apologize for this

error on my part and I am going to correct that error now.

[]

As you can see table 7, under study group 018,

has participants of 1179 for the Gardasil group

and 594(d) for the Placebo group. Below this

study it has the description of what the (d)

means. This shows that the (d) is a Placebo = saline placebo.

Looking at this table you would think that this

would prove the safety of the vaccine. You would

think that you would get a reasonable comparison

of the differences when you add all the

ingredients that go into Gardasil. That is my assumption anyway.

Starting with page 300 of this report is where

you will find the details of study 018. The first

table in this section is table 209 and 210.

[]

As you can see they mention a " non-alum placebo "

and a " carrier solution " placebo.

Population: Protocol 018 was conducted in 47

sites in 10 countries in North America (US),

Latin America (Colombia, Mexico), Europe (UK,

Portugal, Norway, Denmark, Spain) and Asia

(Thailand, Taiwan). The subjects were to be

healthy preadolescents and adolescents who are not sexually active.

For full Inclusion and Exclusion Criteria, see APPENDIX 17

Vaccination schedule: Subjects received vaccine

or placebo (0.5 mL) IM at 0, 2, and 6 months.

Concomitant Vaccines: None planned.

Endpoints

Primary Immunogenicity Endpoints

• Anti-HPV 6, 11, 16, 18 GMTs Week 4 postdose 3

• Pecentage of subjects who seroconverted (change

in serostatus from seronegative to seropositive)

for each of the vaccine HPV types by Week 4

postdose 3. Seropositive is defined as anti-HPV

serum cLIA levels 20, 16, 20, 24 mMU/mL for HPV

types 6, 11, 16, and 18, respectively.

Primary Safety Endpoints

• Occurrence of severe injection site AEs

• Incidence of any VR related SAE

On page 302 of this document they have a section

called " special Procedures. " Under this heading,

the first bullet point, they state something interesting.

Because the true placebo was visually distinguishable from the HPV vaccine, ...

How can they say a " true placebo " when that was

not the case with study 018? The fact is that the

placebo was a " carrier solution " so this

statement is also false and misleading.

Safety Objectives

• In order to address this objective, the study

called for a detailed tolerability analysis, with

emphasis on the following prespecified adverse

experiences: vaccine-related adverse experiences,

VRC-prompted injection-site adverse experiences

(swelling/redness and pain/tenderness/soreness),

VRC-prompted systemic adverse experiences

(muscle/joint pain, headaches, hives, rashes,

diarrhea), severe adverse experiences, and fever.

Risk differences were calculated for AEs

comparing the vaccine and placebo groups across

all vaccination visits with respect to all AEs

with > 1% incidences. p-values were computed for

VRC elicited adverse events only

• Adverse experiences were summarized

descriptively as frequencies and percentages by

vaccination group and type of adverse experience,

by vaccination visit and across all vaccination visits.

• Risk differences and associated exact 95%

confidence intervals were computed comparing the

vaccine and placebo groups across all vaccination

visits with respect to adverse experiences with

1% incidence in either vaccination group.

Then on page 303 they make these statements about

the safety objectives. Basically, they are

stating that the adverse events between the two

groups are less than one percent. Of course,

there would not be a great difference because the

placebo was not a true saline placebo. This is

what they are basing their safety data on, the

difference between the two shots. Not the fact

that there were adverse events with both shots

that to me would make it an unsafe vaccine.

Now I want to go to page 316 where you find the

" Safety Results. " This is what they say about this.

Safety Results

• Overall, a higher proportion of vaccine

recipients reported one or more AEs compared with

placebo recipients. This was largely due to a

higher proportion of vaccine recipients with

injection site AEs compared to placebo

recipients. The proportion of subjects with

systemic AEs was comparable in the 2 groups.

• Overall, 5 SAEs occurred within the 14 days

after any vaccination. All of these occurred

after receipt of the vaccine and none after

placebo. (These are detailed later in the review).

• 2 subjects discontinued due to an AE (both in

the vaccine group). (These are detailed later in the review).

• The AEs postdose 1, 2, and 3 were generally

consistent with those described for the overall

clinical AE summary. Higher proportions of

subjects in the vaccine and placebo reported AEs

(overall, injection site, and systemic AE)

following dose 1 compared with postdoses 2 and 3.

(Source: Tables 11-26, 11-27, 11-28, CSR 018v1, p. 254-6, not shown here)

• The AEs in the 9-12 year olds and 13-15 year

olds were generally comparable to the overall AE

summary. 4/5 of the SAEs occurred in the 13-15 year olds.

[]

• There was a statistically higher proportion of

subjects in the vaccine group with an AE as

compared to the saline placebo group. (See Table 230 below).

[]

• In each vaccination group, a higher proportion

of girls reported an AE compared with the boys. (See Table 231 below).

[]

• The overall proportions of subjects with an AE

were similar when comparing the 9-12 year old

subjects with the 13-15 year old subjects who

received vaccine. The 13-15 year old vaccine

recipients had a lower overall proportion of

subjects with an injection site AE as compared to

9-12 year old vaccine recipients (with the same

pattern noted for placebo). The 13-15 year old

vaccine recipients had a slightly higher

proportion of subjects with systemic AEs as

compared to the 9-12 year old vaccine recipients.

A similar proportion of 9-12 year old vaccine

recipients had systemic AEs as compared to 9-12

year old placebo recipients. (See Table 232 below).

[]

Hey, it gets better. Now let us look at page 318,

section called " Intensities of AEs " (adverse events).

Intensities of AEs

• The proportions of subjects reporting a

moderate or severe injection site AE (of all

subjects with follow-up data) were higher in the

quadrivalent vaccine group (32.5% for moderate,

and 10.6% for severe) as compared to the non-alum

placebo group (23.6% for moderate and 6.8% for severe).

• Among all reported AEs, the frequency of

intensity ratings appeared comparable between the 2 vaccination groups.

• There were 3 AEs reported per vaccine

recipient, and 2 AEs reported per placebo

recipient. (Source: Tables 8-2, and 8-3, CSR 018v1, p. 143, not shown here)

I want you to take note that they decided not to

show this table on this report. I would think

that this would be important information in

regards to the safety of this vaccine but I guess

the person who put this report together from the

FDA did not feel that her cohorts needed to know this information.

Now let us go on to the section titled " Injection

Site AEs. " I want you to note that they also

mention in these tables the non-alum placebo.

Injection Site AEs

• In both vaccination groups, the most common

injection site AE was pain in the 5 days after

any vaccination. (See Table 233 below).

[]

• Significantly higher proportions of vaccine

recipients reported injection site erythema, pain

and swelling as compared to placebo recipients.

Risk differences were compared. (See Table 234 below.)

[]

• The proportions of subjects with injection site

AEs within each gender group were generally

comparable to those observed in the study

overall. In the vaccine group, the proportion of

girls who reported one or more injection site AE

(80.4%) was higher than the proportion of boys

with one or more injection site AE (69.7%). (See Table 235 below).

[]

• The proportion of subjects with specific

injection site AEs within each age stratum are

provided in Table 236 below. Injection site pain,

swelling and erythema were reported in a higher

proportion of vaccine recipients 9-12 years of

age as compared to vaccine recipients 13-15 years of age.

This is getting really long so I am going to cut

to the chase. This is the most disturbing part of

this report in regards to study 018. The creator

of this report did not feel that it was important

to give the reviewers of the safety protocol for

this vaccine this detailed information about " New

Medical Conditions " section directly below.

New Medical Conditions

• The proportions of subjects with new medical

conditions through Month 7 were comparable

between the vaccination and placebo groups.

• The most common new medical conditions during

this time period were headache and URI. (Source:

Table 8-24, CSR 018v1, p. 181-2, not shown here)

• There was one case of autoimmune thyroiditis in

the vaccine group and none in the placebo group.

The sponsor provided additional information about

this condition in general and across studies. A

discussion is included in the safety summary in

this document. (Source: Table 11-79, CSR 018v1, p. 354-63, not shown here)

Follow-up from Month 7 to Month 12

• Subjects (guardians) were contacted at Month 12

of the study to assess for any new medical conditions.

• Overall, 95.0% of subjects randomized (95.3%

Gardasil group and 94.4% of placebo group)

entered the Persistence Phase of Protocol 018.

Five subjects discontinued from the study (3 in

the vaccine group: 2 lost to follow-up and 1

withdrew consent; 2 in the placebo group due to relocation).

• A lower proportion of vaccine recipients

(29.0%) reported a new medical condition between

Day 1 and Month 12 as compared to placebo

recipients (31.0%). This was also noted in new

medical conditions between Month 7 and Month 12. See Tables 245 and 246 below).

• There were no new SAEs reported in this period.

[]

Comments-Conclusion Regarding Data for Protocol 018 (Reviewer's Opinion)

• Protocol 018 provides saline placebo-controlled

safety data for subjects 9-15 years of age (617

girls and 567 boys who received vaccine). This is

of particular interest because the other studies

used alum placebo as a safety comparison.

As you can see tables 245 and 246 just say

placebo. Someone scanning through the 464 pages

of this document like I did initially would be

led to believe that this was referring the saline

placebo. In essence this is the non-alum carrier

solution placebo that was used.

The " Reviewer's Opinion " falsely claims that this

protocol 018 used a saline placebo. As I have

shown you that placebo was in reality a carrier solution placebo.

Nowhere in the Gardasil trials did they ever,

ever use a saline placebo. The generator of this

report led the FDA to believe that they did in

one little study and that is false.

The piece de resistance is the cumulative tables

of the new medical conditions for all study groups.

I want you to note in the last tables, 302 and

303, that these are only of the most common new

medical conditions and those of interest (with

slight inequality between vaccine and placebo).

This was taken from page 392, 10.3.5 New Medical History.

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[]

[]

To summarize this long and detailed article you

have a better than 50% chance of having a new

medical condition after receiving the Gardasil

vaccine. At least those odds are better than the

report of September 11, 2008 which is 73.3%

chance of acquiring a new medical condition. The

only problem is that I have to base this

percentage on the most common new medical

conditions and those of interest. The actual

percentage when everything is taken into

consideration can be as high as the report of

September 11, 2008. We just do not know because

this reporter decided that it was not important.

What all this means is that in the United States

you have the real possibility of 2,902,164 girls

that have a new medical condition. This is better

than the numbers that I gave you in my last

article because I based them on the results of

the report of September 11, 2008.

The other item is that Gardasil never had a

placebo group in any of their studies and that

the reporter that generated this document used

false statements in regards to the saline

placebo. The, so called, saline placebo was in

reality a non-alum carrier solution placebo.

I would suggest that the FDA looks at this new

information and that they pull this vaccine off

the market due to the fact that there is a good

chance that 50% of the girls vaccinated with

Gardasil will have a new medical condition that

can alter their standard of living dramatically

and that it could increase the number of the disabled in this country.

The same recommendation goes to all the countries

that are administering either of the HPV

vaccines. The odds of 50% to 73.3% are too high

in my opinion to continue with this type of vaccination.

For more information about Cervarix and Gardasil

please visit my website at <http://www.cynthiajanak.com/>www.cynthiajanak.com

© A. Janak

--------------------------------------------------------

Sheri Nakken, former R.N., MA, Hahnemannian Homeopath

Vaccination Information & Choice Network, Nevada City CA & Wales UK

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