MercatorNet 4 May 2015
The safety studies: main concerns
No-one can say at this point that Gardasil has or has not caused POF in these young women, says Dr Little. There is simply not enough information available. But it cannot be ruled out, since her research shows there are serious shortcomings in the testing and approval phases of the drug.
From studying laboratory information and clinical trials in adolescent subjects, these are her main findings and concerns:
* No “normal saline placebo” was ever used — although reports stated otherwise — for the young girls’ safety studies. The vaccine was only ever compared with parts of itself in safety studies. This contravenes placebo definitions and requirements. More importantly, it means the prescribing information is incorrect. “Product Information” wrongly states that saline was used as a safety study placebo. The US FDA also misrepresents the younger girl placebo as “saline”. Neither inform the recipient or the prescriber of the correct placebo, which was made up of multiple HPV vaccine components. When prescribers are misinformed, patients cannot give informed consent.
Both the multi-chemical placebo and the HPV vaccine contained a substance whose toxicity to rat ovaries is established at all doses tested, over a tenfold range. There is no dose-response curve to tell us when the injected “polysorbate 80” dosage level begins to have an effect on the mammalian ovary. (It does not begin to have these effects after oral ingestion until it comprises a whole fifth of the rats’ total intake, possibly due to its breakdown by gastric juices).
The TGA tells doctors like Dr Little that, since this substance is present in some foods, it cannot possibly be ovary-toxic when serially injected into young girls. “This is alarmingly unscientific,” she told MercatorNet. “Unfortunately, however, it does represent the level of evidence available to reassure us about its safety for our daughters’ ovaries. Informed consent requires more than un-evidenced reassurances.”
* Masking effects of the Pill. The majority of young women in the safety studies were using hormonal contraception at the time, which masks period changes. They were required by the study to use contraception until seven months after their first vaccination.
* Limited definition of “adverse events”. In safety studies, new medical conditions which arose in girls after seven months from their first vaccination were not recorded as vaccine adverse events.
Only reactions defined as “Serious Adverse Events” were recorded for longer time periods in safety studies. These do not, by definition, include menstrual problems because they are not life threatening and will not land you in hospital.
* Safety studies focus on hospital cases. The principal safety studies done since marketing began in 2007-2008 have focussed on hospital presentations and hospital admissions. These studies have no capacity to detect ovarian failure, says Dr Little, noting that she has never yet hospitalized a girl for missed periods. Another post-marketing safety study has looked for pre-specified diagnoses in records of vaccinated girls, but ovarian damage was not included in the specifications of diagnoses to look for.
* Too few girls in the target age group were studied. There were only ever a few hundred young girls in each of the two safety studies which looked at the vaccine target age group. In one of these two studies more than half of the girls had been lost to follow-up 12 months later, leaving only 240 girls; and in the other, it is not recorded how many had begun to menstruate when they were studied, since the mean age was 11.9 years.
* Boys are under-studied. Although boys get HPV too, and pass it on, only a couple of hundred boys were studied, and most of them were also lost to follow-up at 12 months, leaving only 205 in total. One died suddenly of no apparent cause. With nothing found on post-mortem, the investigators were sure it wasn’t the human papillomavirus vaccine.
* Virgins are more vulnerable but under-studied. Reported “systemic” (unwell) adverse events experienced after Gardasil vaccination are more common and more severe in those not previously exposed to the virus strains — namely, virgins. This is the state of the target group, which is under-represented in safety studies. (This disparity was less marked in the placebo group.)
These are just the most obvious concerns in the evolving story of inadequate research on Gardasil. Japan has withdrawn the vaccine from routine school administration. Dr Little’s research raises questions about the probity of industry-sponsored safety research. It also puts a question mark over prescribing the Pill in the absence of a diagnosis. As she points out, premature menopause in adolescence is easier to diagnose without the presence of hormonal contraception.
Is vaccination of girls worth the risk when screening gives good results?
Vaccination always involves a calculation of risks and benefits. In this case the risks of mass vaccination of pubescent and pre-pubescent girls should be weighed against the incidence of and deaths from cervical cancer in Australia before the HPV vaccine was introduced.
Following the introduction of a national cervical screening programme, these rates more than halved in the decade prior to 2000 in the 20- to 69-year age group in Australia, and 578 new cases were diagnosed in 2000. The incidence was highest in remote areas, with the risk of death from cervical cancer for an Indigenous woman in Australia six times that of a non-Indigenous woman.
In 1989 it was estimated that screening could prevent 90 percent of malignancies. By 2002, the Australian incidence of cervical cancer was 6.2 per 100 000 women and the mortality rate 1.7 per 100 000 women. In 2011 in Australia, there were 229 deaths from cancer of the cervix. Some 72 percent of women diagnosed with cervical cancer survive for at least five years.
In any case, vaccination is not a free pass: up to 30 percent of cervical cancer may still occur in vaccinated individuals so pap smears are still necessary for sexually active women until they reach 70 years of age.
In the light of these facts it is up to the drug companies producing the HPV vaccine and the authorities that approve it to ensure that, in the effort to lower cervical cancer rates more rapidly, they are not putting healthy girls at risk of ovarian damage. Women, if not the licensing authorities, should be demanding comprehensive ovarian research on a drug that could render some of them infertile.