Shocking Flaws in Gardasil Trial Design Prevents Safety Assessment

Story at-a-glance -

  • A number of experts have spoken out against the HPV vaccine since its release. An eight-month investigation revealed shocking flaws in Merck’s clinical trial design, which effectively prevented assessment of safety
  • Many of the side effects experienced during the vaccine trial were simply recorded as “medical history,” and were not treated as adverse events; serious adverse events arising outside of a two-week period post-vaccination were marked down as “medical history”
  • More than 80 million girls, young women and boys have received the HPV vaccine, and many have paid an extraordinarily high price, coming down with nervous system disorders, chronic fatigue and autoimmune diseases
  • According to Merck’s own research, if you have been exposed to HPV strains 16 or 18 prior and then get vaccinated, you may increase your risk of precancerous lesions by 44.6 percent
  • HPV infection is spread through sexual contact and research has demonstrated that using condoms can reduce risk of HPV infection by 70 percent, which is far more effective than the HPV vaccine

By Dr. Mercola

To say that the HPV vaccine is controversial would be a serious understatement. A number of experts have spoken out against the vaccine since its release, and studies have revealed serious problems. Children and teenagers have died or been permanently disabled following HPV vaccination, yet it remains on the market.

The featured 2017 trilogy, "Sacrificial Virgins," looks at the HPV vaccine from a variety of angles. Part 1,1 "Not for the Greater Good," questions the science behind the HPV vaccine and asks "Do we need it?"

Part 2,2 "Pain and Suffering," tells the story of two severely HPV-injured girls in the U.K., highlighting the possibility that the aluminum adjuvant added to Gardasil and Cervarix may be causing the devastating neurological damage seen in young girls and boys.

The third episode,3 "A Penny for Your Pain," looks at legal cases worldwide (in particular Japan, Spain and Colombia), in which victims are seeking compensation for their injuries.

Clinical Trial Participant Speaks Out Against Gardasil

In December 2017, Slate magazine published an article dishing out yet another inconvenient truth about this medically unnecessary vaccine, revealing trials "weren't designed to properly assess safety."4 Slate recounts the story of Kesia Lyng, a 30-year-old Danish woman who, at the age of 19, made the fateful decision to participate in a clinical trial for Merck's Gardasil vaccine.

Gardasil is supposed to prevent human papillomavirus (HPV) infection, which in rare cases may cause cervical cancer if left untreated. "Lyng's grandmother had died of cervical cancer the year before, so when a letter arrived offering her $500 to take part in a crucial international test of Gardasil, the decision was easy," investigative journalist Frederik Joelving wrote in Slate.

"She got her first shot of the vaccine at Hvidovre Hospital in Copenhagen on September 19, 2002. The symptoms snuck up [sic] on her shortly after her second shot on November 14. They never abated. It wasn't until 2016 that she received her diagnosis — chronic fatigue syndrome (CFS) …

In recent years, Lyng has become suspicious that there is a connection between her disease and her Gardasil immunization. Her ailments evoke descriptions found in hundreds of news stories from women who also received the vaccine, as well as several medical case reports from around the world."

Poor Safety Design Has Jeopardized Health of Tens of Millions of Girls

As of March 2016, nearly 90 million doses of HPV vaccines had been distributed among boys and girls in the U.S.,5 and many have paid an extraordinarily high price, coming down with nervous system disorders, CSF and autoimmune diseases. Long-term, the ramifications of this vaccination campaign may turn out to be even more widespread, as trial data from Merck shows that Gardasil vaccinations may actually increase your risk of cervical cancer.6

According to Merck's own research in one of its clinical trials, if you have been exposed to HPV strains 16 or 18 prior to vaccination, you may increase your risk of precancerous lesions caused by these two strains by 44.6 percent.

Reported side effects of Gardasil vaccination include immune-based inflammatory neurodegenerative disorders, suggesting something is causing the immune system to overreact in a detrimental way, sometimes fatally.7 Importantly, a 2012 systematic review8 of pre- and post-licensure trials of the HPV vaccine concluded that the vaccine's effectiveness is both overstated and unproven. According to the authors, the review revealed:

"… evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data.

For example, the claim that HPV vaccination will result in approximately 70 percent reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified.

Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities)."

Trials Were Not Designed to Detect Safety Problems

It's precisely these kinds of design flaws that are highlighted in the December 17, 2017, Slate article.9 Joelving reports that Merck has repeatedly "issued reassurances about the thorough randomized trials the vaccines were subjected to before approval." The public was told that the three HPV vaccines marketed in the U.S. were tested on tens of thousands of individuals around the world, without any compelling evidence of serious side effects having emerged.

While that reads well on paper, the shocking truth appears to be that these trials were never designed to detect and evaluate serious side effects in the first place.

"An eight-month investigation by Slate found the major Gardasil trials were flawed from the outset … and that regulators allowed unreliable methods to be used to test the vaccine's safety," Joelving writes. "Drug regulators tend to look much more seriously at potential side effects that surface during a pre-licensure study, which is what Lyng participated in, rather than after a product has already been found to be safe and been put on the market.

But regulators never learned of Lyng's plight. In fact, her repeated complaints of debilitating symptoms were not even registered in the study as potential side effects … Lyng's experience was not unique. Interviews with five study participants and more than 2,300 pages of documents obtained through freedom-of-information requests from hospitals and health authorities suggest inadequacies built into Merck's major clinical tests of Gardasil.

To track the safety of its product, the drugmaker used a convoluted method that made objective evaluation and reporting of potential side effects impossible during all but a few weeks of its yearslong trials. At all other times, individual trial investigators used their personal judgment to decide whether or not to report any medical problem as an adverse event …

Other health issues went on a worksheet for 'new medical history,' reserved for conditions that bore no relation to the vaccine. This study design put the cart before the horse, asking investigators to decide which symptoms might be side effects, rather than tracking everything in the same way."

The Safety Studies That Really Weren't

When adverse events following vaccination are marked down as "medical history" instead of being tagged and investigated as potential side effects, is it any wonder "no side effects have been found" in any of these trials!?

Actually, even that statement is a gross misstatement of facts, as at least one Gardasil trial of the new nine-valent vaccine reported nearly 10 percent of subjects who received the vaccine suffered "severe systemic adverse events" affecting multiple system organ classes, and over 3 percent reported "severe vaccine-related adverse events."10

Joelving also noted that while Merck claims "new medical history" notations are part of the safety metric, he questioned whether it could actually be used as such, since the work sheet doesn't record symptom severity, duration or outcome. "Even if the company then used the data in subsequent safety assessments, the lack of detail would have hampered meaningful analysis," he rightly states.

The 2012 systematic review11 of Gardasil pre- and post-licensure trials mentioned earlier isn't the only report out there that has offered up severe criticism of Merck's trial tactics. Joelving writes:

"In an internal 2014 EMA report12 about Gardasil 9 obtained through a freedom-of-information request, senior experts called the company's approach 'unconventional and suboptimal' and said it left some 'uncertainty' about the safety results.

EMA trial inspectors made similar observations in another report, noting that Merck's procedure was 'not an optimal method of collecting safety data, especially not systemic side effects that could appear long after the vaccinations were given.'

'If I were a research subject, I would feel betrayed,' Trudo Lemmens, a bioethicist and professor of health law and policy at the University of Toronto, told me. 'If the purpose of a clinical trial is to establish the safety and efficacy of a new product, whether it's a vaccine or something else, I would expect that they gathered all relevant data, including whether it had side effects or not.'"

Sadly, shoddy and incomplete documentation of adverse events, and follow-up periods that are too short to detect problems, can have tragic ramifications, and this is what appears to have happened with the release of Gardasil.

Joelving's investigation reveals at least five other Danish women went on to develop debilitating health problems during the Gardasil trial. One developed severe fatigue, "persistent flu-like symptoms," and had to be admitted to the hospital for a serious infection shortly after one of her vaccinations.

All of her symptoms were marked down as "medical history" and were not processed as adverse events. A year after her vaccination, she developed such debilitating pain she had to use a wheelchair.

To this day, she still sometimes has to use crutches, and has been given a tentative diagnosis of psoriatic arthritis. Another young woman also developed severe fatigue and headaches. She told Joelving she reported it to study personnel, yet there's no mention of these problems anywhere in her file.

Serious Design Flaws and Discrepancies Noted by Oncology Dietitian

This isn't the first time we've been warned about shoddy study designs in HPV trials. In 2013, an oncology dietician also pointed out significant discrepancies13 found in an HPV vaccine effectiveness study published in the Journal of Infectious Diseases,14 which evaluated data from the National Health and Nutrition Examination Surveys (NHANES) 2003-2006 and 2007-2010.

The study noted that while HPV vaccine uptake among young girls in the U.S. had been low, "the estimated vaccine effectiveness was high."

In her article,15 Sharlene Bidini, RD, CSO, points out that the study's conclusion was based on 740 girls, of which only 358 were sexually active, and of those, only 111 had received at least one dose of HPV vaccine. In other words, the vast majority of these girls were actually unvaccinated, and nearly half were not at risk of HPV in the first place since they weren't sexually active.

"If the study authors were trying to determine vaccine effectiveness, why did they include the girls who had not received a single HPV shot or did not report having sex?" she writes.

In the pre-vaccine era, an estimated 53 percent of sexually active girls between the ages of 14 and 19 had had HPV infections. Between 2007 and 2010, the overall prevalence of HPV in the same demographic declined to 43 percent. As noted by Bidini, this reduction in HPV prevalence simply cannot be attributed to the effectiveness of HPV vaccinations. On the contrary, the data clearly shows that it was the unvaccinated girls in this group that had the best outcomes.

"In 2007-2010, the overall prevalence of HPV was 50 percent in the vaccinated girls (14-19 years), but only 38.6 percent in the unvaccinated girls of the same age. Therefore, HPV prevalence dropped 27.3 percent in the unvaccinated girls, but only declined by 5.8 percent in the vaccinated group. In four out of five different measures, the unvaccinated girls had a lower incidence of HPV," she writes.

Another fact hidden in the reported data was that among the 740 girls included in the post-vaccine era (2007-2010), the prevalence of high-risk, nonvaccine types of HPV also significantly declined, from just under 21 percent to a little over 16 percent. So, across the board, HPV of all types, whether included in the vaccine or not, declined.

This points to a reduction in HPV prevalence that had absolutely nothing to do with vaccine coverage. One reason for this could be that, during the same period, reported sexual activity among young people declined, and their use of condoms increased — two very good reasons why HPV infections would also decline.16 Besides, vaccine uptake was very low to begin with.

Exaggerated Immune Response May Trigger Lifelong Health Problems or Death

In 2012, laboratory scientist Sin Hang Lee published a case report in the peer reviewed journal Advances in Bioscience and Biotechnology,17 discussing the presence of DNA fragments of the HPV virus in the blood and tissue of a healthy teenage girl who died in her sleep, six months after receiving her third and final dose of Gardasil. Lee confirmed the presence of HPV-16 L1 gene DNA in the girl's post-mortem blood and spleen tissue — the same DNA fragments found in the vaccine.

According to Lee, the fragments were protected from degradation by binding to the aluminum adjuvant used in the vaccine. He suggested their presence might offer a plausible explanation for the high immunogenicity of Gardasil, meaning that the vaccine tends to provoke an exaggerated immune response. He pointed out that the rate of anaphylaxis in girls receiving Gardasil is far higher than normal — reportedly five to 20 times higher than any other school-based vaccination program.

The dangers of high immunogenicity was also addressed in my 2015 interview with Lucija Tomljenovic, Ph.D., a research scientist at the University of British Columbia. In it, she explains that by triggering an exaggerated inflammatory immune response, vaccine adjuvants end up affecting brain function. Tomljenovic has also investigated the cross-reactivity between the antibodies raised against vaccine antigens. As it turns out, some of them cross-react with your own tissues.

Many viruses and bacteria share genetic similarities with human proteins. For example, there may be a peptide sequence in the wall of the virus that mimics the structure of a human protein. So, the antibody raised against the virus will then recognize the epitopes in your own tissues that mimic the virus. This has the potential to cause severe harm, and can significantly raise your risk of autoimmune disorders.

In collaboration with a team led by professor Yehuda Shoenfeld, a world expert in autoimmune diseases who heads the Zabludowicz Autoimmunity Research Centre at the Sheba Hospital in Israel, Tomljenovic has demonstrated how the HPV vaccine can cause brain autoimmune disorders. It was these findings that prompted the Japanese government to remove the HPV vaccine from its list of recommended vaccines.18

Gardasil and Chronic Fatigue Syndrome

As noted in the Slate article, exaggerated immune activation may also trigger chronic fatigue. Joelving writes:

"Imagining a link between HPV vaccination and CFS is not all that far-fetched, according to Dr. Jose Montoya, a professor of medicine at Stanford University and a CFS expert. The condition usually starts with an insult to the immune system — a severe infection, a car crash, a pregnancy. The first symptoms are flu-like, but months go by and the patient realizes she isn't getting better.

In a few genetically predisposed individuals, Montoya told me, it is 'biologically plausible' that the vaccine, which mimics a natural infection, could also trigger an immune response powerful enough to lead to CFS. To find out if that is the case, trial investigators would need to carefully track participants' symptoms 'for at least one year,' he said."

Gardasil Safety Follow-Up Was Just 14 Days Long

The Gardasil trial Lyng participated in neither tracked symptoms nor followed up on long-term health consequences. Joelving writes about her reaction when faced with the truth:

"As we looked through [her trial records] together … she grew visibly upset. 'What's the use of testing a vaccine if you don't register everything properly?' said Lyng … 'It had enormous consequences for my life' … In Lyng's records … there was no mention of fatigue, one of her most debilitating symptoms. Meanwhile, her family doctor began documenting the problem … nine days after she got her third and final shot of Gardasil."

Meanwhile, Lyng claims she discussed her symptoms with study personnel at each visit, but was met with dismissal. "This is not the kind of side effects we see with this vaccine," they would say — a rather remarkable statement, considering it was an experimental vaccine trial, the purpose of which is to tease out possible side effects.

None of her symptoms were recorded as adverse events. Headache, joint pain, gastroenteritis and influenza were all noted under "medical history." Fatigue was left out altogether.

Joelving also notes that the study protocol had a "clinical follow-up for safety" of just 14 days following each of the three injections. Any health problem, including serious adverse events, occurring after those two weeks were simply posted to the medical history.

"This design put individual investigators in charge of deciding, for most of the trial's duration, what would be assessed and reported as a potential side effect," Joelving writes, adding that "Experts I talked to were baffled by the way Merck handled safety data in its trials." One of the experts he talked to was a drug-safety adviser, who told him:

"'Everything from the first injection to the last plus a follow-up period is what we call treatment-emergent adverse events.' She puzzled over the brief, interrupted follow-up periods in the Gardasil trials, as well as Merck's choice not to report nonserious adverse events for all participants and its dismissal of many events as medical history.

'This is completely bonkers,' she said, requesting not to be named for fear of compromising her position in the industry. 'They've set up a protocol that seems very poorly thought through from a medical and safety perspective.'"

Warnings About Gardasil Clinical Trial Flaws in 2006

Shortly after Gardasil was licensed by the FDA in 2006, there were warnings that Merck's clinical trials, which the FDA used to fast track Gardasil to licensure, were methodologically flawed. In a June 27, 2006, press release issued by the nonprofit National Vaccine Information Center (NVIC) titled "Merck's Gardasil Vaccine Not Proven Safe for Little Girls,"19 the consumer advocacy organization pointed out that:

  • Merck used a bioactive aluminum-containing placebo, rather than a true placebo, in Gardasil clinical trials, even though the vaccine contained an aluminum adjuvant
  • Although Gardasil vaccine recommendations were targeting 12- to 13-year-old girls, Merck did not reveal how many girls under age 16 were in the prelicensure trials (eventually Merck admitted that number was only 1,200 girls, followed for less than two years)
  • Nearly 90 percent of Gardasil recipients and 85 percent of aluminum placebo recipients in the trials, who were followed up on, reported one or more adverse events within 15 days of vaccination
  • Gardasil recipients reported more serious adverse events

NVIC cofounder and president Barbara Loe Fisher said in 2006, "Nobody at Merck, the CDC or FDA know if the injection of Gardasil into all preteen girls — especially simultaneously with hepatitis B vaccine — will make some of them more likely to develop arthritis or other inflammatory autoimmune and brain disorders as teenagers and adults.

With cervical cancer causing about 1 percent of all cancer deaths in American women due to routine pap screening, it was inappropriate for the FDA to fast track Gardasil. It is way too early to direct all young girls to get three doses of a vaccine that has not been proven safe or effective in their age group."

Cruel Example of Why Health Authorities Cannot Be Trusted to Tell the Truth About Vaccine Hazards

September 20, 2018, an article20 in The BMJ highlighted the fact that while health authorities swore the pandemic H1N1 swine flu vaccine was safe and had undergone rigorous testing, internal documents unearthed during a lawsuit reveal there were in fact questions about the vaccine’s safety, yet the public was simply never informed.

The vaccine in question was GlaxoSmithKline’s Pandemrix vaccine, which was linked to a surprisingly high number of cases of narcolepsy across Europe. Associate editor of The BMJ, Peter Doshi, writes:

“In October 2009, the U.S. National Institutes of Health infectious diseases chief, Anthony Fauci, appeared on YouTube to reassure Americans about the safety of the ‘swine flu’ vaccine. ‘The track record for serious adverse events is very good. It’s very, very, very rare that you ever see anything that’s associated with the vaccine that’s a serious event,’ he said …

A similar story was playing out in the U.K., with prominent organizations, including the Department of Health, British Medical Association, and Royal Colleges of General Practitioners, working hard to convince a reluctant NHS workforce to get vaccinated. ‘We fully support the swine flu vaccination programme … The vaccine has been thoroughly tested,’ they declared in a joint statement.

Except, it hadn’t … [G]overnments around the world had made various logistical and legal arrangements to shorten the time between recognition of a pandemic virus and … administration of that vaccine in the population … A year later, signs of a problem with Pandemrix were emerging through postmarket reports of narcolepsy …

Now … new information is emerging from one of the lawsuits that, months before the narcolepsy cases were reported, the manufacturer and public health officials were aware of other serious adverse events logged in relation to Pandemrix …

For a range of concerning adverse events, reports were coming in for Pandemrix at a consistently higher rate than for the other two GSK pandemic vaccines — four times the rate of facial palsy, eight times the rate of serious adverse events, nine times the rate of convulsions. Overall, Pandemrix had, proportionally, five times more adverse events reported than Arepanrix and the unadjuvanted vaccine.

And the raw numbers of adverse events were not small … The last report seen by The BMJ, dated 31 March 2010, shows 5,069 serious adverse events for Pandemrix (72 per 1 million doses), seven times the rate for Arepanrix and the unadjuvanted vaccine combined … But neither GSK nor the health authorities seem to have made the information public — nor is it clear that the disparity was investigated …

[T]he events of 2009-10 raise fundamental questions about the transparency of information. When do public health officials have a duty to warn the public over possible harms of vaccines detected through pharmacovigilance? How much detail should the public be provided with, who should provide it and should the provision of such information be proactive or passive? If history were to repeat itself, does the public have a right to know?”

Talk to Your Kids about HPV and Gardasil

There are better ways to protect against chronic HPV infection and cervical cancer than getting an HPV vaccine. In more than 90 percent of cases, HPV infection is cleared within two years on its own, so keeping the immune system strong is far more important than getting vaccinated.

Additionally, HPV infection is spread through sexual contact and research21 has demonstrated that using condoms can reduce the risk of HPV infection by 70 percent, which is far more effective than the HPV vaccine. Other risk factors for chronic HPV infection including multiple sex partners, smoking, coinfection with herpes, chlamydia or HIV, and long-term oral contraceptive use.

Women chronically infected with HPV for many years, who don't get precancerous cervical lesions promptly identified and treated, can develop cervical cancer.

So, it is important to remember that, even if they get vaccinated, girls and women still need to get a Pap test every few years to check for cervical changes that may indicate precancerous lesions, as there is no evidence to suggest the HPV vaccine will actually prevent cervical cancer. Meanwhile, there's a large amount of evidence suggesting Merck cut corners during its vaccine trials and failed to properly assess the vaccine's safety.