According to a global Periodic Safety Update Report (PSUR)¹ produced by Merck, who manufacture Gardasil and Gardasil 9, there were 21 reports of deaths after HPV vaccination in a six-month period in 2018.
In one case, the patient received five HPV vaccinations whereas three is the recommended maximum number.
The company admits that it seems “biologically plausible” that non-specific immune stimuli, including vaccinations, could precede cases of Immune Thrombocytopenic Purpura (ITP) in susceptible individuals, but insists that there is insufficient evidence to infer that HPV vaccination can cause ITP.
Merck also reports the case of a six-week-old baby being accidentally vaccinated with quadrivalent Gardasil and says that, during the reporting period, there were more than seventy cases of maternal exposure to HPV vaccination during pregnancy.
The PSUR about Gardasil 9, which covers a six-month reporting period from June 10 to December 9, 2018, was submitted by Merck to the European Medicines Agency (EMA).
It states that, during the reporting period, “21 case reports of fatal outcome in a HPV vaccine recipient were identified”.
In the case of one of the deaths, and in numerous cases of reported illness after HPV vaccination, the patient was given several different vaccines at the same time. These include the DTP vaccine, FluMist, Boostrix, Infanrix hexa, the MMR vaccine, the Hib vaccine, and the the Menactra meningococcal conjugate vaccine.
Nineteen of the cases of fatalities were “spontaneous reports” and two were from “noninterventional study reports”.
Four of the 19 spontaneous reports contained very limited information, Merck states. Three of them were medically confirmed and one was consumer reported. One of these deaths was that of a 15-year-old female and another was a female patient “between 20 and 21 years old”, who developed liver failure.
In one of the medically confirmed cases, the patient received five doses of Gardasil 9 and/or quadrivalent Gardasil “and subsequently experienced serious complications (not further specified) and died”, Merck stated.
In this case, Mercks says, the patient was a 15-year-old (also reported as 16-year-old) female patient whose physician had recommended that the patient receive eight doses of Gardasil 9 and/or quadrivalent Gardasil (the reason was not specified).
One additional medically confirmed case is that of a 14-year-old male patient who was said by a health care professional to have a history of headaches (one of the boy’s parents refuted this).
The boy was vaccinated with a single dose of Gardasil 9 and, 22 days later, he developed a headache, mental status changes, and weakness and was hospitalised.
The patient was diagnosed via a magnetic resonance imaging (MRI) scan with acute disseminated encephalomyelitis (ADEM), Merck states.
“In consequence, he was treated aggressively with intravenous (IV) steroids, but he developed cerebral edema and died from cerebral hernia,” the company adds in the PSUR. “It was also stated the primary cause of death was brain death.”
One report, which was received from a Freedom of Information listing, concerns an 11-year-old female who was given a second dose of Gardasil 9 along with a meningococcal vaccination, the diphtheria, pertussis, and tetanus (DTP) vaccination, and a flu shot.
Four days later, the girl went to a hospital emergency department in respiratory distress and septic shock and died on the same day. Merck states that her death was “presumably from Influenza B”.
The company added: “The remaining 13 spontaneous reports were received from social media and contained very limited information in the majority of cases.
“Some postings were received from reporters who did not have first-hand knowledge of the case, some cases referenced other social media posts, some made general statements regarding unspecified numbers of patients and did not include any patient specific data.”
The case that Merck refers to as consumer reported is not a single case, but a general report in which there was an allegation that an unknown number of female patients of unknown ages “were being devastated by 9vHPV”, and that Gardasil 9 was killing people.
One of the two “non-interventional” study reports included minimal data, Merck says. The case involved a 45-year-old female patient, enrolled in a patient support programme, who reportedly received a dose of Gardasil 9 and died.
The second report was received from a consumer and concerned a 40-year-old Asian female who was enrolled in a market research study (the HPV DTC Focus Group Study). Three years after HPV vaccination, the patient developed cervical cancer and subsequently died, Merck states in the PSUR. “Incomplete data did not permit an assessment of lack of effect in this case,” the company added.
In its conclusion about the deaths, Merck states: “Nineteen of the 21 case reports contained limited information including clinical course of adverse events leading to death, autopsy or cause of death and medical history.
“Therefore, incomplete data precludes a proper analysis of these cases.”
Merck says that, with regard to the two spontaneous cases with more detailed information, “one was confounded by concomitant administration of three additional vaccines and the other contained conflicting information regarding medical history and the cause of death”.
No new safety signal was identified, Merck states. The company said it would continue to monitor reports of a fatal outcome in patients receiving the Gardasil 9 vaccine, “as part of ongoing safety surveillance”.
Immune Thrombocytopenic Purpura
A large section of the June–to–December 2018 PSUR is devoted to reports about people who, after HPV vaccination, developed Immune Thrombocytopenic Purpura (ITP), a rare autoimmune disorder in which a person’s blood doesn’t clot properly because the immune system destroys the blood-clotting platelets.
There were 94 reports (76 for quadrivalent Gardasil and 18 for Gardasil 9).
The cases of ITP were few in number, compared to the background incidence and the number of doses distributed, Merck states.
“However, eight of the cases occurred within a plausible risk window of six weeks post-vaccination, and it seems biologically plausible that non-specific immune stimuli, including vaccinations, could precede cases of lTP in susceptible individuals,” Merck said.
“This biologic plausibility led to the proposed change to the CCDS.”
After the previous PSUR for Gardasil 9, covering June 10 to December 9, 2017, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) rapporteur asked Merck to clarify the scientific rationale on which ITP was included as a possible adverse reaction in the Gardasil 9 Company Core Data Sheet (CCDS), and to further discuss ITP in the context of the cumulative experience with quadrivalent Gardasil.
After the June–to–December 2017 PSUR, the PRAC rapporteur’s stated opinion was that “the nature of the cumulative reports did not indicate a causal association”.
In a comment on the June–to–December 9 2018 PSUR the EMA said the PRAC rapporteur agreed that “the safety experience (and causality assessments) for Gardasil (4vHPV) should be considered relevant for Gardasil 9, and vice-versa”.
The EMA said the rapporteur did not consider that Merck had adequately addressed the question about the inclusion of ITP in the CCDS.
The agency said that, for the next PSUR, the expectation was for Merck to provide a discussion on cumulative reports pertaining to both Gardasil 9 and quadrivalent Gardasil, “and to explain the scientific basis (i.e. the causality evaluation) for the inclusion of ITP in the CCDS”.
In response to the EMA, Merck says that “the current available data for Gardasil and Gardasil 9 do not suggest a causal relationship between the vaccines and Immune Thrombocytopenic Purpura”.
ITP is however included in the Summary of product characteristics (SmPC) for quadrivalent Gardasil and Gardasil 9.
Merck states in the SmPC: “Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.”
ITP was added to the CCDS for quadrivalent Gardasil in the 4th quarter of 2009, Merck says.
Merck states that ITP is a “fairly common condition in the general population”. The incidence of ITP in adults, Merck states, is approximately 66 cases per 1,000,000 per year and an average estimate of the incidence in children is 50 cases per 1,000,000 per year.
The company says that, in view of the fact that more than 51 million doses of quadrivalent Gardasil were distributed from the time of market authorisation to May 31, 2009, the overall reporting rate for ITP temporally associated with the administration of quadrivalent Gardasil was 0.2 reports per million doses distributed.
“This rate would be within the background rate of ITP,” Merck states.
The company says that more than 50 million doses of Gardasil 9 were distributed between the date of market authorisation (December 10, 2014) and December 9, 2018, therefore the overall reporting rate for ITP reported as being temporally associated with the administration of Gardasil 9 was 0.35 reports per million doses distributed or approximately one case per every three million doses distributed.
Merck conducted a cumulative safety analysis of all available spontaneous reports of ITP since market introduction for quadrivalent Gardasil and Gardasil 9.
The company states: “This new analysis reveals that there is insufficient evidence to infer a causal relationship of ITP to the qHPV or the 9vHPV vaccines …”
Merck says there were four reports (three for quadrivalent Gardasil and one for Gardasil 9) that were confounded by the concomitant administration of attenuated live vaccines: the Measles-Mumps-Rubella (MMR) vaccine, the live attenuated varicella vaccine, and the live attenuated flu vaccine (FluMist) at the same time that HPV vaccination was carried out.
The company says there were 76 reports of cases of ITP temporally associated with the administration of quadrivalent Gardasil between June 1, 2016, and May 31, 2018. Of these cases, 73 were considered serious and three non-serious.
In 69 of the cases, the patient was female, in five cases the person was male, and, in two cases, the patient’s sex is recorded as unknown. One patient was aged under nine, 49 were aged between nine and 17, 18 were aged 18 to 26, and one was older than 26.
One of the patients died and, in 28 cases, there was no recovery or resolution.
There was complete data in 47 of the cases that showed the time between HPV vaccination and the onset of ITP ranging from one to 6,345 days, with an average of 37 days.
Partial data was provided in 13 case reports that showed the time between vaccination and the onset of ITP ranging from one day to seven years.
In one case, a six-week-old boy was accidentally vaccinated with a dose of quadrivalent Gardasil instead of an infant vaccine.
At the same time, the baby was given the Infanrix hexa vaccine, which combines diphtheria and tetanus toxoids, the acellular pertussis, hepatitis B (recombinant) and inactivated poliomyelitis vaccines, and the adsorbed conjugated Haemophilus influenzae Type B vaccine.
The baby’s mother said the boy experienced flu-like symptoms right after vaccination. At two years of age he was diagnosed with acute myeloid leukaemia (AML) and ITP.
In another case, an 18-year-old female patient, who already had a history of ITP, but had been in remission from 2004 to 2011, was given two quadrivalent Gardasil vaccinations, one in October 2010 and one in January 2011. She relapsed in April 2011. The relapse led eventually to the young woman’s death from an intracranial haemorrhage, Merck states.
Merck insists that, based on the available evidence, the relapse was not related to HPV vaccination.
In another case of ITP, an 11-year-old boy received multiple other vaccines at the same time as Gardasil 9 on a day when he already had a mild cough. On February 6, 2017, the boy received the Fluzone vaccine, the Menactra meningococcal conjugate vaccine, and Boostrix, which combines the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines.
On February 13, the boy required medical assistance as he had petechiae (patches caused by bleeding under the skin) on his legs. He had zero blood platelets, was diagnosed with ITP, and was hospitalised.
Merck again says it considers that the ITP was not related to HPV vaccination.
The company says the boy had known risk factors for developing ITP. Acute abrupt onset ITP is seen mainly in childhood, and often follows a viral illness, Merck says, and the boy had a concurrent mild cough at the time of vaccination.
In another case, a 16-year-old boy was vaccinated with Gardasil 9 on September 20, 2016, even though he was still recovering from a mild viral respiratory infection. The patient’s other conditions included attention deficit disorder (ADD), allergic rhinitis, and a possible food allergy.
On October 12, 2016, the patient experienced ITP and had to be hospitalised.
Again Merck says it considers that the ITP was not related to HPV vaccination. The company says the boy had known risk factors for developing ITP and was recovering from a viral infection before vaccination.
To date, 2317 cases of Immune system disorders following HPV vaccination have been reported to the World Health Organisation’s pharmacovigilance database, VigiBase.
HPV vaccination during pregnancy
In one of the cases of ITP cited in the June–to–December 2018 PSUR, the patient was a 16-year-old girl who was vaccinated with quadrivalent Gardasil when she was 7.5 weeks pregnant.
Merck itself says that the safety and effectiveness of Gardasil has not been established for pregnant women.
The company again states that the evidence in the reported case is not sufficient to suggest a relationship between HPV vaccination and ITP.
Merck says that, during the reporting period, there were seventy initial reports “from the marketed environment” of maternal exposure to a HPV vaccine during pregnancy. Forty-eight of those reports were medically confirmed and 23 were received from consumers.
Five of the seventy cases did not involve in utero exposure, but were cases of a woman receiving Gardasil 9 more than thirty days before her last menstruation.
Eight cases included an outcome of pregnancy: one induced abortion, two abortions (not further specified), and five live births.
Foetal outcome was provided in two of the cases of live birth. In one case there was a normal foetal outcome (the mother was exposed to Gardasil 9 in her first trimester). In the second case, the four-month-old boy was diagnosed with a germ cell tumour and underwent surgery. The outcome was not provided. (Germ cell tumours are growths that form from reproductive cells.)
There were two initial cases received from the “study environment”, Merck says. One case, which involved in utero exposure at ten weeks, resulted in an abortion as in utero “foetal death” was detected on an ultrasound.
There was no outcome reported in the second case.
Merck says that because Gardasil 9 is given to women of child-bearing age pregnancy exposures are likely to occur.
The company insists, however, that “no safety signal associated with exposure during pregnancy has been detected during clinical development”.
Merck says that “enhanced pharmacovigilance activities” are ongoing to monitor pregnancy exposures, including enhanced surveillance of pregnancy exposures to Gardasil 9 reported in the US.
“The pregnancy registry started in January 2015 and is planned to run for a minimum of five years,” Merck said.
“The first, second and third annual reports were completed and filed with previous PSURs. The US FDA will determine whether the registry can be closed after receipt of the five year summary report, projected for August 2020.”
Postural Orthostatic Tachycardia Syndrome
In the June–to–December 2018 PSUR, Merck says there were eight reports of Postural Orthostatic Tachycardia Syndrome (POTS) worldwide that were reported to be temporally associated with the administration of Gardasil 9. Merck says six of the cases were medically confirmed and six included very limited data and were therefore not able to be evaluated against the case definition for POTS.
POTS is a condition in which a change from lying or sitting to standing causes an abnormally big increase in heart rate. Symptoms can include lightheadedness, trouble thinking, blurred vision, or weakness.
One case of POTS and inappropriate sinus tachycardia, reported as temporally associated with Gardasil 9 vaccination of an 18-year old female, met the case definition of POTS, Merck states.
“This report included test results from a full workup, conducted by a paediatric cardiologist,” the company said. It did not, however, provide details of the time period between HPV vaccination and the onset of POTS. There was only an indication that some symptoms may have presented between doses two and three of Gardasil 9.
The report did not include details of the patient’s medical history or concurrent conditions at the time of vaccination, “thereby precluding an assessment of causal association” to vaccination with Gardasil 9, Merck says.
In its conclusion about POTS, Merck states: “POTS is a syndrome that is generally not well understood and occurs in the target HPV vaccination group in the absence of vaccination.”
The company adds: “A local cluster of reports of POTS, involving the bivalent and quadrivalent HPV vaccines, originating from Denmark, reflected the increased media attention on POTS without established causal association.
“Although review of post marketing cases cannot conclusively rule it out, no causal relationship to HPV vaccine has been established.”
About 1,300 female patients who received HPV vaccination have been referred to specialist centres in Denmark with symptoms of POTS or of complex regional pain syndrome (CRPS).
Researchers at the Copenhagen centre found that antinuclear antibodies, which indicate whether someone has an autoimmune condition, were present in 60 percent of a group of patients with adverse effects from HPV vaccination as compared with 25 percent in a control group.
Merck said it had monitored cases of POTS in each PSUR since 2013 at the request of the EMA and, over the years of analysis, had found no evidence to infer a causal relationship to HPV vaccination.
The company asked if it could discontinue presenting an analysis of such cases in each PSUR, and only include new information in the applicable section that would present a change to the safety profile of the vaccine.
Merck said it would, however, continue to monitor reports of POTS in patients receiving Gardasil 9.
Reports of leukaemia
The reports about cases of leukaemia that are included in the June–to–December 2018 PSUR are indicative of the lack of information that is being provided about patients suffering adverse effects after HPV vaccination.
Merck says two case reports were identified. The first included very limited information. It concerned a 12-year-old female who received a dose of Gardasil 9 and 161 days later was diagnosed with leukaemia, muscle inflammation (myositis), and pain. On an unknown date, the patient was hospitalised.
“On two dates, an unknown test was performed, and the results were not reported,” Merck states. “The outcomes of leukaemia, myositis and pain were reported as not resolved. Missing important information includes medical history, comorbid² conditions, concomitant medications and clinical course.”
Merck states that the reporting health care professional did not assess the event as related to vaccination with Gardasil 9.
The second case report relates to a 13-year-old boy who had a history of osteosarcoma, which was treated with chemotherapy.
The boy was enrolled in a clinical trial to evaluate the administration of Gardasil 9 to cancer survivors (he had been off therapy for 27 months).
The patient received three doses of Gardasil 9 and, five months and 26 days after the third dose, he was diagnosed with a secondary malignancy and “cancer therapy-related acute myeloid leukaemia”.
The boy was hospitalised and it is not known whether or not he recovered.
“Missing important information includes comorbid² conditions and concomitant medications,” Merck stated.
“The event has been deemed by the responsible site physician and by the overall responsible physician for the study as unrelated to 9vHPV and definitely related to prior cancer therapy (chemotherapy) that the patient received for treatment of his primary cancer.”
Merck says that five cases of leukaemia were received from the “marketed environment” during the previous eight PSUR report periods.
The first case involved a 11-year-old girl who was diagnosed with chronic myeloid leukaemia. The second case concerned a 16-year-old female. There was a long latency between vaccination and diagnosis, Merck says.
The third and fourth cases lacked sufficient detail for assessment and the fifth case concerned a 13-year-old boy who was diagnosed with acute myeloid leukemia and “secondary primary malignancy”.
The review did not raise a safety concern for reports of leukaemia, Merck said, therefore the company was of the opinion that no additional risk minimisation was required.
Over the years of analysis, Merck said, the company had not found any evidence to date to infer a causal relationship between HPV vaccination and leukaemia.
It’s recorded in the June–to–December 2018 PSUR that Australia’s Therapeutic Goods Administration (TGA) asked Merck for a “signal analysis” of company-held data, from all sources, about serious adverse neurological events following vaccination with quadrivalent Gardasil and Gardail 9 over the previous 12 months.
The TGA asked Merck to provide “an analysis of cases reporting demyelinating disorders (using MedDRA Demyelination SMQ)³, which are the focus of our investigation”.
A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged.
Merck reported that 19 cases with 22 “events” were received for the period June 10, 2017, to June 8, 2018.
All cases were spontaneously reported, Merck says. Nine were medically confirmed and ten were consumer reported.
There were eight cases of Guillain-Barré Syndrome (GBS) and nine of multiple sclerosis. There was one case of Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, which is a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis), and one case of demyelination.
There were three cases of optic neuritis.
In 17 of the cases, the patient was female. One case concerned a male and, in the 19th case, the gender was not reported.
Age was reported in 12 of the 19 cases. Seven of the patients were between 9 and 17 years old, and three were aged between 18 and 26. There was one 39-year-old patient and one aged 40. In seven cases, the age was not given.
Merck says that the review of the cases of Guillain-Barré Syndrome reported as temporally associated with the administration of Gardasil 9 “does not raise a safety concern”.
Only three of the eight cases included sufficient details to properly evaluate the case, Merck says.
The company says that analysis of two of the cases was confounded by the concomitant administration of two other suspect vaccines in one case and by a surgical procedure performed after vaccination, and prior to onset of GBS, in the other. The third report did not identify which HPV vaccine was administered, Merck says.
To date, 391 cases of GBS following HPV vaccination have been reported to VigiBase.
Merck also said that the review of the cases of multiple sclerosis and optic neuritis reported as temporally associated with the administration of Gardasil 9 “does not raise a safety concern”.
The company says the majority of the cases lacked the details required to conduct a proper analysis. Other cases involved a suspected diagnosis of MS, not yet confirmed. One case was confounded by what was described as a strong family medical history of MS.
“The single report that included the most complete data with respect to clinical course, diagnostic test results supportive of an MS diagnosis, as well as treatment and outcome, did not include any medical history/concurrent conditions or the time to onset of the events relative to vaccination,” Merck said.
To date, 416 cases of MS following HPV vaccination have been reported to VigiBase.
Merck also said its review of the cases of Neuromyelitis optica spectrum disorder and demyelination reported as temporally associated to the administration of Gardasil 9 did not raise a safety concern.
“The two case reports lacked details required to make any meaningful assessment,” Merck said.
To date, 21 caes of Neuromyelitis optica spectrum disorder following HPV vaccination have been reported to VigiBase.
Merck says many of the reports gathered about demyelinating disorders lacked confirmed diagnoses as well as other data critical in the analysis of such case reports.
“Some cases are received from reporters who do not have first-hand knowledge of the case but rather are learned through hearsay,” Merck said.
“Additionally, the reporting rates of cases per million doses distributed are low suggesting that the reports are part of the background rates of these events which occur in the population in the absence of vaccination.”
Merck’s conclusion is that “the available scientific evidence does not support an association between 9vHPV vaccine and demyelinating disorders”.
Austrian Health Authority requests quality check on Gardasil 9 batch
The June–to–December 2018 PSUR includes information about a request by the Austrian Health Authority for a quality check on a particular batch of Gardasil 9.
The Austrian Health Authority said that, “due to nine adverse event notifications (with the same vaccine batch number) with dizziness, headache, sickness and/or collapse, a quality defect of the affected batch is assumed”.
It asked Merck to submit a written notification dealing with the described facts and a report with implemented measures within 14 days.
Merck says it initiated a comprehensive investigation into the manufacture (from drug substance manufacture to packaging) of the identified batch of Gardasil 9.
The company’s safety data base was queried for adverse event reports involving the identified batch.
A second query was conducted for reports that included any Gardasil 9 batch numbers known to be related to the batch whose safety was being questioned.
Merck says that the batch conformed to all quality release parameters at the time of release in February 2018 of the “final formulated bulk” and, in April 2018, of the finished product. These parameters included batch documentation review, environmental monitoring data, and test data (release testing data).
“No atypical events occurred that might have negative impact on product quality or safety,” Merck states in the PSUR.
Merck says that a total of 11 cases of adverse events relating to the batch being questioned were identified. All were from Austria, Merck says, and ten of the 11 reports came from the same reporter.
“The onset for all events in nine of the ten non-serious cases was reported to be on the date of vaccination,” Merck said.
In all nine cases the patients were reported as recovering on the date of vaccination, the company added.
In the 10th case, the timing of the onset of the adverse events relative to vaccination was not specified. Duration of the adverse event was not specified, but the patient was reported to have recovered.
Merck says that in the ten cases it describes as “non-serious” the adverse events were nausea (four cases), dizziness (six cases), headache (three cases), and fainting coded as “circulatory collapse” (three cases).
The 11th case, reported as being serious, was a case of hypersensitivity requiring hospitalisation. The patient was reported to have recovered.
Merck says that it identified three cases of adverse events after vaccination with a Gardasil 9 vaccine whose batch number was related to the batch being questioned in Austria. All the cases were in Germany.
One case was reported as serious and “involved a nephrotic syndrome which was not yet resolved at the time of the report”, Merck says.
The remaining two cases, reported as non-serious, included the following events: flatulence (one case), nausea (one case), chest discomfort (one case), pyrexia (two cases), arthralgia (two cases), dizziness (two cases), and dyspnea (one case).
Pyrexia is an abnormal rise in body temperature, arthralgia is joint pain, and dyspnea is the medical term for shortness of breath.
Merck says that the investigation into the manufacturing of the Gardasil 9 batch being checked revealed that “no atypical events occurred that might have a negative impact on product quality or safety”.
The company says that the analysis of adverse events in the 14 case reports referred to above shows that the majority of those events (syncope, dizziness, headache, nausea, hypersensitivity, and arthralgia) are included in the Gardasil 9 EU Product Information sections 4.4 (Special warnings and precautions for use) and 4.8. (Undesirable effects and considered expected).
Merck asserts: “The case reports contain insufficient information to assess any other possible association, and it is important to note that 10 out of the 14 reports came from the same reporter.
“Therefore, there is no safety signal associated with this lot.”
The company added: “The available scientific evidence does not support that the identified batch of Gardasil 9 has a different safety profile than described in the EU SmPC.”
‘Why such lack of detail?’
A question posed by advocates for better pharmacovigilance, including those who have themselves been injured by HPV vaccination or have an injured child, is why is more care not taken to gather full details when adverse events occur. And why are so many vaccines given together, therefore muddying the picture?
The June–to–December 2018 PSUR was obtained from the EMA via an access-to-documents request for information by Surya Arby from the French non-profit organisation the Association Internationale pour une Médecine Scientifique Indépendante et Bienveillante (AIMSIB)4.
“With all the evidence that exists of the dangerous adverse effects of HPV vaccination, what is required for a new safety signal to be triggered?” Arby said.
“What are the experts waiting for to implement a reliable surveillance system to detect safety signals and assess causality?”
Why, Arby asks, is the manufacturer responsible for the causality assessment of its own products? And where are the accurate, well designed, studies?
Michelle Stubbs, whose daughter Asha became seriously ill after HPV vaccination, is also extremely concerned that the company manufacturing the Gardasil vaccines is allowed to police itself and that post-marketing surveillance of adverse reactions to vaccines is conducted by the TGA.
“At a time when the confidence of parents in vaccine safety is clearly on the decline, it is simply not good enough that post-marketing surveillance of adverse reactions to vaccines is being conducted by the regulatory body that deemed the vaccine safe for market,” Stubbs said.
Stubbs, who has received several eye-opening documents from the TGA via Freedom of Information (FOI) requests, and is organising a class-action lawsuit in Australia over the injuries caused by HPV vaccination, has made a new FOI request, this time to the Department of Health, about an incident at the Sacred Heart College in Oakleigh, Victoria, in May 2007, when there was a mass adverse reaction to the newly rolled out quadrivalent Gardasil vaccine.
Twenty-five female students fell ill and five of them were taken to hospital. The then Health Minister, Tony Abbott, assured the public that the incident would be fully investigated and Stubbs is now asking to see details of those investigations.
Asha Stubbs received her first two Gardasil injections in July 2007 and October 2007 when she was 15 years old. When she received her third injection in March 2008, she was 16.
Two weeks after that injection, Asha was diagnosed with ITP.
When Asha was 19, the ITP turned into paroxysmal nocturnal hemoglobinuria (PNH), which is a rare and life-threatening blood disease in which red blood cells are destroyed and blood clots develop.
About six months later Asha was also diagnosed with myelodysplastic syndrome (MDS), in which the bone marrow does not produce sufficient healthy blood cells. She was told she was in the early stages of developing acute myeloid leukaemia.
There is more detail about Asha’s case in this Changing Times article.
‘11.1 million doses of Gardasil 9 distributed worldwide’
Merck says that, during the reporting interval for the June–to–December 2018 PSUR, the estimated number of marketed doses of Gardasil 9 distributed worldwide was approximately 11.126 million (11,126,137)5.
Based on the assumption that each person received 3 doses, about 3.7 million (3,708,712) people are estimated to have been vaccinated.
The estimated number of Gardasil 9 vaccine doses distributed worldwide from market introduction to December 9, 2018, was approximately 50.89 million (50,897,923).
The estimated number of Gardasil 9 vaccine doses distributed in the European Union (EU) between June 10 and December 9, 2018, was about 1.7 million (1,705,2900)5.
The estimated number of Gardasil 9 vaccine doses distributed in the EU from market introduction to December 9, 2018, was approximately 5.2 million (5,200,096).
Merck notes in the June–to–December 2018 PSUR that Gardasil 9 has been given to four neonates, 75 infants and toddlers, and 102 children aged from 23 months to nine years.
Merck asserts in the PSUR: “Overall, the previously established favourable benefit-risk profile for 9vHPV vaccine has been reconfirmed by the efficacy and safety data that have become available during this reporting interval.”
Merck says that Gardasil 9 protects girls against cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58, and genital warts caused by HPV types 6 and 11.
It says the girls will also be protected against a number of precancerous or dysplastic lesions.
Boys, Merck says, will be protected against anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts caused by HPV types 6 and 11; and the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58: anal intraepithelial neoplasia (AIN) grades 1, 2, and 3.
The Gardasil vaccines continue to be vaunted as life-saving, but there is no evidence that HPV vaccination is reducing the incidence of cervical cancer, and reports of adverse effects now total more than 103,433 worldwide. More than 500 deaths are suspected of being linked to quadrivalent Gardasil or Gardasil 9.
- A PSUR is a pharmacovigilance document intended to provide an update of the worldwide safety experience of a medicinal product to regulatory authorities at defined time points post-authorisation. PSURs summarise the benefit-risk information received by the Marketing Authorisation Holder (MAH) and any applicable co-marketers from worldwide sources during the reporting interval.
- In medicine, comorbidity is the presence of one or more additional conditions co-occurring with a primary condition.
- Standardised MedDRA Queries (SMQs) are tools developed to facilitate retrieval of MedDRA-coded data as a first step in investigating drug safety issues in pharmacovigilance and clinical development.
- The AIMSIB’s objectives are to provide critical, independent, scientific, and conflict-free information about medicines, treatments, and medical devices; to inform health professionals and citizens about advertising and media noise about therapies in general; to bring health professionals and users into contact with each other in accordance with these objectives; and to mobilise resources so that national and international agencies dealing with medicines, health products, and food are protected from lobbying and conflicts of interest.
- As dose distribution numbers are only available in full month increments, this statistic relates to the period June 1 to November 30, 2018.