Ms Caron Ryalls
9th March 2012
Freedom of Information (FOI) Request: FOI 12/075
Dear Ms Ryalls, Re: Freedom of Information (FOI) Request - Human papilloma virus (HPV) vaccine
Thank you for your Freedom of Information (FOI) request dated 11th February 2012 requesting information on
the Medicines and Healthcare products Regulatory Agency’s (MHRA’s) policy and methodology on
investigating Adverse Drug Reaction (ADR) reports highlighted by the Yellow Card Scheme in relation to the
Human papilloma virus (HPV) vaccine.
Underpinning vaccine and medicines pharmacovigilance in the UK is the Yellow Card Scheme, which has
been in operation since 1964. This is a voluntary reporting system through which any healthcare professional
or member of the public can report a suspected ADR to any vaccine or medicine on the UK market. A Yellow
Card report is not proof of a side effect occurring, but merely a suspicion by the reporter that the vaccine or
medicine may have caused the side effect. Yellow Card reports may therefore relate to true side effects or
they may be coincidental. More information on the Scheme can be found at www.yellowcard.gov.uk.
All reports of serious ADRs are individually reviewed, and followed up with reporters if necessary to obtain
further clinical details. As well as using clinical judgement to detect new safety signals from such data, we use
specialised IT software and statistical approaches, including disproportionality analyses, to systematically
generate safety ‘signals’ from the Yellow Card data. In carrying out our work, teams of scientists and
physicians with responsibility for portfolios of vaccines and medicines continually assess the emerging safety
data and re-evaluate the balance of risks and benefits. As well as Yellow Card data, we routinely evaluate all
sources of safety data including clinical and epidemiological studies, published medical literature, and
information from other regulatory authorities as well as pharmaceutical companies. We also have access to
electronic data sources and record linkage databases such as the General Practice Research Database
(GPRD) and, if necessary, will conduct ad hoc
evaluation and research using such data. We may also
implement active safety surveillance and/or commission research on a case by case basis.
For HPV vaccine, key aspects of our strategy were to encourage ADR reporting (via letters and other
communication material) and conduct real-time ‘observed vs expected’ (O/E) analysis. The O/E approach
uses statistical methodology to compare, on a near real-time and ongoing basis, the number of reported
cases of ADRs against the normal rates of such illnesses that are expected to occur by chance amongst the
number of girls immunised at each point in time. These analyses adjust for various levels of possible under-
reporting through the Yellow Card Scheme. More details of the HPV strategy and our two year safety analysis
can be found at www.mhra.gov.uk/HPVvaccine.
The MHRA receives around 25,000 Yellow Card reports from within the UK every year. For HPV vaccine,
following administration of at least 5 million doses across the UK since September 2008, we have received
more than 6,000 Yellow Card reports since 2008. In relation to your question regarding under-reporting, this is
likely to be highly variable depending on many factors with serious events more likely to be reported. The
level of ADR reporting may also fluctuate between given years due to a variety of reasons such as a
medicine/vaccines being new (reporting rates are generally higher when a product is first introduced),
stimulated interest/publicity and variations in exposure to the medicine/vaccine.
I can confirm that as of 9th March 2012, the MHRA has received a total of 6,106 reports of suspected
associated with the use of Cervarix vaccine (including, reports where brand is unspecified), in the United
Kingdom, involving 13,857 suspected adverse reactions.
Table 1 below details the number of ADR reports submitted from industry (GlaxoSmithKline), healthcare
professionals and patients, and total number of reports, received for each year of the immunisation
Number of Reports
Professionals Total Number of
Please note that all ADR reports regardless of source are analysed and assessed in the same way. It is
important to be aware that a report of a suspected side effect to the MHRA does not necessarily mean that it
has been caused by the vaccine only that the reporter had a suspicion that it may have. Many factors have to
be taken into account in assessing the relationship between a vaccine and a suspected side effect such as
the possible role of underlying or undiagnosed illness or infection. The number of reports received should not
be used as a basis for determining incidence of a reaction as neither the total number of reactions occurring
nor the exact number of patients using the vaccine is known.
In terms of decision-making, MHRA has in place processes to obtain independent expert advice on the
balance of risks and benefits from the Commission on Human Medicines (CHM) and its sub-committees. As
we also work within a European regulatory framework and as many new vaccines (such as HPV vaccines)
have a single EU-wide marketing authorisation, we work very closely with other EU Member States and the
European Medicines Agency in vaccine pharmacovigilance and regulatory decision making. When
considering balance of benefits and risks, all relevant available data is taken into consideration.
Please be assured that the number and nature of suspected ADRs received following HPV vaccine so far is
very much in line with what the MHRA expected to receive at this time and no serious new risks have been
identified. CHM has advised that the balance of risks and benefits of HPV vaccine remains positive.
As with all vaccines and medicines, the MHRA will continue to closely monitoring the safety of HPV vaccine.
I hope this information is useful to you.
Miss Saira Mahmood
Senior Pharmacovigilance Scientist
Vigilance Intelligence and Research Group
Vigilance and Risk Management of Medicines
Cc: Miss Sarah Heffer, Therapeutic Group Co-ordinator
Cc: Dr Philip Bryan, Unit Manager; Vaccines, Anti-infectives and Advanced Therapies
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