Dr. Joan Gilvarry:

It may also help to answer some of the questions that were posed. I will be as brief as possible.

As has already been stated, the product was licensed by the European Commission and placed on the market across the European Union in 2006. It has also been approved in 130 countries worldwide and it is estimated that 63 million subjects have been vaccinated. No regulatory authority in the world has taken any action to suspend this product. After any medicine or vaccine is licensed, as new information appears and emerges during the marketing experience, the benefit-risk evaluations continue to be carried out by the regulatory authorities which consider if any steps need to be taken where there is a change in the risk-benefit. As part of the system for monitoring the safety of medicines and vaccines, the HPRA has a spontaneous reporting system by which patients and consumers, and all health care professionals, can report any suspected adverse reactions to us. These reports are then reviewed and transmitted into the European agency database, which is called EudraVigilance, for inclusion in global activity so that we can see trends as they emerge.

Specifically with regard to Gardasil, post-marketing monitoring included: review of all the cumulative data in this database; the published literature; epidemiological studies; and any additional clinical trials that were conducted. It also includes assessment of periodic safety update reports, which the company must submit, and which are reviewed by the regulatory authorities at regular intervals. Indeed, the last evaluation was conducted in December 2004 and the EMA determined that the risk-benefit remains positive.

I wish to talk a little bit about the current European-wide review. In July of this year, what is officially called a referral was initiated by the European Commission based on concerns raised by the Danish competent authority - our sister agency in Denmark.

The European Medicines Agency co-ordinated this review and, in accordance with the applicable legal framework, it was conducted by the agency's pharmacovigilance risk assessment committee, PRAC. The PRAC is a committee of the agency that is responsible for assessing and monitoring the safety of human medicines. It is composed of experts, including doctors, pharmacists and scientists from every EU member state, and representatives of patient organisations and health care professionals. The review focused on the two main conditions reported, POTS and CRPS. Reports of these conditions in young women who received the HPV vaccine had been previously reviewed by the PRAC as part of routine safety follow-up procedures, and a causal link was not established. In the context of this review, the PRAC reviewed all the available data in the EudraVigilance database and from clinical trials. It took account of scientific literature, including everything submitted by Denmark in addition to information from Japan. It also review detailed information submitted voluntarily by the public and patient groups, including patient groups in Ireland. The PRAC also sought the scientific advice of the expert vaccine committee at the European Medicines Agency and supplemented it with expertise in neurology, cardiology and pharmacoepidemiology. Following this in-depth scientific review and robust assessment of all the available data, the PRAC members concluded unanimously that the evidence did not support a causal link between HPV and the aforementioned syndromes in children. The review found no evidence that the overall rates of these syndromes in vaccinated subjects differed from expected rates in the age group, even taking account of possible under-reporting. The PRAC also considered specifically the overall overlapping syndromes of POTS with chronic fatigue syndrome. The results of a large, detailed published study showed no link, and that was highly relevant to the review in respect of chronic fatigue syndrome.

The PRAC review concluded on 5 November of this year that there was no reason to recommend changes to the way the vaccine was reviewed or to amend the current product information. As is standard practice with all these reviews at European level, the recommendation went to the European Medicines Agency's committee for medicinal products for human use, CHMP, which is essentially the licensing committee at the agency. Again, it comprises experts from all member states. Extra representation from patient groups was also considered at the time. The CHMP concurred unanimously with the PRAC recommendation that the available evidence did not support a causal link with the syndromes. The CHMP also concurred that there was no need for any changes to the HPV vaccines and the way they were used, or to the product information. That report was published on 20 November. In accordance with standard practice, the opinion from the European Medicines Agency has been submitted to the European Commission for a legally binding decision that will be applicable in all member states. We expect that in the spring of 2016.

Let me say a few words on our national reporting experience, as it has been referred to. At the start of the HSE school immunisation programme in 2010, the Health Products Regulatory Authority wrote to public health doctors and health authorities, as would be normal practice, and asked them to help us with its monitoring by reporting any suspected adverse reactions to us. Up to the end of October 2015, we received 927 reports. Each of those was entered in the European database and has been viewed as part of the European review. The vast majority of the reports reflect the expected pattern of adverse reactions to vaccines, which include syncope - that is, fainting - malaise, headache, myalgia, gastrointestinal symptoms, dizziness and allergic reactions. There have been some reports of chronic and persistent fatigue, chronic muscle pain and, in some cases, multiple other symptoms of headaches and malaise, as we have heard today. Again, all of these reports have been entered in the European database and were considered as part of the review.

Taking into account the totality of the available information, the Europe-wide review, which involved experts from all member states, has concluded the evidence does not support the view that the HPV vaccines Gardasil and Cervarix cause these syndromes, and that the benefits of both of these vaccines continue to outweigh the risks. We will continue to do our job and monitor them, along with the European Medicines Agency and PRAC, in all member states, including Ireland.