I'm with the Public Health Agency of Canada, and we actually do the post-marketing vigilance for vaccines that are used in humans to prevent disease.
With respect to the deaths in question, I think EMEA put out a press release on January 24, 2008, regarding a couple of deaths. Our action at that time was to contact them the next day, January 25, to ask specifically about their concerns in regard to these deaths. We were reassured by the EMEA officials that they felt that Gardasil was not implicated in the deaths.
Also, through the memorandum of understanding between Health Canada and us, as well as Health Canada and the European Medicines Evaluation Agency (EMEA), we were able to specifically request the reports, which we got by January 28 and distributed to Biologics and Genetic Therapies Directorate counterparts as well as ourselves, to reassure ourselves that there was nothing there that was of concern.
Every death is a concern, but there are actions undertaken. We felt that all the proper actions were taken. We communicated through proper channels with the people who knew about the deaths and we were reassured there was not an issue. Similar things had happened in the U.S., where there were nine deaths.
I think it's important to note that if you looked at the pre-licensure trials that included 10,000 women, not all 9- to 12-year-olds—and I'll come to that in a minute—but among the women who were studied in the 10,000, there was a group that got the vaccine and there was a group that got a placebo, but nobody knew who got which. There were an equal number of deaths in both groups, none of which were thought to be due to either the vaccine or the placebo.
The problem with any product like this that is used in mass programs is that deaths occur spontaneously due to other reasons. At least in a clinical trial, if it does occur, you have an opportunity to show there's no difference between the group that got immunized versus the group that got a placebo, which doesn't contain the active ingredient.
In post-marketing surveillance, you don't have that other group; you just have the report of a death, and you have to try to discern whether this would have happened because of the vaccine or some other reason. So our feeling was, in collaboration and communication with our colleagues both at Health Canada as well as internationally, that these were not due to the vaccine.
I don't know if you want me to address also the question about the children, the younger girls. In the trials that were done for the vaccine itself.... I think it was made evident earlier that any product that comes to market may have been tested, and with Gardasil, it was 10,000-plus individuals who were tested. That's a lot, but that's not enough to detect rare events, and that's why you need to have post-marketing surveillance. In rare events such as death, each one needs to be investigated and looked at.
In the pre-licensure trials that were done, they were unable to include large numbers of younger children, because of the need to do specific tests that were thought to be inappropriate to do on prepubertal girls. So the tests were only done for those 13 years of age and up. But they then tried to test whether the immune response the younger girls would have would be equivalent, and you don't need to have nearly as a big a number as that.
So from the point of view of the effectiveness of the drug, that was clearly studied. For the safety of the drug, you wouldn't have enough numbers even in the 10,000. So the smaller number, a few hundred of the 9- to 12-year-olds, clearly wasn't enough, but that's something that's followed in post-marketing surveillance.