The results of this study indicate that a large-scale prospective active surveillance system for ‘near real-time’ vaccine safety monitoring that would be complementary to other initiatives is feasible. Through the use of information technologies, the study was relatively novel in that patients could enrol for the study and securely enter their data online, which improves patient involvement in research as well as dramatically limiting the cost of the study. The online methodology also allowed the study to be set up very quickly in response to the urgent nature of the introduction of the vaccination programme at a time when the pandemic proportions could not yet be predicted. The study was done without any specific external funding. The predominant material costs were the printing of patient information sheets and advertising posters that were sent to GP surgeries.
One advantage of our study design was that it was prospective in nature and it encouraged ‘near real-time’ reporting of event data from patients who experienced no problems after swine flu vaccination, as well as from those experiencing side effects, unlike many other reporting systems that only collect data on affected individuals. Since outcome data were collected at monthly intervals after consent for participation was given, bias introduced by over-reporting from patients who may have participated because they experienced an event was likely to be minimal. We also recruited a group of non-vaccinated individuals who had been offered vaccination but had decided not to have it, as a comparator group, although this group eventually only comprised less than 10% of the total study population. Overall, we recruited approximately 1% of the vaccinated population in Scotland to this study. There was good representation of patients from GP practices throughout Scotland, so we have no reason to believe that the study cohort is not representative of the general Scottish population for whom vaccination was indicated. However, we did not collect the characteristics of individuals offered vaccination who did not participate in the study. Another advantage of our study was that we were able to recruit and follow up a cohort of pregnant women, one of the target groups for vaccination, and also ascertain the outcomes of births in these women as well as those who became pregnant shortly after receiving the vaccine.
Limitations of the study included an incomplete response rate to follow-up requests, some difficulties contacting patients where contact details had been incorrectly completed at time of registration, e.g. incorrect e-mail addresses and no other contact details provided, and the fact that only around one third of general practices in Scotland were able to make our study information available to their patients attending for vaccination (mainly due to timing and workload concerns) 
. We were also not able to distinguish between patients receiving the two available types of vaccination in the UK [Celvapan® (Baxter) and Pandemrix® (GSK)], although it is known that Pandemrix® was much more widely used than Celvapan®during the vaccination programme. We only asked participants to report what they considered to be serious (requiring urgent medical attention) reactions to the vaccine, to allow us to concentrate on capturing more important adverse reactions. Thus minor local side effects and minor systemic reactions are by design likely to be under-reported and recorded, with the additional possibility of differential reporting between exposed and unexposed groups. Data on children were limited because additional approvals to extend the study to include children aged 16 years or less were only obtained towards the end of the study period (February 2010) and any forms received from children who tried to register earlier in the study had to be discarded until the appropriate approvals were in place.
The results of this study support those of most other studies on the safety of swine flu vaccination 
and the results of the MHRA yellow card system surveillance programme suggesting that overall, H1N1 vaccination is safe 
. Ascertaining accurate background rates of events in any population is difficult 
and we acknowledge that this study is unable to inform on excess risk attributable to use of the vaccine, in addition to those risks likely as a result of complex morbidities seen in target vaccination groups, particularly since the number of unexposed participants was low. There were no confirmed cases of GBS in this study, which was one of the main concerns regarding similar influenza vaccinations in the past, although one patient developed widespread neurological symptoms thought to be a form of generalized nerve damage within hours of vaccination. We also had no reported cases of narcolepsy. Narcolepsy was identified as a possible risk of H1N1 vaccination (Pandemrix®) in Scandinavian countries and the possible link is currently undergoing further investigation although at present no causal relationship has been established 
. The six deaths that occurred in vaccinated patients in this study were due to other factors and were judged to be unrelated to vaccination.
There were four miscarriages within the population of 128 women reporting 130 pregnancies in this study (incidence of 3.1%). Miscarriage is recognized to occur in up to 15% of confirmed pregnancies 
, although often remains unrecognized or unreported. The incidence observed in our study was well within the expected incidence in the population. Of the six reported possible congenital abnormalities in neonates born to the pregnant women taking part in the study (all of whom received the H1N1 vaccine), some of these were minor (e.g. umbilical hernia and skin tag on finger) and occur commonly, but all are reported for completeness. There was no pattern of any one type of congenital abnormality that occurred in more than one neonate.
With more time for preparation, more broad inclusion criteria to include special populations such as children earlier, more publicity and funding for recruitment advertising, and if rolled out to the entire UK population (approximately 55 million) rather than limited to Scotland (approximately 5.5 million) we could use this study methodology again to recruit much larger numbers of patients with high quality data at a reasonable research cost.
In conclusion, no significant safety issues were identified in patients exposed to H1N1 influenza A vaccination in this study. The use of web-based technology in the study was successful in reducing costs and allowing the collection of high quality data directly from patients. This method for near ‘real-time’ monitoring, with minimal additional workload for healthcare staff, should be considered as an additional pharmacovigilance tool for other safety studies.