Introduction
Influenza continues to be a considerable health problem in Europe (1-3). Complications associated with influenza are especially present in elderly patients and patients with chronic conditions such as cardiovascular and respiratory disorders (4,5). Vaccination is an effective intervention, reducing mortality and morbidity as a result of influenza, especially in elderly and patients with high risk conditions (5-8). Despite the evidence of effectiveness, there is variation among European countries in uptake rates for vaccination (4,9). Different uptake rates may have consequences on the costs associated with hospital admissions and casualties. A study carried out in Germany in 1996 (1) estimated that each influenza patient costs an average of 632 Euros. This included indirect costs like unfitness for work. In the United States, comparable estimates have been reported (11).
There is very little information available on how countries in Europe inform and recruit at risk populations for influenza vaccination. This information may be useful for identifying each country's ability to reach patients at risk for future pandemic planning at a European level (10). The vaccinations may be distributed by different distribution channels, for example, GPs, public health authorities, occupational health authorities, old people's homes.
The aim of this study is to gain detailed insight into vaccination uptake rates (especially of risk groups), the vaccination campaigns and the practical organisation of the campaigns in European countries. Since monitoring systems may have limitations and biases, we compare our data with uptake rates computed from vaccine sale figures. We expect a high correlation between both types of data.
The following research questions were formulated:
1. Do countries monitor the vaccination rates of the different risk groups? If yes, how do they monitor them and what is the vaccination rate for each group?
2. Which distribution channels are used for which target groups?
3. Which strategies are used to increase uptake rates and how do they affect uptake rates?
4. Are the uptake rates that result from monitoring systems comparable with uptake rates that are calculated on the basis of vaccine sales data?

Methods
A survey was carried out among the countries of the European Economic Region (the European Union and Norway, Switzerland, and Iceland), the pre-accession countries (the Baltic states, Poland, Hungary, the Czech Republic, and Slovenia), and Russia. A questionnaire was sent to influenza experts in these countries. The experts were recruited via EISS (the European Influenza Surveillance Scheme) and EuroGROG (the European "Groupes Régionaux d'Observation de la Grippe"). These experts are nationally recognised clinicians, epidemiologists, and virologists who are responsible for providing EISS and EuroGROG with data on influenza activity in their country. They were asked to fill in the questionnaire themselves, if possible. However, when they did not feel qualified to answer (some of) the questions, we asked them to name the person(s) to contact in their country for further information.
The questionnaire consisted of two parts:
1. Monitoring vaccination uptake:
Questions dealt with: uptake rates and monitoring methods for the different groups at risk
2. Target population recruitment
Questions about: methods used to inform the target population about influenza vaccination; distribution channels used for the different groups at risk; strategies used to increase uptake rates, in particular financial incentives for physicians and patients and personal invitations for patients.
We collected data for the year 2000 (the vaccination campaign of the 2000-2001 influenza season).

Response
The questionnaire was distributed to 52 experts in 32 countries (England, Wales, Scotland, and Northern Ireland were considered as independent countries, since they have independent healthcare systems). We received responses from 33 experts in 27 different countries. Seven experts provided the name of another expert whom they felt would be better qualified to complete the questionnaire. The experts contacted in Sweden indicated that they could not answer the questionnaire because there was no national policy concerning influenza vaccination and that the regional differences were so large that filling in the questionnaire was not possible.
When we received more than one response from a country, the questionnaires were compared. Inconsistencies were dealt with as follows: in the case of no answer from one expert, the answer of the other expert was used. When the difference was small, the most optimistic response was taken. When experts contradicted each other, we contacted them by email to ask for clarifications. In the end, information was available for 26 countries, resulting in a net response rate of 84%. No response was received from Croatia, Greece, Iceland, Russia, or Wales.

Analysis
To study the relationship between vaccine uptake and strategies to increase uptake rates, we used a non-parametric test (Mann Whitney U) to test whether countries that applied the strategy differed in uptake rates from countries without this strategy. For the comparison between uptake rates for the elderly and vaccine sales figures, we used Pearson's correlation. To control for differences in age distribution among the countries, the sales figures were corrected for these differences (the Netherlands was chosen as the reference country).

Results
Monitoring uptake rates
The majority of the countries (18 out of 26, almost 70%) reported that they monitor vaccination uptake rates. In 11 countries, vaccinations are reported to national organisations: in this case the persons who administer the vaccinations (eg the GPs) report to these organisations. These organisations are either public health institutes (3), the ministry of health (3), centres for communicable diseases (3) or another institution (2). Seven countries use national surveys. In this case the population is asked whether they received a vaccination (for example, by telephone survey). Four countries reported the existence of sentinel networks that are used to obtain this information (the Netherlands, Romania, Switzerland, and England). Only in the Netherlands, however, was it possible to calculate uptake rates, differentiated by risk group based on the data of this network. In Switzerland, for instance, it is very difficult to calculate the high risk population denominators, because GPs do not have fixed patient lists (patients are free to choose their GP and are not allocated to a single GP).
Most countries (14 out of 18) that monitor vaccination uptake rates were able to provide data about the elderly (mostly those aged 65 years and older, Hungary provided rates for 60 years and older). Figure 1 presents the variation in vaccination uptake, varying from 15% in Romania to 81% in the Netherlands.

Few data were available for the other risk groups we were interested in (see Table 1). Figures for the total population with chronic disease were provided by France (44% uptake) and Germany (about 50% for 18 years and older (12)). They were not able to break these figures down by disease, however. Denmark reported the figures for Copenhagen, where vaccination is free of charge (66% for the elderly, 78% for elderly with chronic condition and 33% for younger chronic ill). The figures were different to the rest of the country, where a fixed payment is charged (uptake rates of 46%, for the elderly, 57% for the elderly with chronic condition and 28% for the younger chronically ill).

Distribution channels
The GP is the main distribution channel for vaccines to the population at risk (85% of the 26 countries). In 30% of the countries (7 out of 26), public health organisations play an important role. In Belarus and Portugal, all vaccinations are distributed by public health organisations. In Italy, Norway, Poland, Slovenia, and Spain, both distribution channels are used. For the elderly, institutional physicians administer the vaccine in 40% of the countries (in other countries this might not be the task of this physician or countries may not have institutional physicians). The healthy population receives their vaccines either from the GP or by company physicians.

Strategies to increase uptake rates
Most countries make use of mass media to promote influenza vaccination. The main methods used are: newspapers (92%), radio (81%), and television (73 %). Another popular method of informing the public is by flyers in GP's waiting rooms (81%, 21 countries out of 26). In about two thirds of the countries surveyed, people are informed by personal invitation by their GP. France is the only country where a public health organisation (PHO) is involved. Here patients receive a personal voucher from the PHO for a free vaccine.
There is very little reliable information on what percentage of GPs use personal invitations. France and Germany reported that GPs are not allowed to send personal invitations without the patient's prior consent. From the 10 countries that reported the availability of automated mechanisms to select influenza patients from electronic medical dossiers, 60% indicated that only a few GPs used this method. For PHOs, only one country (France) uses electronically assisted patient selection. In our study, we did not find evidence that countries where GPs make use of personal invitations to remind the population at risk reported higher uptake rates (Mann-Whitney-U = 16.5, p = 0.62).
One of the experts from Germany reported that a medical practice cannot invite the public to come to the practice and get vaccinated because that would be against the competition laws (practices should not advertise themselves by any means). Pharmaceutical companies cannot send reminders to the public to get vaccinated as this is considered to be a pharmaceutical advertisement and mentioning a certain product would break the competition laws for companies.

In 15 (out of 26) countries, the vaccination is free of charge for the population at risk. In the other countries (11 out of 26), a fixed payment is usually charged. In Belgium, partial reimbursement depends on the insurance company and is only for people over than 65 years of age. In Norway, the fixed price for the population at risk is one third of the price paid for by the healthy population. In Bulgaria, Lithuania, and Poland, the price varies with the manufacturer of the vaccine. In Denmark, local politicians may decide to offer the vaccine free of charge (for example, in Copenhagen). Table 2 provides an overview of the different payments within each country.

Countries with co-payments for the elderly achieve lower uptake rates compared to those that distribute the vaccines free of charge (Mann-Whitney-U = 4.0, p = 0.05, see Figure 2).

For the healthy population, if the vaccination is carried out by a company physician, it is mainly free of charge (20 out of 23 countries, 87%). When the vaccination is given by the GP, in most countries, a fixed amount is charged (see Table 2). About half of the countries (9 out of 18) that deliver vaccination via public health authorities charge a fixed amount, in two countries the charges are dependent on the income of the person (Ireland and Italy). In two other countries (Hungary and the Slovak Republic) the healthy population does not have to pay the full price, they are subsidised by the health insurance companies.
Company physicians, public health workers and institutional physicians mainly receive salaries without any extra compensation for the vaccinations they administer. In half of the 26 countries, the GPs receive salaries without extra compensation and in the other half either salaries with extra remuneration for vaccinations administered or fee-for-service. We tested the effect of positive financial incentives, here broadly defined as either extra compensation or fee-for-service payment. We found that countries where physicians received extra income for administering vaccinations reported higher uptake rates in the elderly compared to countries where physicians received no such payments (Mann-Whitney-U = 6.0, p=0.02, see Figure 3).

Comparing monitoring data with sales figures
We compared the data that resulted from monitoring vaccine uptake with sales figures per country (Table 3). The countries where both sales figures and monitoring data were available were Denmark, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, Switzerland, and the United Kingdom. The sales figures provide total population uptake rates only and could not be differentiated by risk groups.
The correlation between both data was 0.84 (Pearson correlation coefficient, p > 0.00). However, since age distribution may vary among the selected countries, we standardized for age distribution. This increased the correlation coefficient to 0.91 (p < 0.00).

Conclusions and discussion
According to our study, monitoring of influenza vaccination uptake in Europe is underdeveloped. For the elderly, vaccination uptake is relatively well documented, but this is only the case in slightly over half of the European countries (14 out of 26). For the other population groups, the uptake rates are poorly documented. For example, the only countries with data on the cardiovascular risk group are the Netherlands and Romania. An important problem with these groups is the lack of information on the overall size of the specific population groups. Without population denominators, it is impossible to determine the uptake rate.
The main distribution channel to administer vaccines to people at risk is the GP. In some countries public health organisations are also involved. A minority of the vaccines are administered by company physicians to (mainly healthy) employees or institutional physicians to mainly elderly in old age homes.
There is also a lot of variation in the way uptake rates are monitored. Some countries use surveys (telephone or mail) among the general population, others use compulsory reports made to health authorities by providers of the vaccinations, and a few use the data available from sentinel networks. Each method has its limitations. Collecting information by sentinel networks and (national) surveys may lead to an underestimation of influenza vaccination uptake in certain groups. Sentinel networks miss out vaccination carried out by other channels (for example, company physicians or public health authorities) and surveys may miss out certain groups of the population, for example, persons who have language problems or are too old or too young to participate.

We have some indications that financial incentives for both physician (extra income) and patient (having the vaccination free of charge) might increase vaccination rates. Most of the countries that have payments for those at risk are situated in eastern Europe (five out of eight countries). Especially in these countries, where the average income is low, this contribution may lead to actual barriers for the population at risk. Due to the low number of countries that could provide uptake rates for the elderly, however, a thorough multivariate analysis, taking into account other important healthcare system characteristics was not possible. Priority for vaccination policy and healthcare resources may also play an important role. A previous study of vaccination uptake in the Netherlands (15) found that personal invitations affect uptake rates in a positive way. We found that countries where personal invitations were used did not achieve higher uptake rates compared with countries that did not use this method. This is probably due to the failure of GPs to use their information systems to identify patients who should be vaccinated, since eight countries reported that selection facilities are available in these systems.
The comparison between population uptake rates based on sales figures and uptake rates for the elderly showed a considerable high correlation. However, better estimates for the elderly vaccination rate are obtained by standardising for age distribution. Within this study we could not identify whether the countries with large deviations resulted from different uptake rates in the other target groups or different definitions of target groups (for example, including or excluding healthcare workers). Another source of deviation may be the different methods used to assess uptake rates (sales figures compared with monitoring systems).

The most important limitation of this study is that the information was collected at country level, thus variations within countries may be levelled out. This may affect the findings, especially when payments by patients within a country vary due to differences in insurance policies or when personal invitations are used to increase uptake rates. Another limitation is the fact that the data are reported data, sometimes by only one expert per country.
We recommend that a uniform method to monitor influenza vaccination uptake within risk groups be developed for Europe, in order to obtain comparable data in the different countries. For quality improvement, interventions must be measurable by comparing data before and after the intervention. Also, comparable data enable countries to learn from each other's strategies to improve vaccination rates. The monitoring could be either based on a network of population surveys (for example, telephone surveys) or sentinel networks. The choice for a method requires insight into the limitations of each method, and would require further research. Whatever method is chosen, central coordination will be necessary. This could be accommodated within ESWI or EISS and EuroGROG. EISS and EuroGROG already have a surveillance network for influenza (16). The vaccine distribution data that are already collected by ESWI may be used as a proxy for uptake rates for the elderly after correction for age distribution. However, these data do not provide insight in uptake rates of the other (smaller) risk groups. It also is important to study the ability of countries to provide reliable population data on the incidence of chronic diseases. Without these data, no uptake rates of the chronic ill can be computed. Another problem is the differences between healthcare systems in Europe, which may make a surveillance method appropriate for one country but not applicable for others.

Remerciements / Acknowledgements
Cette étude a été commissionnée par le Groupe de travail scientifique européen sur la grippe (European Scientific Working group on Influenza, ESWI). Nous tenons à remercier tous les experts des pays pour avoir investi leur temps pour notre questionnaire.
This study was commissioned by ESWI (European Scientific Working group on Influenza). We would like to thank all the country experts for investing their time in our questionnaire.