# Abstract

 

## Background Data about the vaccination status of participants are required in epidemiological cohort studies whenever infection or immunity is considered as potential exposure or outcome. Within Pretest 2 of the German National Cohort (GNC) we therefore investigated the acceptance and feasibility of extracting vaccination status from vaccination certificates provided by the participants of the study. 

## Methods This study was conducted in three study centers (Bremen, n = 73; Hamburg, n = 200; Hannover, n = 193). In order to test if an additional reminder would prevent participants from forgetting their vaccination certificates at home persons willing to participate in Pretest 2 were randomly assigned to one of three invitation groups (IG). About one third of the participants received either no further reminder (IG1), a reminder card together with the appointment letter (IG2) or a separate reminder card 4 days before the appointment (IG3). At the study center, vaccination data were scanned or copied and entered into a database using a unique identification number. Participants were also asked to fill in a short questionnaire to assess the completeness of the provided vaccination data. Additionally, in one of the three participating study centers, general practitioners (GP) were asked to provide vaccination data from their records following respective participants' consent. Finally, we compared the influenza data from the vaccination certificates with the influenza data obtained from participants in Pretest 2 by use of a self-administered questionnaire (ID-Screen). 

## Results Due to different starting dates of the study the intended reminder procedure was implemented only in Hamburg and Hannover. In Hamburg, significantly more vaccination certificates were submitted by the group which received the reminder card separately 4 days before the examination (IG3) compared to IG1 and IG2 (*p* = 0.04). In Hannover, in contrast, most vaccination certificates were brought by those who received the reminder card together with the appointment letter. Overall, the use of a reminder card had a positive but not significant effect as 89 % (185/209) of participants who received the reminder card submitted vaccination data versus 81 % (84/104) of participants who did not receive any reminder card (*p* = 0.06). Of all Pretest 2 participants in Hannover, 62 % (120/193) gave written consent for data collection by the GPs. In total, 114 practices were contacted of which 49 (43 %) sent vaccination data. All in all, 360 vaccination certificates with 5065 documented vaccinations were entered into a database, of which 4830 (95 %) were valid for analysis covering a period from 1946 to 2012. The comparison of influenza vaccination data from vaccination certificates to the remembered data from a self-completed questionnaire showed an agreement of data in 46 % (84/184) of cases (Kappa = 0.48). Influenza vaccinations were underreported in 4 % (7/170) of self-completed questionnaires. 

## Conclusion The reliable documentation of vaccinations within the context of the GNC proved to be feasible and thus recommendable at a large scale within the GNC as participants showed high willingness and compliance in providing available vaccination documents. An additional validation by means of documents provided by physicians seems to be possible for more than a quarter of participants. In order to maximize the likelyhood of participants' of bringing their vaccination certificates it would be sufficient to send a reminder card together with the appointment letter. 

## Electronic supplementary material The online version of this article (doi: 10.1007/s00103-014-2050-0) contains supplementary material, which is available to authorized users. # Results 

## Participation The recruitment process for this feasibility study differed among the participating study centers. On the one hand, the invitation procedure consisting of three different invitation groups was implemented in Hamburg and Hannover only, due to a later starting date in Bremen. Consequently, all participants in Bremen invited to Pretest 2 received by default the reminder card together with the appointment letter. On the other hand, participation proportions for this feasibility study could be calculated for Hannover only, as in Bremen and Hamburg the consent for the vaccination data collection was integrated into the consent form of the Pretest 2 baseline assessment whereas in Hannover participants were asked for a separate consent. Recruitment data and participation proportions per invitation group are shown in Fig. [2](#). The participation proportions of the random samples are of special interest because the study protocol for the GNC allows random samples only; therefore, participation proportions will be discussed mainly in this respect. Overall, 400 persons were invited to participate in this feasibility study. In Hannover, 92.2 % (153/166) of Pretest 2 participants gave a separate written consent for the vaccination data collection. Again 92.2 % (141/153) of these participants brought vaccination certificates to the appointment. In Hamburg and Bremen, where participants were not explicitly asked for their willingness to participate in this feasibility study, the proportion of provided vaccination certificates was slightly lower: 80.0 % (128/160, one missing) of invited persons in Hamburg and 75.3 % (55/73) in Bremen provided vaccination data. <figure> <p><img src="" /></p> <figcaption>Flow chart of the recruitment and submitted vaccination certificates. <em>RS =</em> random sample from local registry, <em>CS</em> = convenience sample, consisting of volunteers, e.g. students, friends, colleagues and family members. Invitation group (IG): Appointment letter + … IG1: no further reminder; IG2: a colored reminder card together with the appointment letter; IG3: 4 days before the appointment at the study center a separate, colored reminder card (Fig. <a href="#">1</a>). <em>*</em>Hamburg: 1 missing case with no information about assigned invitation group, <em>**</em>Participation: Participants were asked for a separate consent for the vaccination data collection in Hannover only, <em>***</em>Bremen: No documentation sheet about the invitation process available. 75 % of invited persons provided vaccination data the same day of examination or later.</figcaption> </figure> Considering the overall effect of the reminder card in Hamburg and Hannover, 89 % (185/209) of participants who received a reminder card (regardless if IG2 or IG3) brought their vaccination certificate compared to 81 % (84/104) of those who did not receive any reminder card (IG1; *p* = 0.06). The approach to send a separate reminder card 4 days before the appointment was the most successful; 92 % (94/102) participants of IG3 provided vaccination data compared to 85 % (91/107) in IG2 (*p* = 0.06). Stratifications by study center indicated that in Hannover participants in IG2 provided the most vaccination certificates (95 %), whereas in Hamburg, significantly more vaccination certificates (92 %) were provided in IG3, with no differences between IG1 and IG2 (chi-square^2^: 6.546, df 2, *p* = 0.04). 

## Data provided by physicians Of 193 Pretest 2 participants in Hannover, 120 (62 %) provided written consent for the data collection by general practitioners. In one case the consent was given but the participant had not been in contact with the health care system for a long time so that he could not provide any GP address. In total, 114 practices were contacted of which 43 % (49/114) sent vaccination data. Two practices did not send any data because no vaccination was given during the past 10 years. In most cases the medical staff filled in the paper documentation sheet, with a few providing computerized print-outs. 

## Questionnaire The short questionnaire was completed by 94.7 % (426/450) of participants including the convenience sample. There were considerable differences between the study centers. Whereas in Hamburg all participants completed the questionnaire (200/200), this was the case for 98.9 % (175/177) of the participants in Hannover, and for only 70 % (51/73) in Bremen (data shown in supplement). Thorough data cleaning was necessary because of inconsistent responses. For example, the question, if the participant ever possessed a vaccination certificate was denied by 16 persons of whom 5 persons submitted their vaccination certificate to the study personnel the same day. A problem seemed to exist also if more than one vaccination certificate existed so that participants were not sure to which one to refer. Moreover the high percentage of missing answers for most questions, coded as "don't know/no answer", suggests that these questions were difficult to remember and thus not suitable for a self-administered questionnaire. Of all participants, 96 % had possessed a vaccination certificate once during their life-time, with 91 % possessing one at the moment. There were no differences between random and convenience samples. In all, 37 % of responders indicated that the present vaccination certificate was the first, whereas for 55 % of responders it was the second up to fourth vaccination certificate. In addition, 67 % answered to have brought all available vaccination data to the study center, 54 % included all vaccinations ever received (random sample). Tetanus (18 %), influenza (17 %) and vaccinations received in childhood (13 %) were indicated most often as vaccinations not included in documentation. The question regarding the attitude towards vaccinations was answered by 416/426 (98 %) participants. The attitude towards vaccinations was assessed by 74 % of responders as positive. Of those 18 % being critical, 45 % indicated fear the side effects of vaccinations and 30 % were concerned that vaccinations might overwhelm the immune system. Among other reasons, responders took the chance to explain more in detail their critical attitude against specific vaccinations like influenza vaccination because of bad experiences. Only one person indicated to be in principle opposed to vaccinations; for 8 % of responders vaccinations were no issues of concern. No statistical difference of attitude towards vaccination could be detected between persons who submitted their vaccination certificate compared to those who did not submit any vaccination data. 

## Capturing and availability of vaccination data Overall 372 vaccination certificates were electronically captured or copied the same day of examination, of which 7 % (27/372) of vaccination certificates were lost primarily because of missing identification numbers (ID) on the copy/scan. The procedure of blackening the personal data before capturing the vaccination data electronically was not followed consequently so that in about 17 % of documents this needed to be worked over subsequently. The quality of vaccination certificates was partly poor, especially the older ones (before 1990) often lacked the names of given vaccines (1700 vaccines), or the date of vaccination. In 5 % (222) of cases, the vaccination date was missing, (partly) illegible or cut off during the process of scanning/copying the vaccination data. Some of these data (121 dates) could be recorded as described above. Further problems encountered were the lack of information about vaccines as single or combined vaccination or the illegibility of documented vaccinations. The median time for data entry was 14.3 min per vaccination certificate (minimum of 0.4 min; maximum of 124.3 min). Including the data of physicians, vaccination data could be obtained for a total of 82 % (367/450) of participants or 79 % (367/466) of all eligible Pretest 2 participants. An overview of submitted vaccination data per study center (number of valid vaccination documents and vaccinations) including the sample characteristics of persons submitting vaccination data is shown in Table [1](#). The documented vaccinations covered a period from 1946 to 2012. ::::table-wrap

::: caption
Submitted vaccination data and sample characteristics
:::

______________________________________________________________________

```
                                        Hamburg        Hannover         Bremen        Total                                      
```

______________________________________________________________________

No. of valid documents 158 155 (162^a^) 47 360 (367^a^)

No. of vaccinations 2402 1968 (2186^b^) 510 4880 (5098^b^)

No. of vaccinations/person 15.2 13.9 10.9 14.1

Mean (95 % CI) (13.8--16.6) (12.5--15.3) (8.7--13.0) (13.2--15.0)

**Sample characteristics** **n** **%** **n** **%** **n** **%** **n** **%**

Female 90 57.0 87 53.7 25 53.2 202 55.0

Male 68 43.0 75 46.3 22 46.8 165 45.0

20--29 years 23 14.6 18 11.1 3 6.4 44 12.0

30--39 years 15 9.5 17 10.5 - - 32 8.7

40--49 years 38 24.1 47 29.0 8 17.0 93 25.3

50--59 years 36 22.8 36 22.2 18 38.3 90 24.5

60--69 years 46 29.1 44 27.2 18 38.3 108 29.4

Born abroad 16 10.1 15 9.8 7 14.9 38 10.6

First language German 148 93.7 142 92.8 43 91.5 333 93.0

Married 59 37.3 88 57.5 23 48.9 170 47.5

Single 66 41.8 44 28.8 14 29.8 124 34.6

Full time employed 75 47.5 73 47.7 28 59.6 176 49.2

Monthly household net income (median): 83/146 56.8 73/141 51.8 19/46 41.3 175/333 52.6
2250 € up to \
3000 €



## **N** **158** **162** **47** **367**

*GNC* German National Cohort, *GP* general practitioners, *DEGS* Studie
zur Gesundheit Erwachsener in Deutschland, *GEDA* Gesundheit in
Deutschland aktuell, *CI* confidence interval

^a^(...): Including data of seven participants in Hannover (4 of random
and 3 of convenience sample) who provided physicians' data only (with 33
documented vaccinations) as no vaccination certificates were available

^b^(...): Including all vaccinations documented by physicians
(*n* = 218):::: 

## Comparison of vaccination data provided by participants and physicians For 40 participants in Hannover vaccination data from vaccination certificates and physicians' documentation were available with a total of 630 documented vaccinations covering the period from 1956 to 2013. Most frequently documented vaccinations are shown in Table [2](#). Single vaccinations against poliomyelitis and tetanus were significantly more often, influenza vaccinations significantly less often documented in vaccination certificates than at the physicians' offices. To assess the quality of vaccination documentation, the data captured by vaccination certificates were compared to data provided by physicians. Using the example of tetanus, 27 persons provided tetanus vaccination information documented in vaccination certificates (125 vaccinations) as well as documented by physicians (54 vaccinations). In all, 30 % (38/125) of tetanus vaccinations documented in the vaccination certificates corresponded exactly with tetanus vaccinations documented by physicians for 20/27 persons (74 %). In these cases the date of vaccination, the kind of vaccine and the producer of the vaccine were documented identically in each document. A total of 6 % (7/125) of documented tetanus vaccinations in the vaccination certificates did not correspond to documented tetanus vaccinations by physicians for 6/27 persons (22 %). Tetanus documentation differed because either the name of the vaccine was missing, not consistent or different producers of vaccines were indicated. In addition, 8/54 (15 %) tetanus vaccinations documented by physicians were not documented in the vaccination certificates which accounts for at least 6 % (8/125) of tetanus vaccinations missing in the vaccination certificates. ::::table-wrap
::: caption
Frequency of vaccinations documented in vaccination certificates
compared to vaccinations documented by physicians
:::

______________________________________________________________________

Document by Participant Physician\
(1956--2012) ^a^ (1964--2013) ^a^

______________________________________________________________________

Single poliomyelitis 88 20 % 13 7 %

Single tetanus 68 15 % 14 8 %

Tetanus (combined vaccine) 118 27 % 40 22 %

Influenza 33 7 % 66 36 %

Single hepatitis B 22 5 % 8 4 %
21

Hepatitis A + B 20 5 % 14 8 %



## No. of vaccinations 446 184

Base: 40 participants with vaccination certificates and vaccination
documentation from physicians

^a^The vaccination certificates covered a period from 1956--2012, the
vaccination data sent by physicians from 1964--2013:::: 

## Vaccination status The vaccination coverage of responders (last dose no longer than 10 years ago) for some preventable diseases is shown in table [3](#). ::::table-wrap
::: caption
Vaccination coverage according to vaccination certificates
:::

```
            Hamburg   Hannover   Bremen    Total                                              
```

______________________________________________________________________

```
            n         %         n         %       n        %      n         % (95 % CI)   
```

Tetanus Female 74 82 66 76 21 84 161 80 (59--74)
Male 45 66 49 65 16 73 110 66 (59--74)\
Total 119 75 115 71 37 79 271 74 (69--78)\
Diphtheria Female 69 77 59 68 20 80 148 74 (67--80)
Male 43 63 46 61 16 73 105 63 (56--71)\
Total 112 71 105 65 36 77 253 69 (64--74)\
Polio Female 50 56 39 45 13 52 102 51 (44--58)
Male 26 38 30 40 12 55 68 41 (33--49)\
Total 76 48 69 43 25 53 170 46 (41--51)\
Hepatitis B Female 32 36 23 26 3 12 58 29 (23--35)
Male 17 25 16 21 2 9 35 21 (15--27)\
Total 49 31 39 24 5 11 93 25 (21--30)\
Hepatitis A Female 28 32 23 26 5 20 56 28 (22--34)
Male 23 33 16 21 1 5 40 24 (18--31)\
Total 51 32 39 24 6 13 96 26 (22--31)\
**N** **158** **162** **47** **367**\
Measles^a^ Female 19 79 12 63 - - 31 72 (58--86)
Male 12 86 11 69 2 67 25 76 (60--91)\
Total 31 82 23 66 2 67 56 74 (64--84)\
**N** **38** **35** **3** **76**

Number of persons who received at least one respective vaccination
within the last 10 years

^a^Vaccination against measles in Germany recommended since 1974. Base:
all participants of the age 20--39 years in the respective study centers
who submitted their vaccination certificates:::: 

## Comparison of data from a self-completed questionnaire (ID-Screen) versus vaccination data from vaccination certificates In Pretest 2, the ID-Screen questionnaire, a self-administered questionnaire about infectious diseases, was applied in Hamburg and Hannover (see Castell et al. in this issue). Three questions about influenza vaccination were included: whether an influenza vaccination has ever been received (V1), if yes, in which frequency (V2) and the year of the last influenza vaccination (V3). In total 365 persons answered the influenza questions. Vaccination documents were available for 78 % (284/365) of these participants, which allowed assessing the agreement of self-reported versus documented influenza vaccinations. Half of all responders (184/365) indicated having ever been vaccinated against the flu (Table [4](#)). Agreement with documentations was found for 84 (46 %) of these responders [Kappa 0.48] with up to 20 influenza vaccinations per person. Vaccination was underreported in 4 % (7/170) of cases where the receipt of influenza vaccination was negated but documented in the submitted vaccination records with up to 3 vaccinations per person. The "unvaccinated" responders were mostly vaccinated in 2008--2010 (7/11 vaccinations). The self-reported year of last influenza vaccination was confirmed by vaccination records in 27 % of cases (41/150). In 23 % (35/150) of cases the self-reported year did not correspond to the vaccination records because the year of the last remembered influenza vaccination was before (19 %) or after (5 %) the last influenza vaccination documented in the vaccination records. ::::table-wrap
::: caption
Comparison of influenza data from a self-completed questionnaire (ID-
Screen) versus influenza vaccinations documented in vaccination records
:::

```
             V1: ever vaccinated   V1: confirmed   V2: every year   V3: last year confirmed                        
```

______________________________________________________________________

```
             n                     %              n                %                        n    %     n        %
```

Female 103 52.8 53 51.5 29 28.2 26/87 29.9
Male 81 47.6 31 38.3 27 33.3 15/63 23.8
Total 184/365 50.4 84 45.7 56 30.4 41/150 27.3
60--69 years 73/102 71.6 35 47.9 30 41.1 13/63 20.6
Hamburg 95/200 47.5 39 41.1 31 32.6 17/76 22.4
Hannover^a^ 89/165 53.9 45 50.6 25 28.1 24/74 32.4

*V1: ever vaccinated* Have you ever been vaccinated against influenza?
-- yes (ID-Screen questionnaire)

*V1, confirmed* Agreement between reported influenza vaccination (V1)
and documented influenza vaccinations in vaccination certificates. *V2*
Self-reported regularity of influenza vaccinations in ID- Screen
questionnaire (every year, almost every year, less often than every
year, only once)*V3, last year confirmed* Agreement between
self-reported year of last received influenza vaccination (*n* = 150)
and vaccination date found in vaccination certificates

^a^Hannover only: Including vaccination data provided by physicians::::


Extracted trial result:
Outcome: vaccination certificates were submitted (binary)
Intervention: a separate reminder card 4 days before the appointment (IG3)
Comparator: reminder card together with the appointment letter (IG2)
Intervention events: 94
Intervention group size: 102
Comparator events: 91
Comparator group size: 107
Notes: found in text as fractions of group sizes