Well-Documented Reports in VigiBase Overall
There are a total of 7.0 million reports in VigiBase up until January 2012, having an average completeness of 0.45. 900,000Footnote 2 (13 %) reports have vigiGrade completeness higher than 0.8 and are classified as well-documented for the purpose of our study. Figure 3 shows the variation over time in the proportion of well-documented reports and average completeness in VigiBase (non-cumulative). Both the average completeness and the proportion of well-documented reports were higher until 1980 and have since declined: the average completeness from around 0.50 to 0.45, and the proportion of well-documented reports from around 25 to 13 %.
Well-Documented Reports in VigiBase Since 2007
Between January 2007 and January 2012, 3.3 million reports were entered into VigiBase. The average completeness was 0.46 and 430,000 reports (13 %) were classified as well-documented. The median completeness was 0.41 with an interquartile range of 0.26–0.63. Figure 4 shows the distribution. Figure 5 shows the number of well-documented reports per country, in descending order, for countries with at least 1,000 reports in total since 2007. The graph also indicates the expected number of well-documented reports for each country, which is 13 % of the total number of reports for the country. The five countries with the greatest numbers of well-documented reports are Italy, Germany, Spain, Thailand and the USA. Thirty countries had significantly higher than expected numbers of well-documented reports (shrunk log odds ratio exceeding 0.5, as described in the Empirical Evaluation section) and these are listed in red in Fig. 5. The highest proportion of well-documented reports in a country with at least 1,000 reports is Italy, with 65 %. Tunisia, Spain, Portugal, Croatia and Denmark each have more than 50 % well-documented reports, whereas another 20 countries have more than 30 % well-documented reports. Altogether, 66 % of the well-documented reports come from Europe, whereas the overall proportion of reports from Europe in this data subset is 23 %.
Figure 6 shows the number of well-documented reports per primary reporter, and Fig. 7 shows the proportion of well-documented reports by country for different types of primary reporter. 69 % of the well-documented reports in VigiBase come from physicians. On the whole, 24 % of the reports from physicians are well-documented compared with 16 % for pharmacists, 14 % for ‘other health professionals’ and only 4 % for consumers/non-health professionals, overall. The variation between countries is substantial, however.
Of the countries with at least 1,000 reports in total and 100 consumer/non-health professional reports, Denmark and Norway both have more than 60 % well-documented reports from consumers/non-health professionals, and Italy and The Netherlands have more than 40 % well-documented reports, whereas no other country has a rate exceeding 30 %.
More than 50 % of the reports from ‘other health professionals’ in Spain, Norway and Italy are well-documented. Altogether, there are 15 countries with at least 1,000 reports in total and 100 reports from ‘other health professionals’, for which at least 30 % of the ‘other health professional’ reports are well-documented. From Ireland, 27 % of the ‘other health professional’ reports are well-documented compared with only 9 % of the Irish reports overall.
More than 50 % of the reports from pharmacists in Italy, Portugal and Spain are well-documented, and altogether there are 15 countries with at least 1,000 reports in total and 100 reports from pharmacists, for which at least 30 % of the pharmacist reports are well-documented. From India, 47 % of the pharmacist reports are well-documented compared with 31 % of the Indian reports overall.
For Italy, 74 % of the physician reports are well-documented, and so are more than 50 % of the physician reports from Portugal, Venezuela, Tunisia, Spain, Croatia, Denmark and Norway. Altogether, there are 26 countries with at least 1,000 reports in total and 100 reports from physicians, for which at least 30 % of the physician reports are well-documented. From Nigeria, 29 % of the physician reports are well-documented compared with only 10 % of the Nigerian reports overall.
The primary reporter ‘other’ represents a reported field in the old INTDIS format of ‘Not a doctor or dentist’ and the type of reporter could vary between countries. For Sweden, 71 % of these reports are well-documented. Another six countries with at least 1,000 reports in total and 100 reports from others have more than 30 % well-documented reports in this category. From Peru, 35 % of the ‘other’ reports are well-documented compared with only 2 % of reports from Peru overall.
Reports using the E2B format have an average completeness of 0.44 with 11 % well-documented reports compared with an average completeness of 0.53 with 22 % well-documented reports for the INTDIS format. However, E2B reports via the WHO programme’s electronic reporting system VigiFlow have an average completeness of 0.61 and 29 % well-documented reports.
The completeness of individual dimensions for the three countries with highest completeness, for the different report formats, for physicians and for consumers/non-health professionals, respectively, is displayed in Table 4. For the three countries of interest, we note that Italy has high completeness for all dimensions, whereas Tunisia and Spain would have suffered from greater penalties on lack of information on dose and free-text comments. Reports on the E2B format carry more information on indication for treatment and free-text comments but less information on patient age, outcome and dose than do reports on the INTDIS format. Reports from VigiFlow carry more information on time-to-onset, dose and free-text comments than other E2B reports and INTDIS reports. Reports from consumers/non-health professionals often lack information on patient age, and carry few free-text comments, but provide information on the indication for treatment slightly more often than reports from physicians.
Examples of Prospective Discoveries
Miscoded Age Unit from the USA
An unexpected drop in completeness for reports from the US FDA was observed in 2011, as seen in Fig. 8. From 2010 to 2011 the average completeness decreased from 0.45 to 0.30. Subsequent analyses revealed that from 2011 and onwards, the age unit format on reports from the USA did not conform to the E2B guidelines. As a result, all American reports from 2011 to date lacked age information in VigiBase, and none of them were classified as well-documented (since missing age is penalised by 30 %). This issue was communicated to the US FDA and has been addressed in subsequent versions of VigiBase.
Missing Outcome on Italian Reports
A lower than expected completeness for reports from Italy was observed in 2011. This could be traced to a consistent lack of information on outcome (see Fig. 9). At this time, no Italian reports would have been classified as well-documented. The issue was communicated to the Italian authorities who resubmitted all their reports with the outcome information included. This was done before the initiation of the study at hand. As a result, Italian reports as represented in VigiBase today are the most complete for any country with at least 1,000 reports.