EMA published the EudraVigilance 2020 Annual Report [i] on March 11. The report includes information about the operation and development of EudraVigilance (EV) and key figures from the database with data analysis from the EMA.

Below is a summary of what we see as key figures from that report, and a brief discussion on what picture this data paints about the industry and whether it needs a rethink on how we deal with the data volumes.

In short, a change is needed; the sooner the better.

Total Number of ICSRs

EudraVigilance currently contains over 18.6 million ICSRs in total referring to 10.5 million individual cases.

In 2020, over 1.8 million post-marketing ICSRs reports were collected and managed in EudraVigilance. This is a 9 % decrease to the year before but still clearly a massive number.

• 812,760 ICSRs originated from the EEA and 1,008,451 ICSRs were non-EEA
• This includes 1,216,480 individual cases of which 584,828 individual cases originated from the EEA and 631,652 individual cases non-EEA

Number of ICSRs Reported by MAHs and NCAs

MAHs transmitted almost 1.7 million ICSRs to EV in 2020.

• 1,675,569 ICSRs in total were transmitted to EV by MAHs
• 1,568,920 ICSRs were transmitted by MAHs to EVPM
• 973,779 individual cases
• 251,558 ICSRs were rerouted to NCAs following receipt of the reports from MAHs
• 106,649 ICSRs were transmitted by Sponsors to EVCTM
• 32,609 individual cases

NCAs transmitted 260,000 ICSRs to EV in 2020.

• 259,820 ICSRs were transmitted to EV by NCAs
• 252,291 ICSRs were transmitted by NCAs to EVPM
• 242,701 individual cases
• 7,529 ICSRs were transmitted by NCAs to EVCTM
• 4,665 individual cases

Number of ICSRs Reported by Patients

The number of reports submitted directly by patients and consumers through the NCAs and MAHs was 143,958. This included 117,167 individual cases.

Number of ICSRs Forwarded to the WHO

EMA forwarded 1.2 million ICSRs to the WHO database VigiBase in 2020.

• 1,212,939 ICSRs

Number of ICSRs Downloaded by the MAHs

MAHs made a total of 219,652 download requests, resulting in 8,073,849 ICSRs downloaded from the EudraVigilance database in 2020. The average download size was 37 ICSRs.

Submission Timeliness Compliance by MAHs and NCAs

Compliance rate for serious (15 days) and non-serious (90 days) ADR reports to EVPM in 2020 were:

• MAH Compliance
• Serious: 94.7 % (about the same as before)
• Non-serious: 77.7 % (increasing)
• NCA Compliance
• Serious: 87.6 % (increasing)
• Non-serious: 69.9 % (increasing)

Duplicates

EMA assessed 160,047 duplicate couples in EudraVigilance in 2020. This led to 85,168 master reports generated based on duplicated data.

Signals Reviewed by EMA

1,888 potential signals were reviewed by EMA. Of all signals, 99% originated from either EudraVigilance or Medical Literature Monitoring (MLM), any other source is marginal. Out of the 81 validated signals, less than half led to an update in product information.

81% (1510) originated from EudraVigilance, 18 % (340) originated from scientific literature screening, 0.4 % (<10) originated from cooperation with other regulatory authorities worldwide and 0.4% (<10) of potential signals originated from other sources.

• 1,530 (81 %) signals were not validated
• 138 (7 %) signals are being monitored
• 181 (10 %) signals are ongoing
• 81 (4 %) confirmed signals prioritised and assessed by the PRAC
• 39 validated by EMA, 42 validated by NCAs and 0 validated by MAHs
• 37 (2 %) of the assessed signals resulted in a recommendation for an update of the product information for patients and healthcare professionals
• 27 (1.4 %) evaluation is ongoing in 2021
• 14 via a follow-up signal procedure
• 13 in the upcoming PSURs/PSUSAs
• 16 (0.8 %) continuing with routine safety monitoring of the medicine was considered sufficient
• 2 (0.1 %) of the assessments lead the PRAC to recommend Direct Healthcare Professional Communications (DHPCs) in addition to product information update
• 1 (0.05 %) led to the update of the RMP to fully characterise and investigate the concern in addition to product information update
• 1 (0.05 %) led to referral procedure

Points to Consider

In total, 96 % of signals reviewed by the EMA have not been validated last year. 81 % are already closed. Only 4 % of signals were confirmed. None (0) of the confirmed signals led to immediate actions by the MAH or by the authorities. Also notable is that none of the signals were validated by the MAHs.

With so much time and money spent on reporting ICSRs and Signal Management by the industry, one should question: are we getting to the end output of less than 40 actionable signals/year (for CAP) the best way we can? To us, this is another clear “signal” to call for higher efficiency across the industry.

We are not questioning the correctness of the results of the signal analysis nor the necessity to perform the signal monitoring activities. But as an industry, we should be questioning the motives of some of the stakeholders performing these activities.

The EV report of course doesn’t speak about the industry costs but as insiders, we know very well what is behind processing all those 1.8 million ICSRs a year. Seeing that the end result is only a “handful” of validated signals, we should be loudly questioning if the methods to get through the cycle have been designed with the best intentions by the industry stakeholders; we can’t really question anyone’s ability to be more efficient.

We want to point out on behalf of our industry colleagues that the MAHs have much better compliance than the authorities related to timeliness of reporting cases to EudraVigilance. Clearly, timeliness and overall regulatory compliance is a key indicator of the industry’s performance. This is also what auditors and inspectors should review in detail. But we also think that whoever labels themselves as a stakeholder and plays any part in the industry should consider compliance as the baseline, not the end goal. We’re at a point where we need to add more metrics of quality, and in our view, this should be efficiency – cost or the time effort used (wasted?) is not scrutinized at any point in the current system.

Conclusion

In this post, we’re not providing detail on what the costs are or how exactly we can be more effective – that’s discussed elsewhere in bits and pieces over our website and the content we create. What’s worth mentioning here is that the data is unquestionably on the side of advocates for a rethink of how pharmacovigilance activities should be done.

Unless we change the mindset of the industry stakeholders and business model of companies in a field largely dominated by consultancies, we’ll never get out of the cycle.