(BSPOT54) Special Populations Addressed in Vaccines Approved via the European Medicines Agency

Background: Vaccines are among the most effective public health measures implemented, but their ample distribution to healthy populations can also have unintended consequences (e.g., adverse events), so they should be carefully evaluated and monitored. In the EU, the marketing authorisation (MA) of vaccines is granted via the European Medicines Agency (EMA).

Objectives: To investigate which populations are addressed in vaccines approved via EMA, to describe pivotal trials’ settings and eligibility criteria, and explore what questions remain unanswered after vaccine MA.

Methods: We identified all vaccines (ATC J07) centrally approved between 2012-2022 and collected the following data: populations indicated in summary of product characteristics (SmPCs); pivotal studies supporting vaccine approvals; and risk management plans (RMPs) information. We compared SmPCs and RMPs data available at initial MA and at the end of study follow-up (03/2023).

Results: 31 vaccines approved via EMA between 2012-2022 were included. Initially, only 3 vaccines were indicated for immunocompromised individuals, 1 vaccine was indicated for pregnant individuals and 2 for people who are breastfeeding. Although most vaccines had RMPs acknowledging missing information about pregnancy/breastfeeding (24 vaccines) and immunocompromised populations (25), there was little change in indications in more current SmPCs: 6 vaccines for immunocompromised patients (1 Influenza; 1 Smallpox/Mpox; 1 Shingles; 1 Hepatitis B; and 2 COVID-19), 3 for pregnant (1 Influenza and 2 COVID-19) and 4 for breastfeeding (same as pregnant plus the HPV vaccine). We identified 90 pivotal trials supporting vaccine initial MA, of which less than 10% (7/90) enrolled special populations. We also identified that 59% were conducted in high-income settings and 83% in high-income and/or upper middle-income settings. The country that hosted the greatest number of trials was the United States (51 studies), followed by Germany (16). Preliminary analysis of eligibility criteria showed that most trials excluded populations with underlying chronic diseases, pregnant/breastfeeding, and with immunocompromising conditions/treatment. Other common types of missing information acknowledged in RMPs were concomitant administration with other vaccines, paediatric populations, and long-term safety data. Missing information on effectiveness was seldom acknowledged.

Conclusions: Vaccine trials rarely include special populations and seem to present the same stringent eligibility criteria as trials investigating therapeutic drugs. Several questions remain unanswered after vaccine MA regarding different populations and settings. Real-world data can be an important tool to fill these knowledge gaps.