Under new draft guidance from the European Medicines Agency (EMA), post-marketing studies of safety and effectiveness are required to be launched for seasonal influenza vaccines shortly after the beginning of the vaccination campaign each year. Based on this guidance, biopharma companies must take into account various operational, statistical and epidemiological elements in the planning of annual enhanced safety surveillance efforts, including both active and passive surveillance. This article explores these elements and shares knowledge from various post-authorization safety studies involving follow-up with cohorts of vaccinated individuals and data collection from healthcare professionals.
The main operational consideration in post-marketing seasonal influenza vaccine studies is the need for rapid site start-up to enable patient enrollment during the peak vaccination timeframe, with October and November being the crucial months in the Northern Hemisphere. Use of multiple methods of data collection (e.g., web-based direct-to-patient data collection, telephone interviews, mail questionnaires) to maximize the chance of obtaining high response rates from patients should be given serious consideration.
The increased emphasis on web-based data collection, which is appropriate for many segments of the population, may not be convenient or practical for some demographics such as the elderly. Follow-up with healthcare providers must also be built into the study design, ensuring completeness of recording of adverse events and confirmation of patient-reported adverse health outcomes. Finally, study designs must also be flexible enough to allow recruitment approaches to evolve if original projections for enrollment are not met, such as extending recruitment outside of the initially planned countries if vaccination patterns differ from what was projected.
From a scientific perspective, the biostatistical methods to be used in such surveillance efforts are fairly straightforward, focusing on comparing the frequency of adverse events seen in the current influenza season with that recorded in earlier clinical trials of the same vaccine or rates from the previous season. Approaches to signal detection suitable for real-time surveillance studies may also be used. Epidemiological considerations are also consistent with basic principles that include the need for representativeness of the vaccinated population, and efforts to gather complete information on adverse events to the extent possible including through direct-to-patient contacts where appropriate.
Learnings from studies carried out to date include the need to constantly refine and improve methods for rapidly enrolling large numbers of healthy individuals and tracking rates of response. Of particular importance is the need to be attuned to where the greatest uptake of the vaccine or therapy is occurring, and to be able to follow all patient subgroups, including those that may be less easily accessible such as pediatric populations. Research organizations must be prepared to carry out rapid analysis and reporting to meet the requirements of the EMA guidance. Applying scientific best practices and learnings from previous operational experience in carrying out vaccine surveillance activities and post-authorization safety studies (PASS) can yield robust post-marketing evidence of safety and real world effectiveness. As a result, this is an increasingly crucial component to retaining public confidence in the role of vaccines for maintaining and improving the public health.
Filed Under: Drug Discovery