1. Operational experience and lessons learned on
influenza vaccination post
studies
Ombretta Palucci,
Senior Director of Real World Strategy Lead Unit
authorization
safety
© Copyright 2015 Quintiles

2. Enhanced surveillance of seasonal influenza
vaccines under EMA guidance of April 2014 2

3. Interim guidance on enhanced safety surveillance for
seasonal influenza vaccines in the EU (1)
Objectives of enhanced safety surveillance
• Detect a potential increase in reactogenicity and allergic events
> intrinsic to the product (i.e. not due to a specific batch deviation or local programmatic issue)
> in near real-time in the earliest vaccinated cohort
• Establish a framework for enhanced surveillance that is feasible to implement every year
4/WC pdf
Effective 15 April 2014
Season a pilot year 3

4. Interim guidance on enhanced safety surveillance for
seasonal influenza vaccines in the EU (2)
Options for enhanced surveillance 1.
Active surveillance (PASS)- preferred
Enroll vaccinees in routine clinical practice
Data collection through web-based survey with telephone follow-up or other approaches
> 2.
Passive surveillance 1
>
Estimate a reporting rate as surrogate for incidence rate of AEIs
Numerator - facilitated near real-time vaccine-specific and batch-specific reporting of AEIs
Denominator - reliable near-real time data on actual usage of the vaccine
(not sales/ distribution data) - - 3.
Data mining or other use of electronic health record data 1
>
Noted to be of limited use in identifying the required adverse events of
interest (AEIs) of reactogenicity and allergic events 1
Requires justification and agreement of competent authority. 4

5. Interim guidance on enhanced safety surveillance for
seasonal influenza vaccines in the EU (3)
Requirements for active and passive surveillance •
Include at least 100 vaccinees in each age group: 6 months to 5 years, 6
to 12 years, 13 to 18 years, ≥ 18 years-65 years and > 65 years
Patients followed-up at 7 days post-immunisation for the stated AEIs (or up to 14 days for live attenuated vaccine)
Need to be able to detect a change in the frequency and/or severity of AEIs compared to current product specific information or trial results in first year, and in future years using previous year’s experience as expected • •
Based on selection of early/high use region, patient
numbers should be achievable within one month 5

6. Operational experience and lessons learned on
influenza vaccination post authorization safety studies 6

7. Operational Challenges
Strategies to increase probability of success
Challenges
Lesson Learned •
Vaccine availability
Start of vaccination campaign (start date, age group recommendation)
Vaccination coverage •
Internal and External data mining
Feasibility
Close collaboration with Sponsor •
Country Selection •
Summer period
Regulatory Environment
ICF
Site Contract •
Regulatory Intelligence Database for
Observational Studies
Early submission
Age specific ICF/assent form
Observational site contract template •
Study Set-up •
Country specific vaccination site
setting
Site representativeness to fulfill different age cohort
Site Interest
Site Resources •
Early engagement
Fair market compensation
Leverage existing site influenza network Diversify site setting (pediatricians, boarding schools)
Involve sponsor’s affiliates to share a list of sites using the vaccine
Identify back-up sites • • •
Site Recruitment • 7

8. Operational Challenges
Strategies to increase probability of success
Challenges
Lesson Learned •
Subject pathway
Fulfill all age cohorts
Questionnaire completion •
Provide study material (e.g. subject welcome
package)
Provide subject token of appreciation when possible and approved by EC
Use multiple technologies (i.e. paper, web, phone) to enhance questionnaire completion Active follow-up of non responders (sending of reminders, follow-up calls, etc.)
Age strata recruitment tracking and monitoring through automatic EDC reports • •
Subject Recruitment
and Follow-up • • •
Real time data collection
Real time data cleaning
Real time reporting •
EDC platform fast to set-up and easy to use
e-PRO functionality
Patient Contact Management System module
Customized reports
Remote risk based monitoring
Technology 8

9. Case
Study 9

10. Case Study: Active Surveillance Influenza Vaccine (1)
Influenza season &
Purpose
• Under new draft EMA guidance for vaccine enhanced active surveillance, conduct a pilot PASS to
collect participant self-reported reactogenicity data, supplemented by HCP data on the details of
vaccination, and any medically attended Adverse Events (MAEs) in the seven-day period after
influenza vaccination in a given year
Study design
• Observational prospective cohort study, with site based data collection and participant data collection regarding MAEs through internet survey
• Single EU country
Objectives
• To characterise the reactogenicity (local, systemic and allergic reactions) within seven days after each
influenza vaccination in participants routinely indicated for influenza vaccination in specified age
groups.
• To assess the frequency and severity of MAEs with initial symptom onset within seven days after each 10

11. Case Study: Active Surveillance Influenza Vaccine (2)
Influenza season &
Influenza
Vaccine
(2)
Challenge
Solution
• Seasonal disease context
• Strict and short timelines to set-up the study
• Fast Subjects recruitment
• Summary Safety Report at 30 days from the first doses of the product being used
• Regulatory intelligence to speed up start-up
• Team expertise in Vaccines and observational studies
• Efficient Site selection to identify highly performing sites
• Right EDC system to allow for fast set-up and intuitive use (limited training to users needed)
• Close collaboration with the Sponsor and the local affiliates
• Relevant Site training and close collaboration
• Direct to Subject Follow-up
• Remote risk-based monitoring fit for purpose
Result
Pilot for Full PASS ( )
• 10 Active Sites
• FPI Oct14
• > 260 Subjects in approx. 5 weeks enrolment
• 70% of subjects provided post-enrolment safety data
Full PASS ( )
• 12 Active Sites
• FPI Sep15
• > 400 Subjects in approx. 3 weeks enrolment
• > 82% of subjects provided post-enrolment safety data
Lessons Learned
• Early study set-up together with pre-agreed site specific recruitment numbers accelerates recruitment
• Setting differentiation increase recruitment in the pediatric cohort
• Hands on site training increases timely data entry, e-diary compliance and data quality
• Reminder calls increase subject compliance . 11

12. Conclusion 12

13. Conclusion Collaboration
While challenging due to time constraints of data collection within the
vaccination campaign season, execution of successful enhanced safety surveillance consistent with EMA guidance is possible with:
Collaboration 13

14. Thank
you 14