Document text
Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases
Introduction of Policy Questions for TAK -003
Alfonso Hernandez -Romieu, MD, MPH
ACIP June 22, 2023
Dengue Branch, CDC
We formulated PICO questions based on the
directness of data and risk -benefit differences.
*Persons aged 17 years were considered in this category but were not included in original immunobridging (18 –60 years) or
phase 3 trials (4 –16 years)•4–16 years: 57-month vaccine efficacy from a phase 3
randomized controlled trial
•17*–60 years: Non -inferiority of antibody titer ratios post -
vaccination (2 doses) compared to persons aged 4 –16 years
(i.e., immunobridging )
Result: Developed PICO questions by age -group
We formulated PICO questions based on the
directness of data and risk-benefit differences .
•No efficacy against hospitalizations for DENV -3 among
seronegative vaccine recipients compared to placebo (-87.9%;
95% CI: -573.4, 47.6%).
•Data insufficient to rule out an increased risk among
seronegative vaccine recipients.
Result: Developed PICO questions by serostatus
Hospitalization for DENV -3 and DENV -4 among
seronegative* children was low.
Placebo
n=1832Incidence
density/100
person -yearsTAK-003
n=3714Incidence
density/100
person -yearsVE (95% CI)
DENV -1 14 0.17 6 0.03 78.4% (43.9, 91.7%)
DENV -2 23 0.28 0 0.0 100% (NE, NE)
DENV -3 3 0.04 11 0.07–87.9% (–573.4, 47.6%)
DENV -4 1 0.01 0 0.0 100% (NE, NE)
*Seronegative refers to no serologic evidence of previous dengue infection before vaccination.
We formulated PICO questions based on the
directness of data and risk-benefit differences .
•No efficacy against hospitalizations for DENV -3 among
seronegative vaccine recipients compared to placebo (-87.9%;
95% CI: -573.4, 47.6%).
•Data insufficient to rule out an increased risk among
seronegative vaccine recipients.
Result: Developed PICO questions by serostatus
PICO questions include persons living in
dengue endemic areas only.
•Recommendations for travelers to dengue endemic areas will be
addressed by the work group after the October 2023 ACIP meeting.
•Travelers to endemic areas will require a separate evidence -to-
Recommendations ( EtR) framework including but not limited to:
•public health importance
•benefits and harms
•resource use
PICO Questions
1.Should two doses of TAK -003 be administered routinely to seropositive*
persons aged 4 –16 years living in dengue -endemic areas?
2.Should two doses of TAK -003 be administered routinely to seronegative
persons aged 4 –16 years living in dengue -endemic areas?
3.Should two doses of TAK -003 be administered routinely to seropositive*
persons aged 17 –60 years living in dengue -endemic areas?
4.Should two doses of TAK -003 be administered routinely to seronegative
persons aged 17 –60 years living in dengue -endemic areas?
*Recommendation for seropositive individuals only will require prevaccination screening for previous dengue virus infection.
Seropositive Seronegative
4–16 years
Children/Adolescents•Vaccine Efficacy (VE)
•Safety
•Cost -effectiveness (CE)•VE
•Safety
•CE
17–60 years
Adults•Immunobridging *
•Safety
•CE•Immunobridging
•Safety
•CEData elements used for each policy question
*Immunogenicity in seropositive adults inferred from data in seronegative adults.