Page 35 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

heterogeneous group of people, over longer periods of time which are
necessary to provide ongoing assessment of vaccine safety and
effectiveness. This phase is also done for further research on age at
vaccination, effect of simultaneous administration of other vaccines,
efficacy and adverse events due to changes in vaccine strain, and
interchangeability of vaccine.

Bridging studies in vaccine trials are conducted to support clinical
comparability of efficacy, safety and immunogenicity of new formulation
when there is change in vaccine composition with regard to adjuvant,
preservative, or a change in manufacturing process, site or scale. These are
performed either before or after product licensure. The rationale of
bridging clinical studies is to demonstrate product equivalence to that used
in earlier pre-clinical or clinical testing. When serologic bridging studies
are to be done, only comparison of sera with historical control from an
efficacy trial is warranted, and no clinical trial need be undertaken.

10.2.1 Combination Vaccines
The main goal in efficacy trial design of combination vaccines which
are commonly used nowadays is to evaluate the efficacy of each
antigenic component. When correlates of protection are validated
for each component, immunogenicity end- points should be used.
Prospective controlled trial is required when combination vaccines
are not validated for each component. Further, non-inferiority trials
should be conducted to demonstrate that the combination vaccine is
not inferior in terms of immunogenicity or efficacy, to vaccines with
individual components.

Vaccines Administered Simultaneously with the
Combination Vaccines
When a new vaccine is administered simultaneously with already
licensed vaccines that would be given to the same target population
using the same (or overlapping) schedule, Phase III (Pre –licensure)
studies should be obtained to support immunogenicity and safety
data. With regard to immunogenicity, assessment should be
performed to show that subjects still attain an acceptable immune
response to both the combination vaccine and the other
simultaneously administered vaccine. During such administration,
the immunogenicity should be evaluated early in clinical
development for all components to detect any possible
immunological interference and such assessment would be valuable
before proceeding to a large- scale trial of the investigational
vaccine. These studies will evaluate safety and interference of the
new combination vaccine with one type of simultaneously
administered vaccine.

BMRC ETHICAL GUIDELINE ON HUMAN SUBJECTS Page 31