Page 34 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

10.2 VACCINE TRIALS

According to nature, vaccines can be prophylactic and therapeutic. When a
patient suffering from a particular disease the therapeutic or curative
vaccines may be given, while prophylactic vaccines are given to normal
participants as well as pediatric group. The guidelines to conduct the
clinical trial on investigational vaccines are similar to those governing a
drug trial. The phases of these trials differ from drug trials as given below:

Phase I: In this phase the safety and biological effects including
immunogenicity of a vaccine is determined during introduction of it to the
human population (healthy volunteers). The individuals in these studies
should be at the lowest risk of infection/disease possible. This phase
includes study of dose and route of administration. Pharmacokinetic
studies are generally not required for injectable characteristics of the
immune response to the known or presumed action of vaccine. The class,
subclass, and the function of specific antibody produced and the lag time
for appearance and duration of adequate antibody titre is determined.
Information about the induction of cell-mediated immunity, the cross
reactive antibodies and/or interaction pre-existing antibodies which might
affect immune system is also obtained.

Phase II: This phase range in a target group formed by a limited number
of volunteers like, children, adults or those at risks of exposure to
pathogens. This refers to the initial trials examining effectiveness
(immunogenicity) and dose range as well as pharmacokinetics and safety
issues. Early Phase II is usually an exploratory trial while the late Phase
II is known as critical efficacy study

Phase III: This controlled study enrolled on a larger number of volunteers
(in thousands) through multicenter which focuses on assessment of safety
and effectiveness to prevent disease. These studies determine the
protection offered by the vaccine and provide pivotal data for licensure.
Efficacy in vaccine trials means reduction in incidence of the disease after
vaccination compared to the incidence that occurred before vaccination.
Effectiveness on the other hand provides information of protective rate
deliberated on a given population which includes measurement of direct
and indirect protection to a non - vaccinated person among the defined
vaccinated population determined by vaccine coverage area, and
correlation of vaccine strains with circulating strains.

Phase IV Studies: This phase happens after the vaccine has been
licensed and introduced into use. This stage aims to detect rare adverse
effects as well as to assess long term efficacy. The rarer or unexpected
events may not be seen in smaller Phase II/III studies. To detect these
events, these studies are done in the entire population or a subgroup or

BMRC ETHICAL GUIDELINE ON HUMAN SUBJECTS Page 30