YOU ARE HERE:
Preventive trials: Phase I, II, III
HIV preventive vaccine trials are generally discussed in terms of three phases, I, II and III.
Phase I involves low-risk volunteers, usually from 20 to 80 in number, who receive a candidate vaccine, or perhaps just a component of such a vaccine, and are monitored for between six months and two years to assess immune response and safety. More than forty different vaccine candidates have now undergone Phase I clinical trials. Most have proven to be at least as safe as any other vaccine and most have induced some immune responses.
Phase II trials would include high–risk volunteers, drawn from populations in which efficacy trials might later be carried out. These look at how to maximise immune response in terms of dosage and methods of administration. They would normally be larger than Phase I trials, possibly running into hundreds of volunteers. Only three vaccine candidates had entered Phase II trials by 2003.
Both Phase I and Phase II trials may be placebo-controlled in order to distinguish adverse effects linked to the vaccine from those which are not. The experience of running trials in high-risk seronegative populations has been that many ‘adverse events’ are reported, most of which have nothing to do with vaccination (Ippolito).
The aim of a Phase III trial might be to assess whether a candidate vaccine is able to prevent infection, or to prevent disease in the presence of infection, or to prevent onward transmission of the virus. In other words, to discover whether a potential vaccine works. Through giving the vaccine to larger numbers of people, it is also possible to identify rarer side effects and problems.
In practice, the design of Phase III trials has been dominated by the first objective - preventing HIV infection - although the first such trials also include a follow-up phase aimed at evaluating the second objective - delaying disease. In future trials, the emphasis is likely to shift.
Phase III trials are costly and have an impact on all other aspects of the response to HIV and AIDS. This is because they must recruit populations at high risk of HIV transmission, deliver vaccines and placebos in combination with other prevention interventions, and evaluate the outcomes.
A ‘successful’ Phase III trial would be enough to get a vaccine licensed, at least in the country or region where it is carried out, but the real work of getting vaccines into proper use is then only beginning.
By 2003, only one type of vaccine had entered Phase III trials, as described below.