CMV vaccine trial endpoints.

BACKGROUND: Despite some significant challenges, there are several reasons for being optimistic about the prospect of developing vaccines against cytomegalovirus (CMV). The aim of this paper is to anticipate how positive results might be interpreted by those charged with making recommendations about universal immunisation, given that vaccines are normally expected to be highly cost-effective. PERSPECTIVE: The cost effectiveness of a CMV vaccine will be assessed by means of quality adjusted life years gained, so we should design Phase III trials to capture the required evidence directly. Given a vaccine which is equally effective in all age groups at preventing primary CMV infection, immunisation of teenagers will be more cost-effective than immunisation of toddlers, because benefits which accrue in the future are discounted financially. Protection of women of childbearing age against primary infection is important, but may fail to convince sceptics because of the need to extrapolate to protection against transmission of virus to the fetus. The preference of this author is therefore to select congenital CMV infection as the primary endpoint of a Phase III study. We should also ensure that the primary endpoint of a study immunising seronegative women is congenital CMV infection in babies born to those women, not to women in general, because of the large number of babies born to seropositives.