This is one of two systematic reviews in The Lancet that look at clinical and immunological non-specific effects of childhood vaccines. The systematic reviews were commissioned by the WHO Strategic Advisory Group of Experts (SAGE) to decide if there was enough evidence to consider changes in scheduling or co-administration of certain vaccines.
According to an editorial, the Achilles’ heel of the studies in this review is that there are no established immunological markers for clinically relevant non-specific effects. This is reflected in the large number (143) of different immunological outcomes in the reviewed papers.
The editorial emphasises that the systematic reviews were not intended or designed to assess if these vaccines are safe or should continue to be recommended for children. It reiterates that it is beyond debate that BCG, DTP, and measles containing vaccines are safe, and the data from these reviews must not be hijacked to argue against their recommended use. It suggests that taken together, the two systematic reviews indicate that vaccines could have non-specific effects, but the evidence remains weak. After reviewing both studies, the WHO’s expert group concluded that there was no need to modify current vaccination schedules or policies. It adds that perhaps the most important message from these two well conducted systematic reviews is that further small observational studies will not provide definitive evidence about non-specific effects of childhood vaccines as inherent biases and confounders (especially unknown confounders) cannot be eliminated by simply doing more of the same. If RCT are not feasible, it suggests that large observational study designs incorporating innovative methods to control for confounders, conducted with standardised protocols across multiple settings and countries is the only alternative.