Immunization, Vaccines and Biologicals

Call for public comments on draft protocols of clinical trials to assess the non-specific effects of vaccines


Researchers have advanced that vaccines can have non-specific effects (NSE), i.e. beneficial or detrimental effects on child mortality and morbidity other than those on the target disease. While concluding that no changes in immunization schedules were necessary, WHO Strategic Advisory Group of Experts on Immunization (SAGE) recommended in April 2014 further research of NSE on all-cause mortality. SAGE thus suggested that the Immunization and Vaccines related Implementation Research Advisory Committee (IVIR-AC) be tasked with providing advice on priority research questions and adequate studies.

IVIR-AC agreed with SAGE that additional observational studies are unlikely to provide conclusive evidence on NSE. IVIR-AC thus committed to guiding the development of standard protocols and implementation of high quality prospective studies, including randomized controlled trials where feasible.

The WHO Secretariat followed up on those recommendations and organized two ad-hoc expert consultations on NSE clinical trials. The same group of experts contributed to both consultations. Experts reached consensus on priority questions for NSE clinical trials and outlined trial designs for each of the priority questions. They also reviewed synopses of the proposed trials and made suggestions for the development of complete protocols.

In June 2016, IVIR-AC reviewed the advances and endorsed the process for designing one or more protocols and concluded that IVR needs to complete the preparation of generic protocols.

In April 2017, SAGE was presented with two proposed questions and outlines of study protocols to further evaluate the hypothesis of NSE of vaccines (i) and individually randomized placebo-controlled trial of early versus later vaccination with Bacille Calmette-Guérin (BCG) to estimate its impact on all-cause mortality in infancy and; (ii) a 2x2 factorial double blind randomized placebo-controlled trial to assess the impact of an additional early dose of measles-containing vaccine at 12-16 weeks of age on all-cause mortality.

The agreed next steps includes seeking inputs from other experts on the protocols and their formal publication by the end of 2017.

WHO will collect public comments on the draft protocol synopsis until 15 September 2017. Only suggestions provided via this mechanism will be considered. For any questions about the process, please contact

The draft synopsis can be found here:

The web surveys can be found here: