Non-specific effects of vaccinations in high-income settings: How to address the issue?

“Non-specific effects” of vaccines go beyond the specific protective effects against the targeted diseases. They, if real, could theoretically be beneficial, neutral or negative. Do the non-specific effects of vaccines exist? Almost certainly yes, and they can be important in low-income countries. Are non-specific effects also present in high-income countries? At least to some extent, it seems quite logical. Can non-specific effects be systematically identified by the current systems of side effects/unintended reactions monitoring? Most likely not. Could the Institute of Medicine proposals and some ongoing attempts solve the issue? It seems unlikely. Could there be better, feasible and ethically acceptable ways to achieve the aforementioned objective? A proposal is presented about this issue, with the potential both to solve the problem with the most valid methods, and to overcome the ethical problems that have so far precluded the adoption of RCTs to study possible vaccine non-specific effects, monitored by long follow-up.