evidence: There is a growing awareness about the problem posed by untrustworthy randomized controlled trials (RCTs) in systematic reviews. It appears that some RCTs have been partially or entirely fabricated. We call trials subject to serious research integrity issues "problematic studies", and recent examples can be found in reviews of ivermectin for the treatment of COVID-19. The Cochrane policy Managing Potentially Problematic Studies states that studies should not be included until serious concerns about trustworthiness have been resolved. However, there is no consensus around how to identify problematic studies. [...] The WHO and the Declaration of Helsinki require that every clinical study must be prospectively registered in a publicly accessible study registry (i.e., registration before enrolling the first patient). However, most evidence syntheses ignore violations of this fundamental moral and ethical principle. The Research Integrity Assessment (RIA) (doi:10.1002/jrsm.1599), a tool to assess adherence of randomized-controlled trials (RCTs) to the principles of Good Clinical Practice, and key elements of research integrity in clinical trials, assesses prospective registration and may help evidence synthesis authors to deal with studies which do not comply with the requirements. RIA was piloted in the updated Cochrane review "Ivermectin for preventing and treating COVID-19" revealing that lack of prospective registration was the most frequent reason for the exclusion of studies according to RIA.