[0] Limited [1] Studies of weak design for answering the question OR inconclusive findings due to design flaws, bias, or execution problems [2] Unexplained inconsistency among results from different studies, OR single study unconfirmed by other studies [3] Limited number of studies Low number of subjects studied and/or inadequate sample size within studies [5] Serious doubts about generalizability due to narrow or different study population, intervention or outcomes studied [4] 
Studied outcome is an intermediate outcome or surrogate for the true outcome of interest OR size of effect is small or lacks statistical and/or clinical significance