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If necessary, we will also contact authors for additional information. The Cochrane Collaboration's risk of bias tool will be used. If feasible, it means homogenous data, we will conduct random effects meta-analysis. Subgroup analyses will be conducted for different justifications for placebo use and for studies sponsored/not sponsored by the pharmaceutical industry. Our present findings will indicate the effects of placebo use as comparator regarding efficacy and safety of the oral synthetic medicines. This systematic review will ident