Fig. 7: Assessment of the risk of bias for included experiments (animal and human studies).

a Co-occurrence of potential bias (grading as low or high risk) within animal experiments. Risk of bias was most prevalent in reported age, followed by a combination of age and blinding status. Conversely, information on species, route of drug administration, and dose showed lower risk of bias. b Proportion of each risk of bias (low, unclear or high) by domain of bias studied. Age represents the domain with the most prevalent high risk of bias. c Risk of bias for human intervention studies (observational). Only one study showed a critical risk of bias (domain 5: bias due to missing data), whilst most studies (n = 6, 67%) did not provide sufficient information to assess the risk of bias due to deviations from intended interventions (domain 4). Additionally, the majority of the studies (n = 8, 89%) had a low risk of bias due to selection of participants (domain 2). D1 bias due to confounding, D2 bias due to selection of participants, D3 bias in classification of interventions, D4 bias due do deviations from intended interventions, D5 bias due to missing data, D6 bias in measurement of outcomes, D7 bias in selection of the reported result. d Risk of bias for randomized controlled trials (RCTs). High risk of bias was detected in 7 studies (88%) for bias in selection of the reported results. D1 bias arising from the randomization process, D2 bias due to deviations from intended interventions, D3 bias due to missing outcome data, D4 bias in measurement of outcome, D5 bias in selection of reported result.