Table 4. Summary risk-of-bias assessment by study design.

Qualitative summary of risk-of-bias domains across included studies by study design, informed by principles from RoB 2 and NOS. Domains assessed included selection bias, confounding, and outcome assessment.

RoB 2: Cochrane Risk of Bias 2, NOS: Newcastle-Ottawa Scale

Study design	Selection bias	Confounding	Outcome assessment	Overall risk of bias
Randomised controlled trials	Low	Low	Low	Low
Post-hoc analyses of phase III trials	Low–moderate	Moderate	Low	Moderate
Prospective observational cohort studies	Moderate	Moderate–high	Low–moderate	Moderate
Retrospective cohort and registry studies	Moderate	High	Moderate	Moderate–high
Mechanistic imaging and biomarker studies	Moderate	Moderate	Low	Moderate