Table 4.

Interview themes and relevance to risk of bias

Category	Theme	Relevance to risk of bias
Barriers
Individual	Knowledge	- Little formal training in research methods, therefore bias is likely due to a lack of knowledge of how it is introduced.
Institutional	Clinical care vs. clinical research	- Decisions made clinically rather than per the trial design can lead to protocol deviations, e.g. interference with randomization sequence.
	Culture	- Research is often viewed negatively in the clinical setting, leading to little value placed on following the trial protocol when it deviates from usual care.
	Logistics	- Demands on time and space can put research at a low priority and tasks may not be done according to protocol, e.g. ensuring safeguards are in place to maintain blinding.
Policy	Administration	- Budget constraints can limit hiring external methodological expertise if necessary; ethics requirements for methodology are inconsistent, leaving protocols subject to change.
	Pediatric-specific challenges	- Blinding parents; investigators are less willing to inconvenience families with strict protocols; fewer trials has meant less competition for developing the best methodology.
Facilitators
Individual	Ownership	- The trial will be more successful when the investigators take responsibility for generating support and ensuring rigor.
Institutional	Acceptance	- Researcher understanding of the clinical setting facilitates the acceptance of research methods by the practitioners.
	Cohesive study team	- Consulting experienced trialists and methodologists contributes to a more rigorous and well thought out study, in terms of both validity and feasibility.
	Infrastructure	- Protected research time and dedicated research staff facilitate trial design and conduct.
	Verification	- Checks on the science facilitate high quality, e.g., reliable review processes and guidance from trusted third parties.