Table 4 Interview themes and 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.