We used an explanatory mixed methods design, with semi-structured interviews building upon the results of a quantitative survey. We connected data from the two phases to provide detailed descriptions of the barriers and facilitators pediatric trialists face in designing and conducting studies with high internal validity 28 . We obtained ethical approval from the Health Research Ethics Board at the University of Alberta.

Survey findings indicated that 68.1% of respondents agree that bias is a problem in pediatric RCTs and 72.0% reported that they felt there was sufficient evidence to support the need to change some aspects of how RCTs are conducted. However, knowledge of bias among respondents was variable. There was no consistency in responses to questions which asked the respondent to rate the degree to which they agreed that a study design factor would introduce bias into a study. Identification of specific biases was strongest for sequence generation, blinding, and selective outcome reporting, while there was more uncertainty surrounding identification of problems with allocation concealment, incomplete outcome data, and “other sources of bias” (see Additional file 2). Despite this range of awareness of issues relevant to bias, 94.2% of respondents felt confident in their ability to evaluate the quality of published trials.

The interviews highlighted two important themes regarding barriers and facilitators at the individual level: knowledge and training regarding research methods, and engagement or ownership in the research process (Table 5). While most survey respondents indicated that bias is a problem, the interview data suggested that trialists often do not have the knowledge to first, recognize, and second, address bias in their studies. They often mentioned a lack of formal training, instead relying on skills learned on the job.

Conversely, a sense of ownership can contribute to a rigorous study design. Actively taking responsibility for the direction of the trial was seen as an opportunity for the investigators to generate enthusiasm, gain support, and educate colleagues about the rationale for rigorous methodology and how it impacts the ability to accurately answer the research question.

"“Listen to what [your colleagues] need to execute the study so that when you develop your protocol, you’ve built that into the approach. Or, if you couldn’t, you’ve at least had that dialogue with them about how scientifically you can’t be as flexible as might be ideal… so that they at least understand the rationale.”"

While 93.0% of survey respondents demonstrated an interest in learning about and staying current with literature describing and analyzing research methods, only 50.3% felt that they were able to do so due to other constraints. Logistical issues such as meeting institutional requirements (29.2%) and having sufficient staff (30.4%) were identified as challenges, while access to knowledgeable colleagues (92.8%) was identified as the most significant facilitator (see Additional file 2).

Consistently, interview respondents felt that environmental factors within their institutions were not conducive to research, often as the result of perceptions of research (Table 6). They reported the underlying culture to be overwhelmingly negative towards research at all levels, with resistance from trainees, nurses, physicians, administrators, and the pharmaceutical industry. While respondents felt that the products of research tend to be valued once they are demonstrated to improve practice, they stated that there is little appreciation of the methods necessary to achieve that goal. Logistically, respondents felt that having staff dedicated to research would improve this situation, as research procedures would then not consistently be placed at the lowest priority. Recognition of the division between the paradigms of clinical care (e.g., protecting the interests and comfort of patients) and clinical research (e.g., maintaining clinical equipoise) was also identified as a challenge. Clinical investigators often have difficulty with this distinction, which allows for the possibility of compromised trial protocols.

"“I think a lot of investigators really have a hard time separating what decision they would make clinically from what decision they would make as part of a trial… because the feeling is I want to be convenient to the family, and I really know this stuff because I’m an expert in this clinical area, and I don’t think they realize that there’s a pretty clear demarcation between what you do in clinical care and what you do as research.”"

The degree to which institutional barriers were perceived as a threat to research varied according to the size of the site of the respondent. A clear distinction was noted between larger research-intensive institutions and other sites in which researchers struggled due to a lack of infrastructure. Trialists from the former viewed the conduct of research much more positively and generally felt that they had the necessary resources available to conduct rigorous trials, while those from the latter reported greater levels of difficulty positioning their research as an important part of the clinical landscape.

"“Space, resources, and training for research assistants, research managers, graduate students… there’s all sorts of hurdles and headaches around those things that I think most established clinical research programs… already know how to make the system work.”"

Similar to the survey results, cohesive study teams with positive working relationships were reported as the most significant facilitator to conducting rigorous trials. At the institutional level, this often included combining the expertise of experienced trialists, methodologists, and the staff that would be responsible for implementing the trial; however, this integration was more common at sites with more support for research. Positive relationships were also mentioned in the context of subspecialties, with productive research networks across sites enabling researchers to benefit from a collective expertise, as well as facilitating study-specific elements such as the conduct of multi-centre trials. A final facilitator, which was more prominent in certain institutions than others, was a reliable internal review process. Respondents viewed this as a major asset when it was available, but many felt that existing processes were fragmented and inconsistent.

All interview respondents felt a lack of incentive to conduct pediatric trials. Difficulty in securing funding was frequently mentioned, but beyond that, participants reported that it is challenging to justify including financial support for a methodologist in grant application budgets in an environment where the funds awarded are anticipated to be less than requested. In this context, there is less assurance that study teams can include the necessary expertise. Meeting the requirements of several research ethics boards also presents a challenge, particularly with the preponderance of multi-centre trials in pediatrics. With separate ethics approval processes at each institution, the process can be lengthy and protocols are oftentimes changed to meet the inconsistent requests of the individual review panels (Table 7).

Addressing specific biases, survey and interview respondents reported challenges with blinding most frequently, which included the cost of providing a placebo, difficulties in blinding non-pharmacological interventions, and blinding all relevant parties, including parents. Other issues that were mentioned included difficulty getting adequate follow up in settings without an established clinician-patient relationship, parental resistance to randomization, and group imbalances due to small sample size.

An advantage of this study is that it combines the breadth of survey responses with the depth of interview responses, allowing for a detailed picture of the barriers and facilitators pediatric trialists face in the conduct of methodologically rigorous trials. While the response rate to the survey was low, bringing into question the representativeness of the sample, it was in line with evidence that both electronic surveys 41 and physician surveys 42 are associated with low responses. However, respondents represented a wide range of pediatric specialties, training backgrounds, and geographies, helping to give shape to the subsequent interviews. While they may have represented researchers with a higher level of interest in methodology, the survey responses were used to form the interviews, in which researchers with trial experience were of interest so as to be able to account for the barriers and facilitators in pediatric research with first-hand knowledge. The recruitment of additional survey participants from the membership of MICYRN slightly changed the balance of geographical representation; however the Canadian context was weighted heavily throughout the study, therefore our emphasis was unchanged. The response rate to requests for interview participation was also low, but with our expanded recruitment strategy we were able to achieve saturation. The interviews emphasized the Canadian context and therefore can be used to inform future developments within the national health care and research framework, as well as provide considerations relevant to other settings.