Discussion
infection, ARF, pain
ARF, ADVERSE EVENTS, RECRUITMENT, RHD, INFECTION, STREP
Qualitative research was integrated into the methodology of this trial to better understand the recipient experience of a procedure previously not completed in a volunteer cohort. Given the previously described patient preference for BPG delivery that is less frequent and less painful [An element of phase-1 trials which is challenging to address is adequately preparing participants for what to expect, given that by their very nature, there is little prior experience to draw on. This was evident in SCIP specifically for accurate description of pain and the kinds of discomfort likely to be experienced. Concerningly, the qualitative data highlighted two participants were not expecting an extended infusion, apparently interpreting the information provided during screening and the consent process to mean the procedure was a single and quick needle. To address this unexpected gap between ‘informed consent’ and a clear understanding of the procedures involved, we will be adapting recruitment materials for similar research to include illustrative resources and a greater discussion with study investigators. This combination of verbal, written and even pictorial evidence has been shown to enable higher health literacy and engagement with trial expectations and anticipated outcomes [SCIP participants were generous in their suggestions on how to improve the study for children, with answers to these questions often the most in-depth answers to any on the guide. These ideas, specifically distractions, a slower infusion time and larger doses of lignocaine anaesthesia, are likely to be integrated into SCIP-II highlighting the importance of understanding the participant experience in early phase clinical trials. A critical question that we were unable to address in this study was how the experience of subcutaneous infusion compares with current practice for SP; i.e., IM injections of BPG every three to four-weeks. The next phase of this research is to undertake a similar study in a cohort of children, adolescents and young adults currently living with ARF (SCIP-II, to be completed in New Zealand) and these questions will be explored with participants through qualitative investigation. In addition, as most pain experienced by participants during the infusion pertained to its speed, alternate infusion methods that allow for more control of injection–including hand pushing of syringes–are under investigation for the second phase and are expected to incorporate greater provision of analgesia.Significantly more research is required before it can be determined if this nascent procedure is clinically safe and effective and offers desired penicillin concentrations above that required to protect against Strep A infection. However, as investigations progress, we as authors advocate for considerations to be made regarding culturally appropriate techniques for engagement and clear communication with the target population given the burden of ARF and RHD in Australia specifically is experienced by Aboriginal and Torres Strait Islander people. At Telethon Kids Institute–where this research was conducted–the A strength of this study is that all participants consented to be interviewed and no participant missed a timepoint where qualitative data were collected, likely due to the timepoints of interview (three on the same day) and rapport with the interviewer undertaking questioning at day-7 post interview. Additionally, the same two people conducted all interviews, with the seven-day timepoint completed by the investigator most familiar with participants (having been present at dosing day and the four follow-up appointments since). This allowed for the development of rapport and ultimately, the final interviews were the most in-depth. However, given some adverse events extended beyond 7-days post-infusion, excluding interviews at later follow-up appointments limited opportunities to explore these experiences further. To address this SCIP-II will be involving interviews with participants on infusion day and 28- and 70-days post-infusion. A further study limitation was that all interviews were completed in English which may have repressed the true expression of those for whom this was not their first or most comfortable language. Certain demographic data was not collected (i.e., parental status, preferred language) which impeded a more in-depth analysis of the transcripts and ascertainment of data limitations. Additionally, some transcripts were incomplete where background noise or accents made words unascertainable.