Applying complexity theory to model the operation of clinical trials in human communities

Abstract Background When a vaccine clinical trial enters a human community two independent systems merge into one system with various levels if interdependence. This system exhibits non-linearity and unpredictability, creating challenges for the research team. In this study we explore the researcher experience during clinical trials in human communities, through the lens of complexity theory. Methods We conducted in-depth interviews with a total of 11 researchers working on a phase III vaccine clinical trial in Kenya (Registry name: RTS,S ClinicalTrials.gov; Registry number: NCT00866619; Registry date: March 20, 2009). The interviews captured the researcher’s experience of working in a complex adaptive system and were analysed using thematic coding. Results Both human communities and clinical trials have the attributes characteristic of complex adaptive systems. Challenges researchers encountered working in this merged system include rumours, suspicion related to blood draws, and misconceptions. The researchers highlighted that a foundation of trust and open communication were foundational blocks to embrace the non-linearity of the system. Conclusions We have identified the key role that complexity theory plays in improving clinical trial design. The factors identified by our respondents, as seen through the lens of complexity theory, are integral to informing how clinical trial research can be tailored to the local social setting. Understanding the system (community and trial) as one allowed for the identification of patterns that influence the emergence of the system. This calls for clinical trial design to incorporate iterative practices to better equip research teams to adapt to the emerging behaviour of the system.