Growing interest in embedded research approaches—where research is incorporated into clinical care—has spurred numerous studies to generate knowledge relevant to the real-world needs of patients and other stakeholders. However, it also has presented ethical challenges. An emerging challenge is how to understand the nature and extent of investigators’ obligations to patient-subjects. Prior scholarship on investigator duties has generally been grounded upon the premise that research and clinical care are distinct activities, bearing distinct duties. Yet this premise—and its corresponding implications—are challenged (...) when research and clinical care are deliberately integrated. After presenting three case studies from recent pragmatic clinical trials, we identify six differences between explanatory trials and embedded research that limit the application of existing scholarship for ascertaining investigator duties. We suggest that these limitations indicate a need to account for the implications of usual care and to move beyond a narrow focus on the investigator-subject dyad, one that better reflects the team- and institution-based nature of contemporary health systems. (shrink)

Many drugs used in paediatric medicine are off-label. There is a rising call for the use of adaptive clinical trial designs in responding to the need for safe and effective drugs given their potential to offer efficiency and cost-effective benefits compared with traditional clinical trials. ADs have a strong appeal in paediatric clinical trials given the small number of available participants, limited understanding of age-related variability and the desire to limit exposure to futile or unsafe interventions. Although the ethical value (...) of adaptive trials has increasingly come under scrutiny, there is a paucity of literature on the ethical dilemmas that may be associated with paediatric adaptive designs. This paper highlights some of these ethical concerns around safety, scientific/social value and caregiver/guardian comprehension of the trial design. Against this background, the paper develops a non-static conceptual lens for understanding PADs. It shows that ADs are epistemically open and reduce some of the knowledge-associated uncertainties inherent in clinical trials as well as fast-track the time to draw conclusions about the value of evaluated drugs/treatments. On this note, the authors argue that PADs are ethically justifiable given they have multiple layers of safety, exposing enrolled children to lesser potential risks, create social/scientific value generally and for paediatric populations in particular, specifically foster the flourishing of paediatric populations and can significantly improve paediatric trial efficiency when properly designed and implemented. However, because PADs are relatively new and their regulatory, ethical and logistical characteristics are yet to be clarified in some jurisdictions, the cooperation of various public and private stakeholders is required to ensure that the interests of children, their caregivers and parents/guardians are best served while exposing paediatric research subjects to the most minimal of risks when they are enrolled in paediatric trials that use ADs. Data sharing not applicable as no datasets generated and/or analysed for this study. Not applicable. (shrink)