Novel immune therapies are increasingly based on the molecular differentiation of disease patterns. The related clinical studies are thus more often characterized by the so-called adaptive study designs (umbrella or basket studies including platform studies), which are continuously adjusted based on novel results. This paper analyses new study designs beyond the often-postulated need for regulation in order to identify ethical problems based on typical structural features and to—whenever possible—suggest solutions. To do so, it addresses the following topics: the relationship between (...) social and scientific values of a study as well as aspects of the scientific validity of new forms of evidence; the inclusion of study subjects under the condition of relative uncertainty; specific challenges in the process of ethical approval, and ethical and practical challenges in the process of informing patients and receiving informed consent. Additionally, the topic of a potential risk–benefit assessment of such therapies is addressed. (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)