Ethical challenges in clinical studies with adaptive design in oncology

Abstract

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.

The critical need to accelerate cerebral palsy research with consumer engagement, global networks, and adaptive designs

“…From the beginning, patient information sheets should outline each stage’s possible modifications, with updates provided when, for example, an intervention arm is dropped [ 38 ]. Participant information sheets must openly explain the ‘broad’ nature of consent required in adaptive designs (compared to ‘specific’ consent in a RCT), transparently forecast that later entry participants may receive more benefit (compared to starting recruits), and disclose that there may be differing interventions offered to individuals as the trial progresses [ 39 ]. Consumers will be essential in co-designing explanatory participant information sheets and visuals to ensure that potential participants understand what they are consenting to.…”

“…Beneficence may be afforded in greater measure to adaptive design participants due to the tailoring of the trial design to the patient’s disorder, the ability to transition to intervention arms showing more benefit, and the overall time saved. As ongoing trial adaptations optimize the interventions received, treatment risks are lowered [ 39 ]. Ethical threats created by adaptive designs are manageable but require authentic consumer engagement at every stage of the research cycle.…”