This project will study pressing issues in research ethics in the domain of pediatric oncology. Clinical research is essential to develop and improve treatments for children with cancer. At the same time, pediatric oncology research raises ethical issues. This project focuses on a number of pressing issues in this field.
First, for 10-15 % of children with B-cell acute lymphoblastic leukemia (B-ALL) CAR-T cell therapy is offered as a last resort. Its therapeutic potential could however increase if accepted as frontline/standard therapy, but this is currently considered ethically problematic if children have other options. Moreover, the subsidiarity requirement is often strictly interpreted (implying that adults or adolescents should be enrolled before younger children). The revised Declaration of Helsinki has widened possibilities for research with vulnerable populations, but it is not yet common practice to “drop the age”. You will perform an ethical-legal analysis on ethical frameworks, laws and guidelines and perform a series of focus groups with adolescents, parents, clinician-researchers, regulators, ethical committees, guideline developers, payers, industry employees and policy makers to study under which conditions CAR-T cell therapy could be studied as frontline therapy for children with cancer.
Second, harmonization of clinical trial procedures for pediatric oncology research is essential to speed up clinical trial innovation in Europe. Unlike many other countries in Europe, in the Netherlands, research ethics committees take an integrated approach to ethical and scientific review and review so-called part I and II of a clinical trial simultaneously. One of the open issues is whether an integrated review reduces the number of requests for information (RFIs) and also leads to more adequate ethical questions, specifically related to pediatric oncology. The PhD student will perform quantitative and qualitative work to ethically assess the RFIs for pediatric oncology. This part of the project will be done in close collaboration with Dutch research ethics committees.
Third, adaptive designs are promising new methodologies to speed up knowledge generation in early dose-finding studies, but also require dedicated statistical expertise in the research team and raise ethical questions about informed consent. Together with researchers from the Oncode Accelerator project, we will study how adaptive platform studies in early phase dose-finding trials should be communicated to participants, specifically to parents and children, and what level of understanding is necessary to support valid consent. We will develop a vignette study with different forms of informed consent to study how informed consent for adaptive trials should be formulated.
