Introduction: Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to a paradigm shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies in other cancers have motivated an increasing number of small clinical trials in brain tumors, but this trial design brings ethical challenges.
Methods: We review pertinent ethical considerations for changing clinical trial design for precision medicine in neuro-oncology away from randomized control trials towards smaller, more specific early phase clinical trials and discuss methods to protect patients in this new era of trial design.
Results: The size, specificity, and cost of early phase trial challenge long-held ethical principles: informed consent, vulnerable patient selection, societal value, institutional oversight, and justice. Informed consent protocols must adequately explain the complex genomics behind precision medicine and must provide options for incidental findings from genetic testing. Trials must avoid exploiting vulnerable patients with brain cancers refractory to multiple prior therapies who may become increasingly desperate for cures. The societal values, including improving outcomes while minimizing toxicity and advancing genomic knowledge of brain cancer, of these trials must outweigh their high up-front costs. There will be an increased number of trials; oversight committees must be prepared with members who have expertise in genomics and the ability to monitor an increased number of trials. The high costs of these trials risks excluding patients of low socioeconomic status, so societal justice must be met by ensuring their inclusion. Trial design adjustments to the informed consent, data storage, patient enrolment, and reporting processes may be adjusted to address these ethical challenges.
Conclusions: Clinical trials of precision medicine in neuro-oncology brings ethical challenges, and trial design must adapt to address them.
Patient Care: Clinical trial design in neuro-oncology is rapidly changing with advancements in precision medicine. We outline the changing ethical considerations of this trial design for investigators and also discuss solutions to mitigate these concerns to protect patient safety and autonomy and to continue maximizing outcomes.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Recognize that clinical trial design in neuro-oncology is shifting towards smaller, more specific trials
2) Discuss the challenges to the ethical principles of informed consent, vulnerable patient selection, societal value, institutional oversight, and justice
3) Describe solutions to trial protocols should ensure that these ethical principles are maintained