Dr Sarah Heynemann1, Wendy Lipworth2, Sue-Anne McLachlan 3,4, Jennifer Phillip 4,5,6, Tom John 7,8, Ian Kerridge 1,2,9,
1Sydney Health Ethics, Department of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, 2Department of Philosophy, Macquarie University, Sydney, Australia, 3Department of Medical Oncology, St Vincent’s Hospital, Melbourne, Australia, 4Department of Medicine, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia, 5Department of Palliative Care, St Vincent’s Hospital, Melbourne, Australia, 6Department of Palliative Care, Peter MacCallum Cancer Centre, Melbourne, Australia, 7Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, 8Sir Peter MacCallum Department of Medical Oncology, The University of Melbourne, Melbourne, Australia, 9Department of Haematology, Royal North Shore Hospital, Sydney, Australia
Biography:
Dr Sarah Heynemann is a Melbourne-based, early-career medical oncologist and PhD candidate with Sydney Health Ethics. Her PhD research is exploring ethical and epistemic issues arising at the interface of bioethics, oncology and clinical trials methodology, and she is supervised by a multi-disciplinary team of clinicians and ethicists. She is involved in undergraduate medical ethics teaching with Monash Bioethics, is an Associate Editor for the Journal of Bioethical Inquiry, and sits on the medical ethics sub-committee of the Medical Oncology Group of Australia (MOGA) as well as the scientific committee of the Thoracic Oncology Group of Australasia (TOGA).
Abstract:
Introduction: In 1987, Freedman advanced the notion of ‘collective equipoise’, suggested to be present when a ‘state of genuine uncertainty’ exists amongst the relevant ‘community of experts’ regarding how to navigate a particular clinical dilemma1. Equipoise has since become a more or less expected ethical requirement for Phase III randomised controlled trials (RCTs). However, in oncology, many research questions are now pursued via clinical trial designs which differ methodologically in various ways from conventional two-arm, fixed-design RCTs. Whether or not equipoise can (or should) be applied to these more recent novel trial designs is uncertain.
Approach: We undertook a conceptual ethical analysis of the place and function/s of equipoise in the ethical evaluation of novel late-phase clinical trial designs in oncology.
Results: Equipoise is challenged by (1) an increasingly enmeshed relationship between clinical trials and routine care, as well as (2) the blurring of traditional boundaries between individual trial phases in the post-cytotoxic drug development era2. There are also challenges in applying, locating, and determining when equipoise is (and is no longer) present in trials incorporating recent methodologic innovations (e.g., seamless, platform and multi-arm multi-stage (MAMS) trial designs, and various adaptive techniques).
Potential relevance and impact: Whilst equipoise still has a role in the ethical evaluation of novel trials incorporating randomisation, its use as a guide to the ethical probity of such trials is more limited than for conventional RCTs. A composite approach, using a variety of tools for the ethical evaluation of novel late-phase clinical trial designs is needed.