Participant Safety in Multisite, Randomized, Double-Blind, Placebo-Controlled Clinical Trials in Hospice/Palliative...

Objective: To describe the harms in all arms of six consecutive multi-site, double-blind, placebo-controlled randomised clinical trials. Background: Controversies surround conduct of phase III clinical trials in palliative care. Concerns include risks to participants' safety, use of placebo arms, participants' burden, and justification when therapies are already widely used. Methods: This study collates safety data of the first six studies of the Australian national Palliative Care Clinical Studies Collaborative. On an intention-to-treat basis, all harms are described using standard international definitions, their severity, outcomes, and level of attribution. Results: Studies recruited 1,232 participants: 65/1,232 (5.3%) participants had serious adverse events of which none had a definite (blinded) attribution, all of which settled with ceasing the intervention; 49/1,232 (4.0%) participants had adverse events. No participants on placebo arms had adverse or serious adverse events with definite (blinded) attribution. Discussion: These studies are safe for participants and generate knowledge to support informed patient decision making.