Understanding the Unique Ethical Challenges in Randomized Controlled Trials of Delirium Interventions for Older...

Delirium is a serious acute neurocognitive condition that is common and debilitating in older people who undergo major surgery or are acutely ill. The nature of delirium, baseline comorbidity of older adults and related contextual factors present unique ethical challenges in delirium prevention and treatment trials; yet there is limited literature on how these challenges should be best addressed. The objective of this rapid review was to examine the reporting of key ethical processes for older adults (approval, recruitment, consent, retention) in delirium intervention trials. A rapid search in December 2023 with restricted key terms ("Delirium," "Randomized Controlled Trial"), databases (PubMed, CINAHL), older adult participants and English language, and a final publication date range of 2020 to 2023, resulted in 411 articles screened, 153 full-text reviews, and 51 randomized controlled trial (RCTs) reports (with 11 published protocols) included. Data extraction and synthesis aligned with general guidance for ethical approval, processes and reporting of clinical studies, including for people with key vulnerabilities for research participation. Trials were categorized by degree of ethical reporting and statistical tests explored associated trial characteristics. The 51 RCTs were conducted in diverse countries, with the most sizeable proportion in China (51%). Most trials evaluated a delirium prevention (96%) and/or pharmacological intervention (69%) and were individually randomized (88%), phase 3 (84%), and perioperative (75%). No trial fully reported all ethical processes. Most of the 51 trials fully reported who provided consent (88%), the consent approach (88%), and ethical approval details (63%); around half fully reported safety assessments (59%) and how, where and when participants were recruited (49%). However, few trials fully reported who recruited participants (31%), who obtained consent (22%); how trial information was provided (27%), whether capacity was assessed prior to consent (10%), how participants were supported though the trial design or processes (18%) or in-trial communications (8%). Compared to the 19 trials (37%) with little to no reporting of ethical processes, the 16 (31%) trials with fuller reporting more often had a separately published protocol (56% vs 0%, P < .001), were conducted outside of China (87.5% vs 11%, P < .001) and had lower median consent (56% vs 96%, P < .01) and retention rates (89% vs 96%, P < .05). These results will help inform future efforts focused on improving the conduct and reporting of ethical processes in delirium trials.