A Randomised Controlled Trial of Enhanced Informed Consent Compared to Standard Informed Consent To Improve Patient Understanding of Early Phase Oncology Clinical Trials

i. General background

Early phase oncology clinical trials are becoming increasingly complex with a rapidly increasing array of investigational agents, combinations of these agents and a variety of trial designs which incorporate the importance of personalised approaches and the hope of fast tracked drug discovery. Informed consent for early phase oncology trials has always been a contentious area, and now it continues to be of relevance for the wider oncology community and the Phase 1 trial community. A 2018 study demonstrated significant gaps in understanding of patients regarding the nature and intent of early phase oncology trials. There has been a longstanding debate in the medical oncology community about the nature of Phase 1 trials and the ethics of allowing vulnerable patients to participate in clinical research where the primary purpose is to establish the safe dose. Opponents of the argument point to the need to understand both sides and that patients need to understand enough to consent, which is not necessarily full comprehension. The fact that this group of patients is hopeful, optimistic and desperate has been well characterized and no doubt plays a role in their ability to process information presented to them by the clinical research team.

ii. Empirical research showing patients misunderstand early phase clinical trials

Multiple studies have shown that advanced cancer patients (ACP) misunderstand the nature and purpose of Phase 1 oncology trials. Most recently, Hlubocky et al. demonstrated through audiotaping clinical encounters between 101 ACPs, and 29 oncologists that ACPs had a poor understanding. Only 26% were able to recall the primary purpose of the trial as safety and only 7% were able to recall that there was a risk of major adverse effects such as organ damage. The study also demonstrated deficiencies in clinician communication, with only 40% of encounters containing a direct statement on the research purpose being to establish safety, toxicity and dosage. In 2010, a similar study of 17 oncologists and 52 patients in the United Kingdom showed that several key areas of information including prognosis were omitted from the clinical encounter.Joffe and colleagues also conducted a survey of trial participants (including phase 1, 2 and 3 clinical trials) and investigators and showed significant deficits in understanding. Furthermore, in a survey of 95 patients on Phase 1 trials, Pentz and colleagues demonstrated that 68.4% of patients had a therapeutic misconception by failing to answer two core questions correctly ("Is the research study mostly intending to help research and gain knowledge or mostly intending to help you as a person?" and "Does the research study or your doctor decide the treatments?"). There was also a misunderstanding of the risk associated with participating in an early phase clinical trial and that they do not correctly grasp the key difference between individualized care and clinical research. There was a correlation between lower education and lower family incomes with therapeutic misconception. Overall there is extensive empirical evidence to suggest that a significant proportion of advanced cancer patients considering early phase oncology clinical trials harbour misconceptions about the nature and design of these trials.

iii. Participant Information Sheets are too long, too complex and fail to meet the information needs of patients