The literacy barrier in clinical trial consents: a retrospective analysis

Background: Historically, the readability of consent forms in medicine have been above the average reading level of patients. This can create challenges in obtaining truly informed consent, but the implications on clinical trial participant retention are not fully explored. To address this gap, we seek to analyze clinical trial consent forms by determining their readability and relationship with the associated trial's participant dropout rate. Additionally, we explore a potential method for simplifying these forms. Methods: We analyzed the readability of consent forms of federally funded interventional clinical trials, which were completed in the United States on or before January 1, 2023, and were posted online and made accessible on ClinicalTrials.gov. We correlated their readability with trial dropout rates. As an exploratory analysis, a subset of these forms was simplified using a large language model, with expert medicolegal review. Findings: Across 798 included federally funded trials, the mean (±SD) Flesch-Kincaid Grade Level of their consent forms was 12.0 ± 1.3, equivalent to a high school graduate reading level and significantly higher than the 8th grade average reading level of adults in the United States (U.S.) (P < 0.001). In risk-adjusted analyses, each additional Flesch-Kincaid Grade Level increase in a clinical trial's consent form was associated with a 16% higher dropout rate (incidence rate ratio, 1.16; 95% confidence interval, 1.12-1.22; P < 0.001). Our exploratory analysis of a simplification method showed promising results in lowering the reading level while preserving medicolegal content. Interpretation: The average readability of informed consent forms of federally funded clinical trials exceeds the reading comprehension skills of the majority of adults in the U.S., potentially undermining clinical trial participant retention rates. Future work should explore the use of large language models and other tools as possible means to close this literacy barrier and potentially enhancing clinical trial participation. Funding: This research received no sources of funding. The authors have no conflicts of interest to report.