Informed Consent in Clinical Trials

Background: Informed consent, a critical enabler of clinical research, depends on the provision of relevant information, capacity to consent and voluntariness. However, systematic reviews consistently indicate that research participants often have a poor understanding of the research studies in which they are enrolled. This thesis aims to explore the current approach to informed consent and provide methodological evidence for how it can be improved. Methods: To explore this important topic, I have conducted a series of investigations which include: a quantitative analysis of the understandability of clinical research participant information leaflets/informed consent forms (PILs/ICFs) using measures of syntactic and semantic complexity and health literacy-based criteria; the compilation of a set of guidelines for preparing accessible and understandable PILs/ICFs using an expert consensus conference methodology; a survey to elicit the perspectives of research participants and staff regarding contextual factors about the process of informed consent; the development of an enhanced PIL/ICF and educational website which aims to help prospective participants understand a Human Immunodeficiency Virus/obesity clinical trial; and a rapid systematic review to investigate compliance in reporting ethical declarations, including informed consent, in COVID-19 medical publications. Results: Clinical research PILs/ICFs sampled were found to be higher than the recommended reading age and most did not include a visual/infographic. The final guidelines for preparing accessible PILs/ICFs agreed by the expert consensus conference encompassed five categories: Layout, Formatting, Content, Language and Confirming Readability. The survey indicated that research participants are generally positive about their experience of the informed consent process but emphasised the importance of allocating adequate time. Research staff are concerned about whether research participants have understood the study information and cited lack of time and physical space, as barriers to optimal informed consent discussions. In the review of COVID-19 publications, confidentiality was generally maintained but some case studies included a combination of details which would have enabled participant identification. Compliance with reporting of informed consent was higher in the second sample of publications (i.e., later in the pandemic) for both case studies and observational studies as was compliance with ethics committee approval for observational studies. Conclusions: Clinical research PILs/ICFs should be prepared based on the available evidence regarding accessibility and understandability. Sufficient time and resources should be dedicated to facilitating informed consent discussions. Further empirical research should evaluate the effectiveness of interventions such as multimedia, on the quality of informed consent.2022-11-09 JG: Author's signature removed from PD