Exploring Barriers to Inclusivity: Systematic Analysis of Exclusion Criteria and Potential Bias in Clinical Cancer Trials for Psychiatric and Neurological Conditions in European Protocols.

Abstract

Background: Cancer clinical trials often employ exclusion criteria that can impact vulnerable populations, particularly individuals with psychological, psychiatric, or neurological conditions.

Aims: This study aimed to analyze the prevalence and nature of exclusion criteria in clinical trials for prostate, breast, and lung cancers.

Methods: The EU Clinical Trials Register identified 51 protocols uploaded between 2022 and 2024. Thematic content analysis categorized exclusion criteria, and the justifications provided, while frequency analysis quantified their prevalence.

Results: After excluding five protocols (two non-English and three inaccessible), the final dataset comprised 46 protocols: 13 for prostate cancer (22.8%), 24 for breast cancer (42.1%), and 9 for lung cancer (15.8%). Exclusion criteria targeting vulnerable populations were present in 78.3% of protocols, categorized into five themes: psychiatric conditions (24.6%), neurological conditions (22.8%), other psychological conditions (22.8%), legal/guardianship status (5.3%), and unspecified conditions (24.6%). Compliance concerns (39.1%) were the most common justification, followed by informed consent challenges (32.6%), safety risks (13%), drug interference (10.9%), and not in the best interest (4.3%). Notably, 29.1% of protocols lacked justification for exclusions, raising ethical and transparency concerns.

Conclusions: The exclusion of vulnerable populations may limit the inclusivity and generalizability of cancer research. Heuristic biases and systemic practices can potentially influence this. Exploring the role of these factors and considering adaptive trial designs, along with providing detailed justifications for exclusion criteria, could support more equitable and representative clinical research.