Demystifying Clinical Trials in Oncology: A Foundational Guide for Students and Beginners with Emphasis on LMICs

Clinical trials form the foundation of evidence-based medicine (EBM), especially in the field of oncology, where ongoing innovations in surgery, chemotherapy, radiotherapy, immunotherapy, and targeted agents are transforming patient outcomes. These trials not only evaluate the efficacy and safety of novel interventions but also serve as a critical tool to establish standard-of-care protocols. However, a major challenge remains: while the global cancer burden is rapidly increasing, the participation and representation of patients from low- and middle-income countries (LMICs) in clinical research remain disproportionately low. This mismatch is concerning, as LMICs now account for more than 70% of global cancer deaths, yet contribute to less than 10% of oncology clinical trials. Contributing factors include limited infrastructure, inadequate funding, ethical and regulatory hurdles, low research literacy, and logistical challenges. Moreover, many international trials conducted in high-income countries often lack external validity for LMIC settings due to differences in patient demographics, comorbidities, treatment compliance, and access to care. This paper offers a comprehensive, beginner-friendly overview of clinical trials, designed specifically for medical students, residents, and early researchers in oncology. It systematically explains essential trial concepts including phases (I–IV), trial design (randomization, blinding), sample size estimation, ethical considerations, analysis methods, and endpoint definitions (e.g., OS, PFS, QoL). Additionally, the paper highlights common biases in trial conduct and interpretation, and the importance of context-specific trials in ensuring equitable global oncology care. By focusing on practical knowledge and conceptual clarity, this review aims to empower budding clinicians and researchers—especially from LMICs—to not only interpret existing literature critically but also to initiate, design, and contribute to clinical trials that are ethically sound and regionally relevant. Bridging this gap is essential for advancing oncology care in resource-constrained settings and ensuring that progress in cancer treatment benefits all populations equitably.