Real-World Evidence and Signal Detection: Emerging Methodologies in Indian Pharmacovigilance Practice

Real-World Evidence (RWE) derived from Real-World Data (RWD) has gained global prominence as a critical complement to traditional clinical trial data for post-marketing safety surveillance. Regulatory agencies including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and CIOMS emphasize the value of RWE in enhancing signal detection, improving risk assessment, and informing regulatory decisions. In pharmacovigilance (PV), RWE enables longitudinal follow-up, supports detection of rare and delayed adverse drug reactions (ADRs), and enhances safety monitoring in diverse, real-world populations. India’s rapidly evolving healthcare ecosystem with a vast heterogeneous population, mixed public-private systems, and increasing digitalization presents a strong opportunity for RWE-based PV. Initiatives such as the Pharmacovigilance Programme of India (PvPI) have strengthened spontaneous reporting, but integration of RWD sources such as electronic health records (EHRs), claims data, registries, and digital health platforms remains nascent. The absence of standardized data architectures, limited penetration of EHRs, fragmented registries, and variable data quality present significant barriers to large-scale active surveillance. Simultaneously, emerging analytical methodologies, including machine learning (ML) and artificial intelligence (AI), are being increasingly applied to large RWD sources for early detection of safety signals and prediction of risk patterns. These innovations hold promise for application within the Indian regulatory context. This review synthesizes global and Indian perspectives on RWE for signal detection, outlines current frameworks, evaluates available RWD sources, and examines emerging methods including AI/ML. It also discusses operational, regulatory, and ethical challenges in India and proposes a roadmap for strengthening RWE-based pharmacovigilance systems. By consolidating insights from open-access scientific literature and regulatory guidance, this review aims to support PV scientists, regulators, and healthcare policymakers in harnessing RWE to enhance drug safety and public health in India.