Off-Label Drug Use in High-Need Clinical Fields: Evidence, Risks, and Regulatory Pathways

Off-label drug use, defined as prescribing an authorized medicine outside its approved indication, dosage, route of administration, or patient population, remains a widespread and necessary element of clinical practice. This practice is particularly common in high-need specialties such as onco-hematology and rare diseases, where approved therapeutic options are limited and patient populations are frequently too small to support dedicated licensing trials. It is also especially prevalent among paediatric patients, who are frequently treated with medicines authorized only for adult populations due to the scarcity of dedicated paediatric trials. Beyond these specialized sectors, off-label prescribing occurs routinely across general inpatient and outpatient care. While using approved medicines for unapproved indications addresses urgent unmet medical needs, the lack of systematic evidence regarding efficacy and safety can compromise the benefit-risk balance and expose patients to preventable adverse drug reactions.Regulatory, monitoring, and reimbursement policies governing off-label prescribing vary substantially across jurisdictions. Certain countries have instituted statutory decrees, temporary recommendations for use, and designated reimbursement mechanisms to safeguard patient safety and support equitable access. In contrast, other jurisdictions leave prescribing decisions entirely to individual clinical judgment. In this context, this Research Topic aims to connect real-world clinical outcomes research with drug evaluation and health policy development.We welcome original contributions that generate real-world evidence on off-label drug utilization across clinical specialties, highlighting onco-hematology and rare diseases, and paediatric populations as primary examples, while critically evaluating the oversight mechanisms established to protect patient health. Submissions may examine pharmacovigilance and safety signal detection for off-label regimens, real-world clinical effectiveness and outcomes studies, comparative regulatory and reimbursement frameworks across healthcare systems, cost-effectiveness and access implications for patients, and institutional policies designed to reduce inappropriate use while preserving legitimate clinical access. Studies using spontaneous reporting databases for pharmacovigilance signal detection must adhere to the READUS-PV reporting guidelines; isolated data mining studies, i.e. those not supported by additional clinical evidence, will not be considered.All article types accepted by the Drugs Outcomes Research and Policies section are welcome, including Original Research, Systematic Reviews, Reviews, Policy Briefs, and Policy and Practice Reviews. We particularly encourage contributions featuring cross-disciplinary or international comparative perspectives.In accordance with section policy, this collection does not consider clinical studies of medicinal products which have not yet received a marketing authorization, preclinical studies, studies of medical devices not containing drugs, or studies on nutraceuticals, vitamins, wound-healing products, herbal medicines, or traditional medicines. Through this collection, the section seeks to consolidate empirical evidence and policy analyses to support informed, safer prescribing practices worldwide. Topic editors: Lucia Gozzo, Giovanni Luca Romano, Gloria Ravegnini, Pier Paolo Olimpieri Source: https://www.frontiersin.org/research-topics/86018/off-label-drug-use-in-high-need-clinical-fields-evidence-risks-and-regulatory-pathways