Background: Pharmacovigilance suffers from considerable underreporting. This is particularly the case for novel oncology therapeutics where regulatory approval is supported by clinical trials with small sample sizes and limited follow-up to observe later treatment-related adverse events. Furthermore, causation is rarely confirmed outside controlled settings such as clinical trials, and particularly absent in conventional RWE sources.
Objectives: To evaluate the ability of published case reports to serve as a source of pharmacovigilance for novel oncology therapeutics as well as the prevalence of reporting of clinician confirmed causality.
Methods: We assessed structured patient journey data extracted from approximately 30,000 peer reviewed oncology case reports published since 2015 and available from the OpenCase(TM) database. The reviewed cases covered hematological cancers (myelomas, leukemias, and lymphomas) and solid cancers (lung, breast, colorectal, and bladder) and represented case reports from over 125 nations. Adverse events (AEs) and key patient journey data were extracted using state-of-the-art natural language processing (NLP) models with validated accuracy of over 92%.
Results: A total of 58.5% cases reported at least one adverse event after or during a treatment period. Of these, the median number of reported adverse events were 4 (IQR: 2 - 8). There were 12,551 unique AEs after normalizing with the MedDRA database using a state-of-the-art AI model. The ten most frequently reported AEs were pain, fever, weight loss, fatigue, post-op complications, fatigue, anemia, infection, bleeding, and dyspnea, ranging from 897 to 2606 occurrences. Clinical confirmation of causation (i.e., treatment-related adverse event) was available for at least one adverse event in over half of the case reports. The majority of these were related to immune checkpoint inhibitors, but toxicity due to chemotherapies and complications due to surgery were also common.
Conclusions: In conclusion, our evaluation suggests that peer reviewed oncology case reports represent a rich source of reported adverse events, often with clinically confirmed causality, which could substantially augment adverse events reporting of oncology therapeutics.
