Hypersensitivity Adverse Event Reporting in Clinical Cancer Trials: Barriers and Potential Solutions to Studying Severe Events on a Population Level

Abstract

ABSTRACT HYPERSENSITIVITY ADVERSE EVENT REPORTING IN CLINICAL CANCER TRIALS: BARRIERS AND POTENTIAL SOLUTIONS TO STUDYING ALLERGIC EVENTS ON A POPULATION LEVEL by Christina Eldredge The University of Wisconsin-Milwaukee, 2020 Under the Supervision of Professor Timothy Patrick Clinical cancer trial interventions are associated with hypersensitivity events (HEs) which are recorded in the national clinical trial registry, ClinicalTrials.gov and publicly available. This data could potentially be leveraged to study predictors for HEs to identify at risk patients who may benefit from desensitization therapies to prevent these potentially life-threatening reactions. However, variation in investigator reporting methods is a barrier to leveraging this data for aggregation and analysis. The National Cancer Institute has developed the CTCAE classification system to address this barrier. This study analyzes the comprehensiveness of CTCAE to describe severe HEs in clinical cancer trials in comparison to other systems or terminologies. An XML parser was used to extract readable text from adverse event tables. Queries of the parsed data elements were performed to identify immune disorder events associated with biological and chemotherapy interventions. A data subset of severe anaphylactic and anaphylactoid events was created and analyzed. 1,331 clinical trials with 13088 immune disorder events occurred from September 20, 1999 to March 2018. 2409 (18.4%) of these were recorded as “serious” events. In the severe subset, MedDRA terminology, CTCAE or CTC classification systems were used to describe HEs, however, a large number of studies did not specify the system. The CTCAE term “anaphylaxis” was miscoded as “other (not including serious)” in 76.2% of events. The CTCAE classification system severity grades levels were not used to describe any of the severe events and the majority of terms did not include the allergen and therefore, in dual or multi- drug therapies, the etiologic agent was not identifiable. Furthermore, collection methods were not specified in 76% of events. Therefore, CTCAE was not found to improve the ability to capture event etiology or severity in anaphylaxis and anaphylactoid events in cancer clinical trials. Potential solutions to improving CTCAE HE description include adapting terms with a low percentage of HE severity miscoding (e.g. anaphylactic reaction) and terms which include drugs, biological agents and/or drug classes to improve study of anaphylaxis etiology and incidence in multi-drug cancer therapy, therefore, making a significant impact on patient safety.