Manual normalisation of the ADRs

We extracted 5,098 distinct ADRs from the Brat annotation files. We used the UMLS 2015AB REST API and the downloaded MedDRA 18.1 files to find perfect matches to the exact ADR strings. The primary terminology for FDA pre-marketing and post-marketing drug safety evaluation purposes is MedDRA. Therefore, we initially restricted the UMLS searches to MedDRA, and only used the appropriate semantic types from other UMLS sources if the ADR could not be mapped to MedDRA. The 1,383 perfectly matched MedDRA Preferred Terms (PTs) were split into four parts and reviewed manually by one of the annotators. The unmatched terms were also split into four parts, mapped manually by one of the annotators, and then the mappings were verified by another annotator. The disagreements were reconciled by all annotators.

In the process, we identified 114 ADRs that could not be mapped to MedDRA PTs, e.g., label text denoting ‘decreased embryo viability’. These terms were submitted to editor representatives from MedDRA for review. MedDRA editors suggested alternate mappings, some underspecified, for 39 unmapped terms and 2 annotations were deleted on their suggestions. 73 terms remain unmapped.

We also identified 102 additional underspecified terms, e.g., we could only map the label text ‘flexor tendon ruptures’ to the MedDRA PT 10043248 ‘Tendon rupture’. We submitted these additional 102 terms to the MedDRA editors. After their review, 83 ADRs remained underspecified, while 19 had alternate mappings suggested by the editors. For example, we coded the ADR ‘renal tubular injury’ to the MedDRA PT 10061481 ‘Renal injury’, whereas MedDRA editors suggested using ‘Renal tubular dysfunction’ instead, and further proposed to add ‘Renal tubular injury’ as a Preferred Term to the next version of MedDRA dictionary.