Exploratory Web-Based SMARTI-I Tool Facilitates Drug Safety, Tolerability Evaluations

San Francisco – Researchers from Teva Pharmaceuticals have developed a web-based Safety Monitoring and Reported Tolerability Issues Index (SMARTI-I) system to help identify safety and tolerability issues, especially during formulary decision making. The SMARTI-I tool was described during a poster session at the AMCP meeting. The poster was titled Safety Monitoring and Reported Tolerability Issues Index (SMARTI-I): An Exploratory Evidence-Based Strategy to Summarize Aggregate Drug Safety Data.

In general, 3 different types of tolerability and safety issues can be computed from current commercially available systems. Aggregate data can be determined based on the number of adverse events (AEs) for a specific product divided by the total number of AEs for the relevant drug class; reported AEs can be aggregated by International Classification of Diseases, Tenth Revision (ICD-10) codes so that events for a specific condition can be determined; and risk adjustments of AEs based on severity can be used with measures such as Charlson indices.

Initial research evaluations used the SMARTI-I exploratory methodology to obtain aggregate drug safety data on disease-modifying therapies (DMTs) for the treatment of relapsing-remitting multiple sclerosis (RRMS). In a web-based format, users queried commercially available drug reference software to search for DMTs approved for the treatment of RRMS; searched for DMTs under clinical development for RRMS; downloaded AE data for approved and experimental DMTs; exported downloaded data into a Microsoft^® Excel spreadsheet; and opened the SMARTI-I system and imported the spreadsheet data. Based on the imported data, the SMARTI-I system was able to map AEs to the ICD, Ninth Revision, Clinical Modification (ICD-9-CM) or ICD-10, Clinical Modification (ICD-10-CM) codes specific to RRMS.

An evaluation of approved DMTs and DMTs under evaluation for use in RRMS identified 190 different ICD-10-CM AE codes. Meanwhile, an evaluation restricted to approved agents revealed 100 ICD-10-CM AE codes.

The investigators noted that based on these results, the addition of 4 drugs currently under evaluation to treat RRMS would be associated with an increase of safety and tolerability issues by 90%. The investigational drugs included in the analysis were often approved for other indications, from which safety and tolerability data were obtained. They added that approximately 35% of the ICD-10-CM mapped AEs and tolerability issues were observed for 3 approved DMTs; 2 other DMTs were associated with 59% and 63% of all ICD-10-CM AE codes. Specific DMTs were not identified by name.

The most frequent AEs identified for approved DMTs included chest pain (unspecified), depression, dizziness, dyspnea, headache, infection, nausea, and vomiting.

The investigators also conducted an analysis of DMTs, AEs, or tolerability issues restricted to skin disorders, to characterize the ability of the SMARTI-I system to evaluate safety and tolerability related to a specific body functional system.

The investigators emphasized that there may be limitations to the SMARTI-I approach that have yet to be determined, and that data aggregated from the SMARTI-I system should therefore be verified through other sources, when possible. Currently, the SMARTI-I system may be a helpful tool for identifying possible safety and tolerability issues that require additional research, according to the authors.

This study was supported by Teva Pharmaceuticals.