Gilsenan AW, Ritchey ME, Hauber B, Andrews EB. Considerations when applying a structured benefit-risk assessment to drug delivery combination products. Poster presented at the 35th Annual ICPE Conference; August 28, 2019. Philadelphia, PA. [abstract] Pharmacoepidemiol Drug Saf. 2019 Aug 20; 28(S2):952.


BACKGROUND: Structured benefit-risk assessments (BRA) using frameworks such as the CIRS-BRAT or PROACT-URL have been evaluated for use primarily with drugs. Applying the BRA to drug delivery combination products (DDCP) can lead to different challenges than when used for a drug alone.

OBJECTIVES: To identify specific considerations when applying the CIRS-BRAT framework to a DDCP compared with a drug alone using a triptan example.

METHODS: The CIRS-BRAT framework includes defining a decision frame (including population, timeframe, and choice of comparator), identifying key benefits and risks, gathering and assimilating relevant data, and generating visualizations to communicate the results of the assessment. Unique considerations for each step in the application of the framework were identified to determine whether modification would be needed when applied to DDCP.

RESULTS: The published drug-only triptan example used an active comparator and timeframe within 24 hours. Key benefits were reduced pain, decreased sensitivity to light, reduction in functional disability, and reduction in nausea and vomiting. Key risks included transient triptan sensations, central nervous system adverse events, and chest-related adverse events. When considering BRA for iontophoresis as DDCP with a triptan, the decision frame remained the same, although special consideration should be given in population and comparator selection. Improved quality of life due to the convenience of DDCP was identified as a new benefit outcome, and skin burn was identified as a new risk outcome. In this instance, where DDCP impacts patient convenience, patient preference data could be important to include in a BRA. No differences in the framework were necessary for identification and extraction of source data nor for customization of the framework, though device-specific regulatory documentation could be useful when considering new benefits and/or risks associated with a device. Additionally, weighting via patient preferences could be applied. Display and interpretation are no different.

CONCLUSIONS: The CIRS-BRAT framework can be followed for DDCP, as noted in this triptan example, although additional considerations related to comparator, population, patient preferences, and timing may be more challenging to resolve compared with conduct of a BRA with a drug alone.

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