PhRMA BRAT (The Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team)

Recommended for further appraisal for use in benefit-risk assessment

1. Description

BRAT (Benefit-Risk Action Team) standardises and supports the decision and communication of a BR assessment between pharmaceutical companies and the regulators through a 6-step process: define decision context, identify outcomes, identify data sources, customise framework, assess outcome importance, and display and interpret key BR metrics.

2. Quantitative frameworks

The BRAT framework emphasises the value tree (criteria tree) build-up, data selection and data preparation. Benefits and risks are not integrated in this framework, but are assessed separately. This was a conscious proposal to avoid synthesising data into complex statistical models which may not be easily understood by readers. BRAT framework is aimed at assisting the communication of benefit-risk assessment of medicines between the pharmaceutical company and the regulators. The summary of its components is shown below:

BRAT advocates the use of a "Data Source Table" . A data source table consists of the key information that is to be used in the benefit-risk assessment model.

Data source table is followed by the "Master Data Summary Table".

At the last step in the application of BRAT framework, a "Key Benefit-Risk Summary Table" is presented alongside a "Forest Plot" of the effects for each criterion. This method was tested in the Efalizumab, Natalizumab, Rimonabant, Telithromycin and Warfarin case studies.

3. References

[1] Coplan PM, Noel RA, Levitan BS, Ferguson J, Mussen F. Development of a framework for enhancing the transparency, reproducibility and communication of the benefit-risk balance of medicines. Clin Pharmacol Ther 2011 Feb;89(2):312-5
[2] Levitan BS, Andrews EB, Gilsenan A, Ferguson J, Noel RA, Coplan PM, et al. Application of the BRAT framework to case studies: observations and insights. Clin Pharmacol Ther 2011 Feb;89(2):217-24 .
[2] Hammond JS, Keeney RL, Raiffa H. Smart choices. A practical guide to making better life decisions. New York: Broadway Books; 2002.
[3] European Medicines Agency. Benefit-risk methodology project work package 3 report: Field tests. London: European Medicines Agency; 31 Aug 2012. URL: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500112088.pdf. Report no: EMA/718294/2011.