The evaluation of a new medical product has always required a benefit-risk (BR) assessment. In the past, however, the assessment tended to be informal and was often subjective, involving judgment based on separate assessments of efficacy and safety. Different regulatory agencies sometimes came to different conclusions when faced with essentially the same data in the applications. The need to improve transparency, consistency, and communication in this process has never been greater.
The field of structured BR assessment has evolved rapidly in the last few years, as evidenced by a large number of regulatory and industry-wide initiatives on structured BR assessment. For example, FDA released a guidance in 2013 on a structured BR assessment framework (FDA Citation2013) to organize its review of a product's benefit and risk, and to communicate benefit-risk assessment decisions at the point of approval or post-market regulatory decision. By 2017, FDA will use the BR framework in the review of all new drug and biologic licensing applications. Most recently, in June 2016, the ICH Expert Working Group finalized the Common Technical Document (CTD) Section 2.5.6 guidance on Benefit-Risk Evaluations (ICH Citation2016), providing a standard on the requirement of content and presentation of BR information in regulatory submissions. In addition, it provides more detail and greater specificity on the decision problem, therapeutic context, identification of key benefits and risks, along with the aspects generally to be considered when describing the benefit-risk assessment.
In the wake of these initiatives, the field of structured BRA has blossomed with major advances in methodology and implementation. As a result, a large number of methods have been proposed to facilitate the BRA process (Guo et al. Citation2010; Phillips et al. Citation2010; Mt-Isa et al. Citation2014; Jiang and He Citation2016). This special issue on BR assessment continues the theme to the body of BR assessment literature by providing practical considerations and approaches for emerging issues in BR assessment. The special issue consists of nine articles that highlight several important aspects of the evaluation of benefit risk. These include an article on key changes in benefit-risk assessment guidelines and implications for data analysis in drug development; a set of papers on quantitative approaches to BR analysis, including an extension of the stochastic multi-criteria discriminatory method and the comparison of number needed to treat and the number needed to harm; and articles focusing on issues such as a patient-centric approach to BR evaluation, different data sources, multiplicity subgroup analysis, data visualization, endpoint selection, weight determination, and uncertainty evaluation for benefits and harms. Lastly, a commentary on BR evaluation from regulatory perspective and the role of statisticians in this process is also included.
We would like to express our sincerest gratitude to all of the contributors who made this special issue possible. They are leading experts in structured BR assessment from industry, regulatory agencies and academia. Their in-depth knowledge, thought-provoking considerations and practical advice based on a wealth of experience make this special issue unique and valuable for a wide range of audiences. We hope that you will find this issue helpful as well.
Finally, our special thanks to José Pinhero and Jina Lee for their enthusiasm and support for this special issue.
References
- Food and Drug Administration (FDA). (2013), Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making. Draft PDUFA V Implementation Plan, available at http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM329758.pdf
- ICH. (2016), ICH New Expert Working Group Finalized Guideline, available at http://www.ich.org/products/ctd.html
- Guo, J. J., Pandey, S., Doyle, J., Bian, B., Lis, Y., and Raisch, D. W. (2010), “A Review of Quantitative Risk–Benefit Methodologies for Assessing Drug Safety and Efficacy-Report of the ISPOR Risk–Benefit Management Working Group,” Value Health, 13, 657–666.
- Phillips, L. D., Fasolo, B., Zafiropoulos, N., and Beyer, A. (2010), Benefit–Risk Methodology Project Work Package 2 Report: Applicability of Current Tools and Processes for Regulatory Benefit–Risk Assessment, Report No.: EMA/549682/2010. Available at http://www.ema.europa. London: European Medicines Agency.
- Mt-Isa, S., Hallgreen, C., Wang, N., Callréus, T., Genov, G., Hirsch, I., Hobbiger, H., Hockley, K., Lucian, D., Phillips, L., Quartey, G., Sarac, S., Stoeckert, I., Tzoulaki, I., Micaleff, A., and Ashby, D. (2014), “Review of Methodologies for Benefit and Risk Assessment of Medication Pharmaco-Epidemiological Research On Outcomes of Therapeutics by a European Consortium,” Pharmaco-Epidemiology and Drug Safety, 23, 667–678.
- Jiang, Q., and He, W. eds., (2016), Benefit-Risk Assessment Methods in Drug Development: Bridging Qualitative and Quantitative Assessments. Boca Raton, FL: CRC Press.