Benefit-risk assessment to inform non-inferiority and superiority study designs (BRAINS)

Benefit-risk is a methodology used to simultaneously evaluate multiple outcomes of a treatment for example the effectiveness on the primary health outcome, safety and cost.



By assessing the trade-off between these different outcomes, it allows decisions to be made on the most overall beneficial treatment to be utilised in practice. This methodology is already commonly used within the pharmaceutical regulatory setting and there is a need to transfer this to National Institute for Health Research (NIHR) and Medical Research Council (MRC) funded trials.

BRAINS is a methodological project which has been funded by MRC based on feedback from NIHR funding panels. The overall aim of the project to ascertain best practice of when to use this methodology and create guidance aimed at those designing trials that could benefit from using this methodology.

The project is made up of four work packages:

  1. A survey relating to current use of Benefit-Risk (Survey now closed – results due early 2020)
  2. Rapid literature review of current recommended practice (PROSPERO Registration:, results due early 2020)
  3. An expert consensus workshop (Workshop completed September 2019)
  4. Produce a guidance document to aid the inclusion of benefit-risk methodologies within publicly-funded clinical trials. (Results due mid 2020)

Professor Steven Julious is the Principal Investigator with Nikki Totton taking responsible for the day to day management of the project. Additionally, there is input from a range of methodologists from various backgrounds to assist the applicability of the study.

Project team

Name Role Organisation
Professor Steven Julious Principal Investigator University of Sheffield
Nikki Totton Executive Group University of Sheffield 
Professor Dyfrig Hughes Executive Group Bangor University
Associate Professor Jonathan Cook Executive Group University of Oxford 
Katie Biggs Rapid Review Lead University of Sheffield
Dr Lizzie Coates Co-Applicant  University of Sheffield 
Dr Andrew Cook Co-Applicant  University of Southampton
Dr Simon Day Co-Applicant Clinical Trials Consulting & Training Limited
Dr Necdet Gunsoy Advisory Member AbbVie
Professor Catherine Hewitt Co-Applicant University of York
Veronique Robert Advisory Member Servier Laboratories
Dr Praveen Thokala Advisory Member University of Sheffield


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