I was fortunate enough to attend the 32nd International Conference on Pharmacoepidemiology and Therapeutic Risk Management as a speaker on behalf of the European Cancer Patient Coalition, and my presentation was related to the practical implications for patients, industry and regulators, of the creation of the Revised ICH* Benefit-Risk Assessment Guideline. Perhaps some of you are familiar with this revision, but just in case, I would like to share some comments with you. (*ICH is the International Council on Harmonisation that oversees scientific and technical aspects of pharmaceutical product registration in Europe, the US and Japan.)
I participated in a debate with Dr. Tarek Hammad and Dr. Rebecca Noel, both of whom are very empathetic towards patient involvement. Dr. Hamman and Dr. Noel have participated in the ICH Expert Working Group M4E (R2) to provide format and structure to the revision of the ICH Guideline, in the section on Benefit-Risk Conclusions of the Common Technical Document, bringing a new perspective and value on the insertion of patient preferences, considering the therapeutic context, disease condition, and current therapies, among other factors, looking for a very real-world justification to define innovation value. ICH has done notable work to reach a consensus in standardizing the content and presentations of benefit-risk information in regulatory submissions, rethinking the way we deal with the benefit-risk assessment.
The new guideline recommends patient perspective data to be considered when describing the therapeutic context, benefits and risks, and underlines the need to accurately characterize and incorporate pertinent patient preferences in the approval process. These preferences may be obtained directly from patients or their proxies using qualitative, quantitative, or descriptive methods. It is remarkable to see the view of health outcomes in this more holistic way.
However, there is a lack of additional guidance to aid industry in structuring their benefit/risk assessment, which leads to some methodological issues that need to be resolved. Such as: what is the realistic role of a quantitative approach in a benefit-risk assessment? What to do with trials that are prematurely terminated due to obvious efficacy? Should the B-R profile be the endpoint? How can the patient have a say in the evaluation as emerging evidence accrues?
There are also specific challenges for new, breakthrough, or orphan drugs to consider. Methodological challenges stem from the need to account for what is “lost in translation” due to the way evidence is generated. There is a need to generate more precise markers that depict the extent of benefits and risks on an ongoing basis.
While this revision opens a door to partner with patients for conducting preference studies and to structure patient-focused benefit-risk assessment, the implementation of a consistent approach remains a challenge. We cannot forget that there is a lack of obligation to put these guidelines into effect.
Another key question is, of course, to what extent and how can patient communities and their representatives get involved in this emerging work.