Seven steps to take assessment of clinical benefit of anticancer medicines to the next level
The ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) Working Group has looked into new ways to improve the validity of the ESMO-MCBS. Focusing on trials’ methodologies and quality, the analysis published in ESMO Open discusses ten issues that may affect study outcomes and identifies seven potential sources of bias that need to be addressed in the future revisions of the scale to avoid misrepresentations derived from flawed trial design, implementation and data analysis.
More articles of interest
In September 2020, the below two articles have been published in ESMO Open. The studies aimed at evaluating the applicability of the scale and at assessing the reasonableness of the generated scores in order to identify shortcomings that could be rectified in future amendments.
In January 2020, the manuscript ‘EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for hematological malignancies’ has been published. The study presents the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies. Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies.
In 2017, an article addressing the methodology behind the ESMO-MCBS and providing a detailed statistical assessment was published in ESMO Open. The article is freely downloadable.
Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold.
This dual rule addresses two goals:
- Inclusiveness - not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit;
- Discernment - penalising trials designed to detect a small inconsequential benefit.
The ESMO-MCBS is intended to both assist oncologists in explaining the likely benefits of a particular treatment to their patients as well as to aid public health decision makers' prioritise therapies for reimbursement. From its inception the ESMO-MCBS Working Group has invited questions and critiques to promote understanding and to address misunderstandings regarding the nuanced use of the scale, and to identify shortcomings in the scale to be addressed in future planned revisions and updates. The ESMO-MCBS V.1.0 has attracted many questions regarding its development, structure and potential applications. These questions, together with responses from the ESMO-MCBS Working Group, have been edited and collated, and are herein presented as a supplementary resource.
The ESMO-Magnitude of Clinical Benefit Scale versions v1.0 and v1.1
The ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) version 1.0 (v1.0) was published in May 2015 and was the first version of this validated and reproducible tool to assess the magnitude of clinical benefit from new cancer therapies. A correction of the manuscript of the ESMO-MCBS v.1.0 has been published in Annals of Oncology.
The ESMO-MCBS is designed to be a dynamic tool with planned revisions and updates based upon recognition of expanding needs and shortcomings identified.
The revised version of the scale, ESMO-MCBS v1.1, launched in 2017, incorporates 10 revisions and allows for scoring of single-arm studies.
The 2015 and 2017 articles can both be found in Annals of Oncology and are freely downloadable.
In this podcast Teresa Amaral, member of the ESMO YOC, interviews Professor Martine Piccart (Scientific Director of the Institut Jules Bordet, Universite Libre de Bruxelles, Belgium) who shares valuable insights on the work that has been done in the field of access to essential cancer medicines by the ESMO-Magnitude of Clinical Benefit Scale (ESMO – MCBS) Working Group