Do contemporary randomized controlled trials meet ESMO thresholds for clinically meaningful benefit?

Five years of EMA-approved systemic cancer therapies for solid tumours—a comparison of two thresholds for meaningful clinical benefit

“…Kim & Prasad [4] have also focused primarily on 5 years of cancer drugs approved by the FDA, showing that the majority of approved therapies had unknown effects or did not have any improvement in OS; in 67% of instances, approvals were also shown to be the result of surrogate outcomes. In addition, some of our authors have demonstrated that only one-third of anticancer therapies from randomised trials of the last 5 years (notably of which only a minority were FDA-registration trials) meet ESMO-MCBS thresholds for MCB [9].…”

“…The use of the lower CI limit for generating ESMO-MCBS grades not only introduces an optimistic perspective, but also systematically favours drugs with a low certainty in resultsda systematic bias that should be avoided in an evidence-based value framework. As in this study, a lowered realisation of the arbitrary benefit threshold when the best estimate of the HR is used has been previously in a different cohort of anticancer agents [9]. The adapted ESMO-MCBS also focuses on any toxicity data presented in the trial, adjusting grades by a threshold percentage difference in experimental and control toxicities in forms a and b ( Table 1 and Table A. 4), as opposed to only statistically significant toxicity end-points, which are less stringently addressed in forms evaluating OS benefit.…”

21 Five years of EMA-approved systemic cancer therapies for solid tumours – a comparison of two thresholds for meaningful clinical benefit

“…The use of the lower CI limit for generating ESMO-MCBS grades not only introduces an optimistic perspective, but also systematically favours drugs with a low certainty in resultsda systematic bias that should be avoided in an evidence-based value framework. As in this study, a lowered realisation of the arbitrary benefit threshold when the best estimate of the HR is used has been previously in a different cohort of anticancer agents [9]. The adapted ESMO-MCBS also focuses on any toxicity data presented in the trial, adjusting grades by a threshold percentage difference in experimental and control toxicities in forms a and b (Table 1 and Table A.4), as opposed to only statistically significant toxicity end-points, which are less stringently addressed in forms evaluating OS benefit.…”