4334 - Magnitude of Clinical Benefit in Trials Supporting US Food and Drug Administration (FDA) Accelerated Approval (AA) and European Medicines Agency (EMA) Conditional Marketing Authorisation (CMA) and Subsequent Trials Supporting Conversion to Full Approval

Background

AA and CMA regulations were established by the US FDA and EMA, respectively, to improve access to drugs for life-threatening diseases. Here, we evaluate the magnitude of clinical benefit as measured by European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in trials supporting AA and CMA and confirmatory trials supporting conversion to regular approval (RA).

Methods

We searched the FDA and EMA websites to identify anticancer drugs that had received AA (since December 1992) or CMA (since March 2006) until December 31, 2017, and to assess the status of conversion to RA. Drug labels and reports of trials were reviewed to apply ESMO-MCBS v1.1. Substantial benefit was defined as a grade of A or B for trials of curative intent and 4 or 5 for those of palliative intent. Agreement between ESMO-MCBS grades for AA/CMA and RA was assessed using Cohen’s κ statistic.

Results

AA was granted for 52 indications based on 64 trials; 61% were subsequently converted to RA based on 36 trials. The median time between AA and RA was 2.8 years. Confirmatory trials were still not completed for 19 (37%) indications. ESMO-MCBS v1.1 was applied to 55 (85%) trials supporting AA and 16% showed substantial benefit. ESMO-MCBS v1.1 could be applied to 30 (83%) trials supporting conversion to RA and 63% showed substantial benefit. CMA was granted for 14 indications based on 15 trials. Only 20% of trial supporting CMA showed substantial benefit. 7 (50%) indications initially receiving CMA were converted to RA (median=4.1y). ESMO-MCBS v1.1 could be applied to 8 trials supporting conversion to RA and 50% showed substantial benefit. Among studies that we could calculate ESMO scores for both RA and AA/CMA, grades were identical for 18/27 cases (κ = 0.40) for AA and 5/8 for CMA (κ = 0.25).

Conclusions

A minority of trials supporting AA and CMA meet the criteria for substantial benefit using ESMO-MCBS. However, among trials supporting conversion to RA, more than half showed substantial benefit. There is only fair concordance in ESMO-MCBS scores between initial and confirmatory studies.

Clinical trial identification

Legal entity responsible for the study

Hospital de la Santa Creu i Sant Pau.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.