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Public health policy and health economics

1550 - Comparison of the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in Clinical Trials Supporting US Food and Drug Administration (FDA) Approval of Orphan vs. Non-orphan Drugs.


11 Sep 2017


Public health policy and health economics


Bioethical Principles and GCP


Consolacion Molto Valiente


Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440


C. Molto Valiente1, A. Tibau1, A. Ocana Fernandez2, A. Templeton3, L. del Carpio Huerta1, J. Del Paggio4, A. Barnadas1, C. Booth5, E. Amir6

Author affiliations

  • 1 Oncology Department, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, 8026 - Barcelona/ES
  • 2 Medical Oncology Department And Translational Research Unit, Albacete University Hospital, Albacete/ES
  • 3 Department Of Medical Oncology, St Claraspital and Faculty of Medicine, University of Basel, Basel/CH
  • 4 Division Of Cancer Care And Epidemiology, Queen’s University Cancer Research Institute, Kingston/CA
  • 5 Departments Of Oncology And Public Health Sciences, Queen’s University Cancer Research Institute, K7L 3N6 - Kingston/CA
  • 6 Division Of Medical Oncology & Hematology, Department Of Medicine, Princess Margaret Cancer Centre and the University of Toronto, M5G 2M9 - Toronto/CA


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Abstract 1550


The Orphan Drug Act provides incentives to manufacturers to develop drugs for rare diseases. The ESMO-MCBS is a validated tool, aimed at quantifying the clinical benefit for cancer drugs. Here, we compare the characteristics of clinical trials leading to approval by the FDA of orphan and non-orphan drugs and apply the ESMO-MCBS thresholds for meaningful clinical benefit.


We searched the Drugs@FDA website to identify anticancer drugs approved between January 2006 and December 2016. These were then categorized as orphan or non-orphan drugs as determined by the FDA. For each drug, we subsequently collected data on clinical trial design and methodology and compared these between orphan and non-orphan drugs. For drugs supported by randomized controlled trials (RCTs), we applied a ESMO-MCBS grade. Comparisons were performed using Mann Whitney U or Chi squared tests.


Of the 137 studies included, 109 (80%) were RCTs. These led to the approval of 63 individual drugs for 118 indications. Among these indications, 54 (46%) received orphan drug designation. Compared to non-orphan drugs, trials supporting orphan drugs approval had a smaller sample size (median 369 vs 687, P=.001), were less likely to evaluate experimental cytotoxic chemotherapy or endocrine therapy than targeted therapy (8% vs 21%, P=.005) were less often randomized (73% vs 86%; P=.047) and were more likely to assess intermediate endpoints rather than overall survival (71% vs 51%, P=.01). A similar proportion of orphan and non-orphan drugs approved for palliative use met the ESMO-MCBS threshold for meaningful benefit (29% vs 27%; P=.86). There were too few studies performed in the curative setting (n = 7) to perform statistical testing.


Compared with trials used to approve non-orphan cancer drugs, trials for orphan drugs are smaller, more likely to explore experimental biological therapies, use single-arm trials and intermediate end points. A similarly low proportion of approved orphan and non-orphan drugs meet the ESMO-MCBS threshold for meaningful benefit.

Clinical trial identification

Not applicable

Legal entity responsible for the study





All authors have declared no conflicts of interest.

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