Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j4530 (Published 04 October 2017) Cite this as: BMJ 2017;359:j4530
- Courtney Davis, senior lecturer1,
- Huseyin Naci, assistant professor of health policy2,
- Evrim Gurpinar, MSc candidate in international health policy 2,
- Elita Poplavska, assistant professor3,
- Ashlyn Pinto, MSc candidate in global health2,
- Ajay Aggarwal, academic clinical oncologist4 5
- 1Department of Global Health and Social Medicine, King’s College London, London WC2R 2LS, UK
- 2LSE Health, Department of Health Policy, London School of Economics and Political Science, London, UK
- 3Faculty of Pharmacy, Riga Stradins University, Riga, Latvia
- 4Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
- 5Institute of Cancer Policy, King’s College London, London, UK
- Correspondence: C Davis
- Accepted 28 September 2017
Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.
Design Retrospective cohort study.
Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.
Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs.
Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).
Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.
Contributors: CD conceived the study and acquired funding. CD, HN, and AA designed the study. EP, AP, and EG undertook data extraction and some analysis. CD undertook the primary analysis with input from HN and AA. CD drafted the first manuscript, with HN and AA contributing to subsequent iterations. All authors provided critical input on the manuscript and approved the final version for publication. CD is guarantor.
Funding: This study was supported by project funding from Health Action International. The study funder did not have any role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication. CD is a member of Health Action International Europe Members Association. EP is a member of Health Projects for Latvia, which is affiliated to Health Action International, and a board member of the Health Action International Europe Association. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
Competing interests: All authors have completed the ICMJE uniform disclosure at www.icmje.org/coi_disclosure.pdf and declare: EG, AP, and EP were supported by project funding from Health Action International; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: The lead author affirms that this manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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