More than half (57%) of cancer drugs authorised by the European Medicines Agency (EMA) between 2009 and 2013 came onto the market without any clear evidence they improved the quality or quantity of patients’ lives, according to research from King’s College London and the London School of Economics and Political Science (LSE). After a median follow-up of five years, almost half of the drugs (49%) still showed no quality or quantity of life benefit and of those that did, these benefits were judged to be clinically insignificant around 50% of the time.
The research team found most cancer drugs are approved by the EMA using only surrogate measures which, although indicators, are not strong predictors of survival – whether living longer or feeling better.
Dr Courtney Davis, a medical and political sociologist in the department of global health and social medicine at King’s and lead author of the study, said: “We evaluated the evidence base for all new drugs entering the market over a 5-year period and found that the majority came onto the market without clear evidence that they improved patients’ survival or quality of life. A large number of people are undergoing treatment for cancer and little new information is available to guide patients and their treating clinicians regarding drug effectiveness. When expensive drugs that lack robust evidence of clinical benefit are approved and reimbursed within publicly funded healthcare systems, individual patients may be harmed and public funds wasted.”
This low level for authorisation means a significant number of cancer drugs, available on the European market and often promoted as “breakthrough therapies”, may have no actual demonstrable benefit over existing treatment options or placebo. This may lead to false hope and exposure to unnecessary drug toxicity for some patients as well as being a significant waste of important resources and funding.
The team also found that even after a median follow-up of five years, almost half of the drugs (49%) still showed no quality or quantity of life benefit and of those that did, these benefits were judged to be clinically insignificant around 50% of the time. As a result of these findings, the researchers are calling on the EMA to increase its evidence bar for the market authorisation of new drugs.
Huseyin Naci, assistant professor in LSE’s department of health policy, and one of the authors of the study, said: ‘It is remarkable that so few cancer drugs enter the European market without any clear data on outcomes that matter to patients and their doctors: longer survival and better quality of life. There is a clear need to raise the bar for approving new cancer drugs.’
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.
Courtney Davis, Huseyin Naci, Evrim Gurpinar, Elita Poplavska, Ashlyn Pinto, Ajay Aggarwal