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Only half of new cancer drugs extend or improve life

Trials should have to evaluate survival directly, not rely on modelled measurements of survival

Louise Prime

Thursday, 05 October 2017

Barely half of new cancer drug indications approved by the European Medicines Agency (EMA) had evidence that they offered a survival or quality of life gain over existing treatments or placebo, according to a new study1 published today in The BMJ. Its authors suggest this shows that regulatory evidence standards are failing to meet the needs of patients, clinicians, and healthcare systems. Experts have called for health technology assessment programmes to demand that the pharma industry evaluates survival directly in methodologically rigorous trials, rather than relying on modelling using surrogate markers.

A research team led from King’s College London and the London School of Economics designed a study to determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. They analysed publicly accessible regulatory and scientific reports on cancer approvals by the EMA from 2009 to 2013, looking at the design features, comparators and endpoints in pivotal and post-marketing trials; and considered the evidence for benefit on overall survival or quality of life (and its magnitude) both at time of approval, and after market entry.

They reported that the EMA approved 48 cancer drugs, with 68 cancer indications, during that period. Of these, 57% (39 indications) came onto the market on the basis of a surrogate endpoint and without evidence that they extended survival or improved the quality of patients’ lives – and even after a median of 5.4 years on the market, only an additional eight drug indications had shown survival or quality of life gains.

They reported: “Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up, only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (44%) remained uncertain.”

They commented that although certain limitations might have affected their study results, their findings raise the possibility that regulatory evidence standards “are failing to incentivise drug development that best meets the needs of patients, clinicians, and healthcare systems”.

The author of a linked editorial2 argued that the high cost and toxicity of cancer drugs means we should only expose patients to them when they can reasonably expect an improvement in survival or quality of life. But he pointed out that when drugs do offer survival advantages, the gains are often marginal; that the small benefits of cancer drugs typically occur in trials conducted in unrepresentative patient populations; and that many of the surrogate outcomes used for drug approval are poorly correlated with survival.

He said these facts together “paint a sobering picture” and called for “rigorous testing against the best standard of care in randomised trials powered to rule in or rule out a clinically meaningful difference in patient-centred outcomes in a representative population”. He added: “The use of uncontrolled study designs or surrogate endpoints should be the exception not the rule.”

BMJ associate editor Dr Deborah Cohen concurred,3 and listed examples of methodological problems with trials that the EMA has either failed to identify or overlooked, including trial design, conduct, analysis and reporting.

She pointed out that hype and misleading reporting of studies can put pressure on governmental bodies to reimburse a drug. But, she said “regulatory sanctioning of a comparator that lacks robust evidence of efficacy, means the cycle of weak evidence and uncertainty continues”. 

She concluded: “Patients will continue to have their hopes dashed if regulators approve drugs using designs that are not methodologically rigorous.”


  1. Davis C, Naci H, Gurpinar E, et al. 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 2009-13. BMJ 2017; 359: j4530 doi: 10.1136/bmj.j4530
  2. Prasad V. Do cancer drugs improve survival or quality of life? BMJ 2017; 359: j4528 doi: 10.1136/bmj.j4528
  3. Cohen D. Cancer drugs: high price, uncertain value. BMJ 2017; 359: j4543 doi: 10.1136/bmj.j4543

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