EMA

EMA counters the academics who criticized the cancer drug approval process

As more cancer drugs are approved and prices continue to rise, questions have circulated on whether these drugs are extending patient survival or improving quality of life. A research article published in the BMJ last week reviewed the approval of drugs by the EMA from 2009 to 2013 and noted that most drugs entered the market without evidence of survival benefits or QoL. But rather than refute the BMJ article’s findings in a response published Thursday, Francesco Pignatti, head of oncology, hematology and diagnostics at the EMA, wrote that the article’s findings “are not surprising to anyone familiar with cancer drug development.”

The BMJ research is part of a large and growing number of questions circulating on gains made with recent cancer drug approvals. “When there were survival gains over existing treatment options or placebo, they were often marginal,” the UK and Latvian professors who conducted the research noted in its conclusion.

Vinay Prasad

Vinay Prasad, assistant professor of medicine at Oregon Health and Science University, has been a vocal critic of the wave of recent approvals and wrote the accompanying editorial to the BMJ article, in which he called the regulatory system “broken.” He’s previously written in Focus on how most cancer drugs “cost too much and give us too little” in response to an op-ed in Focus on a JAMA study he co-authored.

Back in June, Richard Pazdur, FDA’s director of the Oncology Center of Excellence, also discussed in a blog post how to measure patient benefit with cancer treatment.

EMA Response

Francesco Pignatti

Pignatti offered four reasons why in many situations “demonstrating a clear effect on survival or QoL is not feasible and a benefit can be shown on the basis of other endpoints”:

  1. Overall survival may be difficult to detect because control-group patients in a randomized clinical trial “switch to the experimental treatment after progression, or multiple subsequent lines of effective treatments ‘dilute’ the effect of a drug used in earlier lines.” In such cases, EMA says, progression-free survival (defined as “the time during which treatment can induce and maintain a response or at least delay the growth of cancer”) has been the efficacy outcome used for approval.
  2. When tumor shrinkage and response duration are observed on the basis of a single-arm trial in a well-defined population with high unmet need, RCTs can be considered unethical or infeasible, and early approval mechanisms are used. Though he cautions that this “applies to a minority of cases and requires that the course of the disease is highly predictable, that there are no good therapeutic alternatives and that there are sufficient supportive clinical and non-clinical data to show a positive benefit-risk balance.”
  3. In terms of QoL, he notes that this “is rarely used as the primary efficacy endpoint in cancer clinical trials and convincing clinical benefits in terms of QoL are only rarely shown. This, however, does not mean that EMA does not value such studies, which are encouraged even if often they do not lead to robust conclusions.”
  4. And finally, he notes that “giant leaps” in benefits are “relatively rare” and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale used by the researchers in the BMJ article “was never designed for the purpose of clinical decision-making and was mainly constructed on the basis of oncologists’ views rather than a systematic evaluation of patient preferences.”

Pignatti adds that conducting trials “according to the most rigorous methodology is strongly encouraged” but is not “a pre-requisite for approval provided that existing uncertainties can be addressed on the basis of the totality of the data, including future studies, where appropriate … restricting approvals of cancer drugs only to situations where there is indisputable evidence of improvement in survival or QoL will not improve the lives of cancer patients.”


First published here. Regulatory Focus is the flagship online publication of the Regulatory Affairs Professionals Society (RAPS), the largest global organization of and for those involved with the regulation of healthcare and related products, including medical devices, pharmaceuticals, biologics and nutritional products. Email news@raps.org for more information.



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