Monitoring evidence on overall survival benefits of anticancer drugs approved by the European Medicines Agency between 2009 and 2015

Abstract

The introduction provisional approval strategies increases the approval of anticancer drugs with ambiguous benefit-risk profiles. Thus, in many instances, there is lacking evidence about overall survival (OS) at the time of marketing authorisation. Our objective was to monitor and characterise therapies with ambiguous benefit-risk profiles and identify any postapproval updates on median OS after at least 3 years of approval by the European Medicines Agency (EMA). Methods: We included all originator anticancer drugs with initially ambiguous benefit-risk profiles that received marketing authorisation by the EMA between January 1, 2009 and May 31, 2015. Our monitoring timeframe was at least 3 years after EMA approval. To identify study updates, the following three sources were included: clinicaltrials.gov, European Public Assessments Reports and PubMed. Results: In total, we identified 102 eligible approval studies. Out of these, a negative difference in median OS or no information was available in 43 (42.2%) instances. During monitoring, 14 updates with accessible positive information on OS could be identified. Including monitoring results, there are still 29 remaining therapies (28.4%) where no or negative information (n Z 24 [23.5%] and n Z 5 [4.9%], respectively) regarding OS is present at least 3 years after EMA approval. Conclusion: One-third of oncology drugs with ambiguous benefit-risk profiles at the time of approval fail to demonstrate a survival benefit even after several years of marketing

Publicly accessible evidence of health-related quality of life benefits associated with cancer drugs approved by the European Medicines Agency between 2009 and 2015

“…We further obtained information from the European Public Assessment Reports and from the original publications of the approval studies. A previously published study that monitored OS benefit over time was used as our general data basis [22]. In the present study, cancer drugs for indications with missing initial information on HRQoL outcomes at the time of approval were included and selected for monitoring.…”

Approval of Cancer Drugs With Uncertain Therapeutic Value: A Comparison of Regulatory Decisions in Europe and the United States

“…Research on special approval pathways has pointed toward questionable novelty of drugs that benefited from these programs, 6,10 a higher number of safety events in the United States (although not in Europe), 11,12 and an erosion of the evidence landscape, with robust evidence on the efficacy and safety of new medicines often unavailable at the time of marketing authorization and unlikely to become available in a timely manner in the postapproval phase. [13][14][15][16] Whilst the programs discussed here all aim to reduce the amount of time it takes for drugs to be approved onto the market, AA in the United States and CMA in the EU are particularly illustrative from a regulatory perspective because they shift part of the evidence generation for regulatory decision making from the preapproval to the postapproval period. This allows drugs to enter the market based on evidence that regulators consider to be preliminary and in need of further substantiation.…”

Decision Making Under Uncertainty: Comparing Regulatory and Health Technology Assessment Reviews of Medicines in the United States and Europe

“…With a median follow-up postapproval between 3 and 5.4 years, there was no evidence of survival benefits in 28-58% of approved oncology indications in the United States and Europe. [9][10][11][12][13][14] Correlation of surrogate measures with survival is often low. 15 Regulators and HTA bodies have key similarities in their evaluations of new drugs, as they are usually based on the same clinical evidence.…”

“…Although previous studies have recognized that postapproval testing commitments recommended by regulators are often changed, delayed, or not fulfilled, it is also true that most of these postapproval obligations are not intended to increase insight into comparative or clinically relevant long-term effects. [9][10][11][12]18,20,[30][31][32] Although some HTA bodies in Europe may ask for additional studies, most HTA bodies do not have the authority to compel these trials to be completed.…”