In a recent article in the BMJ (online, 4 October 2017), Davis and coworkers evaluated overall survival and quality of life (QOL), of 48 cancer drugs approved by the European Medicines Agency (EMA) in 2009–2013[1]
. They concluded: a) 57% of patients neither had survival benefits nor an improved QOL; b) most drugs were approved without corroboration of survival benefits; c) no conclusive corroboration of survival benefits remained at a minimum of 3.3 years after market entry.
Society creates regulations that require marketed medicines to improve the life of citizens. It, therefore, comes as some surprise to learn the above.
The European drug approval process adheres to safety and efficacy, but not specifically to survival benefits. Since the 1970s, the United States has operated under a stringent centralised system through the Food and Drug Administration (FDA), as a consumer protection agency. By contrast, since 1993, the European Commission has operated through a network of centralised and decentralised bodies across the European Union (EU) member states, to maintain inter-state commercial interests and overall harmony. In the EU, there are serious concerns that drug approval might be too fast, to the detriment of patient safety[2]
. Also, not all trial data are submitted in new drug applications. This tarnishes the transparency of drug approval data. The non-published data is not made available to the public at the EMA[2]
. Whereas, the FDA allows online and by request review.
The American Economist Joseph Stiglitz received the Nobel Prize for “gaming theory”. The theory states there are subtle collusive behaviors that incline prices to remain high, regardless of market forces. Richard Thaler received the Nobel Prize for the “nudge theory”. The theory states that small interventions influence incentives and decision-making. Therefore, nudges can be manipulative to advance individuals or groups. The pharmaceutical lobby has mastered both. This translates into a monopoly on pricing and a bias-listing of drugs. The top eight European industry trade associations had seven times more expenditure in the lobby since 2012[3]
. The pharmaceutical industry and the EU are joined at the hip, through the largest public–private partnership, extensive meetings with the European Commission officials, and active participation in advisory groups.
Booth and Eisenhauer revealed that the design of many randomised, controlled trials is flawed because the use of progression-free survival as a primary endpoint is not based on a proven surrogacy to overall survival or QOL[4]
. This practice, which approves new drugs, is effectively lowering the bar to offer meaningful outcomes to patients.
The scientific and clinical bodies must tailor cancer drugs to their suitable therapeutic setting. Tamoxifen was approved for metastatic breast cancer, and initially used aimlessly in oestrogen receptor (ER)-positive and negative breast cancer patients. This conjured few survival benefits, until translational research identified the correct strategy in early-stage ER-positive breast cancer. This is credited with saving millions of lives[5]
.
Approval of cancer drugs, if it is based on scientific and economic rigor with social accountability, has the potential to achieve survival benefits.
Balkees Abderrahman
Postdoctoral fellow
University of Texas MD Anderson Cancer Center
References
[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] Van Norman GA. Drugs and devices: comparison of European and US approval processes. JACC Basic Transl Sci 2016;1(5):399–412. doi: 10.1016/j.jacbts.2016.06.003
[3] Tansey R. Policy prescriptions: the firepower of the EU pharmaceutical lobby and implications for public health: Corporate Europe Observatory 2015. Available at: https://corporateeurope.org/sites/default/files/20150904_bigpharma_web.pdf (accessed November 2017)
[4] Booth CM, Eisenhauer EA. Progression-free survival: meaningful or simply measurable? J Clin Oncol 2012;30(10):1030–1033. doi: 10.1200/JCO.2011.38.7571
[5] Jordan VC. Tamoxifen: catalyst for the change to targeted therapy. Eur J Cancer 2008;44(1):30–38. doi: 10.1016/j.ejca.2007.11.002
