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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 doi: https://doi.org/10.1136/bmj.j4530 (Published 04 October 2017) Cite this as: BMJ 2017;359:j4530

Re: 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

In their recent article, Davis et al1 show that nearly three quarters of the anticancer drugs approved by EMA in the years 2009-2013 do not attain a meaningful survival benefit or a quality of life improvement in spite of very high costs. The article gives voice to many medical oncologists and hematologists around the world who are alarmed by the escalating cost system without significant demonstration of efficacy and cost effectiveness.
The authors rightly point to the responsibility of regulatory authorities such as EMA in approving expensive drugs with little if any survival benefit. The situation is not different in the United States, where between 2008 and 2012 the US Food and Drug Administration approved most uses of cancer drugs without evidence of survival or improved quality of life (67%, 36/54)2. In her commentary, Cohen3 underlines the potential conflict of interest of EMA who receives 89% of its entire budget from the drug industry fees, thus creating doubts over the independence of the agency. Here we would like to add to these issues our responsibility as cancer clinicians in perpetrating this vicious circle of unsustainable costs in spite of limited efficacy and increasing financial burden to the health care systems.
In medical oncology, financial relationships have increased through the years and have influenced clinical research, scientific visibility and career development.4 The issue is particularly important in our discipline given the increasing volume of investments made by the pharmaceutical industry in cancer treatment.5 In this escalating prize system6, pharmaceutical companies tend to orient a significant part of their investments towards marketing and promotional activities (at least 20-30% of the final drug price)7,8, rather than to research and development, a notion which is rarely publicly available. In a recent analysis on 10 approved cancer drug in the US9, the median cost to develop a drug was $648.0 million, a figure significantly lower than prior estimates, and the revenue since approval was substantial (median, $1658.4 million; range, $204.1 million to $22 275.0 million).
Direct financial relationships between industry and physicians and/or researchers, consisting of stock options, advisory fees, honoraria, speaking fees, travel and lodging expenses, have become common practice in modern medicine but represent an important source of conflict of interest and avoidable expenditures. In addition, they violate the first principle of the Hyppocratic oath to make the patient’s interest first without undue external influences, thus blemishing the concept of medical professionalism.
What can be done to stop this ill system? First of all, we propose a stringent policy of conflict of interest by the governments which should ban direct financial relationships between pharmaceutical industry and individual doctors as well as regulatory authorities, scientific journals, academic societies and patient advocacy groups. This may be a concrete approach to select better treatments and reduce drug prices.
References
1. Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. 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 Oct 4;359:j4530.
2. Kim C, Prasad V. Cancer drugs approved on the basis of a surrogate end point and subsequent overall survival: An analysis of 5 years of US Food and Drug Administration approvals. JAMA Intern Med 2015;359:1992-4. doi:10.1001/jamainternmed.2015. 5868 pmid:26502403.
3. Cohen D. Cancer drugs: high price, uncertain value. BMJ. 2017 Oct 4;359:j4543.
4. Moy B, Bradbury AR, Helft PR et al. Correlation between financial relationships with commercial interests and research prominence at an oncology meeting. J Clin Oncol. 2013 Jul 20;31(21):2678-84.
5. Global Oncology Trend Report a Review of 2015 and Outlook to 2020. IMS Institute for healthcare informations. http://www.imshealth.com/en/thought-leadership/quintilesims-institute/re....
6. Saltz LB. Perspectives on Cost and Value in Cancer Care. JAMA Oncol. 2016;2(1):19-21.
7. Socolar D, Sager A. Pharmaceutical marketing and research spending: The evidence does not support PhRMA’s claims. Presented at the American Public Health Association Annual Meeting (session 2018.0), Atlanta, GA. 2001.
8. Anderson R. Pharmaceutical industry gets high on fat profits. By Business reporter, BBC News 6 November 2014. http://www.bbc.com/news/business-28212223
9. Prasad V, Mailankody S. Research and Development Spending to Bring a Single Cancer Drug to Market and Revenues After Approval. JAMA Intern Med. 2017 Sep 11. doi: 10.1001/jamainternmed.2017.3601. [Epub ahead of print] PubMed PMID: 28892524.

Competing interests: No competing interests

13 October 2017
Andrea DeCensi
Medical Oncologist
Gian Mauro Numico, Fausto Roila
Galliera Hospital, Genoa, Italy
Mura delle Cappuccine 14, 16128 Genova, Italy