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From Regulatory Knowledge to Regulatory Decisions: The European Evaluation of Medicines

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Abstract

Medicines regulators have generally adopted a scientistic view of medicines evaluation, which they present as an exercise that should—and indeed can—be purely “objective,” based only on knowledge produced through validated research protocols. The growing body of social science literature analyzing the regulation of medicines has questioned this pretense of objectivity and underlined the socio-political construction of evidence on the risks and benefits of medicines. But while the European Medicines Agency has become the dominant regulatory body in Europe and a key player at world level, very few studies have investigated its actual practices. Based on interviews with European regulators, but also on direct observations of several meetings of the European Medicines Agency’s main expert committee, this article aims to analyze how regulatory knowledge is defined and then transformed into regulatory decisions. First, it describes the main characteristics of European medicines regulation and the historical definition of what can count as “objective” evidence on the safety and efficacy of medicines. Second, it demonstrates that experts use many different types of knowledge in building their opinions: the results of studies, but also knowledge about firms’ past and present strategies, about patients’ needs and future behavior, about the state of research and clinical practices, and about legal and policy-making issues. Third, it explains why, in spite of the various forms of knowledge involved, experts manage to produce consensual opinions on medicines and why these opinions are considered genuine decisions in the sector.

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Notes

  1. Instead of measuring actual clinical efficacy, through recovery or mortality rates, the trial proves the effect of a drug on a biological marker believed to be directly correlated with the patient’s disease (for example, the size of the tumor in cancer).

  2. Theses interviews were conducted with members of European scientific committees (1975–2003; n=22), with members of EU institutions (European Commission, European Parliament, EMA; n=34); with interested parties (industries, patient organizations; n=23).

  3. I was exceptionally granted permission to observe them for two months in 2000.

  4. Thalidomide was a sedative product prescribed to pregnant women to treat morning sickness, but it was proven to damage the fetus; it harmed thousands of people throughout the world. Following this disaster, the Kefauver-Harris Drug Amendments were notably passed in 1962 in the United States formally requiring pharmaceutical companies to provide proof of product efficacy.

  5. Patients are randomly allocated to an “experimental group” (they receive the drug) or to a control group (they receive a placebo or a comparator) and the results of the two groups are compared.

  6. In a double blind clinical trial, neither the patients nor the physicians know if they are taking/prescribing the tested drug or the comparator.

  7. Their “external” reliability is limited due to the extremely strict criteria used to select patients; they are incapable of identifying rarely occurring but serious problems; they are not very attentive to the long-term effects of medicinal treatments (Evans 2009).

  8. ICH initially comprised six parties: the regulatory authorities of the European Union (the EMA and the European Commission), Japan and the United States and their respective industry associations (the EFPIA as concerns Europe). It was recently reformed to include more members and become a real global forum.

  9. Cerivastatin was marketed in the late 1990s to treat hypercholesterolemia. Bayer voluntarily withdrew it from the market worldwide in 2001, after almost one hundred reported deaths. On this crisis and its consequences, see Demortain (2008).

  10. Rofecoxib (Vioxx®) was a nonsteroidal anti-inflammatory drug marketed by Merck & Co in the late 1990s. This arthritis and acute pain medication was withdrawn from the world market in 2004, due to safety concerns about an increased risk of cardiovascular events.

  11. The second class of antiretroviral medicines developed to treat HIV/AIDS.

  12. Non-inferiority trials simply establish that the new medicine is not significantly less effective than the comparator treatment.

  13. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500004628.pdf.

  14. Some members, who represent “small” medicines agencies, i.e., with more limited resources and expertise, will have a tendency to rely heavily on the rapporteur’s opinion.

  15. The EMA introduced a new policy on 1st January 2015 and now publish clinical study reports (CSRs) for every successful application. The first reports are available since October 2016.

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Acknowledgment

I would like to thank David Demortain for his valuable discussions and very helpful suggestions on this paper, as well as the two anonymous referees for their constructive comments.

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  1. National Institute of Health and Medical Research (Inserm), IRIS, 54 bd Raspail, 75006, Paris, France

    Boris Hauray

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Hauray, B. From Regulatory Knowledge to Regulatory Decisions: The European Evaluation of Medicines. Minerva 55, 187–208 (2017). https://doi.org/10.1007/s11024-017-9323-3

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