Improving pharmacovigilance in Europe

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1694 (Published 12 April 2010) Cite this as: BMJ 2010;340:c1694
  1. Nicholas Moore, professor of pharmacology ,
  2. Bernard Bégaud, professor of pharmacology
  1. 1University of Bordeaux, Bordeaux, France
  1. nicholas.moore{at}pharmaco.u-bordeaux2.fr

    New legislation is proposed and greater transparency sought

    Prescribing a drug requires understanding the balance between benefits and harms.1 Knowing these requires access to information, which can come from clinical trials or pharmacovigilance. Information about clinical trials has been much improved by trial registration in a publicly accessible database, which facilitates systematic reviews and retrieval of unpublished studies, and allows patients to volunteer for these studies.2

    In the linked analysis article (doi:10.1136/bmj.c1578), Garratini and colleagues,3 like others before them,4 call for further transparency so that study results and individual patient data are made public too, with of course respect for patient confidentiality. This would allow an independent reanalysis of study results,4 and the reanalysis of combined patient safety data to ensure that the risks of drugs are not greater than their benefits and that claims of efficacy are not exaggerated.3 This would apply to studies that were submitted to obtain drug registration.

    Another benefit of making individual patient data publicly available is the possibility of identifying predictors of individual patient outcomes. These could then be tested in real life postmarketing effectiveness studies to ensure that drugs are given only to patients who would benefit most. The gain would be individual for patients. Collective gains would also come from reduced spending on drugs and reduced exposure to drugs.5 This might reduce a drug’s market size, which drug companies may not like.

    However, clinical trials are only a small part of a drug’s life. Drugs need to be followed from the premarketing clinical trial environment into the real world. New risks may then appear for several reasons, such as the trial population not representing the end user, patients having concomitant diseases or taking other drugs, patients’ genetic make-up being different, or the drug being used off-label.

    Pharmacovigilance has come a long way since the 1960s and thalidomide. Spontaneous reporting systems have been set up, and communication between drug companies, patients, and prescribers has improved. All companies must have a qualified employee in pharmacovigilance. Exchange of information between regulators and industry has been reinforced. A European working party on pharmacovigilance (PVWP) was set up at the founding of the European Medicines Evaluation Agency (EMA) in 1995.

    European regulators and regulations evolve over time. A new round of legislation is being prepared6 7 8 and has been widely discussed.9 10 It is reviled by some as being too much and by others as being too little, accused of giving away control to the industry or of stifling commercial initiative by excessive administration. This legislation, which is to be discussed in the European Parliament this coming April, should be adopted by the Council of Ministers in early June. It proposes several changes, some of which simply clarify or reinforce previous obligations such as exchange of information between regulators and industry; others, such as the transfer of responsibility from the industry to public health (Sanco) directorates, may potentially change the structure of pharmacovigilance in Europe. Some welcome this transfer, but others worry that Sanco lacks the experience of the wiles of industry that the Industry Directorate has.

    Another major evolution that started some years ago is the transition from mostly passive pharmacovigilance systems based on spontaneous reporting to more proactive initiatives, such as risk management plans, risk minimisation, and the development of pharmacoepidemiology, supported by the European Network of Centres of Excellence in Pharmacovigilance and Pharmacoepidemiology (ENCEPP) at the EMA. In fact the authorities will have the power to demand these post-authorisation studies, a power that previously existed only in a few member states. Drug companies are asked to state what problems they anticipate with their new drugs, how they plan to monitor them, and how they expect to minimise the consequences. There is concern that risk management plans could reduce preapproval studies and spontaneous reporting efforts,10 even though spontaneous reporting is part of the plan.

    The PVWP will become the pharmacovigilance risk assessment advisory committee (PRAAC). Its powers are still being discussed. The reinforcement and extension of the common database of adverse drug reactions in Europe (EUDRAvigilance), accessible to all national authorities and possibly others, could increase the power to detect new signals. It would include direct patient reports of adverse drug reactions, whose real benefits and place in pharmacovigilance are still debated. Overall, regulations are trying to streamline processes and make them more efficient, but time will tell how effective they are.

    However important regulations are, they are not the solution to everything. Most adverse drug reactions that result in hospital admission are well known effects of old drugs and might well have been avoided if patients and prescribers were better trained.11 This aspect could also be improved alongside the proposed legislation.12


    Cite this as: BMJ 2010;340:c1694


    • Analysis, doi:10.1136/bmj.c1578
    • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No non-financial interests that may be relevant to the submitted work.

    • Provenance and peer review: Commissioned; not externally peer reviewed.


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