Overview of Guidelines and Recommendations for the Planning, Conduct and Reporting of Company-Sponsored Observational, Noninterventional Studies in Europe

Abstract

Much of current clinical and public health knowledge comes from observational research and non-interventional studies (NIS). An increasing number of guidelines and recommendations have been developed to strengthen the methodology, conduct and reporting of different types of NIS. The purpose of this article is to provide an overview of the guidelines and recommendations on NIS that are most important to those medical and scientific professionals in the pharmaceutical industry who are less familiar with this topic. Therefore EU regulatory and legal documents, together with the websites of relevant scientific organizations (e.g. International Society for Pharmacoepidemiology, European Network for Pharmacoepidemiology and Pharmacovigilance, Strengthening the Reporting of Observational Studies in Epidemilogy [STROBE] and the industry self-regulating body, European Federation of Pharmaceutical Industries and Associations), have been reviewed and summarized. In order to exclude it from the scope of the Clinical Trials Directive, article 2c defines a noninterventional trial as “a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorisation. The assignment of a patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice, and the prescription of the medicine is clearly separated from the decision to include a patient in a study. No additional diagnostic or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data”. General principles for the accurate planning, ethical conduct and appropriate scientific reporting of companysponsored NIS on medicinal products include the preparation of a detailed protocol and seeking approval from an ethics committee, where not restricted by local law or regulation. Patients should provide informed consent for participation and investigators should be compensated only for their efforts in the context of the data collection. Responsibility for a company-sponsored NIS falls within the remit of its scientific service; any involvement by marketing or sales personnel is restricted to administrative tasks and the NIS must not be linked to the promotion of any medicinal product. Reports of all serious adverse reactions arising from observational post-approval safety studies should be reported on an expedited basis (i.e. within 15 days) to the local competent authority; for any other NIS, the same criteria and timelines apply as for adverse reactions reported spontaneously by healthcare professionals. An NIS should be registered in a study repository prior to initiation and findings, including the discussion of limitations due to potential bias and confounders, should be published according to the STROBE guidelines. The current legal adoption of the new Directive/84/2010 on pharmacovigilance, as well as the development of the new Clinical Trials Directive planned for 2012, will shape the future of NIS. As the role of noninterventional, observational research increases within the product lifecycle planning of a medicinal product, sound planning, ethical conduct and transparent reporting of such studies will be a key task formedical and scientific professionals in the pharmaceutical industry.