Clinical Efficacy and Safety: The Concept of Benefit–Risk

This chapter looks at clinical efficacy and safety as different concepts that are measured and debated as distinct properties of a medicinal product. It describes clinical efficacy and safety in terms of their probabilities and magnitudes of effects and discusses how they are inevitably, inextricably intertwined through their contributions to the overall benefit–risk profile of the medicinal product. It also mentions statistics and probability techniques that were occasionally used in the eighteenth century in support of medicine and public health. The chapter refers to the Clinical Trial Regulation (Regulation (EU) No 536/2014), which harmonises the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System. It considers a clinical trial as an art of scientific investigation, while double-blind randomised controlled trials are the standard for regulatory approval.

Clinical trials challenges - impact of the new clinical trial regulation on the conduct of clinical trials

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Redundant trials can be prevented, if the EU clinical trial regulation is applied duly

The problem of wasteful clinical trials has been debated relentlessly in the medical community. To a significant extent, it is attributed to redundant trials – studies that are carried out to address questions, which can be answered satisfactorily on the basis of existing knowledge and accessible evidence from prior research. This article presents the first evaluation of the potential of the EU Clinical Trials Regulation 536/2014, which entered into force in 2014 but is expected to become applicable at the end of 2021, to prevent such trials. Having reviewed provisions related to the trial authorisation, we propose how certain regulatory requirements for the assessment of trial applications can and should be interpreted and applied by national research ethics committees and other relevant authorities in order to avoid redundant trials and, most importantly, preclude the unnecessary recruitment of trial participants and their unjustified exposure to health risks.

Poor implementation of the EU clinical trial regulation is a major threat for pragmatic trials in European countries

The principle of pragmatism in clinical trials has been broadly recognised as a way to close the gap between research and practice. In this contribution, we argue that the conduct of pragmatic clinical trials in Europe may be hampered by poor implementation of current European Union's Clinical Trial Regulation No. 536/2014.