Joyce M. Hoek ^1,2* Jonna M. Brenninkmeijer ¹ Ymkje Anna De Vries ³ Rob R. Meijer ¹ Don Van Ravenzwaaij ¹

• ¹ Department of psychology, University of Groningen, Groningen, Netherlands
• ² Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands, Netherlands
• ³ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, Groningen, Netherlands, Netherlands

Medicine regulators need to judge whether a drug’s favourable effects outweigh its unfavourable effects based on a dossier submitted by an applicant, such as a pharmaceutical company. Because scientific knowledge is inherently uncertain, regulators also need to judge the credibility of these effects by identifying and evaluating uncertainties. We performed an ethnographic study of assessment procedures at the Dutch Medicines Evaluation Board (MEB) and describe how regulators evaluate the credibility of an applicant’s claims about the benefits and risks of a drug in practice. Our analysis shows that regulators use an investigative approach, which illustrates the effort required to identify uncertainties. Moreover, we show that regulators’ expectations about the presentation, the design and the results of studies can shape how they perceive a medicine’s dossier. We highlight the importance of regulatory experience and expertise in the identification and evaluation of uncertainties. In light of our observations, we provide two recommendations to reduce avoidable uncertainty: less reliance on evidence generated by the applicant; and better communication about, and enforcement of, regulatory frameworks towards drug developers.