Nocebo effects of a simplified package leaflet compared to unstandardised oral information and a standard package leaflet: a pilot randomised controlled trial

BACKGROUND: The term “nocebo effect” describes the phenomenon that the mere knowledge and anticipation of possible negative consequences of an intervention can increase the probability of experiencing these consequences. Our objective was to assess whether different information presentations on adverse events (AEs) in package information leaflets (PILs) could influence the nocebo effect. METHODS: We included patients undergoing orthopaedic surgery in this pilot randomised controlled trial (pRCT). Patients were assigned by random, computerised and centralised allocation to one of three groups: Simplified-PIL, No-PIL or Standard-PIL on ibuprofen. The Simplified-PIL was written in plain language, and AEs were reported with a focus on avoiding biased risk perception. Only the outcome assessment was blinded. RESULTS: We included 35, 33 and 34 patients in the Simplified-PIL, No-PIL and Standard-PIL groups, respectively. All patients were included in the intention-to-treat analysis. Six patients in the Simplified-PIL, four in the No-PIL and eight in the Standard-PIL group reported an AE. This corresponds to relative risks of 0.80 (95% confidence interval (CI) 0.27–1.90) for the Simplified-PIL and 0.50 (95% CI 0.14–1.46) for the No-PIL compared with the Standard-PIL group. The Simplified-PIL increased knowledge, reduced anxiety and improved adherence, although statistical uncertainty was high for all of these outcomes. CONCLUSIONS: This pRCT provides the first hints on the way information on AEs is reported in PILs can affect the nocebo effect. This pRCT shows that a definitive RCT is feasible. If the results are confirmed in a definitive large RCT, a revision of the current practice for designing PILs should be considered. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03428035. Registered 2 February 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-019-3565-3) contains supplementary material, which is available to authorized users.