Mitigating the Nocebo Effect in Biosimilar Use and Switching: A Systematic Review

OBJECTIVES: This systematic literature review aims to: (i) review strategies that have been applied and/or tested for minimizing the nocebo effect in clinical practice, within and outside the context of biosimilar switching, and (ii) propose recommendations for effective mitigation strategies to minimize the nocebo effect in the context of biosimilar switching.

METHODS: Biomedical databases PubMed and Embase were screened up to end of April 2023 with a search string consisting of the following search terms “nocebo”, “biosimilar”, “mitigation”, “strategy”, and “prevention” and related synonyms. The search strategy was supplemented by snowballing of the included studies. The quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses, the Scale for the Assessment of Narrative Review Articles, and the Mixed Methods Appraisal Tool.

RESULTS: Out of 1617 screened records, 60 met the inclusion criteria. Among these, 10 (17%) were conducted within the biosimilar switching context, with seven testing specific mitigation strategies. Among the remaining 50 studies conducted outside the biosimilar switching context, 46 tested mitigation strategies. In total, 13 distinct mitigation strategies were identified, which can be employed within the context of biosimilar switching: (i) open non-verbal communication, (ii) positive framing, (iii) empathic communication, (iv) validating communication, (v) shared decision-making, (vi) self-affirmation, (vii) education of patients and healthcare professionals about the nocebo effect, (viii) education of patients and healthcare professionals about biosimilars, (ix) soft-skills training for healthcare professionals, (x) personalized information, (xi) supporting information, (xii) multidisciplinary approach, (xiii) organization of the switch.

CONCLUSIONS: This review has identified a comprehensive set of strategies to mitigate the nocebo effect, which can be applied by healthcare professionals in the context of biosimilar switching. We suggest implementing a combination of mitigation strategies for patients and healthcare professionals to utilize before, during, and after a switch.