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. 2024 Nov;38(6):429-455.
doi: 10.1007/s40290-024-00541-y. Epub 2024 Nov 29.

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

Elif Car  1 , Yannick Vandenplas  1 , Teresa Barcina Lacosta  1 , Steven Simoens  1 , Isabelle Huys  1 , Arnold G Vulto  2   3 , Liese Barbier  1
Affiliations

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

Elif Car et al. Pharmaceut Med. 2024 Nov.

Abstract

Background: In the context of biosimilar use and switching, a patient's negative perception of a biosimilar might trigger a nocebo effect, where negative expectations unrelated to its pharmacologic action may lead to worsened symptoms, resulting in less perceived therapeutic benefit or worsened adverse events. Considering the crucial role biosimilars have in reducing health care costs and expanding access to safe biologics globally, it is essential to develop and implement effective strategies to mitigate the possible occurrence of such nocebo effects.

Objective: The aim of this systematic literature review was two-fold: (i) to review strategies that have been applied and/or tested for minimising the nocebo effect in clinical practice, within and outside the context of biosimilar switching, and (ii) to propose recommendations on useful mitigation strategies to minimise the occurrence of the nocebo effect in the context of biosimilar switching.

Methods: Biomedical databases PubMed and Embase were screened up until the 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: Of the 1617 identified and screened records, 60 met the inclusion criteria. Among these, 10 (17%) were conducted within the context of biosimilar switching, 7 of which specifically tested strategies to mitigate the nocebo effect. Among the remaining 50 studies conducted outside the biosimilar switching context, 46 tested mitigation strategies. Across the included studies, 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 health care professionals about the nocebo effect, (viii) education of patients and health care professionals about biosimilars, (ix) soft-skills training for health care professionals, (x) personalised information, (xi) supporting information, (xii) multidisciplinary approach, (xiii) organisation of the switch.

Conclusion: This review has identified a set of strategies that have been tested to mitigate the nocebo effect, which can be applied by health care professionals in the context of biosimilar switching with the aim of mitigating the occurrence of a nocebo effect. We recommend implementing a combination of mitigation strategies for patients and health care professionals to utilise before, during, and after a switch. It should be noted that given the limited number of studies specifically testing nocebo mitigation strategies within the biosimilar switching context to date, it is not yet possible to draw definite conclusions about the effect size of each mitigation strategy individually or in combination.

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Conflict of interest statement

Declarations. Conflict of interest: SS, IH and AV are founders of the KU Leuven Fund on Market Analysis of Biologics and Biosimilars following Loss of Exclusivity (MABEL Fund). AV is involved in consulting, advisory work and speaking engagements for a few companies, i.e., Accord, Amgen, Biogen, Effik, Medicines for Europe, Pfizer/Hospira, Mundipharma, Roche, Novartis, Sandoz. SS was involved in a stakeholder roundtable on biologics and biosimilars sponsored by Amgen, Pfizer and MSD; he has participated in advisory board meetings for Pfizer, Organon and Amgen; he has contributed to studies on biologics and biosimilars for Hospira, Celltrion, Mundipharma, Pfizer and Biogen; and he has had speaking engagements for Abbott, Amgen, Biogen, Celltrion and Sandoz. EC, YV, TBL, and LB have no conflicts of interest to declare. All authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. Funding: This work was supported by the KU Leuven and the Market Analysis of Biologics and Biosimilars following Loss of Exclusivity (MABEL) Fund. Ethics approval: Not applicable. Patient consent to participate/publish: Not applicable. Availability of data and material: Not applicable. Code availability: Not applicable. Author’s contributions: EC: study implementation (title/abstract screening, full-text screening, data extraction, and data analysis), preparation of draft manuscript, review of draft manuscript, and interpretation of results. YV: study design, study implementation (title/abstract screening, full-text screening, and data extraction), review of draft manuscript, and interpretation of results. TBL: study implementation (title/abstract screening, full-text screening, and data extraction), review of draft manuscript, and interpretation of results. SS: review of draft manuscript and interpretation of results. IH: review of draft manuscript and interpretation of results. AGV: review of draft manuscript and interpretation of results. LB: study design, study implementation (title/abstract screening and full-text screening), review of draft manuscript, and interpretation of results. All authors have read and approved the final version of the manuscript.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram: identification, review, and selection of articles included in the systematic review
Fig. 2
Fig. 2
A comprehensive framework to mitigate the nocebo effect throughout the biosimilar switching process. formula image: strategies that can be carried out through human interactions between HCPs and patients. formula image: strategies that can be carried out through educational initiatives. formula image: strategies that can be carried out through tools including information sheets, educational videos about biosimilars, and so on
See this image and copyright information in PMC

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