• Simon Lohse.
• Institute for Science in Society, Radboud University, Nijmegen, The Netherlands.
• J Eval Clin Pract. 2023 Apr 1; 29 (3): 554564554-564.

RationaleAlthough precision medicine is seen by many as one of the most promising advances in the field of medicine, it has also raised critical questions at various levels. Many of these concerns revolve around an observation described by Kimmelman and Tannock as the 'paradox of precision medicine': somewhat surprisingly, uncertainty seems to be a key characteristic of precision medicine in practice.Aims And ObjectiveTo better understand this concept and the underlying issues, a scoping review was undertaken to search for factors stated in the literature as contributing to or being aspects of uncertainty in precision medicine.MethodsA systematic search of the literature was conducted in three databases (Pubmed, Web of Science, and Jstor) and complemented with a systematic hand-search. The initial search provided 1.252 items of which 51 articles for selected as eligible for further analysis. These articles were coded with MAXQDA and categorized into four main themes (a-d) of uncertainty. The main results were summarized and discussed with a view to the interrelations between different aspects and implications for precision medicine in practice.ResultsThe mapping of different aspects and sources of uncertainty leads to the key result that 'uncertainty' should be understood as a cluster concept. Uncertainties are identified in many different respects and situated at different levels: Most complexity-related issues (theme a) can best be understood as ontological ('world-sided') aspects of the uncertainty paradox. Conceptual (theme b) and evidence-related uncertainties (theme c) are situated on an epistemological or methodological level, addressing foundational and normative challenges related to knowledge production in precision medicine. Finally, theme (d) targets issues on the level of material precision medicine practices. These levels are helpful to understand the different dimensions of the uncertainty paradox.ConclusionsUncertainty may not merely be a transient effect of the novelty of the precision medicine paradigm. Rather, it should be seen as a consequence of the ontological, epistemological and practical complexity of precision medicine, implying that uncertainty will not necessarily be reduced by more research. This finding encourages further investigations to better understand the interactions among various factors and aspects of uncertainty in precision medicine and the resulting implications for research and medical practice.© 2022 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.

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