Relevance-Based Score for MIPD Model Selection: Systematic Review and External Evaluation of popPK Tacrolimus Models in Adult Transplant Recipients.

Model-informed precision dosing relies on population pharmacokinetic models, so prediction quality depends on which model is chosen, hence the need for an explicit selection criterion.

The authors developed a 23-item relevance score (training dataset, study design, evaluation methodology, covariates, parameter precision) to help select a population pharmacokinetic model before using it for model-informed precision dosing. A systematic review identified 28 tacrolimus models in adult transplant recipients, each scored for relevance and externally evaluated on an independent dataset from Rennes University Hospital (86 patients), then ranked with a 14-point external evaluation score based on predefined bias and imprecision limits. The mean relevance score was 22.3/56 (range 6-38), with higher scores linked to larger and richer datasets, prospective or multicentric designs, and clinically relevant covariates. Individual predictions showed acceptable bias and imprecision, whereas population predictions were consistently inaccurate, AUC concordance (56%-94%) being mainly limited by overestimation, and the best external score reached only 6/14. Correlation between relevance-based and external scores was moderate (Pearson 0.56; Spearman 0.61).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The operational message is less the score itself than its only moderate correlation with actual performance: judging a model from its published description does not remove the need for external evaluation on one's own patients before clinical use. The consistent inaccuracy of population predictions confirms that none of these models can set a reliable starting dose without a measured concentration, refocusing MIPD on Bayesian adjustment after initial sampling. External validation in a single center with 86 patients remains narrow, and transportability to other transplant populations still has to be checked.

Analysis by Dr Thibaut Benquey