An Application of Machine Learning in Pharmacovigilance: Estimating Likely Patient Genotype From Phenotypical Manifestations of Fluoropyrimidine Toxicity
Correia Pinheiro, Durand, Dogné (2020) An Application of Machine Learning in Pharmacovigilance: Estimating Likely Patient Genotype From Phenotypical Manifestations of Fluoropyrimidine Toxicity Clin Pharmacol Ther (IF: 6.7) 107(4) 944-947
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Abstract
Dihydropyrimidine dehydrogenase (DPD)-deficient patients might only become aware of their genotype after exposure to dihydropyrimidines, if testing is performed. Case reports to pharmacovigilance databases might only contain phenotypical manifestations of DPD, without information on the genotype. This poses a difficulty in estimating the cases due to DPD. Auto machine learning models were developed to train patterns of phenotypical manifestations of toxicity, which were then used as a surrogate to estimate the number of cases of DPD-related toxicity. Results indicate that between 8,878 (7.0%) and 16,549 (13.1%) patients have a profile similar to DPD deficient status. Results of the analysis of variable importance match the known end-organ damage of DPD-related toxicity, however, accuracies in the range of 90% suggest presence of overfitting, thus, results need to be interpreted carefully. This study shows the potential for use of machine learning in the regulatory context but additional studies are required to better understand regulatory applicability.© 2020 European Medicines Agency. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158217http://www.ncbi.nlm.nih.gov/pubmed/31955411
http://dx.doi.org/10.1002/cpt.1789
