Methodological conduct of prognostic prediction models developed using machine learning in oncology: a systematic review

Paula Dhiman*, Jie Ma, Constanza L. Andaur Navarro, Benjamin Speich, Garrett Bullock, Johanna A.A. Damen, Lotty Hooft, Shona Kirtley, Richard D. Riley, Ben Van Calster, Karel G.M. Moons, Gary S. Collins

*Corresponding author for this work

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Background: Describe and evaluate the methodological conduct of prognostic prediction models developed using machine learning methods in oncology. Methods: We conducted a systematic review in MEDLINE and Embase between 01/01/2019 and 05/09/2019, for studies developing a prognostic prediction model using machine learning methods in oncology. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Prediction model Risk Of Bias ASsessment Tool (PROBAST) and CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) to assess the methodological conduct of included publications. Results were summarised by modelling type: regression-, non-regression-based and ensemble machine learning models. Results: Sixty-two publications met inclusion criteria developing 152 models across all publications. Forty-two models were regression-based, 71 were non-regression-based and 39 were ensemble models. A median of 647 individuals (IQR: 203 to 4059) and 195 events (IQR: 38 to 1269) were used for model development, and 553 individuals (IQR: 69 to 3069) and 50 events (IQR: 17.5 to 326.5) for model validation. A higher number of events per predictor was used for developing regression-based models (median: 8, IQR: 7.1 to 23.5), compared to alternative machine learning (median: 3.4, IQR: 1.1 to 19.1) and ensemble models (median: 1.7, IQR: 1.1 to 6). Sample size was rarely justified (n = 5/62; 8%). Some or all continuous predictors were categorised before modelling in 24 studies (39%). 46% (n = 24/62) of models reporting predictor selection before modelling used univariable analyses, and common method across all modelling types. Ten out of 24 models for time-to-event outcomes accounted for censoring (42%). A split sample approach was the most popular method for internal validation (n = 25/62, 40%). Calibration was reported in 11 studies. Less than half of models were reported or made available. Conclusions: The methodological conduct of machine learning based clinical prediction models is poor. Guidance is urgently needed, with increased awareness and education of minimum prediction modelling standards. Particular focus is needed on sample size estimation, development and validation analysis methods, and ensuring the model is available for independent validation, to improve quality of machine learning based clinical prediction models.

Original languageEnglish
Article number101
JournalBMC Medical Research Methodology
Issue number1
Publication statusPublished - 8 Apr 2022


  • Bias
  • Humans
  • Machine Learning
  • Medical Oncology
  • Prognosis
  • Research Design
  • Methodology
  • Machine learning
  • Prediction


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