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Individual participant data validation of the PICNICC prediction model for febrile neutropenia
  1. Bob Phillips1,2,
  2. Jessica Elizabeth Morgan1,2,
  3. Gabrielle M Haeusler3,
  4. Richard D Riley4
  5. On behalf of the PICNICC Collaborative
  1. 1Centre for Reviews and Dissemination, University of York, York, UK
  2. 2Leeds Children's Hospital, Leeds, UK
  3. 3Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  4. 4Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK
  1. Correspondence to Dr Bob Phillips, Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK; bob.phillips{at}


Background Risk-stratified approaches to managing cancer therapies and their consequent complications rely on accurate predictions to work effectively. The risk-stratified management of fever with neutropenia is one such very common area of management in paediatric practice. Such rules are frequently produced and promoted without adequate confirmation of their accuracy.

Methods An individual participant data meta-analytic validation of the ‘Predicting Infectious ComplicatioNs In Children with Cancer’ (PICNICC) prediction model for microbiologically documented infection in paediatric fever with neutropenia was undertaken. Pooled estimates were produced using random-effects meta-analysis of the area under the curve-receiver operating characteristic curve (AUC-ROC), calibration slope and ratios of expected versus observed cases (E/O).

Results The PICNICC model was poorly predictive of microbiologically documented infection (MDI) in these validation cohorts. The pooled AUC-ROC was 0.59, 95% CI 0.41 to 0.78, tau2=0, compared with derivation value of 0.72, 95% CI 0.71 to 0.76. There was poor discrimination (pooled slope estimate 0.03, 95% CI −0.19 to 0.26) and calibration in the large (pooled E/O ratio 1.48, 95% CI 0.87 to 2.1). Three different simple recalibration approaches failed to improve performance meaningfully.

Conclusion This meta-analysis shows the PICNICC model should not be used at admission to predict MDI. Further work should focus on validating alternative prediction models. Validation across multiple cohorts from diverse locations is essential before widespread clinical adoption of such rules to avoid overtreating or undertreating children with fever with neutropenia.

  • haematology
  • infectious diseases
  • oncology
  • statistics

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  • Contributors RSP led the PICNICC Collaborative and identified the data sources. RSP and RDR planned the analysis, and undertook initial interpretation of the results. JEM and GMH validated the data analysis. RSP, JEM and GMH provided clinical interpretation of the findings. RSP drafted the manuscript. All authors reviewed, edited and confirmed their acceptance of the final submitted version.

  • Funding This work was undertaken as part of an NIHR Post-Doctoral Fellowship award (NIHR Post-Doctoral Fellowship 10872).

  • Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care (DHCS).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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