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General medicine
Conventional compared to network meta-analysis to evaluate antibiotic prophylaxis in patients with cancer and haematopoietic stem cell transplantation recipients
  1. Juan Pablo Diaz Martinez1,2,
  2. Paula D Robinson3,
  3. Bob Phillips4,
  4. Thomas Lehrnbecher5,
  5. Christa Koenig6,
  6. Brian Fisher7,
  7. Grace Egan8,
  8. L Lee Dupuis9,10,
  9. Roland A Ammann6,
  10. Sarah Alexander8,
  11. Sandra Cabral3,
  12. George Tomlinson1,2,
  13. Lillian Sung2,8
  1. 1Biostatistic Research Unit, Toronto General Hospital, Toronto, Ontario, Canada
  2. 2Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  3. 3Pediatric Oncology Group of Ontario, Toronto, Ontario, Canada
  4. 4Leeds General Infirmary, Leeds Teaching Hospitals, NHS Trust, Leeds, United Kingdom and Centre for Reviews and Dissemination, Leeds Children's Hospital, Leeds, UK
  5. 5Pediatric Hematology and Oncology, Johann Wolfgang Goethe, Universität Frankfurt am Main, Frankfurt am Main, Hessen, Germany
  6. 6Division of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital University Hospital Bern, Bern, Switzerland
  7. 7Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  8. 8Haematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada
  9. 9Department of Pharmacy and Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
  10. 10Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Lillian Sung, Haematology/Oncology, Hospital for Sick Children, Toronto, Canada; lillian.sung{at}sickkids.ca

Abstract

Our purpose was to compare conventional meta-analysis and network meta-analysis to evaluate the efficacy of different prophylactic systemic antibiotic classes in patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). We included randomised trials if patients had cancer or were HSCT recipients and the intervention was systemic antibacterial prophylaxis. Three types of control groups were used: (1) placebo, no antibiotic and non-absorbable antibiotic separately; (2) placebo and no antibiotic combined; and (3) all three combined. These gave different network geometries. Strategies synthesised were fluoroquinolone, trimethoprim-sulfamethoxazole, cephalosporin and parenteral glycopeptide versus control groups. In total 113 trials met the eligibility criteria. Where treatment effects could be estimated with both conventional and network meta-analysis, values were generally similar. However, where events were sparse, network meta-analysis could be more precise. For example, trimethoprim-sulfamethoxazole versus placebo for infection-related mortality showed a relative risk ratio (RR) of 0.55, 95% CI (0.21 to 1.44) with conventional, and RR 0.43, 95% credible region (0.20 to 0.82) with network meta-analysis. Cephalosporin versus fluoroquinolone was comparable only indirectly using the network approach and yielded RR 0.59, 95% credible region (0.28 to 1.20) to reduce bacteraemia. Incoherence (difference between direct and indirect estimates raising concerns about network meta-analysis validity) was observed with network geometry where control groups were separated, but not where control groups were combined. In this situation, conventional and network meta-analysis yielded similar results in general. Network meta-analysis results could be more precise when events were rare. Some analysis could only be performed with the network approach. These results identify scenarios in which network meta-analysis may be advantageous.

  • infectious diseases
  • oncology
  • statistics & research methods
  • infection control
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Footnotes

  • JPDM and PDR are joint first authors.

  • GT and LS are joint senior authors.

  • Contributors JPDM, PDR, GT and LS conceptualised the study, designed the study, analysed the network meta-analysis and wrote the manuscript. GE and PDR collected the data and conducted the conventional meta-analysis. All authors critically revised the manuscript for important content. All authors approve the final version of the manuscript.

  • Funding This meta-analysis was funded by the Pediatric Oncology Group of Ontario (POGO). It was editorially independent from the funder. LS is supported by a Canada Research Chair in Pediatric Oncology Supportive Care.

  • Competing interests BF’s institution receives research funding from Pfizer and Merck, and he serves on a Data Safety Monitoring Board for Astellas. TL has received research grants from Gilead Sciences, is a consultant to Astellas, Basilea, Gilead Sciences and Merck/MSD, and served at the speaker's bureau of Astellas, Gilead Sciences, Merck/MSD and Pfizer.

  • Patient consent for publication Not required.

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

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