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Original article
Reporting of data monitoring committees and adverse events in paediatric trials: a descriptive analysis
  1. Allison Gates1,
  2. Patrina Caldwell2,3,
  3. Sarah Curtis4,
  4. Leonila Dans5,
  5. Ricardo M Fernandes6,
  6. Lisa Hartling1,
  7. Lauren E Kelly7,8,
  8. Ben Vandermeer1,
  9. Katrina Williams9,
  10. Kerry Woolfall10,
  11. Michele P Dyson1
  1. 1 Alberta Research Centre for Health Evidence, University of Alberta, Edmonton, Alberta, Canada
  2. 2 Discipline of Child and Adolescent Health and Centre for Kidney Research, University of Sydney, Sydney, New South Wales, Australia
  3. 3 Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia
  4. 4 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
  5. 5 Department of Medicine, University of the Philippines, Manila, Philippines
  6. 6 Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
  7. 7 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  8. 8 Clinical Trials Platform, George and Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada
  9. 9 Developmental Medicine, Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia
  10. 10 Department of Psychological Sciences, University of Liverpool, Liverpool, UK
  1. Correspondence to Dr Michele P Dyson; mdyson{at}ualberta.ca

Abstract

Objectives For 300 paediatric trials, we evaluated the reporting of: a data monitoring committee (DMC); interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints.

Methods For this cross-sectional evaluation, we randomly selected 300 paediatric trials published in 2012 from the Cochrane Central Register of Controlled Trials. We collected data on the reporting of a DMC; interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. We reported the findings descriptively and stratified by trial characteristics.

Results Eighty-five (28%) of the trials investigated drugs, and 18% (n=55/300) reported a DMC. The reporting of a DMC was more common among multicentre than single centre trials (n=41/132, 31% vs n=14/139, 10%, p<0.001) and industry-sponsored trials compared with those sponsored by other sources (n=16/50, 32% vs n=39/250, 16%, p=0.009). Trials that reported a DMC enrolled more participants than those that did not (median [range]): 224 (10–60480) vs 91 (10–9528) (p<0.001). Only 25% of these trials reported interim analyses, and 42% reported stopping rules. Less than half (n=143/300, 48%) of trials reported on adverse events, and 72% (n=215/300) reported on harm-related endpoints. Trials that reported a DMC compared with those that did not were more likely to report adverse events (n=43/55, 78% vs 100/245, 41%, p<0.001) and harm-related endpoints (n=52/55, 95% vs. 163/245, 67%, p<0.001). Only 32% of drug trials reported a DMC; 18% and 19% did not report on adverse events or harm-related endpoints, respectively.

Conclusions The reporting of a DMC was infrequent, even among drug trials. Few trials reported stopping rules or interim analyses. Reporting of adverse events and harm-related endpoints was suboptimal.

  • data collection
  • ethics
  • general paediatrics

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors MPD conceptualised the study, designed the data collection instrument, oversaw all aspects of the work, verified and analysed the extracted data and contributed to drafting the manuscript. AG verified and analysed the extracted data, contributed to drafting the manuscript and revised the manuscript following input from the coauthors. PC, SC, LD, LH, LEK, RMF, KaW and KeW contributed to the interpretation of the extracted data and revised manuscript drafts critically for important intellectual content. BV contributed to the data analysis and interpretation of the extracted data and revised manuscript drafts critically for important intellectual content. All authors approved the manuscript as submitted and agree to be accountable for all aspects of the work.

  • Funding This work was supported by the Canadian Institutes of Health Research (#KRS 140989).

  • Disclaimer The funder played no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; the preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Competing interests None declared.

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

  • Data sharing statement The data collected and analysed from trials included in this study will be available to researchers via reasonable request from the corresponding authors. The data will be available immediately following and for 5 years after article publication. Our data extraction guide is available as a supplementary file.

  • Presented at Parts of this research were presented as a poster at our local research day (Pediatric Research Day, Department of Pediatrics, University of Alberta, Edmonton, Canada) on 16 May 2018 under the title: ’The safe and ethical participation of children in research: a descriptive analysis of the conduct and reporting of trials published in 2012'.

  • Patient consent for publication Not required.

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