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Original article
Validation of a classification system for treatment-related mortality in children with cancer
  1. Hadeel Hassan1,2,
  2. Menie Rompola1,2,
  3. Adam Woolf Glaser1,2,
  4. Sally Elizabeth Kinsey1,2,
  5. Robert Stephen Phillips1,3
  1. 1 Department of Paediatric Haematology and Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  2. 2 Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
  3. 3 Centre for Reviews and Dissemination, University of York, York, UK
  1. Correspondence to Dr Hadeel Hassan; hadeelhassan{at}


Background Death not directly due to cancer has been termed ‘treatment-related mortality’ (TRM). Appreciating the differences between TRM and disease-related death is critical in directing strategies to improve supportive care, interventions delivered or disease progression. Recently, a global collaboration developed and validated a consensus-based classification tool and attribution system.

Objectives To evaluate the reliability of the newly developed consensus-based definition of TRM and explore the use of the cause-of-death attribution system outside the centre it was initially validated (Toronto, Canada). In the initial study, reviewers listed multiple causes of death. In this study, reviewers identified a primary cause for simplicity.

Setting The paediatric haematology and oncology department at Leeds Teaching Hospital in Leeds, UK.

Participants Two consultants and two clinical research associates (CRAs).

Methods Thirty medical records of the most recent deaths in children with cancer, 2 and 4 weeks prior to death, were anonymised and presented to the participants. Reviewers independently classified deaths as ‘treatment related mortality’ or ‘not treatment related’ according to the algorithm developed. When TRM occurred, reviewers applied the cause-of-death attribution system to identify the primary cause of death. Inter-relater reliability was assessed using the kappa statistic (k).

Main outcome Inter-relater reliability between CRA and consultants.

Results Reliability of the classification was deemed ‘very good’ between CRA and consultants (k=0.86, 95% CI 0.72 to 0.97). Ten deaths were classified as TRM, of which infection was the most frequent cause identified. Reviewers disagreed on the primary cause of death (eg, respiratory vs infection) when applying the cause-of-death attribution system in six cases and probable and possible causes in four cases. The study identified how the algorithm may not detect TRM in patients receiving non-curative therapy.

Conclusions The classification and cause of death attribution system could be implemented in different healthcare settings. Adaptation of the classification tool in patients receiving non-curative interventions and the cause of death attribution system should be considered.

  • oncology
  • haematology
  • palliative care

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 and the use is non-commercial. See:

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  • Contributors HH wrote the manuscript, and RSP edited the manuscript. MR, SEK and AWG contributed to the review process.

  • Funding This work was supported by Candlelighters charity who funded Dr HH’s PhD, for which this research was conducted.

  • Competing interests None declared.

  • Ethics approval This study was approved by the University of Leeds School of Medicine Ethics Committee (Ref: MREC15-118) and did not require NHS ethics approval.

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

  • Data sharing statement No additional data available.

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