The comprehensive complication index a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials

Ksenija Slankamenac, Nina Nederlof, Patrick Pessaux, Jeroen De Jonge, Bas P L Wijnhoven, Stefan Breitenstein, Christian E. Oberkofler, Rolf Graf, Milo A. Puhan, Pierre Alain Clavien

Research output: Contribution to journalArticle

Abstract

Objective: To test whether the newly developed comprehensive complication index (CCI) ismore sensitive than traditional endpoints for detecting betweengroup differences in randomized controlled trials (RCTs). Background: A major challenge in RCTs is the choice of optimal endpoints to detect treatment effects.Mortality is no longer a sufficientmarker in studies, and morbidity is often poorly defined. The CCI, integrating all complications including their severity in a linear scale ranging from 0 (no complication) to 100 (death), is a new tool, which may be more sensitive than other traditional endpoints to detect treatment effects on postoperative morbidity. Methods: The CCI was tested in 3 published RCTs from European centers evaluating pancreas, esophageal and colon resections. To compare the sensitivity of the CCI with traditional morbidity endpoints, for example, presence of any (yes/no) or only the most severe complications, all postoperative events were assessed, and the CCI calculated. Treatment effects and sample size calculations were compared using the CCI and traditional endpoints. Results: Although RCTs failed to show between-group differences using any or most severe complications, the CCI revealed significant differences between treatment groups in 2 RCTs-after pancreas (P = 0.009) and esophageal surgery (P = 0.014). The CCI in the RCT on colon resections confirmed the absence of between-group differences (P = 0.39). The required sample sizes in trials are up to 9 times lower for the CCI than for traditional morbidity endpoints. Conclusions: This study demonstrates superiority of the CCI to traditional endpoints. The CCI may serve as an appealing endpoint for future RCTs and may reduce the sample size.

Original languageEnglish (US)
Pages (from-to)757-763
Number of pages7
JournalAnnals of Surgery
Volume260
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

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Keywords

  • Complication
  • Comprehensive complication index
  • Morbidity
  • Outcome research
  • Randomized controlled trial
  • Sample size
  • Valid endpoint

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

Slankamenac, K., Nederlof, N., Pessaux, P., De Jonge, J., Wijnhoven, B. P. L., Breitenstein, S., Oberkofler, C. E., Graf, R., Puhan, M. A., & Clavien, P. A. (2014). The comprehensive complication index a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials. Annals of Surgery, 260(5), 757-763. https://doi.org/10.1097/SLA.0000000000000948