TY - JOUR
T1 - The comprehensive complication index a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials
AU - Slankamenac, Ksenija
AU - Nederlof, Nina
AU - Pessaux, Patrick
AU - De Jonge, Jeroen
AU - Wijnhoven, Bas P L
AU - Breitenstein, Stefan
AU - Oberkofler, Christian E.
AU - Graf, Rolf
AU - Puhan, Milo A.
AU - Clavien, Pierre Alain
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Complication
KW - Comprehensive complication index
KW - Morbidity
KW - Outcome research
KW - Randomized controlled trial
KW - Sample size
KW - Valid endpoint
UR - http://www.scopus.com/inward/record.url?scp=84926097549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926097549&partnerID=8YFLogxK
U2 - 10.1097/SLA.0000000000000948
DO - 10.1097/SLA.0000000000000948
M3 - Article
C2 - 25379846
AN - SCOPUS:84926097549
SN - 0003-4932
VL - 260
SP - 757
EP - 763
JO - Annals of Surgery
JF - Annals of Surgery
IS - 5
ER -