Beyond P Values: Novel Minimal Important Difference of the Comprehensive Complication Index (CCI®) that reflects a Meaningful Outcome for Patients Undergoing Major Abdominal Surgery

Abstract

Objective: To estimate the Minimal Important Difference (MID) of the Comprehensive Complication Index® (CCI®) in patients undergoing abdominal surgery.

Background: The CCI® is a validated metric that quantifies cumulative surgical morbidity. While the CCI® is a sensitive endpoint to detect treatment effects, a statistically significant effect does not necessarily translate into clinical relevance. Relevant differences from the patients' perspective are best captured by the MID.

Methods: Individual patient data were extracted from surgical studies reporting CCI® at 30 days and using Patient Reported Outcome Measures (PROMs) with established MIDs at baseline and 30 days. To determine the MID for the CCI® we used an anchor-based approach as recommended by methods guidelines. A PROM was selected as an anchor only if the Spearman correlation coefficient between its change in score (baseline to 30 d postoperative) and the CCI® was ≥|0.30|. We used linear regression to estimate the MID of the CCI® across different anchors, and triangulation to determine a single MID.

Results: Data were extracted from three published randomized controlled trials (RCTs) and one prospective observational study (n=1583 patients) in major abdominal surgery. In colorectal surgery cohorts, two sub-scores of the Short Form-36, two sub-scores of the Multidimensional Fatigue Inventory-20, the EuroQol-5-Dimension Index Score, and the EuroQol Visual Analog Scale showed a correlation with the CCI® of ≥|0.30|. This resulted in MID estimates for the CCI® ranging from 6.1 to 22.2. In hepato-pancreato-biliary surgery, one sub-score of the Short Form-36, and two sub-scores of the PROM Information System-29 questionnaire qualified as anchors providing MID estimates ranging from 6.2 to 13.8.

Conclusion: We propose a mean difference of 12 points in the CCI® between treatment groups as a relevant difference in patients undergoing abdominal surgery. This MID provides an important foundation for sample size calculations and interpretation of RCTs and large real world observational studies.

Keywords: CCI; MID; anchor-based approach; clinical significance; comprehensive complication index; minimal important difference; outcome reporting; patient reported outcome measures.