The chemotherapy-induced peripheral neuropathy (CIPN) outcome measure standardization (CI-PeriNomS) study: From consensus to validity and reliability in CIPN assessment

Background: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a debilitating and dose limiting complication of cancer treatment. However, the impact of CIPN has never been studied in a clinimetric manner, in its impact on quality of life. This study was performed to select appropriate outcome measures and to establish, for the first time with a clinimetric approach, their validity and reproducibility. Methods: After literature review and a consensus meeting, face/content validity were obtained for the following scales: the National Cancer Institute Common-Toxicity-Criteria (NCI-CTC), the Total Neuropathy Score (TNSc), the modified INCAT sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CIPN20 quality of life measures. 281 patients with stable CIPN were examined through an EU/US collaboration involving 20 oncology/neurology centers. For each scale the inter- and intra-rater agreement was evaluated by means of weighted K-Cohen coefficients and 95% confidence intervals, when analyzing qualitative ordinal scales and by means of Spearman's rank correlation coefficient and t-test when analyzing quantitative ordinal scales. The adopted weights for the estimate of K-Cohen coefficients were the Fleiss-Cohen weights. For validity purposes, the Kruskal-Wallis equality-of-populations rank test was performed relating the mISS and TNSc to the NCI-CTC grades. Results: Proper, although slightly different, inter-/intra-observer scores (i.e. r > 0.7) were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also high for the EORTC QLQ-C30 and for the recently developed and never formally tested CIPN20. Acceptable validity scores were obtained through correlation between the the mISS and TNSc to the NCI-CTC scores (p values ranging from 0.04 to < 0.001). Conclusions: Proper validity and reliability scores were demonstrated for the set of selected outcome measures in CIPN. These results will allow to base new trials on a solid methodological background, although future studies are warranted to investigate the responsiveness issues.