Abstract

1. |---------------------- Anchor Based ----------------------| Comparing and Validating Simple Measure of Patient-reported Peripheral Neuropathy for NCCTG Clinical Trials: a Pooled Analysis of 2440 Patients Heshan Liu1, Angelina D. Tan1, Axel Grothey1, Paul L. Schaefer2, Jan C. Buckner1, Charles L. Loprinzi1, Roscoe F. Morton3, Jeff A. Sloan1 1Mayo Clinic, Rochester, MN; 2Toledo Community Hospital Oncology Program, Toledo, OH; 3Medical Oncology & Hematology Associates – Pleasant, Des Moines, IA; Abstract Background: The introduction of new anti-cancer therapies which cause patients(pts) to incur peripheral(PN) has required the development of new methods to assess this treatment outcome. This study compared and validated alternative methods of assessing Patient-reported PN in a series of North Central Cancer Treatment Group (NCCTG) clinical trials. Methods: Data were combined from 5 NCCTG trials (2440 pts) that used single-item questions scaled 0-100 relating to numbness and tingling respectively in fingers and toes to measure PN. Patient quality of life (QOL) was assessed using UNISCALE, Symptom Distress Scale (SDS), Profile of Mood States (POMS), Brief Pain Inventory (BPI) and Subject Global Impression of Change (SGIC). Associations between items were tested using Bland-Altman method and correlation. Wilcoxon tests compared QOL scores between pts with PN (score >40) vs. no PN. Change in PN and QOL was compared with a 20-point change defined as clinically meaningful. Minimal important differences (MID) were estimated using both anchor-based approach and distribution-based methods. Results: At baseline, the proportion of patient-reported PN was 11% (numbness) and 10% (tingling); and 18% on each at last assessment. The correlation between PN items at baseline and last assessment was 0.8, with an average difference of <1 point on the 100-point scale. The MID estimate of SGIC in overall QOL, Physical Condition and Emotional State were 24, 21, 25 for numbness (respectively); and 19, 18, 17 for tingling (respectively). The distribution-based MID estimate was 12 for both PN items. Pts with substantial PN reported an average of 10 points lower QOL, mood and worse SDS and a 20 point-deficit in the BPI interference items. Pts with ≤20 points worsening in PN reported significant declines in SDS (p<0.001), worst pain (p<0.02), but not in POMS (p=0.64) or overall QOL (p=0.86). Conclusions: The two PN items for numbness and tingling were redundant. Anchor-based MID methods produced larger and inconsistent estimates relative to the distribution-based methods. Evidence of criterion validity and responsiveness indicates that these simple measures of PN can be used successfully in cancer clinical trials. • Background • Peripheral neuropathy(PN) is a common and intrusive side effect of chemotherapy. • The assessment of PN is typically done via the common toxicity criteria (CTC), although patient reported outcome-based assessments have potentially greater sensitivity. • The purpose of this investigation was to asses the relative sensitivity of the CTC and simple single-item numerical analogue scale assessments in detecting the onset and severity of PN in patients receiving oxaliplatin. Overall Patient Characteristics Correlation between PN and QOL Items at Baseline QOL Scores by Peripheral Neuropathy Minimum Important Difference All P values<.025 Distribution Based --- ---| PN assessments are measuring something unique PN impacts overall QOL, symptom distress and pain 10-point MID is supported. Anchor-based MID’s larger Trials Included in the Analyses • Conclusions • Simple single-item measures of PN are psychometrically sound • Either of the two items for assessing PN (numbness or tingling) can be used (redundant) Comparison of change from Baseline QOL Scores by Decreasing PN Score Bland Altman Plot at Baseline r between PN numbness and tingling : 0.81 r between average and difference : 0.08 • Contact Information • Heshan Liu, M.S. liu.heshan@mayo.edu • Jeff Sloan, Ph.D. jsloan@mayo.edu The two PN assessments are psychometrically comparable Individual changes in PN correspond to changes in mood and pain