title: Comparing and Validating Simple Measures of Patient-Reported Peripheral Neuropathy for Oncology Clinical Trials: NCCTG N0897 (Alliance) A Pooled Analysis of 2440 Patients.
abstract: BACKGROUND
  Current standard evaluation of Peripheral Neuropathy (PN) is based on an investigator-reported classification system that is commonly unable to correctly reflect the subjective symptoms for patients. Thus more reliable methods to assess PN are needed. This study assessed alternative methods of assessing patient-reported PN in 5 North Central Cancer Treatment Group (NCCTG) clinical trials.
  
  
  METHODS
  Two single-item assessments relating to numbness and tingling were used to measure PN. Patients' Quality Of Life (QOL) was also assessed using the Uniscale, Symptom Distress Scale (SDS), Profile of Mood States (POMS), Brief Pain Inventory (BPI) and Subject Global Impression of Change (SGIC). Wilcoxon tests compared QOL scores between patients with PN (score > 50) vs. no PN (score ≤ 50). Changes from baseline in QOL were compared by Wilcoxon rank sum test with a 20-point change in PN defined as clinically meaningful. Both distribution-based and anchor-based approaches were used to derive estimates of Minimal Important Differences (MID). Standardized Response Means (SRM), Effect Sizes (ES) and Guyatt's responsiveness statistic were used to measure responsiveness.
  
  
  RESULTS
  The proportion of patients reporting numbness (tingling) at baseline was 10.7% (10.0%) and 18.4% (17.8%) at last assessment. The correlation between numbness and tingling at baseline was 0.81, and at last assessment was 0.83. Patients with substantial PN reported an average of 10 points lower overall QOL, mood and worse symptom distress and 20 points lower in the BPI interference items. Patients having a ≤ 20 point worsening in PN score reported significantly worse in symptom distress and BPI worst pain, but not in POMS or overall QOL. The MID estimates were similar between numbness and tingling items but varied depending on the approach used. Responsiveness statistics indicated that the two PN assessments are sensitive and responsive instruments for cancer patients with PN.
  
  
  CONCLUSIONS
  The two PN items for numbness and tingling were redundant. Evidence of criterion validity and responsiveness indicates that these simple measures of PN can be used successfully in cancer clinical trials.
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Heshan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Angelina D
authors.initials: AD
authors.lastname: Tan
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.affiliation: Toledo Community Hospital Oncology Program, Toledo, OH, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
keywords: Minimum Importance Difference; Oncology Trials; Peripheral Neuropathy; Pooled Analysis; Quality of Life