Moving towards multiple site outcomes in spinal cord injury pain clinical trials: An issue of clustered observations in trial design and analysis

Abstract

Introduction

Pain remains a problem for many with spinal cord injury (SCI), and there is a need for sound, randomized clinical trials examining the efficacy of existing and novel therapeutics. SCI-related pain is complex, as more than one type of pain is often experienced. The purpose of this report is to (i) demonstrate how to design and power calculation of a clinical trial of SCI pain using multiple pain sites per individual; (ii) discuss consequences of failing to adjust for this; and (iii) provide intraclass correlation (ICC) estimates for common pain outcome measures that may be used to power future clinical trials in SCI pain.

Method

Using an existing dataset from a past SCI pain clinical trial, the ICC was calculated for common pain outcome measures to illustrate appropriate corrections for powering, analyzing and interpreting results from multiple pain sites per individual. The problem associated with not accounting for multiple pain sites per individual and the effect on the Type I error rate is also shown.

Results and Discussion

Not accounting for the ICC can lead to (1) incorrect power estimates in the design of a trial, and (2) an inflated Type I error rate with a higher likelihood of misinterpretation of outcomes.

Conclusions

Powering for future SCI pain trials and statistical analysis of trial outcomes may be substantially compromised if methods do not account for the intra-individual associations between pain sites, ultimately affecting study interpretations and evidence-based practice. We present ICC estimates based on SCI pain data for purposes of estimating power for future trials.

Keywords:

• Spinal cord injury
• Pain
• Clinical trials
• RCT
• Intraclass correlation coefficient
• ICC

Acknowledgment

Data used to illustrate design and analysis issues in this report were originally collected for a clinical trial that was funded by the National Institute on Disability and Rehabilitation (NIDRR) grant no. H133N060021. Support for development of the manuscript was also provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grant no. P60AR048095-06A1.