Personalized Outcomes in Neuropathic Pain: A Clinical Relevance and Assay Sensitivity Analysis from a Randomized Controlled Trial

Karim Saab; Umang Gada; Eva Culakova; Brian Burnette; Carla Jorgensen; Dhaval Shah; Gary Morrow; Karen Mustian; Michael B Sohn; Robert R Edwards; Roy Freeman; Dale J Langford; Michael P McDermott; Jennifer S Gewandter

doi:10.1093/pm/pnae095

Personalized Outcomes in Neuropathic Pain: A Clinical Relevance and Assay Sensitivity Analysis from a Randomized Controlled Trial

Pain Med. 2024 Oct 4:pnae095. doi: 10.1093/pm/pnae095. Online ahead of print.

Authors

Affiliations

¹ Department of Anesthesiology and Perioperative Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
² Department of Surgery, Supportive Care in Cancer, University of Rochester Medical Center, Rochester, NY.
³ Cancer Research of Wisconsin and Northern Michigan NCORP, Green Bay, Wisconsin.
⁴ NCORP of the Carolinas-Prisma Health NCORP/Greenville, Greenville, SC.
⁵ Helen F. Graham Cancer Center and Research Institute, Christiana Care, Newark, DE.
⁶ Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY.
⁷ Department of Anesthesia, Brigham and Women's Hospital, Boston, MA.
⁸ Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
⁹ Department of Anesthesiology, Critical Care & Pain Management, Pain Prevention Research Center, Hospital for Special Surgery, New York, NY, Department of Anesthesiology, Weill Cornell Medicine, NY, NY.

PMID: 39365731
DOI: 10.1093/pm/pnae095

Abstract

Objective: To explore the clinical relevance and assay sensitivity of using personalized outcomes using data from a randomized clinical trial (RCT) in people with chemotherapy induced peripheral neuropathy (CIPN).

Design: This study is a secondary analysis that leveraged data from a RCT of transcutaneous electrical stimulation for CIPN to test whether personalized outcomes could minimize potential floor effects and increase the assay sensitivity of pain clinical trials (ie, ability to detect a true treatment effect).

Setting: Participants were recruited for a RCT from community oncology clinics in the U.S.

Participants: Adults with CIPN (N = 72) who reported on average ≥4 intensity (measured via a 7-day baseline diary) for at least one of the following pain qualities hot/burning pain, sharp/shooting pain and/or cramping.

Methods: Personalized outcomes were defined based on participants' unique presentation of pain qualities at baseline, measured via 0-10 numeric rating scales (NRS), or ranking of the distress caused by the pain qualities. Analysis of covariance models estimated the treatment effect as measured by personalized and non-personalized outcomes.

Results: The adjusted mean difference between groups was higher using personalized outcomes (ie, 1.21-1.25 NRS points) compared to a non-personalized outcome (ie, 0.97 NRS points), although the standardized effect sizes were similar between outcomes (0.49-0.54).

Conclusions: These results suggest that personalized pain quality outcomes could minimize floor effects, while providing similar assay sensitivity to non-personalized pain quality outcomes. Personalized outcomes better reflect an individual's unique experience, inherently providing more clinically relevant estimates of treatment effects. Personalized outcomes may be advantageous particularly for clinical trials in populations with high inter-individual variability in pain qualities.

Keywords: Assay Sensitivity; Chemotherapy Induced Peripheral Neuropathy; Inter-individual variability; Neuropathic pain; Personalized Outcomes.