1. 2018;21;E583-E592Clinical Benefits of Direct-to-Definitive Testing for Monitoring Compliance in Pain Management
   Comprehensive Review
   Stacy Melanson, MD, PhD, Milenko Tanasijevic, MD, MBA, Jayme L. Dahlin, MD, PhD, Michalis Kantartjis, BS, Ralitsa Gencheva, BS, and Athena Petrides, PhD.

BACKGROUND: The technical advantages of direct-to-definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine testing for monitoring patient compliance in pain management are well known. However, the design and implementation of LC-MS/MS methods are more controversial, including factors such as determining appropriate cutoffs, specimen processing (e.g., specimen hydrolysis), reporting of qualitative and/or quantitative results, and test menu.

OBJECTIVES: The objective of the research was to compare the clinical performance of our previous urine pain toxicology panel, a combination of immunoassay (IA) screens and LC-MS/MS, to our current pain toxicology panel, which features direct-to-definitive LC-MS/MS for 34 drugs and metabolites.

STUDY DESIGN: Six months of results from our previous pain toxicology panel were compared to 5.5 months of results from our current pain toxicology panel, enabling us to make conclusions regarding clinical performance.

SETTING: The research took place at Brigham and Women’s Hospital in Boston, MA.

METHODS: The percentage of false positive IA results was evaluated for our previous pain toxicology panel. The positivity rates for each drug and/or metabolite were calculated for both the previous and current panels, including rates of detection of both prescribed and illicit drugs. The turnaround time (TAT), direct and send-out costs associated with each approach, as well as projected cost savings were also determined.

RESULTS: False positive rates with IA ranged from 0% to 29%; the highest false positive rate was seen for 6-acetylmorphine (6-AM). The elimination of IA, addition of metabolites, and/or lowering of cutoffs increased the detection rate of 6-AM, benzoylecgonine (cocaine metabolite), fentanyl, morphine, and oxycodone. The ability to differentiate compliance from simulated compliance improved after eliminating specimen hydrolysis. The TAT improved significantly and projected yearly cost savings with the current panel was $95,003 (USD). In our opinion, qualitative results appeared sufficient to assess compliance in the majority of cases.

LIMITATIONS: Our study was performed in a single academic center in a specific geographic region; therefore, our results may not be generalizable to other types of centers or regions.

CONCLUSION: Direct-to-definitive LC-MS/MS testing has several clinical benefits, including reduction of false positive results, improved assessment of patient compliance, decreased TAT, and increased detection of drug use and abuse. Cost savings were also realized using this approach.

KEY WORDS: Direct-to-definitive, LC-MS/MS, immunoassay, sensitivity, cost, pain management, turnaround time, patient compliance