Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers.
BACKGROUND
The nicotine metabolite ratio (NMR), the ratio of 3-hydroxycotinine to cotinine, is a biomarker used in smoking cessation research, with several retrospective studies suggesting that NMR predicts treatment outcome. To be maximally useful in tailoring treatment, estimates of NMR should be stable over time. The present study is the first to examine the short-term test-retest reliability of NMR among treatment-seeking smokers.


METHODS
Blood NMR was assessed at two time points, approximately 2-3 weeks apart and prior to intervention, among 72 healthy adult smokers (49% female; 35% non-White) enrolled in a cessation trial (http://ClinicalTrials.gov ID: NCT01314001).


RESULTS
Mean NMR was stable from Time-1 to Time-2, with no significant change between assessments; test-retest reliability for NMR values was excellent (ICC[2,1] = 0.87). Test-retest reliability remained acceptable to high when NMR was categorized, as in recent clinical trials. Classification of participants as slow (quartile 1, NMR ≤ 0.24) or normal/fast NMR (quartiles 2-4, NMR ≥ 0.25) was consistent from Time-1 to Time-2 for 96% of participants (κ = 0.89). Though classification of participants into NMR quartiles was less consistent from Time-1 to Time-2 (67% agreement; weighted κ = 0.73), all reclassifications occurred between adjacent quartiles.


CONCLUSIONS
Overall, these data support the use of a single NMR assessment for association studies with smoking phenotypes and in smokers seeking to quit, and they encourage large-scale efforts to determine optimal NMR cutpoints for tailoring treatment selection.
Department of Psychology, University at Buffalo, SUNY, Buffalo, NY;
Diana A
DA
Hamilton
School of Public Health and Health Professions, University at Buffalo, SUNY, Buffalo, NY; Departments of Medicine and Health Behavior, Roswell Park Cancer Institute, Buffalo, NY;
Martin C
MC
Mahoney
Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada;
Maria
M
Novalen
Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada;
Meghan J
MJ
Chenoweth
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA;
Daniel F
DF
Heitjan
Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.
Caryn
C
Lerman
Departments of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada;
Rachel F
RF
Tyndale
Department of Psychology, University at Buffalo, SUNY, Buffalo, NY; lhawk@buffalo.edu.
Larry W
LW
Hawk
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003367:Cotinine / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000097:blood*; D010342:Patient Acceptance of Health Care; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012907:Smoking / Q000097:blood* / Q000628:therapy*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine