Table 2.
Percent change from phase 2 to week 12 in biomarkers.
| Biomarker | Observed |
Model-Based |
||||
|---|---|---|---|---|---|---|
| VLNC cigarettes |
NNC cigarettes |
Estimated Mean Differencea (95% CI) | P-value | |||
| N | Median (IQR) | N | Median (IQR) | |||
| CO | 163 | −0.36 (−0.79, −0.05) | 172 | −0.17 (−0.47, 0.14) | −0.14 (−0.27, 0.00) | 0.043 |
| TNE/creatinine | 162 | −0.21 (−0.83, 0.35) | 171 | −0.07 (−0.32, 0.18) | −0.74 (−1.07, −0.40) | <0.0001 |
| Total NNAL/creatinine | 162 | −0.51 (−0.85, −0.10) | 171 | −0.05 (−0.31, 0.38) | −0.93 (−1.12, −0.74) | <0.0001 |
| CEMA/creatinine | 161 | −0.34 (−0.82, 0.21) | 170 | 0.08 (−0.38, 0.61) | −0.75 (−0.99, −0.52) | <0.0001 |
| HMPMA/creatinine | 160 | −0.28 (−0.65, 0.43) | 170 | −0.01 (−0.32, 0.75) | −0.39 (−0.57, −0.21) | <0.0001 |
| 2-HPMA/creatinine | 159 | −0.16 (−0.57, 0.38) | 170 | −0.02 (−0.43, 0.65) | −0.17 (−0.36, 0.02) | 0.087 |
| 3-HPMA/creatinine | 159 | −0.10 (−0.56, 0.55) | 170 | −0.07 (−0.45, 0.53) | −0.05 (−0.26, 0.16) | 0.65 |
| SPMA/creatinine | 162 | −0.37 (−0.74, 0.28) | 170 | −0.01 (−0.37, 0.44) | −0.52 (−0.76, −0.28) | <0.0001 |
Acronyms: VLNC, very low nicotine content (0.4 mg nicotine/gram tobacco); NNC, normal nicotine content (15.8 mg nicotine/gram tobacco); IQR, Interquartile Range; CO, carbon monoxide; TNE, total nicotine equivalents; total NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides, biomarker for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; CEMA:2-cyanoethylmercapturic acid, biomarker for acrylonitrile; HMPMA: 3-hydroxy-1-methylpropylmercapturic acid, biomarker for crotonaldehyde/methylvinyl ketone; 2-HPMA: 2-hydroxypropylmercapturic acid, biomarker for propylene oxide; 3-HPMA: 3-hydroxypropylmercapturic acid, biomarker for acrolein; SPMA: S-phenylmercapturic acid, biomarkers for benzene.
Week 12 data was extracted from Supplementary Table S6a that included biomarker values across weeks. Estimated mean difference of VLNC vs. NNC for percent change (defined as [Week 12—Phase 2]/Phase 2; for example, −0.36 means a 36% decrease) in carbon monoxide (CO) or for the shifted log-transformed percent change (defined as log [percent change + 1]) in other biomarkers, based on linear mixed model for repeated measures with fixed effects of condition, time, and their interaction, adjusting for study site, whether the visit time is pre-COVID or not, and any baseline characteristics which are different at P < 0.20 (gender, education, nicotine metabolite ratio, Wisconsin Index of Smoking Dependence Motives Primary Dependence Motives, and longest time of quit); no imputation.