In response to Mr Lee’s comment¹ which follows previous responses^2,3 and my paper,⁴ I offer further explanation to resolve an apparent misunderstanding of the validity and reliability of cotinine/creatinine ratio (CCR) measurement and his mishandling of the formula of misclassification. I also express concerns about the lack of scientific integrity in his reporting⁵ of the Japanese spousal study, including his authorship.

As I demonstrated,⁴ all indices of nicotine exposure (ambient room, personal sampler monitors, and salivary cotinine) were well correlated but correlated poorly with CCR, raising doubts about the validity of the CCR measurement. Yet Lee maintains that CCR measurement in this study was the gold standard for distinguishing true smokers from falsely reporting smokers.

There are several possibilities about why the CCR measurement may have been invalid and unreliable in this study. In 1991 when I sent the urine samples to the RJ Reynolds laboratory (where the measurement was performed), I was informed that all the dry ice sent with the sample had sublimated before it reached the laboratory. This suggests that the sample was not maintained at low temperature before analysis. Cotinine measurement is temperature …