Limits of detection of chemopreventive efficacy: karyometry of skin biopsies.
OBJECTIVE
This study was designed to establish estimates of the smallest effects due to chemopreventive intervention detectable by karyometry in skin biopsies.


METHODS
Estimates of the smallest change of statistical significance and estimates of the power of the test were derived for several key features descriptive of the distribution of nuclear chromatin. Results from triplicate biopsies from the same case were used to provide estimates of the within-case, biopsy-to-biopsy variance.


RESULTS
Generally, a change in feature value due to chemopreventive intervention can be statistically secured when it amounts to 5% to 10%. In clinical trials where matched baseline and end of study biopsies from the same cases are available, paired comparison ANOVA can detect a 2% change on samples of 25 cases. Establishing efficacy in individual cases requires a change in feature values on the order of 10% to 15%.


CONCLUSIONS
Karyometry provides a sensitive, quantitative method for the assessment of efficacy of chemoprevention. The effects of within-case, biopsy-to-biopsy variance need to be considered only in the evaluation of individual cases and are on the order of 5% in skin biopsies.
Bartels
Peter H
PH
College of Optical Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Yozwiak
Michael L
ML
Bartels
Hubert G
HG
Liu
Yun
Y
Hess
Lisa M
LM
Alberts
David S
DS
D001706:Biopsy / Q000379:methods*; D018890:Chemoprevention / Q000379:methods*; D003937:Diagnosis, Differential; D006801:Humans; D007620:Karyometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology* / Q000517:prevention & control; D014801:Vitamin A / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
D014815:Vitamins; D014801:Vitamin A