Summary
Objectives:
When the combined diagnostic imaging technique PET/CT is considered promising with
respect to diagnosis/staging of a certain cancer type, a systematic investigation
by means of clinical diagnostic studies in the target population is necessary to evaluate
the usefulness of PET/CT compared to the current standard. It is often difficult to
decide in advance whether it is appropriate to plan a superiority or non-inferiority
study. We propose a statistical analysis strategy which is flexible enough to cope
with both aims alike.
Methods:
In opposition to clinical studies on drugs, each patient can be subjected to both
PET/CT and the current standard, leading to paired observations of binary data (e.g.,
cancer = yes/no, stage = 0/1+). The analysis strategy focuses on point estimates and
confidence intervals for the difference (or relative increase) in accuracy measures.
Results:
Formulas for approximate 95% confidence intervals for the differences in sensitivity,
specificity, positive and negative predictive values between PET/CT and the standard
procedures are given, respectively. The strategy can also be applied if results obtained
with a golden standard are not available in patients in whom both PET/CT and the standard
procedure gave negative results. Sample sizes can and should be determined in an adaptive
manner.
Conclusions:
Diagnostic studies to assess the merit of PET/CT in the diagnostic work-up of cancer
patients can and should start with phase II studies focusing on 95% confidence intervals
for differences in diagnostic measures. Even if the gold standard procedure is incomplete,
the statistical analysis strategy given here may still be applicable.
Keywords
Sensitivity - specificity - predictive values - feasibility - sample size
