PET/CT in cancer: Methodological considerations for comparative diagnostic phase II studies with paired binary data.
OBJECTIVE
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.
Gerke
O
O
Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. oke@stat.sdu.dk
Vach
W
W
Høilund-Carlsen
P F
PF
D003627:Data Interpretation, Statistical; D005240:Feasibility Studies; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D018401:Sample Size; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed