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Methods Inf Med 2008; 47(06): 470-479
DOI: 10.3414/ME0540
Original Article
Schattauer GmbH

PET/CT in Cancer

Methodological Considerations for Comparative Diagnostic Phase II Studies with Paired Binary Data
O. Gerke
1   Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
2   Department of Statistics, University of Southern Denmark, Odense, Denmark
,
W. Vach
2   Department of Statistics, University of Southern Denmark, Odense, Denmark
,
P.F. Høilund-Carlsen
1   Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
› Author Affiliations
Further Information

Publication History

Received: 11 February 2008

Accepted: 10 July 2008

Publication Date:
18 January 2018 (online)

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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
 

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