| AJNMMI Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |
Am J Nucl Med Mol Imaging 2012;2(3):344-352
Original Article
Interim analyses in diagnostic versus treatment studies: differences and
similarities
Oke Gerke, Poul Flemming Høilund-Carlsen, Mads Hvid Poulsen, Werner Vach
Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Centre of Health
Economics Research, Department of Business and Economics, University of Southern Denmark, Campusvej 55, DK-5000 Odense
C, Denmark; Department of Urology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Clinical
Epidemiology, Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Stefan-Meier-Str. 26, D-
79104 Freiburg, Germany
Received April 29, 2012; accepted June 25, 2012; Epub July 10, 2012; Published July 30, 2012
Abstract: The purpose of this paper was to contrast interim analyses in (randomized controlled) treatment studies with interim
analyses in paired diagnostic studies of accuracy with respect to planning and conduct. The term ‘treatment study’ refers to a
(randomized) clinical trial that aims to demonstrate the superiority or noninferiority of one treatment compared with another, and the
term ‘diagnostic study’ to a clinical study that compares two diagnostic procedures, using a third diagnostic procedure as the gold
standard. Though interim analyses in treatment studies and paired diagnostic studies show similarities in a priori planning of
timing, decision rules, and the consequences of the analyses, they differ with respect to (1) the need for sample size adjustments,
(2) the possibility of early decisions without early stopping, and (3) the impact of keeping results secret. These differences are due,
respectively, to certain characteristics of paired diagnostic studies: the dependence of the sample size on the agreement rate
between the modalities, multiple aims of diagnostic accuracy studies, and the advantages of early unblinding of results at the
individual level. We exemplified our points by using a recent investigation at our institution on the detection of bone metastases from
prostate cancer in patients with histologically confirmed prostate cancer in which 99mTc-MDP whole body bone scintigraphy was
compared to positron emission tomography/computed tomography with 18F-fluorocholine as tracer, using magnetic resonance
imaging as a reference. (ajnmmi1204002).
Keywords: Study design, diagnostic imaging, PET/CT, efficacy studies, accuracy studies, sample size
Address all correspondence to:
Dr. Oke Gerke
Department of Nuclear Medicine
Odense University Hospital
Sdr. Boulevard 29, 5000
Odense C, Denmark.
Tel: ++45 3017 1885, fax: ++45 6590 6192,
E-mail: oke.gerke@ouh.regionsyddanmark.dk
Original Article
Interim analyses in diagnostic versus treatment studies: differences and
similarities
Oke Gerke, Poul Flemming Høilund-Carlsen, Mads Hvid Poulsen, Werner Vach
Department of Nuclear Medicine, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Centre of Health
Economics Research, Department of Business and Economics, University of Southern Denmark, Campusvej 55, DK-5000 Odense
C, Denmark; Department of Urology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark; Clinical
Epidemiology, Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Stefan-Meier-Str. 26, D-
79104 Freiburg, Germany
Received April 29, 2012; accepted June 25, 2012; Epub July 10, 2012; Published July 30, 2012
Abstract: The purpose of this paper was to contrast interim analyses in (randomized controlled) treatment studies with interim
analyses in paired diagnostic studies of accuracy with respect to planning and conduct. The term ‘treatment study’ refers to a
(randomized) clinical trial that aims to demonstrate the superiority or noninferiority of one treatment compared with another, and the
term ‘diagnostic study’ to a clinical study that compares two diagnostic procedures, using a third diagnostic procedure as the gold
standard. Though interim analyses in treatment studies and paired diagnostic studies show similarities in a priori planning of
timing, decision rules, and the consequences of the analyses, they differ with respect to (1) the need for sample size adjustments,
(2) the possibility of early decisions without early stopping, and (3) the impact of keeping results secret. These differences are due,
respectively, to certain characteristics of paired diagnostic studies: the dependence of the sample size on the agreement rate
between the modalities, multiple aims of diagnostic accuracy studies, and the advantages of early unblinding of results at the
individual level. We exemplified our points by using a recent investigation at our institution on the detection of bone metastases from
prostate cancer in patients with histologically confirmed prostate cancer in which 99mTc-MDP whole body bone scintigraphy was
compared to positron emission tomography/computed tomography with 18F-fluorocholine as tracer, using magnetic resonance
imaging as a reference. (ajnmmi1204002).
Keywords: Study design, diagnostic imaging, PET/CT, efficacy studies, accuracy studies, sample size
Address all correspondence to:
Dr. Oke Gerke
Department of Nuclear Medicine
Odense University Hospital
Sdr. Boulevard 29, 5000
Odense C, Denmark.
Tel: ++45 3017 1885, fax: ++45 6590 6192,
E-mail: oke.gerke@ouh.regionsyddanmark.dk
 |  |  |  |  |  |  |