TY - JOUR
T1 - A potential for seamless designs in diagnostic research could be identified
AU - Vach, Werner
AU - Bibiza, Eric
AU - Gerke, Oke
AU - Bossuyt, Patrick M.
AU - Friede, Tim
AU - Zapf, Antonia
N1 - Funding Information: Funding: This article is supported by the Deutsche Forschungsgemeinschaft (ZA 687/1-1). Publisher Copyright: © 2020 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Background and Objective: New diagnostic tests to identify a well-established disease state must undergo a series of scientific studies from test construction to finally demonstrating a societal impact. Traditionally, these studies are performed with substantial time gaps in between, resulting in a long time period from the initial idea to roll out in clinical practice including reimbursement. Seamless designs allowing us to combine a sequence of studies in one protocol may hence accelerate this process. Currently, a systematic investigation of the potential of seamless designs in diagnostic research is lacking. Methods: We identify major study types in diagnostic research and their basic characteristics with respect to the application of seamless designs. This information is used to identify major hurdles and opportunities for seamless designs. Results: The following major study types were identified: Variable construction studies, cut point finding studies, variable value studies, single-arm accuracy studies, comparative accuracy studies, change-in-management studies, observational discordant pair studies, randomized discordant pair studies, and randomized diagnostic studies. The following characteristics were identified: Type of recruitment (case-control vs. population-based), application of a reference standard, inclusion of a comparator, paired or unpaired application of a comparator, assessment of patient-relevant outcomes, and possibility for blinding of test results. Two basic hurdles could be identified: 1) Accuracy studies are hard to combine with postaccuracy studies in a seamless design for the following reasons. First, because the former are required to justify the latter and application of a reference test in outcome studies may be a threat to the integrity of the study. 2) Randomized diagnostic studies are probably best placed as singular studies at the end of the process, as all other questions should be clarified before performing such a study. However, otherwise there is a substantial potential for seamless designs. All steps from the construction to the comparison with the comparator can be combined in one protocol. This may include a switch from case-control to population-based recruitment as well as a switch from a single-arm study to a comparative accuracy study. In addition, change-in-management studies can be combined with an outcome study in discordant pairs. Conclusion: There is a potential for seamless designs in diagnostic research. It is wise to have the whole sequence of necessary studies in mind and to plan a full programme than rather individual studies one by one.
AB - Background and Objective: New diagnostic tests to identify a well-established disease state must undergo a series of scientific studies from test construction to finally demonstrating a societal impact. Traditionally, these studies are performed with substantial time gaps in between, resulting in a long time period from the initial idea to roll out in clinical practice including reimbursement. Seamless designs allowing us to combine a sequence of studies in one protocol may hence accelerate this process. Currently, a systematic investigation of the potential of seamless designs in diagnostic research is lacking. Methods: We identify major study types in diagnostic research and their basic characteristics with respect to the application of seamless designs. This information is used to identify major hurdles and opportunities for seamless designs. Results: The following major study types were identified: Variable construction studies, cut point finding studies, variable value studies, single-arm accuracy studies, comparative accuracy studies, change-in-management studies, observational discordant pair studies, randomized discordant pair studies, and randomized diagnostic studies. The following characteristics were identified: Type of recruitment (case-control vs. population-based), application of a reference standard, inclusion of a comparator, paired or unpaired application of a comparator, assessment of patient-relevant outcomes, and possibility for blinding of test results. Two basic hurdles could be identified: 1) Accuracy studies are hard to combine with postaccuracy studies in a seamless design for the following reasons. First, because the former are required to justify the latter and application of a reference test in outcome studies may be a threat to the integrity of the study. 2) Randomized diagnostic studies are probably best placed as singular studies at the end of the process, as all other questions should be clarified before performing such a study. However, otherwise there is a substantial potential for seamless designs. All steps from the construction to the comparison with the comparator can be combined in one protocol. This may include a switch from case-control to population-based recruitment as well as a switch from a single-arm study to a comparative accuracy study. In addition, change-in-management studies can be combined with an outcome study in discordant pairs. Conclusion: There is a potential for seamless designs in diagnostic research. It is wise to have the whole sequence of necessary studies in mind and to plan a full programme than rather individual studies one by one.
KW - Acceleration of research
KW - Change-in-management studies
KW - Diagnostic accuracy
KW - Diagnostic studies
KW - Randomized diagnostic studies
KW - Seamless designs
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85093969124&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/32991994
U2 - https://doi.org/10.1016/j.jclinepi.2020.09.019
DO - https://doi.org/10.1016/j.jclinepi.2020.09.019
M3 - Article
C2 - 32991994
SN - 0895-4356
VL - 129
SP - 51
EP - 59
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
ER -