Article
Acceleration of diagnostic research: Is there a potential for seamless designs?
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Authors
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Werner Vach
- University Hospital Basel, Department of Orthopaedics and Traumatology, Basel, Schweiz
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Eric Bibiza-Freiwald
- University Medical Center Hamburg-Eppendorf, Institute of Medical Biometry and Epidemiology, Hamburg, Deutschland
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Oke Gerke
- Odense University Hospita, Department of Nuclear Medicine, Dänemark; University of Southern Denmark, Department of Clinical Research, Dänemark
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Tim Friede
- University Medical Center Goettingen, Department of Medical Statistics, Goettingen, Deutschland
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Antonia Zapf
- University Medical Center Hamburg-Eppendorf, Institute of Medical Biometry and Epidemiology, Hamburg, Deutschland
| Published: | February 12, 2020 |
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Outline
Text
Background/research question: New diagnostic tests to identify a well-established disease state have to undergo a series of scientific studies from test construction until 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 until full establishment in clinical practice including reimbursement. Seamless designs allow us to combine a sequence of studies in one protocol and may hence accelerate this process. A systematic investigation of the potential of seamless designs in diagnostic research is missing.
Methods: We summarized the major study types in diagnostic research and identified their basic characteristics with respect to apply seamless designs. This information was 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 pairs studies, randomized discordant pairs studies, 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, possibility for blinding of test results.
Two basic hurdles could be identified: 1) Accuracy studies are hard to combine with post-accuracy studies, as the first are required to justify the latter and as 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 prior to performing such a study.
However, there is a substantial potential for seamless designs since all steps from the construction until 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. Examples from the literature illustrate the feasibility of both approaches.
Conclusion: There is a potential for seamless designs in diagnostic research.
Competing interests: The authors declare no conflicts of interest.
