UMMS Affiliation

Department of Population and Quantitative Health Sciences

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Document Type



Biomedical Devices and Instrumentation | Biostatistics | Clinical Trials | Diagnosis | Equipment and Supplies | Health Services Research | Neoplasms | Surgical Procedures, Operative | Therapeutics


Study design and statistical analysis are crucial in pivotal clinical trials to evaluate the effectiveness and safety of new medical devices under investigation. In recent years, innovative intraoperative in vivo breast tumor diagnostic devices have been proposed to improve the accuracy and surgical outcomes of breast tumor patients undergoing resection. Although such technologies are promising, investigators need to obtain statistical evidence for the effectiveness and safety of these devices by conducting valid clinical trials. However, the study design and statistical analysis for these clinical trials are complicated. While these trials are designed to provide real-time intraoperative diagnosis of cancerous tissue, they also have clear therapeutic objectives to lower the reoperation rate of breast cancer surgery. This research article introduces the new concept of neutral diagnosis (ND), and the ND clinical trial design as an innovative study design to evaluate the effectiveness and safety of diagnostic devices with direct therapeutic purposes. A joint modeling approach is adopted to make inferences on the effectiveness and safety of these devices for non-neutral diagnosis (non-ND) clinical trials. Simulation studies were conducted to show the efficiency of the ND trials and strength of the joint modeling approach in the non-ND clinical trials. An example on a diagnostic medical device that provides real-time, intraoperative diagnosis of breast cancer tumor tissues during breast cancer surgeries is comprehensively discussed and analyzed.


Cancer, Diagnostic devices, Drug-device combination product, Neutral diagnosis, Surgical resection

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© 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (

DOI of Published Version



Contemp Clin Trials Commun. 2019 Aug 21;16:100436. doi: 10.1016/j.conctc.2019.100436. eCollection 2019 Dec. Link to article on publisher's site

Journal/Book/Conference Title

Contemporary clinical trials communications

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PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.