دورية أكاديمية
A standardized metric to enhance clinical trial design and outcome interpretation in type 1 diabetes
| العنوان: | A standardized metric to enhance clinical trial design and outcome interpretation in type 1 diabetes |
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| المؤلفون: | Ylescupidez, Alyssa, Bahnson, Henry T., O’Rourke, Colin, Lord, Sandra, Speake, Cate, Greenbaum, Carla J. |
| المساهمون: | JDRF, U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases, *The JDRF grant and the NIDDK R03 grant are to CS. All NIH/NIDDK funds were to support the TrialNet network and collection of data analyzed in this manuscript, these were not grants to CS. |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | The use of a standardized outcome metric enhances clinical trial interpretation and cross-trial comparison. If a disease course is predictable, comparing modeled predictions with outcome data affords the precision and confidence needed to accelerate precision medicine. We demonstrate this approach in type 1 diabetes (T1D) trials aiming to preserve endogenous insulin secretion measured by C-peptide. C-peptide is predictable given an individual’s age and baseline value; quantitative response (QR) adjusts for these variables and represents the difference between the observed and predicted outcome. Validated across 13 trials, the QR metric reduces each trial’s variance and increases statistical power. As smaller studies are especially subject to random sampling variability, using QR as the outcome introduces alternative interpretations of previous clinical trial results. QR can provide model-based estimates that quantify whether individuals or groups did better or worse than expected. QR also provides a purer metric to associate with biomarker measurements. Using data from more than 1300 participants, we demonstrate the value of QR in advancing disease-modifying therapy in T1D. QR applies to any disease where outcome is predictable by pre-specified baseline covariates, rendering it useful for defining responders to therapy, comparing therapeutic efficacy, and understanding causal pathways in disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-42581-z |
| الإتاحة: | https://doi.org/10.1038/s41467-023-42581-zTest https://www.nature.com/articles/s41467-023-42581-z.pdfTest https://www.nature.com/articles/s41467-023-42581-zTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.AD9482EF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-42581-z |
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