Principled type I error rate inflation in two-arm clinical trial designs with external control information borrowing
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arXiv
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| Main Authors: | , , , |
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| Format: | Preprint |
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2025
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| _version_ | 1866914000951836672 |
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| author | Calderazzo, Silvia Wiesenfarth, Manuel Weru, Vivienn Kopp-Schneider, Annette |
| author_facet | Calderazzo, Silvia Wiesenfarth, Manuel Weru, Vivienn Kopp-Schneider, Annette |
| contents | External information borrowing is often considered in order to improve a clinical trial's efficiency. The Bayesian approach borrows such external information by specifying an informative prior distribution. A potential issue with this procedure is that external and current information may conflict, but such inconsistency may not be predictable a priori. Robust prior choices are typically proposed to limit extreme worsening of operating characteristics (OCs) in these situations. However, trade-offs are still present and in general no power gains are possible if strict control of type I error (TIE) rate is desired. In this context, principled justifications for TIE rate inflation can be of interest. Here we investigate two-arm trials, with a focus on external/historical control information borrowing. We investigate frequentist OCs trade-offs and propose an interpretable approach for external information borrowing. The approach analytically links observed potential prior-data conflict with allowances for TIE rate inflation and power loss. The approach does not rely on a robust prior specification, but can instead be interpreted as an adaptive choice of Bayes test decision thresholds under the available informative prior. A development for both Normal and binomial outcomes is provided. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2508_16348 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Principled type I error rate inflation in two-arm clinical trial designs with external control information borrowing Calderazzo, Silvia Wiesenfarth, Manuel Weru, Vivienn Kopp-Schneider, Annette Methodology External information borrowing is often considered in order to improve a clinical trial's efficiency. The Bayesian approach borrows such external information by specifying an informative prior distribution. A potential issue with this procedure is that external and current information may conflict, but such inconsistency may not be predictable a priori. Robust prior choices are typically proposed to limit extreme worsening of operating characteristics (OCs) in these situations. However, trade-offs are still present and in general no power gains are possible if strict control of type I error (TIE) rate is desired. In this context, principled justifications for TIE rate inflation can be of interest. Here we investigate two-arm trials, with a focus on external/historical control information borrowing. We investigate frequentist OCs trade-offs and propose an interpretable approach for external information borrowing. The approach analytically links observed potential prior-data conflict with allowances for TIE rate inflation and power loss. The approach does not rely on a robust prior specification, but can instead be interpreted as an adaptive choice of Bayes test decision thresholds under the available informative prior. A development for both Normal and binomial outcomes is provided. |
| title | Principled type I error rate inflation in two-arm clinical trial designs with external control information borrowing |
| topic | Methodology |
| url | https://arxiv.org/abs/2508.16348 |