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| Main Authors: | , , , , |
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| Format: | Preprint |
| Published: |
2024
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2407.18341 |
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| _version_ | 1866910036014399488 |
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| author | Mou, Yunhan Kyriakides, Tassos Hummel, Scott Li, Fan Huang, Yuan |
| author_facet | Mou, Yunhan Kyriakides, Tassos Hummel, Scott Li, Fan Huang, Yuan |
| contents | Composite endpoints consisting of both terminal and non-terminal events, such as death and hospitalization, are frequently used in cardiovascular clinical trials. The Finkelstein-Schoenfeld (FS) test provides a way to employ a hierarchical structure to combine fatal and non-fatal events by giving death information an absolute priority, which may limit the contribution of clinically meaningful non-fatal events. To provide a more flexible alternative, we propose the Finkelstein-Schoenfeld with Multiple Thresholds (FS-MT) test, which extends the standard FS test by incorporating multiple thresholds applied sequentially and alternating across endpoints. A weighted adaptive approach is also developed to help determine the thresholds in FS-MT. The proposed approach retains the statistical properties of the FS test while allowing more flexible use of information from lower-priority events. We evaluate the operating characteristics of the proposed test through simulations that vary the follow-up time, the correlation between events, and the treatment effect sizes. A case study based on the Digitalis Investigation Group clinical trial data is presented to further illustrate our proposed method. An R package ``FSMT'' that implements the proposed methodology has been developed. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2407_18341 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Generalizing the Finkelstein-Schoenfeld Test to Incorporate Multiple Alternating Thresholds Mou, Yunhan Kyriakides, Tassos Hummel, Scott Li, Fan Huang, Yuan Methodology Composite endpoints consisting of both terminal and non-terminal events, such as death and hospitalization, are frequently used in cardiovascular clinical trials. The Finkelstein-Schoenfeld (FS) test provides a way to employ a hierarchical structure to combine fatal and non-fatal events by giving death information an absolute priority, which may limit the contribution of clinically meaningful non-fatal events. To provide a more flexible alternative, we propose the Finkelstein-Schoenfeld with Multiple Thresholds (FS-MT) test, which extends the standard FS test by incorporating multiple thresholds applied sequentially and alternating across endpoints. A weighted adaptive approach is also developed to help determine the thresholds in FS-MT. The proposed approach retains the statistical properties of the FS test while allowing more flexible use of information from lower-priority events. We evaluate the operating characteristics of the proposed test through simulations that vary the follow-up time, the correlation between events, and the treatment effect sizes. A case study based on the Digitalis Investigation Group clinical trial data is presented to further illustrate our proposed method. An R package ``FSMT'' that implements the proposed methodology has been developed. |
| title | Generalizing the Finkelstein-Schoenfeld Test to Incorporate Multiple Alternating Thresholds |
| topic | Methodology |
| url | https://arxiv.org/abs/2407.18341 |