One-sample survival tests in the presence of non-proportional hazards in oncology clinical trials
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| Format: | Preprint |
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2025
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| _version_ | 1866917393200054272 |
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| author | Szurewsky, Chloé Yin, Guosheng Teuff, Gwénaël Le |
| author_facet | Szurewsky, Chloé Yin, Guosheng Teuff, Gwénaël Le |
| contents | In oncology, conduct well-powered time-to-event randomized clinical trials may be challenging due to limited patietns number. Many designs for single-arm trials (SATs) have recently emerged as an alternative to overcome this issue. They rely on the (modified) one-sample log-rank test (OSLRT) under the proportional hazards to compare the survival curves of an experimental and an external control group. We extend Finkelstein's formulation of OSLRT as a score test by using a piecewise exponential model for early, middle and delayed treatment effects and an accelerated hazards model for crossing hazards. We adapt the restricted mean survival time based test and construct a combination test procedure (max-Combo) to SATs. The performance of the developed are evaluated through a simulation study. The score tests are as conservative as the OSLRT and have the highest power when the data generation matches the model underlying score tests. The max-Combo test is more powerful than the OSLRT whatever the scenarios and is thus an interesting approach as compared to a score test. Uncertainty on the survival curve estimated of the external control group and its model misspecification may have a significant impact on performance. For illustration, we apply the developed tests on real data examples. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2506_18608 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | One-sample survival tests in the presence of non-proportional hazards in oncology clinical trials Szurewsky, Chloé Yin, Guosheng Teuff, Gwénaël Le Applications Methodology In oncology, conduct well-powered time-to-event randomized clinical trials may be challenging due to limited patietns number. Many designs for single-arm trials (SATs) have recently emerged as an alternative to overcome this issue. They rely on the (modified) one-sample log-rank test (OSLRT) under the proportional hazards to compare the survival curves of an experimental and an external control group. We extend Finkelstein's formulation of OSLRT as a score test by using a piecewise exponential model for early, middle and delayed treatment effects and an accelerated hazards model for crossing hazards. We adapt the restricted mean survival time based test and construct a combination test procedure (max-Combo) to SATs. The performance of the developed are evaluated through a simulation study. The score tests are as conservative as the OSLRT and have the highest power when the data generation matches the model underlying score tests. The max-Combo test is more powerful than the OSLRT whatever the scenarios and is thus an interesting approach as compared to a score test. Uncertainty on the survival curve estimated of the external control group and its model misspecification may have a significant impact on performance. For illustration, we apply the developed tests on real data examples. |
| title | One-sample survival tests in the presence of non-proportional hazards in oncology clinical trials |
| topic | Applications Methodology |
| url | https://arxiv.org/abs/2506.18608 |