A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects
A delayed treatment effect is a commonly observed phenomenon in tumor immunotherapy clinical trials. It can cause a loss of statistical power and complicate the interpretation of the analytical findings. This phenomenon also poses challenges for interim analysis in the context of phase II/III seamle...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1186456/full |
| _version_ | 1797688641653309440 |
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| author | Long-Shen Xie Hui Lu |
| author_facet | Long-Shen Xie Hui Lu |
| author_sort | Long-Shen Xie |
| collection | DOAJ |
| description | A delayed treatment effect is a commonly observed phenomenon in tumor immunotherapy clinical trials. It can cause a loss of statistical power and complicate the interpretation of the analytical findings. This phenomenon also poses challenges for interim analysis in the context of phase II/III seamless design or group sequential design. It shows potential to lead researchers to make incorrect go/no-go decisions. Despite its significance, rare research has explored the impact of delayed treatment effects on the decision success rate of the interim analysis and the methods to compensate for this loss. In this study, we propose an analysis procedure based on change points for improving the decision success rate at the interim analysis in the presence of delayed treatment effects. This procedure primarily involves three steps: I. detecting and testing the number and locations of change points; II. estimating treatment efficacy; and III. making go/no-go decisions. Simulation results demonstrate that when there is a delayed treatment effect with a single change point, using the proposed analysis procedure significantly improves the decision success rate while controlling the type I error rate. Moreover, the proposed method exhibits very little disparity compared to the unadjusted method when the proportional hazards assumption holds. Therefore, the proposed analysis procedure provides a feasible approach for decision-making at the interim analysis when delayed treatment effects are present. |
| first_indexed | 2024-03-12T01:34:43Z |
| format | Article |
| id | doaj.art-f6efd76a02bf46508ed7ee280705deae |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T01:34:43Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f6efd76a02bf46508ed7ee280705deae2023-09-11T12:25:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-09-011410.3389/fphar.2023.11864561186456A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effectsLong-Shen XieHui LuA delayed treatment effect is a commonly observed phenomenon in tumor immunotherapy clinical trials. It can cause a loss of statistical power and complicate the interpretation of the analytical findings. This phenomenon also poses challenges for interim analysis in the context of phase II/III seamless design or group sequential design. It shows potential to lead researchers to make incorrect go/no-go decisions. Despite its significance, rare research has explored the impact of delayed treatment effects on the decision success rate of the interim analysis and the methods to compensate for this loss. In this study, we propose an analysis procedure based on change points for improving the decision success rate at the interim analysis in the presence of delayed treatment effects. This procedure primarily involves three steps: I. detecting and testing the number and locations of change points; II. estimating treatment efficacy; and III. making go/no-go decisions. Simulation results demonstrate that when there is a delayed treatment effect with a single change point, using the proposed analysis procedure significantly improves the decision success rate while controlling the type I error rate. Moreover, the proposed method exhibits very little disparity compared to the unadjusted method when the proportional hazards assumption holds. Therefore, the proposed analysis procedure provides a feasible approach for decision-making at the interim analysis when delayed treatment effects are present.https://www.frontiersin.org/articles/10.3389/fphar.2023.1186456/fulltumor immunotherapydelayed treatment effectchange pointinterim analysisdecision-making |
| spellingShingle | Long-Shen Xie Hui Lu A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects Frontiers in Pharmacology tumor immunotherapy delayed treatment effect change point interim analysis decision-making |
| title | A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects |
| title_full | A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects |
| title_fullStr | A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects |
| title_full_unstemmed | A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects |
| title_short | A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects |
| title_sort | change point based analysis procedure for improving the success rate of decision making in clinical trials with delayed treatment effects |
| topic | tumor immunotherapy delayed treatment effect change point interim analysis decision-making |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1186456/full |
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