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Improved surrogacy regressions for clinical trial endpoints in relapse/refractory and newly diagnosed multiple myeloma
Thesis   Open access

Improved surrogacy regressions for clinical trial endpoints in relapse/refractory and newly diagnosed multiple myeloma

Rhys Jonathan Butler
Master of Science (M.S.), Drexel University
Dec 2023
DOI:
https://doi.org/10.17918/00001910
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Butler_Rhys_20234.38 MBDownloadView
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Butler_Rhys_2023_Suppl122.96 MBDownloadView
Spreadsheet (supplemental) Revised RRMM Open Access Open Access (License Unspecified)
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Butler_Rhys_2023_Suppl235.52 MBDownloadView
Spreadsheet (supplemental) Revised NDMM Open Access Open Access (License Unspecified)

Abstract

United States. Food and Drug AdministrationMultiple Myeloma Objective response rate Overall survival Progression-free survival Surrogate endpoints Biomedical Engineering
Use of surrogate endpoints such as objective response rate (ORR) and progression-free survival (PFS) is common in multiple myeloma (MM) risk-benefit modelling for treatment approval, and notably accelerated approval. Yet, there is conflicting evidence supporting their surrogacy between themselves and overall survival (OS). This systematic review characterises all published single arm trials and randomised controlled trials (RCTs) in MM using ORR, PFS, TTP and OS endpoints between 1999 and 2022 (databases provided in supplemental information), and assesses the strength of surrogacy between each relationship, to determine if current data can support improve estimations for survival endpoints. The regressions were evaluated with the coefficient of determination with Pearson's correlation, and the F-test was used in cases of multivariate regressions. The analysis demonstrated that current regressions overpredict survivability endpoints, but there are multivariate models that can accurately predict clinical outcomes with patient characteristics and surrogate endpoints for both RRMM and NDMM.

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