Speaker
Description
In oncology trials, tumour-based endpoints, like Progression-Free Survival (PFS), Disease-Free Survival (DFS) or Relapse-Free Survival (RFS), are widely accepted. However, their use is more controversial compared with Overall Survival (OS), due to the subjectivity of tumour assessment, and their sensitivity to censoring rules, as they are more prone to obtaining different results depending on the type of primary analysis and censoring rules employed, and, therefore, to bias.
Sensitivity analyses reassess study outcomes with varying methodologies, assumptions, and/or censoring rules. Therefore, they are used to evaluate how dependent the primary results are on methodological choices, assessing their robustness and the potential impact of bias.
However, the choice of analyses to include in the study remains a subjective one.
In our meta-study, we focus on assessing the reproducibility of main studies that supported EMA authorisations of oncological medicines; but also aim to evaluate the robustness of their conclusion using different censoring rules; and analyse, when possible, the difference in results between the primary and the sensitivity analyses to identify possible trends in the choice of primary analyses.
We identified all oncologic indications that received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) between January 2020 and December 2024. Using the European public assessment report (EPAR), we then identified the RCTs referred to as ‘main studies’ and randomly sampled 60 of them.
For each sampled RCT, we requested the IPD, protocols, and information on how the study was conducted to reanalyse the two main efficacy endpoints (PFS and OS) to assess the reproducibility of their results. Both endpoints will be analysed according to the original primary analysis and then using different ways to handle censoring to evaluate the robustness of the study findings.
Moreover, for each sampled RCT, we extracted publicly available information about the Hazard Ratios (HRs) and confidence intervals (CIs) for PFS and OS, as well as their sensitivity analyses.
The median number of reported sensitivity analyses for PFS is 2, with a range of 0 to 12, while for OS, the median is 0, with a range of 0 to 6.
We are also in the process of comparing the differences in HRs and CIs between the primary and sensitivity analyses for each endpoint and assessing the presence of possible trends in the choice of primary analysis.
This type of studies is necessary to improve the transparency and trustworthiness of RCTs’ results.
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