Sensitivity analyses to increase number of data points
Some of the trials identified in the literature review only included patients who had failed ≥2 prior therapies before enrolment. Several other trials included both treatment-naïve and treatment-experienced patients. Some trial sponsors published subgroup analyses specific to those patients who had failed ≥2 prior treatments. Therefore, we conducted sensitivity analyses in which these subgroup data were included alongside the overall phase 3 study population. In other words, each trial could contribute to two data points in the sensitivity analyses. Having two data points per trial has critical statistical limitations, due to double-counting of some patients (namely, patients who had ≥2 prior treatment failures); however, this approach was used to assess the robustness of the results by increasing the number of data points in the analysis. To address this methodological limitation, the mean and standard error (SE) for patients with 0 or 1 failed prior therapies were computed by the authors (see Appendix S1 ). The meta-regression was then rerun and compared with the aforementioned sensitivity analysis (i.e., with potentially two data points per trial: placebo effect for patients with 0 or 1 prior failures, and placebo effect for patients with ≥2 prior failures).