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).