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This large systematic review and meta-regression analysis examined whether samples of randomized clinical trials of face-to-face therapy (FTF) and internet-based therapy (IBT) for depression differ with regard to the prognostic risk factors of the included patients. The findings suggest that indirect comparisons of FTF and IBT may be problematic because, in terms of reporting prognostic risk factors, samples of RCTs may not be drawn from the same clinical population.