In a situation where there is no direct (head-to-head) trial comparison with usual care (or standard of care) for the healthcare system of interest, it may not be possible to construct a connected evidence network based on available trials to support any required indirect comparison with usual care. For example, there may be no trials comparing the new medicine and usual care with the same alternative therapy option (such as placebo). It is also possible that patient groups in a study directly comparing alternative therapies are sufficiently different to preclude the study being pooled with other studies as part of a network meta-analysis.