These are examples where the patient sample in the trials does not precisely match the licenced indication (eg pembrolizumab in melanoma: prior drug exposure [31]), or the restricted indication under consideration in the TA; for example, a drug may be restricted to patients with a specific mutation (eg erlotinib in NSCLC: EGFR-TK mutation [32]), to a specific line of treatment (eg olaparib in ovarian cancer: 4th or later line [30]) or a particular tumour types (eg nintedanib: NSCLC with adenocarcinoma histology [28]). Here, TKT is linked to melanoma.