Strength of clinical evidence leading to approval of novel cancer
medicines in Europe: a systematic review and data synthesis.
Abstract
Aim We aimed to evaluate the quality of clinical evidence that
substantiated approval of cancer medicines by European Medicines Agency
(EMA) in the last decade. Methods We performed a systematic review and
data synthesis of EMA documents in agreement with PRISMA guidelines. We
included European Public Assessment Reports, Summaries of Product
Characteristics, and published randomized controlled trials (RCTs) on
anti-cancer drugs approved by EMA from 2010 to 2019, and excluded drugs
not indicated for targeting solid or hematological tumors and
non-innovative treatments. We synthesized frequencies of approvals
differentiating between unblinded and blinded RCTs with and without
overall survival (OS) as predefined primary outcome measure. We assessed
frequency of post-approval RCTs for indications without at least one RCT
at the time of approval. Results Of 199 approvals, 159 (80%) were
supported by at least one RCT, 63 (32%) by at least one RCT having OS
as the primary or co-primary endpoint, 74 (37%) by at least one blinded
RCT, and 30 (15%) by at least one blinded RCT having OS as the primary
or co-primary endpoint. Whereas 40 approvals (20%) were not supported
by any RCT and, of those, 9 (22%) were followed by a post-approval RCT.
Discussion While the majority of approvals of cancer medicines approved
by EMA was supported by at least one RCT, we noted substantial
methodological heterogeneity of the studies.