Is the Real-World Evidence for Effectiveness and Safety of Biosimilars Vis-à-vis Originators FDA Compliant?

OBJECTIVES:

Food and Drug Administration (FDA)’s Biosimilars Action Plan recommends increased use of real-world evidence (RWE) instead of costly clinical outcome studies for biosimilars. According to the “Framework for FDA’s Real-World Evidence Program, 2018”, to consider the RWE robust enough for supporting regulatory decisions, the Real-World Data (RWD) should be fit for use, study design should provide adequate scientific evidence, and study conduct should meet FDA regulatory requirements. We set out to evaluate whether the published evidence from real-world studies meet these requirements.

METHODS:

MEDLINE database was searched systematically for free full original research articles published in English since 2018, describing real-world studies in humans, which evaluate effectiveness and/or safety of biosimilars vis-à-vis the respective originators. “Assessment of Real-World Observational Studies” (ArRoWS) critical appraisal tool was used to assess the risk of bias.

RESULTS:

Out of 36 records retrieved, 21 articles (11 review articles, 10 articles not describing safety/effectiveness, one article not evaluating biosimilar) were excluded and one article did not pass the quality assessment. Eventually, 14 articles describing eight prospective and six retrospective real-world studies were included in the review. Rheumatoid arthritis (n=4) and ankylosing spondylosis (n=4) were the most studied diseases. Biosimilars of Infliximab (n=4), filgrastim (n=4), and rituximab (n=2) were most investigated. Source of RWD for the studies were patient clinical records (n=5), databases (n=4), eCRF/EMR (n=3), and registries (n=2). Majority of articles reported that biosimilars were as effective (n=13) and safe (n=12) as originators, however the evidence could not conform the FDA requirements for RWD fitness of use (n=3), study design (n=1), and conduct of the study (n=3), in 50% papers. Of the remaining studies, 57% did not use a reporting guideline like STROBE.

CONCLUSIONS:

Real-world researchers should conform to FDA framework and planning templates like STaRT-RWE to make the evidence fit for regulatory use.