A decade comparison of regulatory decision patterns for oncology products to all other non-oncology products among Swissmedic, European Medicines Agency, and US Food and Drug Administration

Consensus of regulatory decisions on the same Marketing Authorization Application (MAA) are critical for stakeholders. In this context, regulatory decision patterns from the Swissmedic (SMC), the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA) were analyzed for hemato-oncology products (OP) and non-oncology products (NOP). We compared 336 SMC regulatory decisions between 2009 and 2018 on new active substances with the EMA and the FDA for OP (n = 77) and NOP (n = 259) regarding approval rates, consensus, and divergent decisions. For OP MAA, we analyzed the underlying reasons for divergent decisions; for consensus decisions, the similarity and strictness of labeling. For OP, the approval rate for the SMC was 88.4%, the EMA 91.3%, and the FDA 95.7%. For NOP, the SMC had an approval rate of 86.2%, the EMA of 93.8%, and the FDA of 88.8%. The consensus decision rate among agencies was 88.4% for OP and 84.4% for NOP. The main clinical driver for divergent decisions for OP was nonrandomized trial design and low patient numbers. Comparing the approved indication wordings, the highest similarity was between the SMC and the EMA, and lowest for the FDA and the EMA. Investigating label strictness, the FDA numerically had the highest but not-statistically significant number of strict labels. The approval rate stratified by disease area (OP and NOP) differed among the SMC, the EMA, and the FDA. High concordance in regulatory decisions was observed between agencies for OP as well as NOP. Reasons for divergent decisions regarding OP were mainly due to scientific uncertainties. Comparing strictness of indications, numerical but no statistically significant differences were observed between agencies.Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? There is currently no solid knowledge regarding differences of approval and rejection rates as well as the reason for divergent decisions for oncology products versus non-oncology products across major regulating agencies.WHAT QUESTION DID THIS STUDY ADDRESS? The study addresses the question if there are statistical differences in the approval patterns among three major health authority agencies over a recent 10 -year time frame stratified by disease area and the underlying scientific root cause for divergent decisions in oncology between agencies.WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The study confirms the adequate decision making of regulatory agencies which are highly consistent. Divergent decisions in the oncology disease area are investigated and scientifically explained. This counteracts criticism expressed by payers and healthcare providers that regulatory agencies come frequently to divergent decisions based on the same clinical data submitted.HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The data indicate that scientific uncertainties due to non-controlled trial design and inadequate patient numbers are the main driver for divergent decisions. Applicants must perform adequate clinical studies in terms of patient numbers and comparators in order to avoid or reduce the uncertainties leading to divergent decisions of regulating agencies.

Automated summary

Consensus among regulatory agencies is crucial for stakeholders. This study analyzed regulatory decision patterns from Swissmedic (SMC), FDA, and EMA for hemato-oncology products (OP) and non-oncology products (NOP). The study found differences in approval rates, consensus, and divergent decisions among the agencies, with the main driver for divergent decisions in OP being nonrandomized trial design and low patient numbers.