Additional safety risk to exceptionally approved drugs in Europe?

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The safety profile of new drugs is not well known at the time of market approval and serious safety issues are regularly identified for marketed drugs. • Drugs intended to meet an unmet medical need can be approved for the market with less safety data than is usually required, using the Exceptional Circumstances and Conditional Approval applications in European Central procedure. • It is unknown whether for drugs approved using Exceptional Circumstances and Conditional Approval procedures have an increased probability of serious safety issues identified post approval than for drugs approved through the standard procedures. WHAT THIS STUDY ADDS • Using the Exceptional Circumstances and Conditional Approval procedures does not lead to more post‐marketing safety alerts or safety‐related withdrawals when used for drugs with unmet medical needs. AIMS Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear ‘unmet medical need’. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues. METHODS A retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan‐Meyer survival analysis and Cox‐regression to correct for covariates. RESULTS In total 289 new drugs were approved. Forty‐six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P= 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11‐year follow‐up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log‐rank P= 0.726). This difference remained not significant in the Cox‐regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate. CONCLUSION The EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issue