title: Additional safety risk to exceptionally approved drugs in Europe?
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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 issues emerging after market approval.
authors.affiliation: Department of Clinical Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. a.h.arnardottir@med.umcg.nl
authors.forename: Arna H
authors.initials: AH
authors.lastname: Arnardottir
authors.forename: Flora M
authors.initials: FM
authors.lastname: Haaijer-Ruskamp
authors.forename: Sabine M J
authors.initials: SM
authors.lastname: Straus
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Eichler
authors.forename: Pieter A
authors.initials: PA
authors.lastname: de Graeff
authors.forename: Peter G M
authors.initials: PG
authors.lastname: Mol
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D017277:Drug Approval / Q000331:legislation & jurisprudence* / Q000379:methods; D005060:Europe; D005500:Follow-Up Studies; D006801:Humans; D055553:Prescription Drugs / Q000009:adverse effects*; D012015:Reference Standards; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D055553:Prescription Drugs