1. The association between European Medicines Agency approval and Health Technology Assessment recommendations Iga Lipska 1,2, Anke Hövels 2, Neil McAuslane 1 1 Center for Innovation in Regulatory Science, London, UK 2 Utrecht Institute for Pharmaceutical Sciences, Division Pharmacoepidemiology & Clinical Pharmacology, Utrecht, The Netherlands Abstract Objective To find the association between duration of the process of marketing authorization (MA) approval at European Medicines Agency (EMA) and health technology assessment (HTA) recommendations in European Union (EU) countries Methods EMA MA timing for new active substances (NASs) during 2007-2009 were analyzed based on publicly available information. HTA recommendations (positive, positive with restrictions, negative, not assessed) issued for the same medications in 6 EU countries (SMC, Scotland; AOTM Poland; CVZ, The Netherlands; HAS, France; NICE, UK; INFARMED, Portugal) were also analyzed based on public information. Hypothesizing that EMA approval process timing might be an indicator of complexity and potential issues in the dossier, the potential for longer EMA approval times being associated with less beneficial HTA recommendation was investigated. Analyses were performed per country as EMA decisions are centralized but HTA recommendations are taken independently by member states Results 86 NAS were approved by EMA in 2007-2009; mean time of approval was 460 days (median 423 days). In total, we expected 516 HTA recommendations (86 drugs assessed by 6 organizations). We found in total 138 positive, 77 positive with restrictions, 67 negative recommendations. 234 expected recommendations for 6 HTA included in this study were not assessed (45,3% of all expected recommendations) (Figure 1). The association between HTA recommendation and approval time (in days) was analyzed using Spearman’s rho rank correlation (Table 1). There was statistically significant negative correlation between approval time and HTA recommendation in the Netherlands (Table 2, Figure 2). More time needed for EMA approval was associated with less beneficial HTA recommendations. Correlations in other countries were not statistically significant. Conclusions Our research indicates that a longer EMA approval process is associated with a less beneficial HTA recommendation in the Netherlands. Further research is required to determine whether this indicates that the same issues that cause delays at EMA are also problematic at HTA authorities Conclusions Our research indicates that a longer EMA approval process is associated with a less beneficial HTA recommendation in the Netherlands. Further research is required to determine whether this indicates that the same issues that cause delays at EMA are also problematic at HTA authorities Figure 1: HTA recommendations of NASs approved by EMA in 2007-2009 Figure 2: HTA recommendations in the Netherlands rhop-valuen Scotland -0.1490.21870 Poland -0.0680.69735 Netherlands -0.277*0.04752 France -0.1290.27274 England -0.2560.23723 Portugal 0.0190.92626 Total-0.124*0.03786 Table 1: Spearman’s rho correlation coefficients between EMA approval time and HTA recommendations. rho – Spearman’s rho correlation coefficient; p – value – statistical significance; n – number of drugs assessed HTA recommendations in the Netherlands Approval time/days negativepositive with restrictionspositive 0-30000%133,3%266,7% 300-34900%240,0%360,0% 350-39900%444,4%555,6% 400-449215,4%538,5%646,2% 450-49900%480,0%120,0% 500-549133,3%1 1 550-599114,3%228,6%457,1% 600-649250,0%125,0%1 650-69900%150,0%1 700-7491100,0%00%0 Table 2: HTA recommendations in the Netherlands Center for Innovation in Regulatory Science http://www.cirsci.org/ http://www.cirsci.org/