EMEA Performance Indicators Pre-Authorisation Bo Aronsson EMEA - PowerPoint PPT Presentation

EMEA Performance Indicators Pre-Authorisation Bo Aronsson EMEA EMEA-EFPIA Info Day 2009 1

Contents • Analysis Period • EMEA questionnaires • Results • Summary • Work in progress (Predictors of outcome) • Conclusions 2

Analysis Period • EMEA Data Set: All applications with outcome between 1 January 2003 and 31 December 2008 – Period of questionnaires follows annual reporting to Management Board – Source: • Questionnaires to (co-)rapporteurs • Scientific Memory Database • EFPIA Data Set: October 06-October 08 3

EMEA Questionnaires EMEA Questionnaires • Two versions have been used in 2003-2008 • “Old” version, implemented in 2000 – 10-point Scale (0 dissatisfied to 10 satisfied) • “New” version implemented in 2007 – Keep some of the same domains from “old” questionnaire – Includes new domains (e.g., Scientific Advice) – 5-point Likert Scale (1 agree to 5 disagree) – Note: validation ongoing • Questionnaires administered after day 80 • Average scores between Rapporteur/Co-rapporteur, per product • Exclusion of duplicates 4

EMEA Questionnaires Compared Item V2000 No. V2007 No. Dossier Presentation Q NC C 3 Q NC C 3 Evidence- Data/Design Q NC C 3 Q NC C 11 Overview NC C 2 - Summary Q NC C 3 - Study Reports Q NC C 3 - SPC, PL, Labelling Yes 3 - Scientific Advice - Yes 4 Communication - Yes 1 RMP/PVP - Yes 5 Q= quality, NC=non-clinical, C=clinical, CPh=clinical pharmacology; CE=clinical efficacy, CS=clinical safety, PVP=pharmacovigilance plan. 5

Data Set 2003-2008 (N=209) • Allows to explore 2 domains and Parts of Dossier – Presentation of the Dossier for Q, NC and C – Evidence (Data/Studies) included in the dossier for Q, NC and C Year 2003 2004 2005 2006 2007 2008 Total No. Questionnaires ("new" + "old") 21 32 33 43 36 44 209 No. "old" quest. 21 32 33 43 35 14 178 No. "new" quest. 1 30 31 No. Outcomes 30 36 36 50 59 70 281 Compliance (%) 70 89 92 86 61 63 74 6

Product Characteristics (N=209) Frequency Percent Orphan Status 56 26.79 ATC A 29 13.88 B 11 5.26 C 15 7.18 J 37 17.70 L 50 23.92 N 23 11.00 V 15 7.18 Other 29 13.87 Outcome Positive 157 75.12 Scientific Advice 85 40.67 7

Questionnaire Results •All scores converted to 10-point Scale (0 dissatisfied to 10 satisfied) 8

Presentation of Dossier (N=209) 10 8 6 Score 4 2 0 Quality Non-clinical Clinical 9

Evidence by Module (N=209) 10 8 6 Score 4 2 0 Quality Non-clinical Clinical 10

Score 10.00 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 1-Jan-03 1-May-03 Presentation By Time (N=209) 29-Aug-03 27-Dec-03 25-Apr-04 23-Aug-04 21-Dec-04 20-Apr-05 18-Aug-05 Outcome 16-Dec-05 15-Apr-06 13-Aug-06 11-Dec-06 10-Apr-07 Poly. (Clinical) Poly. (Non-clinical) Poly. (Quality) Clinical Non-clinical Quality 8-Aug-07 6-Dec-07 4-Apr-08 2-Aug-08 11 30-Nov-08

Score 10 0 1 2 3 4 5 6 7 8 9 1-Jan-03 1-May-03 Evidence by Module by Time (N=209) 29-Aug-03 27-Dec-03 25-Apr-04 23-Aug-04 21-Dec-04 20-Apr-05 18-Aug-05 Outcome 16-Dec-05 15-Apr-06 13-Aug-06 11-Dec-06 10-Apr-07 8-Aug-07 Poly. (Clinical) Poly. (Non-clinical) Poly. (Quality) Clinical Non-clinical Quality 6-Dec-07 4-Apr-08 2-Aug-08 12 30-Nov-08

Evidence by Orphan (N=209) Quality Non-clinical Clinical 10 10 10 8 8 8 6 6 Score 6 4 4 4 2 2 0 2 No Orphan No Orphan No Orphan 13

Is the Score Associated with Outcome and Clock-stop? 14

Success by Outcome Year (N=209) PERCENT 100 90 80 70 60 50 40 30 20 10 0 2003 2004 2005 2006 2007 2008 YearFinal IsPos 0 1 15

Clinical Evidence versus Outcome (N=209) Data Clinical 10 8 6 Score 4 2 Neg. Pos. 16

Average Score and Clock-stop (N=209) 10.00 9.00 (all Presentation/Evidence for Q, N, C) 8.00 7.00 Average Score 6.00 5.00 4.00 3.00 2.00 1.00 0.00 0 200 400 600 800 Clock-stop (Days) 17

Summary • Majority satisfaction – No new time trends – Orphan status associated with lower satisfaction with Evidence for all modules (and Presentation, data not shown) • Satisfaction with Clinical Evidence associated with outcome and clock-stop • Need to improve compliance with questionnaire • Future – Further validate new questionnaire and explore new domains (work in progress) – Predictors of Outcome (work in progress) 18

Predictors for Outcome - SA Work in progress 19

Proportion of MAAs MAAs that received SA (by that received SA (by Proportion of outcome year) outcome year) SA given 60% 56% 50% 47% 40% 38% 30% 20% 10% 0% 2006 (n=50) 2007 (n=59) 2008 (n=70) 20

Distribution of Scientific Advice over eligibility - Distribution of Scientific Advice over eligibility -2008 2008 Eligibility with/without SA 2008 35 30 25 18 20 No SA 3 SA 15 10 16 1 11 5 6 4 5 5 0 1 0 Biotech Mandatory Orphan New Active Significant WHO Generic Indication Substance Innovation/Patients interest 21

Did the Company follow SA? • 31 “new” questionnaires in Compliance study period – 16 with SA given – 6/16 (35%) show poor compliance according to Rapporteurs (score <5) Poor • Is SA or compliance to SA Good related to outcome? 22

Size of company, success rate and Compliance with SA Pharma Number Success Proportion Compliance size applications rate with SA with SA Top 20 83 89% 46% 84% largest* 21-150** 53 72% 34% 63% 151+*** 56 50% 29% 36% Regnstroem et al., (in manuscript) *Top 20 largest (n=83) defined as being among the 20 largest companies **21-150 (n=53) defined as being among the 21 – 150 largest companies ***151+ (n=56) defined as not being among the 150 largest companies based on Total revenues 2005 according to Scrips Pharmaceutical League Tables 2006. 23

Predictors of Outcome Odds Ratio Estimates Effect Point Estimate 95% Wald Confidence Limits Company Size (1: 151+; 2: 1.904 1.079 3.36 21-150; 3: Top 20 largest) Clinical Evidence (0-10) 1.485 1.16 1.901 Major Objection on RCT 0.301 0.122 0.744 (No vs Yes) SA & Compliant vs . (No SA 9.593 1.175 78.311 or Not Compliant) Data on ranking was only available for 148 applications (work in progress) Stepwise logistic regression. Compliance, retrospectively assigned in Regnstroem et al. (in manuscript) 24

Conclusions • Most important factors associated with outcome – Compliance with Scientific Advice – Company Size – Rapporteurs’ satisfaction with Clinical Evidence submitted – Major Objections on the Lack or Randomised Controlled Trials 25

Acknowledgments • Analysis – Francesco Pignatti – Franz Koenig – Jan Regnstroem • Data Management – Esther Cozar Calvente – Nadia Kresse – Monica Simeoni 26