1. Should regulators be involved? Bert Leufkens, Chair Medicines Evaluation Board

2. 8-10-2010 Selling sickness Leufkens 2 Declaration of interests Professor of Pharmacoepidemiology, Utrecht Institute of Pharmaceutical Sciences, 0.4 FTE. Chairman of the Dutch Medicines Evaluation Board (MEB), since mid 2007. Co-opted member of CHMP PhVWP, 2006-2009; since 2009 co-opted member of CHMP. Director WHO-Utrecht Collaborating Centre on Pharmaceutical Policy Analysis, since 2008. This talk reflects my personal views; I am being inspired and challenged on a daily basis by many colleagues from these ‘environments’.

3. 8-10-2010 Selling sickness Leufkens 3 Selling sickness is not a new phenomenon

4. 8-10-2010 Selling sickness Leufkens 4 Incomplete innovation: two scenarios

5. 8-10-2010 Selling sickness Leufkens 5 Orphanisation: the antibiotic pipeline is almost empty ECDC/EMA, 2009

6. 8-10-2010 Selling sickness Leufkens 6 Public health effects of medicines Direct clinical effects (e.g. analgesics and pain relief, antivirals and AIDS survival, biologicals and infection risk, NSAIDs and GI bleeding). Disease prevention (e.g. vaccines and childhood disease, statins and prevention of CV risk). Effects on other medical interventions (e.g. PPIs and GI surgery, anaesthesia and surgery, cyclosporin and organ transplantation). Society effects (e.g. contraceptives and demo-graphics, psychotropic drugs and transformation of the mental health system, disease mongering).

7. 8-10-2010 Selling sickness Leufkens 7 Regulating marketing approval Regulatory governance Regulatory learning

8. 8-10-2010 Selling sickness Leufkens 8 The soul of regulators: knights or knaves Knights of safeguarding public health on behalf of the public, of idealism and altruism. Knaves of procedures, of risk avoidance, of bureaucratic constructs and self-interest.

9. 8-10-2010 Selling sickness Leufkens 9 Key questions in the lifecycle of a medicine

10. 8-10-2010 Selling sickness Leufkens 10 Where can regulators contribute?

11. 8-10-2010 Selling sickness Leufkens 11 Outcomes and making comparisons societal effects HTA clinical outcome biomarker placebo standard treatment alternative scenario

12. 8-10-2010 Selling sickness Leufkens 12 Low susceptibility to misuse Ranking evidence and susceptibility of misuse Thyroid drugs ICS for asthma Insuline Glaucoma drugs High level of evidence Hypnotics Growth hormone Dementia drugs Antibiotics Expectorants Proton pump inhibitors Bégaud B, Bergman U, Eichler H-G, Leufkens HG, Meier PJ. Br J Clin Pharmacol 2002; 54: 528-34.

13. 8-10-2010 Selling sickness Leufkens 13 Therapeutic indications in oncology over time Tafuri G et al. Eur J Cancer 2010; 46: 471-5.

14. 8-10-2010 Selling sickness Leufkens 14 Post-approval RCTs of etanercept, 2000–2008 Luijn JCF van et al. Scand J Rheumatol 2010;

15. 8-10-2010 Selling sickness Leufkens 15 Are we serving patient’s interests by labelling new drugs as second line? Schiller Y et al. Neurology 2008; 70: 54-65.

16. 8-10-2010 Selling sickness Leufkens 16 Summarizing The current regulatory system is marketing authorization holder (industry) driven. Unless there is a safety issue or serious doubt about the B/R of a product (e.g. rosiglitazone). The approved indication opens a window for appropriate, beneficial use and intended patient outcomes. A ‘wrong’ indication opens also a window for off-label use, of not targeting the right patients, etc. (‘regulatory gap’). Regulators are always too strict, too slow, too fast, too forgiven, too cozy, etc. Transparency on how regulatory decisions are made is key for restoring trust from society (one of MEB’s priorities).

17. 8-10-2010 Selling sickness Leufkens 17 Trust in the banking system has been badly shaken

18. 8-10-2010 Selling sickness Leufkens 18 Critical regulatory features in three industries

19. 8-10-2010 Selling sickness Leufkens 19 EMBO reports 2010; 11: 572-8.

20. 8-10-2010 Selling sickness Leufkens 20 Health is not only about drugs: four scenarios Crommelin D, Stolk P, Besancon L, Shah V, Midha K, Leufkens H. Pharmaceutical sciences in 2020. Nat Drug Discov 2010; 9: 99-100.