regulatory harmonization, a regulatory perspective hubert leufkens, medicines evaluation...
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Regulatory harmonization, a regulatory perspective
Hubert Leufkens, Medicines Evaluation Board/Utrecht University
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
• 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 and Regulation, since 2008.
• This talk reflects my personal views; I am being inspired and challenged on a daily basis by many colleagues from these ‘environments’.
Declaration of interests
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
Non-harmonized world of cellphone adaptors
Feira da Ladra, Lisbon's Flea Market, Summer 2012
College ter Beoordeling van Geneesmiddelen
There are many reasons to harmonize drug development and regulation, i.e. to
• ensure equal access to patients.• improve work-sharing and efficient use of scarce
regulatory resources.• avoid redundant use of animals in toxicity testing.• limit number of study subjects in regulatory BE
testing and pivotal clinical trials. • facilitate international trade and commerce.• contribute to a sustainable/affordable model of drug
development.• promote (global) trust in medicines.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
The stakes are high ....
• Novo Nordisk shares fell 14% in the afternoon of February 11 2013.
• FDA requests additional cardiovascular outcomes data from a dedicated cardiovascular outcoms trial before the review of the NDA (Tresiba) can be completed.
• Authorities in the EU and Japan have already approved the drug.
• Novo Nordisk CEO adds ‘the FDA is more risk-averse than its counterpart in the EU which looks more at the benefits’.
Leufkens Regul Harmonization
WSJ 2013 February 12: 20.
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Leufkens Regul Harmonization
Science 2011 Apr 8; 332(6026): 174-5.
Regulatory systems• Patient safety
• Public health
• Innovation
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Leufkens Regul Harmonization
Question Today's challenges
Robust definition and diagnosis of disease?
Psychiatric morbidities, sepsis, somatic functional disorders
Clinically relevant endpoints to evaluate drug effects?
PFS and OS in oncology, HbA1C or outcomes data in diabetes
Identifiable target population (indication) that may benefit?
Biomarkers to identify responders, to evaluate response
What kind of comparison is useful, needed and feasible?
Placebo, active controls and dynamics in treatment options
Key questions in the lifecycle of a medicine
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Five archetypes of problematic dossier crunching
• We don’t like this product at all.• Lost in details.• We struggle, asking for more data makes
us feel good.• Reluctant to cross borders, risk avoidance.• Why are we so positive?
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
… Football, like most American sports, is heavily rule-bound.
…Soccer is a more principles-based game. There are fewer rules, and the referee is given far more authority than officials in most American sports to interpret them and to shape game play and outcomes…
A bad or biased ref can ruin a soccer match in the way that no bad ref can ruin a football match, the lesson being that regulator independence is key in a principles system...
Principles-based versus rule-based regulation
Economist. Metaphor of the day, April 21, 2008
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Leufkens Regul Harmonization
Nat Rev Drug Discov 2012; 11: 903-4.
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Leufkens Regul Harmonization
Elgazayerly AN, de Graeff PA, Leufkens HG.N Engl J Med 2012 Mar 22 ;366 :1160-1.
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
2011 Jun 1;29(16):2266-72.
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
Scrip 2011 Nov 25:18.
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
JAMA 2008; 300: 1887-1896.
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
placebo standard treatment alternative scenario
societal effects
HTA
clinical outcome
biomarker
Outcomes and making comparisons
College ter Beoordeling van Geneesmiddelen
Leufkens Regul Harmonization
Rethinking the regulatory system: The Escher-project