Transcript February 13 - Plenary Keynote

Regulatory harmonization,
a regulatory perspective
Hubert Leufkens, Medicines Evaluation Board/Utrecht University
College ter Beoordeling van Geneesmiddelen
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 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’.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Non-harmonized world of cellphone adaptors
Feira da Ladra, Lisbon's Flea Market, Summer 2012
Leufkens Regul Harmonization
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’.
WSJ 2013 February 12: 20.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Regulatory systems
• Patient safety
• Public health
• Innovation
Science 2011 Apr 8; 332(6026): 174-5.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Key questions in the lifecycle of a medicine
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
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
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
Principles-based versus rule-based regulation
… 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...
Economist. Metaphor of the day,
April 21, 2008
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Nat Rev Drug Discov 2012; 11: 903-4.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Elgazayerly AN, de Graeff PA, Leufkens HG.
N Engl J Med 2012 Mar 22 ;366 :1160-1.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
2011 Jun 1;29(16):2266-72.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Scrip 2011 Nov 25:18.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
JAMA 2008; 300: 1887-1896.
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Outcomes and making comparisons
societal
effects
HTA
clinical
outcome
biomarker
placebo
standard treatment alternative scenario
Leufkens Regul Harmonization
College ter Beoordeling van Geneesmiddelen
Rethinking the regulatory system: The Escher-project
Leufkens Regul Harmonization