Revision of European Guidelines on clinical investigation of medicinal
products: Treatment
Treatment of
of Chronic
Chronic Obstructive
Obstructive Pulmonary
Pulmonary Disease
Disease (COPD)
(COPD)
products:
Arantxa Sancho
Sancho López
López 11,, Mª
Mª Luisa
Luisa Suárez
Suá
Gea 22,, Antonio
Antonio Gómez
Gó
Outes 22,, Gonzalo
Gonzalo Calvo
Calvo Rojas
Rojas 33
Suárez Gea
Gómez Outes
Arantxa
11 Departamento
Departamento de
de Farmacología
Farmacologí
Clí
Hospital Puerta
Puerta de
de Hierro
Hierro Majadahonda,
Majadahonda, Madrid
Madrid
Farmacología Clínica,
Clínica, Hospital
22 División
Divisió
de Farmacología
Farmacologí
Evaluació
Clí
Agencia Española
Españ
de Medicamentos
Medicamentos yy Productos
Productos Sanitarios
Sanitarios (AEMPS),
(AEMPS), Madrid
Madrid
División de
Farmacología yy Evaluación
Evaluación Clínica,
Clínica, Agencia
Española de
33 Departamento
Departamento de
de Farmacología
Farmacologí
Clí
Hospital Clinic,
Clinic,
Barcelona
Farmacología Clínica,
Clínica, Hospital
Clinic, Barcelona
INTRODUCTION
Figure 1. Process for drafting a guideline
In order
order to
to help
help applicants
applicants to
to prepare
prepare the
the dossier
dossier for
for aa MAA,
MAA, the
the
In
European Medicines
Medicines Agency,
Agency, prepares
prepares Scientific
Scientific Guidelines.
Guidelines.
European
The Committee
Committee for
for Human
Human Medicinal
Medicinal Products
Products (CHMP)
(CHMP) delegated
delegated these
these
The
tasks in
in different
different Working
Working Parties.
Parties. The
The Efficacy
Efficacy Working
Working Party
Party (EWP)
(EWP) has
has
tasks
been responsible
responsible for
for the
the development
development and
and update
update of
of clinical
clinical scientific
scientific
been
guidelines (Figure
(Figure 1).
1).
guidelines
Efficacy Working Party (EWP)
Implementation
Adoption of final guideline for publication
Preparation of final version of guideline
Collection of comments
AIM
Preparation of initial draft guideline
To describe
describe the
the key
key aspects
aspects of
of the
the update
update of
of the
the European
European guideline
guideline on
on
To
clinical investigation
investigation of
of medicinal
medicinal products
products in
in the
the treatment
treatment of
of chronic
chronic
clinical
obstructive pulmonary
pulmonary disease
disease (COPD)
(COPD) (CPMP/EWP/562/98).
(CPMP/EWP/562/98).
obstructive
Adoption/release for consultation of concept paper
Development of a concept paper
Appointment of Rapporteur/Co-Rapporteur
Selection of topic
METHODS
Co-Rapporteurs, from
from Spain
Spain and
and Sweden,
Sweden, were
were appointed
appointed by
by the
the
Co-Rapporteurs,
Committee for
for Proprietary
Proprietary Medicinal
Medicinal Products
Products (CHMP)
(CHMP) Efficacy
Efficacy Working
Working
Committee
Party (EWP).
(EWP). Based
Based on
on the
the complexity
complexity of
of the
the disease,
disease, internal
internal and
and
Party
external experts
experts were
were also
also involved.
involved.
external
The following
following issues
issues were
were considered
considered when
when updating
updating the
the guideline:
guideline:
The
1) Implementation
Implementation of
of updated
updated clinical
clinical guidelines;
guidelines;
1)
2) Implementation
Implementation of
of new
new scientific
scientific knowledge
knowledge (e.g.
(e.g. epidemiological
epidemiological and
and
2)
pathophysiological information;
information; reversibility
reversibility test
test of
of pulmonary
pulmonary function
function in
in
pathophysiological
COPD patients
patients and
and possible
possible influence
influence on
on outcome;
outcome; severity
severity staging
staging of
of
COPD
the disease;
disease; definition
definition of
of exacerbation
exacerbation and
and severe
severe exacerbation);
exacerbation);
the
3) usefulness
usefulness and
and validation
validation of
of biomarkers;
biomarkers;
3)
4) updated
updated requirements
requirements for
for pivotal
pivotal study/ies,
study/ies, including:
including: a)
a) possible
possible
4)
influence of
of concomitant
concomitant pharmacological
pharmacological (e.g.
(e.g. acetylcysteine)
acetylcysteine) and
and nonnoninfluence
pharmacological treatments
treatments (e.g.
(e.g. smoking
smoking cessation,
cessation, surgical
surgical
pharmacological
measurements, physical
physical action,
action, pneumo-sport);
pneumo-sport); b)
b) standardisation
standardisation of
of
measurements,
clinical trials,
trials, recommendation
recommendation of
of primary
primary [e.g.
[e.g. rate
rate of
of moderate/severe
moderate/severe
clinical
exacerbations, pre-bronchodilator
pre-bronchodilator Forced
Forced Expiratory
Expiratory Volume
Volume in
in one
one
exacerbations,
second (FEV1)]
(FEV1)] and
and secondary
secondary endpoints;
endpoints; c)
c) critical
critical discussion
discussion of
of active
active
second
controlled clinical
clinical trials
trials vs.
vs. placebo-controlled
placebo-controlled trials;
trials; d)
d) discussion
discussion on
on
controlled
clinically relevant
relevant differences
differences in
in key
key endpoints;
endpoints; e)
e) duration
duration of
of pivotal
pivotal
clinically
studies;
studies;
5) Discussion
Discussion of
of safety
safety requirements
requirements (e.g.
(e.g. investigation
investigation of
of drug
drug
5)
interactions, data
data on
on renal
renal and
and hepatic
hepatic dysfunction);
dysfunction); and
and
interactions,
6) implementation
implementation of
of pharmaceutical
pharmaceutical particularities
particularities [need
[need of
of spacer
spacer
6)
development in
in case
case of
of orally
orally inhaled
inhaled treatment
treatment with
with Metered
Metered Dose
Dose
development
Inhalers (MDI’s),
(MDI’s), statement
statement of
of orally
orally inhaled
inhaled treatment
treatment and
and flow
flow rate
rate
Inhalers
dependency].
dependency].
RESULTS
The first
first step
step included
included the
the elaboration,
elaboration, adoption
adoption and
and consultation
consultation of
of the
the
The
concept paper
paper EMEA/CHMP/EWP/8197/2009
EMEA/CHMP/EWP/8197/2009 (need
(need for
for revision
revision of
of the
the
concept
COPD guideline).
guideline). The
The preliminary
preliminary concept
concept paper
paper was
was circulated
circulated to
to
COPD
interested learned
learned societies
societies and
and patients
patients associations
associations on
on February
February 2009.
2009.
interested
Any organisation
organisation or
or individual
individual was
was allowed
allowed to
to submit
submit comments
comments using
using aa
Any
publicly available
available template.
template. The
The first
first step
step ended
ended on
on 31st
31st May
May 2009.
2009. The
The
publicly
second step
step (ongoing)
(ongoing) includes
includes the
the drafting
drafting of
of the
the guideline
guideline and
and further
further
second
consultation and
and adoption.
adoption. Three
Three versions
versions were
were drafted
drafted and
and internally
internally
consultation
discussed at
at the
the EWP
EWP before
before aa final
final version
version was
was agreed
agreed in
in the
the July
July 2010
2010
discussed
EWP meeting.
meeting. The
The draft
draft revised
revised guideline
guideline has
has been
been released
released for
for
EWP
consultation. Deadline
Deadline for
for comments
comments is
is March
March 2011
2011 (Figure
(Figure 2).
2).
consultation.
Figure 2. Draft guideline
*
*
* Comments to the drafted revised guideline can be sent to the
[email protected]
CONCLUSIONS
ACKNOWLEDGEMENTS
The
The update
update of
of European
European guidelines
guidelines on
on clinical
clinical investigation
investigation follows
follows aa well
well established
established
public procedure
procedure in
in which
which many
many agents
agents are
are involved
involved (Rapporteurs,
(Rapporteurs, EWP
EWP members,
members,
public
CHMP, internal
internal and
and external
external experts,
experts, interested
interested parties
parties and
and individuals).
individuals).
CHMP,
AA final
final version
version of
of the
the COPD
COPD Guideline
Guideline can
can be
be expected
expected by
by end
end 2011.
2011.
POSTER: 37
37
POSTER:
Thanks to
to the
the clinical
clinical experts
experts consulted
consulted during
during the
the
Thanks
elaboration of
of this
this draft,
draft, Dr
Dr F.J.
F.J. García
García Río,
Río, Hospital
Hospital La
La
elaboration
Paz, Madrid,
Madrid, and
and Dr
Dr G.
G. Peces
Peces Barba,
Barba, Fundación
Fundación Jiménez
Jiménez
Paz,
Díaz, Madrid.
Madrid.
Díaz,