E-drug: ISDB on EU consultation on child medicines
-------------------------------------------------------------------------
Dear colleagues,
The International Society of Drug Bulletins (ISDB) and the proposed
regulation for medicines in children.
Too much emphasis on medicines and not enough on health needs.
All the more reason to switch EMEA from DG Trade to DG Health
and Consumer Protection.
Preamble
The ISDB welcomes the Commission's decision to raise the issue of
medicines in children. Clinical research on independently agreed
needs in children is lacking. Some drugs are approved in children
despite poor evaluation in this population. Sometimes drugs are
used without proper approval (off-label use), without dose finding
studies and child formulation. As in the elderly, treatments for
serious illnesses are often inadequately studied. So encouraging
research in children is a welcome move, provided that trials to be
encouraged are for treatments for which there is a need as
established independently of industry. To begin with, an inventory
of current practices and needs should be drawn up, based on
experience (especially off-label use) in all EU countries, as well as in
Central and Eastern European countries. Such trials should be
subsidised or completely paid for by public funds - which would
also imply that the data from the trial would be public 'property',
certainly not a company's intellectual property. That would apply
with special force to drugs that are not, or no longer, in patent.
Such trials of generic drugs are needed to underpin clinical use of
many important drugs. They should be encouraged at least as much
as trials of patented drugs.
We warn against repeating the same errors as in adults. Indeed,
many drugs for adults are useless, or me-too products. Some of
them are poorly studied, and others are too risky. Admittedly, drug
consumption is too high in adults, non-drug options are disregarded,
and some patients are not given essential drugs.
The Commission's move is a good opportunity to perform better in
terms of selection of helpful medicines and appropriate evaluation,
as defined in the ISDB Declaration on Therapeutic Advance in
Medicines. More attention should be drawn to information to
professionals and the public, and to drug packaging. We encourage
the creation of a European Paediatric Therapeutic Formulary based
on essential drugs and real health needs in children, and not only a
further market niche.
True, there are around 75 millions children in Europe, but most of
them do not need drug treatments. Worse, they probably receive
too many antibiotics, cough medicines, antidepressants, etc. We
would like to stress that rational drug use, including wrong use,
overuse or lack of use, should start in children. The Commission
should be wary of strengthening the belief that medicines are the
only solution to all health problems. On the other hand, many
serious illnesses are not treated at all, or treated with inadequately
established drugs (for example in children with cancer,
cardiovascular diseases). Advances such as those of formulations
for some antiepileptics are uncommon.
In order to have treatments that meet real health needs, the expert
group who will decide on the choice of essential drugs and should
include paediatricians working in hospital and the community,
general practitioners, pharmacovigilance experts, as well as
public-health scientists. We welcome the Commission's commit-
ment towards greater transparency in regulation of medicines in
children, but fail to understand why the same should not apply to
adults as well. We also fail to understand why transparency of R&D
costs is not ensured. The cost of clinical trials as stated in the
Commission's proposals is overestimated and lacks hard evidence,
even if we consider the need for pharmacokinetic and dose finding
studies, 2 or 3 well conducted trials, and formulation studies. A
reasonable price could be granted, however, for drugs concerning
few children (as in orphan drugs), provided that transparency of trial
results and R&D cost is ensured.
The extension of patent protection is an inappropriate measure
because it does not direct research towards useful innovation and
proper use of existing drugs. Moreover such incentives are difficult
to control: the US 'pediatric exclusivity' provision is estimated to
give companies six times the amount in return of the money
invested. It creates a lucrative incentive for companies to test their
most valuable drugs on children, rather than those drugs most
needed.
ISDB COMMENTS ON THE COMMISSION'S PROPOSALS
1. Incentives for research
The ISDB agrees that appropriate studies for medicinal products for
which protection of intellectual property exists should be
encouraged. [See below for definition of appropriate clinical trials]
But we are against systematically introducing an additional period of
market exclusivity as a reward for submitting one or more validated
clinical studies on children of one or more age groups.
We believe incentives should be based on drug price. Reasonable
prices should be offered as a reward for medicines that provide
substantial therapeutic advance compared to existing options, on
conditions that appropriate clinical trials are done and transparency
of trial results and R&D cost is ensured. Unless these conditions are
met, we urge governments and organisations paying for medicines
to refuse reimbursement of these products for children.
The ISDB welcomes the performance of appropriate studies for
already marketed medicinal products for which no intellectual
property exists, on condition that well designed clinical trials are
carried out (see definition below) and trial results are made public.
We welcome the Creation of a fund by the European Community,
whose resources should be dedicated to appropriate research and
clinical trials for inadequately treated illnesses in children. This fund
must be managed by representatives of the public and professionals
with no links with industry. A control procedure must be set up by
a Commission of the EU Parliament to check that resources are
dedicated to public-health need priorities. We understand that this
fund would be partly fuelled by EU citizens' money. So drug
companies benefiting from the fund must be requested to ensure
access to trial data and transparency of R&D costs when
negotiating drug prices.
2. New applications for marketing authorisations - legal requirement
for clinical trials in children
We think research needs should be defined according to public
health priorities. Need identification must be ensured in
collaboration with expert paediatricians having no links with
industry. Many drugs are currently used off the label. This
experience must be evaluated and used in the design of clinical
trials.
What are appropriate clinical trials?
Clinical trials are difficult to carry out in children. Parent consent
may be hard to get, and the number of patients is often lower than
in adults. So it is even more important than in adults that strict
methodological and ethical requirements are met. The questions
tested must be clinically relevant, which means for example that
equivalence trials must not be authorised. Trial designs must be
robust and capable of producing strong evidence. Unblinded trials or
trials with ill-chosen comparator drugs, or non-comparative trials
must not be authorised. Non comparative trials must not be
authorised as well. Enrolment criteria must be strictly defined to
avoid problematic subgroup analysis. Pharmacovigilance based on
long-term follow-ups must be requested, especially in children
treated with anticancer agents, or with drugs whose long-term
toxicity is unknown but suspected.
We welcome the Use of the database foreseen by Directive
2001/20/EC for information on clinical trials.
But we recommend that the European Community set up a trial
registry of all trials (completed or not) done in children. Every trial
should be registered at inception. The child trial register must be
regularly updated, showing whether the trial has begun, is still
continuing or has been completed. It should be made accessible to
health-care professionals and the public.
4. Developing European excellence - establishment of an EU
scientific expert group
Based on past performance of the European agency, the ISDB is
very sceptical about the creation of an EU expert group or working
party within the European Medicines Evaluation Agency (EMEA)
with specific responsibility for all aspects relating to the
development, availability and follow up of paediatric medicines.
Unless this working group includes a majority of representatives of
the public and professionals with no links with industry, we would
oppose its creation within the EMEA.
5. Encouraging submission of trials in Europe that have been
accepted internationally
Avoiding duplicating clinical trials is a legitimate concern. But as in
adults the relevance and the quality of these internationally
accepted trials must be guaranteed, notably through properly
implemented ICH paediatrics guidelines, strict supervision of trials
and implementation of Good Clinical Practices. These conditions are
not routinely fulfilled in all countries. This proposal assumes that
trials can be (or will be) submitted only by pharmaceutical
companies applying for market authorisation. There seems however
to be no reason why other interested parties should not submit
relevant trial data - e.g. professional bodies, or academic
institutions. ISDB suggests that submissions from such sources
should be explicitly encouraged too.
6. Post-authorisation issues - possible need for long term follow-up
We understand that the Commission's proposals have added
pharmacovigilance as the traditional icing on the cake. More than in
adults, pharmacovigilance must be planned when designing clinical
trials (see above). EU citizens and professionals caring for children
must have easy access to pharmacovigilance data, if only to
encourage proper reporting of adverse events. Pharmacovigilance
requirements must be part of drug pricing negotiations.
7. Creation of a Pan-European network of clinical excellence for
performance of paediatric studies
ISDB supports this proposal, but such a network should include
physicians in primary care (GPs) as well as paediatricians, because
far more prescriptions for children are written in primary care than
in specialist paediatric practice. As part of the network one or more
training centres for investigators should be established. At present
most countries have few trained and experienced clinicians who can
perform good clinical studies.
Christophe Kopp
ISDB president
for ISDB members in Europe
christophe.kopp@wanadoo.fr
www.isdbweb.org
--
To send a message to E-Drug, write to: e-drug@usa.healthnet.org
To subscribe or unsubscribe, write to: majordomo@usa.healthnet.org
in the body of the message type: subscribe e-drug OR unsubscribe e-drug
To contact a person, send a message to: e-drug-help@usa.healthnet.org
Information and archives: http://www.healthnet.org/programs/edrug.html