7 Regulating clinical trials
| (34128)
12751/12
+ ADDs 1-3
COM(12) 369
| Draft Regulation on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC
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| Legal base | Articles 114 and 168(4)(c) TFEU; co-decision; QMV
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| Department | Health
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| Basis of consideration
| Minister's letters of 23 September and 26 November 2013
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| Previous Committee Reports
| HC 83-v (2013-14), chapter 4 (12 June 2013);
HC 86-xxxix (2012-13), chapter 7 (24 April 2013);
HC 86-xvi (2012-13), chapter 7 (24 October 2012);
HC 86-xi (2012-13), chapter 9 (5 September 2012)
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| Discussion in Council
| No date set |
| Committee's assessment
| Politically important |
| Committee's decision
| Not cleared; further information requested
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Background and previous scrutiny
7.1 Clinical trials provide essential information
on the safety, efficacy and therapeutic benefits of particular
drug treatments and increasingly involve participants at different
trial sites across a number of Member States. Since 2004, the
authorisation and conduct of clinical trials within the EU has
been regulated by the Clinical Trials Directive. The Commission
believes that the Directive has improved the safety and ethical
soundness of clinical trials across the EU, as well as the reliability
of the data obtained. However, it also acknowledges that, since
its entry into force, the Directive has increased costs and contributed
to a decline in clinical trials in the EU, describing it as "arguably
the most heavily criticised piece of EU legislation in the area
of pharmaceuticals."[25]
7.2 The draft Regulation would repeal the Directive,
introduce a new and less costly authorisation procedure, and seek
to ensure that the rules governing the conduct of trials are differentiated
to take account of the degree of risk associated with each trial.
An EU portal, linked to a database, would provide a single point
of entry for the submission of all the information needed to assess
the therapeutic and public health benefits of a proposed clinical
trial, as well as potential risks to patients taking part in the
trial. The EU portal would be used for all clinical trials.
For trials involving more than one Member State, a single 'reporting
Member State' would be responsible for making an initial assessment,
taking into account any views communicated by other Member States
in which the clinical trial is proposed to take place. Each Member
State would be responsible for assessing those aspects of the
draft Regulation which the Commission describes as "intrinsically
national, ethical or local" — these include the well-being
of those participating in the clinical trial and requirements
for obtaining their informed consent, the suitability of the clinical
trial site and of those conducting the trial, and compensation
arrangements.
7.3 In an attempt to reduce the financial burden
associated with clinical trials, the Commission draws a distinction
between 'low intervention' clinical trials (where the risk to
participants only marginally exceeds that already inherent in
normal clinical practice) and others where there may be additional
risk. For the latter, each Member State would be required to
set up a national indemnification mechanism, which would operate
on a not-for-profit basis, in order to help non-commercial sponsors,
such as academics involved in medical research, to obtain the
necessary insurance cover as premiums in the commercial insurance
market have (the Commission suggests) become unaffordable.
7.4 The Government welcomes the draft Regulation,
supports the introduction of "a proportionate and risk-adapted
approach" to clinical trials, and considers that it has the
potential to reduce regulatory, administrative and financial burdens.
Whilst endorsing the use of a single EU portal for all clinical
trial applications in the EU, the Government has pressed for a
clearer description of how the single authorisation procedure
would work, focusing in particular on the relationship between
the reporting Member State and other Member States likely to be
involved in a clinical trial. It has questioned the need for
each Member State to establish a national indemnification mechanism
for clinical trials which are not considered to be low risk, as
well as the Commission's proposal to carry out inspections. Our
earlier Reports provided a detailed overview of the draft Regulation,
the Government's position and the views of stakeholders.[26]
7.5 We have noted that there is a broad consensus
on the need to change the existing regulatory framework for clinical
trials within the EU and that the Commission's proposal appears
to be on the right track. We have asked the Government to provide
progress reports on negotiations which address, in particular,
possible improvements to the assessment and authorisation procedure
proposed by the Commission, the strength of the case for a national
indemnification scheme (or suitable alternative to contain the
costs of insurance cover), and the nature of the inspections to
be carried out by the Commission.
The Minister's letters of 23 September and 26
November 2013
7.6 In his first letter, the Parliamentary Under-Secretary
of State for Quality (Earl Howe) provides a helpful update on
the progress of negotiations within the Council and the European
Parliament. Turning first to the European Parliament, he notes
that the lead Committee (ENVI) unanimously adopted 290 amendments
to the Commission's original proposal and that its rapporteur
has a mandate to begin trialogue discussions with the Council
and Commission with the aim of reaching an "agreement in
principle" before the end of the year. He continues:
"One of the main concerns
of the European Parliament is to ensure increased transparency
on clinical trial data and a number of amendments have been made
in this area. These include specifying in the Regulation the content
of the summary of clinical trial results that will be made public
for every clinical trial in the EU and obliging marketing authorisation
holders to publish clinical study reports that have been submitted
in support of a marketing authorisation application within one
month of a regulatory decision having been made. I support these
amendments which I believe will increase transparency."
7.7 The Minister reports that there have been significant
developments within the Council of Ministers and that the Lithuanian
Presidency "is also working towards an agreement in principle
with the European Parliament before the end of 2013." The
Minister supports "speedy progress" to improve the way
in which clinical trials are authorised across the EU and expresses
confidence that negotiations are proceeding in line with the Government's
negotiating objectives. He sets out the Government's position
on two of the key issues in the negotiations: inspections led
by the European Commission, and the introduction of a national
indemnification mechanism. On the former, he explains:
"The European Commission
proposes audits of third country regulatory systems to ensure
that they comply with principles similar to the Regulation, as
well as audits of Member States to verify that compliance with
the Regulation is correctly supervised. I wrote to you that the
Government was seeking further clarifications on the need for
these provisions.
"It has now become clear
that the European Commission's role will be limited to the audit
of Member States' regulatory systems, whilst the inspection of
clinical trial activity will remain a responsibility of the Member
States. I consider that these audits can play a useful role in
ensuring harmonised implementation of the Regulation across Member
States, which has been one of the difficulties under the current
Directive. The joint assessment process for multi-state trials
increases the importance of ensuring that all Member States apply
the Regulation in a consistent way.
"As for third country
audits, I consider that these could help increase our knowledge
of whether clinical trial data has been generated in a regulatory
system that ensures subject safety, subject rights and data reliability.
This is important because clinical trial data from third countries
is used in support of Marketing Authorisations. This will however
not take away the need to decide whether an inspection of clinical
trial activity needs to be triggered in a third country when an
application for a marketing authorisation is assessed.
"For the reasons above,
I support the principles of the Commission proposal."
7.8 As regards the Commission's proposal to require
Member States to introduce national indemnification mechanisms
(not-for-profit, government-run schemes aimed at non-commercial
clinical trials), the Minister recalls the Government's initial
scepticism as to their effectiveness and sustainability. He
continues:
"I have explored the
need for a scheme through a public consultation and a further
specific survey of stakeholders on insurance practice and have
concluded that the Government should oppose the obligation to
set up a National Indemnification Scheme.
"The Commission's impact
assessment in this area is weak and is based on one report which
found that premiums for insurance of commercial trials have increased
by 800%. The same report states that this increase was not seen
in academic research. The evidence that the Commission uses in
its impact assessment does not therefore seem to support the rationale
for its proposal which is aimed at academic researchers. My officials
have raised this with the Commission but the Commission has been
unable to provide further evidence that would support their proposal
for a National Indemnification Mechanism.
"The outcomes of the
public consultation did not give me a clear picture of the actual
size of the problem as it relates to the UK. My officials have
therefore circulated a survey to all respondents to the public
consultation to ascertain how much the scheme would be used, to
get a better idea of the impact on resources and to better understand
problems in insuring clinical trials. 30 responses were received,
the majority of which from non-commercial researcher. Respondents
gave very clear signals in a number of areas:
· Premiums appear not
to have risen in the past 10 years. On the contrary, many respondents
indicated they had seen a decrease in premiums over the last decade.
This does not support the Commission's suggestion of an 800 percent
increase;
· Sponsors do not generally
appear to experience difficulties obtaining insurance. Some respondents
did raise that it is sometimes difficult to obtain insurance for
multi-state trials but this is a consequence of the obligation
in some Member States to take out national insurance;
· Insurance is not perceived
as a hurdle for the conduct of trials in the UK;
· There does not appear
to be a lack of competition in the UK clinical trials insurance
market. Respondents indicated that they had sufficient choice
in insurers. This does not support the Commission suggestion that
sponsors have limited choice in insurance;
· Claims appear to have
been limited but could potentially be high. Although respondents
indicated that pay outs have been limited, one respondent referred
to a pay out of £500,000;
· It is not evident
that sponsors would actually use the national indemnification
mechanism. Many respondents said that [they] this would depend
on whether the conditions would be similar to their current insurance
and some said they would only use it if it was free of charge.
"The outcomes of the
survey do not confirm that there is an insurance problem as suggested
by the Commission. The evidence that has been gathered by my officials
demonstrates that the insurance market for clinical trials is
working in the UK and that insurance is not generally considered
a problem by sponsors.
"Based on the evidence
gathered I can only conclude that the Commission is seeking a
solution for a problem that does not exist, at least not in the
UK. Moreover, I have concerns about how the scheme would be able
to sustain itself when the Government would not be able to charge
academic sponsors. Commercial sponsors would need to pay for the
scheme but they have indicated that they have no interest in the
scheme. The costs of pay-outs and for running the scheme would
have to be borne by the Government. The UK is not alone in these
concerns. Discussions in Council have demonstrated that there
is no support from Member States."
7.9 The Minister's second letter explains that the
Lithuanian Presidency has been given a mandate by the Council
to start trialogue negotiations with the European Parliament and
the Commission. He continues:
"The Council's position
largely reflects the Government's negotiating objectives as outlined
in my Explanatory Memorandum of 6 August 2012. One point of concern
that remains is the timelines for authorising clinical trials
which a majority of Member States would like to see lengthened.
With David Willetts, Minister of State for Universities and Science,
I have written to Ministers across the EU to urge them to agree
competitive timelines that promote research in Europe.
"Given the helpful position
of the European Commisison and European Parliament on this issue,
I am hopeful that the trialogue negotiations will lead to an agreement
on sensible and globally competitive timelines for authorising
clinical trials. My officials continue to engage with MEPs, the
Presidency, the Commission and stakeholders on timelines and other
issues as the negotiation progresses."
7.10 The Minister undertakes to write again once
the outcome of negotiation is clearer and expects, at that stage,
to ask us to lift our parliamentary scrutiny reserve.
Conclusion
7.11 We thank the Minister for his progress reports
and note that there is the prospect of an agreement in principle
on the draft Regulation before the end of the year. Before agreeing
to lift our scrutiny reserve, we will wish to receive further
information from the Minister on:
· the changes that
have been made to the procedure for authorising clinical trials
(including the relevant timescales) and, in particular, how the
Member State carrying out the initial clinical assessment will
take into account the views of other Member States in which a
clinical trial is proposed to take place;
· whether the Commission's
proposal for the introduction of a national indemnification mechanism
for certain types of clinical trials will be retained in the draft
Regulation or, if not, what will replace it;
· any other significant
changes to the Commission's original proposal; and
· his assessment
of the impact that the changes are likely to have on the authorisation,
conduct and publication of the conclusions of clinical trials
in the EU, as well as the availability of clinical trial data.
7.12 Meanwhile, the draft Regulation remains under
scrutiny.
25 See p.17 of ADD 2. Back
26
See head note. The draft Regulation is also considered in some
detail in the Report of the House of Commons Science and Technology
Committee on Clinical Trials, Third Report (2013-14) HC 104. Back
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