Documents considered by the Committee on 4 December 2013 - European Scrutiny Committee Contents


7 Regulating clinical trials

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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
Legal baseArticles 114 and 168(4)(c) TFEU; co-decision; QMV
DepartmentHealth
Basis of consideration Minister's letters of 23 September and 26 November 2013
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)

Discussion in Council No date set
Committee's assessment Politically important
Committee's decision Not cleared; further information requested

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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Prepared 11 December 2013