Science and Technology CommitteeWritten evidence submitted by Ethical Medicines Industry Group (EMIG)

Summary

This submission is based on a paper submitted by EMIG to the EMA as part of the on-going work to determine a holistic approach to the release of clinical trial data that meets the needs and addresses the concerns of all stakeholders.

With regard to Marketing Authorisation Applications (MAA) EMIG supports the principle of the intent to publish clinical research data once a regulatory opinion has been given on a MAA (or variation thereof). There are however significant issues that need to be addressed in order for this process to be holistic and robust. These are:

To ensure the integrity of “raw” data re-analyses, there should be a “gate-keeper” function and requests for data release should be accompanied by a clear prospective “project plan”.

A critical issue is how this would operate and be funded.

Plans must be implemented to mitigate the risk of unfair competition for products which rely on data protection.

Consideration could be given to extending and standardising the time for data protection of SPCs, potentially through an ICH mechanism.

The incentives to innovate must be maintained, but with due consideration given to fair competition and overall medicines affordability.

EMIG welcomes the opportunity to engage constructively with the Science and Technology Select Committee, the MHRA, EMA and other organisations to design, implement and manage a “clinical research data release” system that meets the needs of all stakeholders in healthcare, most important of which are patients.

Introduction

1.1 The Ethical Medicines Industry Group (EMIG) welcomes this opportunity to submit to the Science and Technology Committee inquiry into Clinical Trials. This paper was authored by Dr Mark Edwards, EMIG R&D Director, with significant input from the EMIG membership, who collectively represent multinational and specialty pharmaceutical companies, and organisations with specific legal and biostatistical expertise.

1.2 EMIG is the biopharmaceutical trade association that represents the interests of over 200 companies and organisations, mostly SMEs, based in the UK. Our members range from start-ups, whose prime focus is often research and development (R&D), to highly developed businesses delivering essential products to patients and health services in the UK and internationally. Whilst providing important medicines to patients, the small and mid-sized life sciences industry is also a significant contributor to the UK economy. In the UK, SMEs constitute approximately 90% of the total number of biopharmaceutical companies and it is estimated that 80% of innovation is derived from these small companies. EMIG member companies employ approximately 20,000 people in the UK and have a combined annual turnover of £4 billion.

1.3 This paper aims to articulate a holistic perspective on the issue of data release from clinical trials. It aims to be constructive, fair and balanced, in order to facilitate a progressive dialogue.

1.4 EMIG would be delighted to give oral evidence to the Select Committee if it would be valuable or if any of the points in this submission require further detail.

The European Commission’s Proposed Revisions to the Clinical Trials Directive

2.1 EMIG is a member of the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), which represents small to medium-sized companies and associations operating in Europe. As a member, EMIG supports EUCOPE’s position in response to the European Commission’s Clinical Trials Directive.1 The Commission’s proposal foresees a new assessment process for clinical trials which would provide for less reporting, lower insurance costs and shorter timelines. This approach is broadly welcomed. We believe that the new regulation will help to speed up the approval process and increase the number of clinical trials conducted in the EU, whilst at the same time ensuring patient safety.

2.2 Whilst welcoming the proposed revisions, EMIG believes there are points requiring further clarification, namely:

(a)The protection of commercially confidential data in the new database;

(b)The inclusion of ethical aspects in the assessment procedure;

(c)The consideration of the specifics of clinical trials in rare and ultra-rare diseases when applying the provisions of the Regulation;

(d)The informed consent requirement in emergency situations;

(e)Establishment of one language for the application dossier for the complete procedure.

Transparency and Disclosure of Clinical Data

The EMIG “base case”

3.1 First and foremost in setting the regulatory framework for clinical trials are patients. Patients who volunteer to take part in clinical research, where the risk/benefit of an experimental medicine or the effectiveness of an approved product may not be established and doing so is therefore the primary objective of the study, or programme of studies must be respected and protected. Patients with serious, life-shortening or terminal diseases also frequently take part in clinical research with the knowledge that they may not directly derive long-term benefit from their participation, but do so out of a sense of altruism. They may, for example, have themselves derived quality- and/or quantity-of-life benefits from medicines that previous patient volunteers helped to research. In turn, they may now wish to play their part to help future patients to benefit from advances in medicines. Being able to understand what conclusions were made from their participation in clinical research, to share learnings with other patients, and to know that other researchers would be able to progress research further as a consequence of their participation, are all important issues for patient volunteers.

3.2 In the UK, the Faculty of Pharmaceutical Physicians has publicly advocated full publication of study results for some time.2 Contained in this document are two explicit statements regarding the publication and sharing of the results of clinical research:

“Publication

There should be openness and honesty in sharing the results of research. It is unethical to withhold the publication of any results of research on any pharmaceutical product whether the results are positive, negative or inconclusive.

Sharing Findings

All studies should be performed to increase knowledge in some useful way, and there should be openness and honesty in the sharing of this knowledge with the wider world. Study findings need to be communicated, whatever the outcome, for the benefit of the community at large. The sponsor should have a clear policy regarding study publication which should be agreed with the clinical researcher prior to study initiation, and neither the sponsor nor the researcher should seek to prevent publication or the admission of trial results within the public domain. Communications on clinical studies must be a correct objective representation of all the findings, allowing others, in their turn, to give well-balanced risk-to-benefit advice to patients and their families. It is especially important that negative results or adverse safety data are communicated to regulators and clinicians in a timely manner where this information may affect prescribing practices and the protection of patients.”

3.3 EMIG fully endorses these statements and believes that all sponsors of all types of clinical research have a fundamental duty to patient volunteers to ensure that the results and conclusions from all clinical research (including post-marketing studies in industry) in which they have participated should be made publicly available in the form of Sections 1–15 of ICH-3 compliant Clinical Study Reports (CSRs).3

3.4 We believe that the EMA proposals demonstrate a step-change further to the above, inasmuch its intent is to publish “raw” clinical research datasets, which, inter alia, will therefore contain patient-level data. We do not believe this is problematic as long as the process for data release is designed, implemented and managed carefully (see below). We would like to see the Science and Technology Select Committee join with organisations like EMIG to ensure the proposals can be implemented in a way that can offer real benefits to patients and introduce a new openness in the clinical trial environment.

3.5 Notwithstanding our belief that the EMA could have explained the rationale for its intent to release clinical trial data much more clearly than it chose to do, we understand that this is predicated fundamentally by the growing expectation within the EU Commission over the last few years, that all EU public organisations will move from a default position of privacy, to one of openness. Accordingly, the EMA is mandated to move from, “why should we support open access?” to “why shouldn’t we support open access?”. The key reason however, where open access should not be supported by the regulators, is where the needs of transparency are outweighed by important, but temporary, confidentiality aspects that would impair the ability to continue objectively to research the intervention under study.

3.6 In terms of the topic under discussion here therefore, it must be up to the data’s sponsor organisation to articulate the objective scenarios where release of clinical research data would be to the detriment of the continuity of ongoing research and to gain timely agreement on that with the EMA. In this instance, EMIG regards a “refusal to play ball” as not credible, which should understandably be overruled. Otherwise, anyone can make the “detriment” argument and “because it is confidential it is not open to scrutiny”.

3.7 However, we would like the Science and Technology Committee to join with us to request clarity and confirmation from the EMA as soon as possible with regard to precisely what data is intended to be released. There is a considerable lack of understanding on this in organisations, which is a barrier to building a collective and progressive agreement on the way forward. There must, however, be a clear distinction drawn between data from clinical trials and other data such as highly commercially sensitive analytical or manufacturing methods that form a critical part of the Common Technical Document (CTD), that should not be released.

3.8 Our current understanding is that it is only the clinical research components of a regulatory submission that will be released. The non-clinical aspects eg structural, chemistry, manufacturing and control data are commercially sensitive and therefore are not for consideration.

3.9 However, even within this there needs to be a distinction made between “results” and “raw” data. With the former, we believe all companies should be encouraged to state that they will release all primary and secondary parameters and safety data, as well as protocol details, selection parameters, demographics and analysis plans in a specific minimum timeframe. The release of raw data-sets represents an entirely different scenario and needs special consideration (see below).

3.9.1Overall, we believe that measures which will increase transparency in clinical research could prove to be valuable in driving better-designed and more cost-effective clinical development programmes. For example, it could enable clinical trial programmes to be designed more quickly and targeted more effectively to the likely responsive patient populations, thereby complementing the increasing focus on personalised medicine. It could also correspondingly reduce the number of unnecessary clinical development programmes, with benefits to patient safety and R&D portfolio budget management. Furthermore, clinical trial planning would be improved through wider access to data on variability of data and effect sizes, which would enable more informed sample size calculations to be conducted. Patient safety would also benefit from the enhanced ability of researchers to access full data-sets to assess safety signals. It is recognised that such independent analyses, but often using less robust information, occur now. Sub-optimal analyses can only inevitably lead to sub-optimal conclusions and sometimes these will be dangerous to public health. Routine controlled access to fuller data-sets will help avoid these disasters. For HTA purposes, the existence of full study results or study data would improve the quality of evidence synthesis reviews through the provision of more complete data. This should result in more accurate inputs to health economic models thereby enhancing assessment of cost-effectiveness of products.

3.9.2Accordingly, we support fully the principle of the EMA’s intent to publish clinical research data once it has issued an opinion (negative or positive) on a drug’s marketing authorisation application, or subsequent variations.

3.9.3However, there exists a number of legitimate concerns for industry, which largely centre on the “why”, “who” and “when” aspects of such data release. These are elaborated below, together with potential solutions. Our principal request is that a robust “gate-keeping” process is developed and implemented to ensure that the release of clinical research data and in particular, “raw” data-sets, is done in a manner that safeguards its integrity and acknowledges the concerns below. We assert that it is to no one’s benefit, and in particular, regulatory authorities, to support uncontrolled “fishing” expeditions for data by any type of organisation (public, private or charitable). This is not about data release per se, but rather the separate concerns about selective reanalysis.

3.9.4Making an analogy therefore, to the pharmaceutical formulation of many medicines that has helped thousands of patients over the years, we believe that it will be the “controlled release” of clinical research data that is key to meet the needs and aspirations of all stakeholders.

Concerns and Ideas for Solutions

4.1 Whilst all sponsors of clinical research should be open to sharing publicly all of the information used to design, execute and report it, in terms of that proposed for release by the EMA, EMIG believes data-sharing needs to be carried out with all due attention paid to the method of release. For example, full open access could be envisaged for data where key parameters have been analysed. Safety data specifically should also follow this route. As mentioned above, ideally all companies should be willing to do this, and this shouldn’t require EMA “management”.

4.2 However, where raw data-sets are being considered for release, this must follow a controlled process, with well-constructed, prospective requests made by an “applicant” to a future “gatekeeper” authority. Inter alia, these requests need to articulate clearly the hypothesis to be tested and its analysis plans. In turn, there may be a role for the company and the EMA to review these reanalyses together, subsequently to reassess the validity and benefit/risk of a product as a result.

4.3 In simple terms, having a well-meaning, but less than regulatory-standard re-analysis of benefit/risk performed, could compromise or even seriously risk patient safety. A fully open uncontrolled “free for all” access to data also risks the dangers of “cherry-picking” parts of the full dataset, which could give rise to erroneous conclusions and consequently to not evaluating the “whole” and putting the new results in their correct context.

4.4 In addition, we are concerned that should selective data re-analyses be allowed in an uncontrolled manner, there is a serious risk of undermining the careful prior work of and conclusions on benefit/risk made by the regulatory agencies. These reviews are hugely thorough in terms of the time taken carefully to review submission dossiers and the number of highly detailed questions for clarification that are sent to the sponsor as a consequence. Every bit of the regulatory review process is designed to ensure the very best understanding of a new product’s benefit/risk, which of course is fundamental to safeguard patients. A priori therefore, this must not be put at risk by making allowance for open selective data re-analyses.

4.5 To mitigate these risks, EMIG therefore proposes that a robust, but straightforward “application” process is put in place for those wishing to access data. Similar to the process recently launched by GSK, data could be made available to requesters, following receipt of a prospective research proposal and analysis plan. This would need to include an independent peer-review via a central mechanism in order to decide if the data should be released. The obvious body to manage this is the EMA. However, we would question whether the EMA currently has the resource and the funding to do this? If not, what would the EMA’s “designate” body look like? How would this be funded? Funding therefore is a critical issue, not least because the small and mid-sized company sector ie the very sector that the European Commission seeks specifically to support in terms of its growth and sustainability, does not have the resources to fund such an undertaking. Additionally, the management of a large data repository would be very expensive and would need to be done properly.

4.6 One idea might be to look at the organisational principles of the Innovative Medicines Initiative (IMI), to assess the feasibility of a public-private partnership to establish an independent and collectively-funded third party to perform peer-review, and perhaps adjudicate disputes eg should secondary analyses suggest different results from an original clinical study report (CSR)?

4.7 A second concern surrounds the potential “commercial sensitivity” of clinical research data. At face value, if the intent is to publish only that part of a regulatory submission that relates to the clinical research ie the design methodologies, raw data and results, and NOT also other pre-clinical structural and formulation data which could be highly commercially sensitive, it is difficult to see what is truly commercially sensitive. Indeed, as highlighted above, there are potentially significant gains to be had by enabling access to more anonymised datasets.

4.8 Perhaps therefore the issue here is not so much the clinical data per se, but how it could be used by competitors in certain circumstances. For instance, not all products are covered by patents and instead, rely on data protection laws. The EMA has said that it will not allow submissions within the EU from anyone other than the Marketing Authorisation Holder (MAH), using data released after an initial application, but there is nothing to stop a generics company or anyone else from compiling an application package and submitting it in other territories. Without mitigation, this could have completely unintended consequences for EU patients; a scenario could be envisaged where EU submissions occur only after applications have been made in all of the other regions. This would achieve the unwanted outcome of putting EU citizens at the back of the queue for some new medicines.

4.9 Taking this one stage further, some have suggested that the only answer to the requirement for hard endpoint/outcome AND head-to-head superiority before the approval of drugs and full disclosure of all assets afterwards, is a radical overhaul of the patent system. Could this be a step too far? It is possible. But, what, in a new environment of open access to all clinical research data, could be done to achieve a balance that maintains fairly the incentives for inventors and their funders to continue to invest and innovate in the development of new health technologies; the rights of generic manufacturers to compete and national public health needs for cheaper medicines to achieve affordable overall medicines budgets?

4.9.1Suggestions include:

For products covered by data protection rules, the international regulatory authority community collaborates to put in place additional checks and audits world-wide to ensure that submissions comprise only studies conducted by the originator companies.

To extend the duration of the Supplementary Patent Certificate (SPC) so that the overall data protection is always 20 years.

An ICH Working Group is convened to address holistically the issue of data exclusivity.

4.9.2Importantly, this issue should not detract from the fundamental aims of achieving greater openness for clinical research data. Yet it is a key “covariable” for which a solution is needed in order to achieve full consensus among all stakeholders, and therefore progress for all. EMIG therefore requests that the Science and Technology Select Committee works with organisations such as the EMA to influence this happening.

February 2013

APPENDIX

EUCOPE SUBMISSION

EUCOPE Position on the Proposal for a Regulation on clinical trials on medicinal products for human use (COM 2012 369) and repealing Directive 2001/20/EC published by the Commission on 17 July 2012.

Summary

The Commission proposal foresees a new assessment process for clinical trials. This provides for less reporting, lower insurance costs and shorter timelines. EUCOPE generally welcomes this approach. We are convinced that the new regulation will help to speed up the approval process and—equally important—will increase the number of clinical trials conducted in the EU while at the same time ensuring patient safety.

Points that require further clarification are:

1.the protection of commercially confidential data in the new database;

2.the inclusion of ethical aspects in the assessment procedure;

3.that the specifics of clinical trials in rare and ultra-rare diseases are sufficiently considered when applying the provisions of the Regulation;

4.the informed consent requirement in emergency situations; and

5.establishment of one language for the application dossier for the complete procedure.

EUCOPE particularly welcomes:

1.the introduction of a single EU portal for the submission of data relating to clinical trials which is held by the European Commission and free of charge for sponsors;

2.the two-part assessment procedure, distinguishing aspects where Member States cooperate and aspects where each Member State acts individually;

3.the integration of the ethic evaluation in the assessment procedure. However, it might be helpful to clarify that ethical aspects and the decision of Ethics Committees are part of the assessment procedure in order to prevent duplication of assessments, compliance with timelines and the harmonization of documents (Annex I). Member States are free to choose the persons and the entity to review ethical documents set out in Annex I;

4.the adoption of the tacit approval and the withdrawal concept which will ensure compliance with the timelines;

5.the risk-based approach distinguishing between low-interventional clinical trials, general clinical trials and clinical trials with an advanced therapy investigational medicinal product. This distinction takes effect on the timelines, the reporting and the insurance requirements.

However, we see a need for amendments with regard to the following aspects:

A. Protection of Commercially Confidential Data in the New EU Database (Art. 78 COM Proposal)

Article 78 provides for the establishment of an EU database to enable the co-operation between Member State authorities which shall be publicly available unless the data is considered to be commercially confidential information (Art. 78(3)).

As data needed for the approval of a clinical trial often contains a significant amount of know-how and personal information it:

1.needs to be clearly defined what constitutes “commercially confidential information”; and

2.that intellectual property is considered automatically as commercially confidential; and

3.a consultation of the sponsor should be implemented.

1. Intellectual property of the sponsor

The protection of personal data for individual privacy, intellectual property, and commercially sensitive information is a core principle of EU and Member State legislation and is binding in particular for the European Commission when access to document legislation is concerned. Article 4(2) of Regulation 1049/2001 regarding public access to European Parliament, Council and Commission documents stipulates that “the institutions shall refuse access to a document where disclosure would undermine the protection of commercial interests of a natural or legal person, including intellectual property…” This clarification urgently needs to be included in the new clinical trial legislation as the Commission as the holder of the database should respect the intellectual property of sponsors as foreseen for example in Regulation 1049/2001 (see above).

Also, it should be borne in mind that the Commission only recently explicitly stated “that keeping valuable information secret is often the only or the most effective way that companies have to protect their intellectual property” (Public consultation on the protection of business and research know-how http://ec.europa.eu/internal_market/consultations/2012/trade-secrets_en.htm).

Therefore, the existing Article 78(3) of the Proposal should be amended as follows:

“... confidentiality is justified on any of the following grounds:

...

protecting commercially confidential information, including intellectual property;”

2. Definition of the term “commercially confidential information”

The general concept of transparency of information is fully supported by EUCOPE. However, it needs to be considered that even today a vast amount of information about clinical trials is publicly available on the EU Clinical Trials Register website (www.clinicaltrialsregister.eu—see attached screenshots). The published data fields are the following:

Identification of the clinical trial and the sponsor;

Identification of the medicinal product;

Identification of the indication under study;

General descriptive information on the clinical trial and the patient population included:

major objective, principal inclusion and exclusion criteria of the clinical trial,

phase of the clinical trial and design (eg randomised, controlled),

comparators (medicines/other treatments) if this is part of the clinical trial, and

number of patients anticipated in the clinical trial, age range(s) and gender.

(Communication from the Commission regarding the guideline on the data fields contained in the clinical trials database (2008/C 168/02))

This level of transparency is secured under the existing legal framework. The concept of transparency is generally welcomed by research-driven mid-sized pharmaceutical companies. The Commission’s view that the public needs access to additional information beyond what is already available (see examples attached) is comprehensible but needs to be debated on substance in the European Parliament and in the Council. It needs to be borne in mind that know-how and valuable confidential intellectual property especially regarding the manufacturing, certain technological approaches and certain data in the development of an innovative medicinal product are of crucial value. The European Court of Justice has stated in Case C 453/03 (ABNA) that the publication of detailed product data is against the principle of proportionality as far as the authorities dispose of such data. Therefore, such publication may not be justified by the objective of protecting public health. Without any protection of this value innovation might be impeded significantly. Clinical trials would even more than today be conducted in third countries in order to safeguard the innovation and the intellectual property. This would contradict the main objective of the proposal.

In order to provide for legal clarity and predictability for patients, industry and public bodies a definition would be advisable. EUCOPE suggests including the following definition into Article 2(31)—(new) of the Proposal:

“Commercially confidential information is considered to be any information, including know how, trade secrets and information which is not in the public domain or publicly available and where disclosure could undermine or damage the economic interest or competitive position of the proprietor of such information. Information contained in the investigational medicinal product dossier (IMPD) pertaining to the pharmaceutical and non-clinical pharmaco-toxilogical testing results and detailed clinical development plan other than the summary of the approved clinical trial protocol shall be considered as commercially confidential information.”

Whereas the EU largely safeguards that detailed regulatory data cannot be used by competitors before the data exclusivity period has expired, competitors could use this data in third countries with a less strict or even not existing data exclusivity regime.

3. Consultation of the sponsor

The concept of transparency regarding clinical trial data as put in practice today is welcomed by EUCOPE. This concept could be further discussed in case the protection of commercially confidential information is secured by a consultation of the proprietor of the information/the sponsor. Only the consultation of the sponsor safeguards that his know-how especially regarding the manufacturing and certain technological approaches in the development is protected. The Commission alone cannot assess this. Therefore, the consultation of the sponsor is mandatory.

The involvement and consultation of the proprietor of the information before dissemination is also foreseen by law in access to documents legislation. All EU institutions must consult third parties according to Article 4(4) of Regulation (EC) No. 1049/2001 (http://www.europarl.europa.eu/register/pdf/r1049_en.pdf) before the information can be disclosed in order to assess whether the content is commercially confidential. The same degree of involvement is foreseen in EU competition law. This procedure must urgently be followed especially when sensitive clinical data is concerned.

Therefore, the existing Article 78(3) of the Proposal should be amended as follows:

“The EU database shall be publicly accessible unless, for all or parts of the data and information contained therein, confidentiality is justified on any of the following grounds:

[....]”

“The Commission shall consult the sponsor with a view to assess whether the request of information contains commercially confidential information before making it publicly available. The information can be made publicly available if the sponsor does not object in writing within 30 days after the Commission has notified to the sponsor that it intends to disclose this information. The Commission shall be empowered to adopt delegated acts in accordance with Article 85 in order to specify this procedure.”

This would avoid disputes from the beginning and be in line with the approaches of the EU institutions in the legislation regarding access to documents and EU competition law.

B. Ethic Evaluation in the Assessment Procedure

The current proposal does not explicitly refer to the involvement of ethics committees in the assessment procedure. This led to occasional assumptions that ethical aspects are generally not to be involved in future assessments of clinical trials. This, however, is a misconception. EUCOPE would like to underline that aspects clearly related to ethical matters are referred to in Recital 63 and Article 44. Ethical aspects are part of the assessment procedure in Article 7 since they are mentioned in Annex 1 of the Proposal. Yet the inclusion of ethical review is not explicitly mentioned. To resolve all doubts and give clarity, EUCOPE strongly suggests supplementing Article 9 of the proposed regulation by a paragraph 4 as follows:

“All ethical aspects are subject to this regulation and shall be assessed by an independent body chosen at the national level.”

C. Clinical Trials in Rare and Ultra-Rare Diseases

It is important that the future Regulation takes into account the therapeutic developments as well as the latest EU policies on rare and ultra-rare diseases (inter alia laid down in Council Recommendation of 8 June 2009 on an action in the field of rare diseases). Rare and ultra rare-diseases are a serious threat to the health of EU citizens as they are life-threatening or chronically debilitating. Despite their rarity, there are many different types of rare and ultra-rare diseases that affect millions of people. For this purpose, it has to be clarified that the specifics of clinical trials in these diseases are sufficiently considered when applying the provisions of the Regulation. Clinical trials in these diseases must be judged for statistical relevance with methodology that takes appropriate account of the patient population and potentially low levels of diagnosis. Therefore EUCOPE suggests including a new Recital 23 into the text of the Regulation:

“Whereas most clinical trials are intended for the evaluation of therapies for larger patient populations, this Regulation shall not discriminate against persons suffering from rare diseases and ultra-rare diseases and shall take into account the specificities of conditions with low patient populations when assessing a trial.”

D. Clinical Trials in Emergency Situations

Article 32(1)(e) of the Proposal provides that in emergency situations informed consent may be obtained after the start of the clinical trial, provided that the clinical trial poses a risk to, and imposes a minimal burden on, the subject. However, since an emergency situation requires a sudden life-threatening or other sudden serious medical condition, it would be very difficult for a physician to assess the actual risk the clinical trial poses on the patient. Whether this risk is minimal or above minimal could be hard to predict and therefore, it has to be feared that physicians will rather refrain from including the patient into a clinical trial than facing a potential dispute about the involved risk. This might lead to a situation where patients are denied the only available form of treatment for a serious disease. Therefore, Article 32(1)(e) should be amended in the following way:

“the clinical trial poses a minimal tolerable risk to, and imposes a minimal tolerable burden, on the subject.”

E. Language Requirements

The Proposal states that it should be left to Member States to establish the language requirements for the application dossier but that Member States should consider accepting a commonly understood language in the medical field as the language for the documentation not destined to the subject (Article 26). It should be clarified that once a Member State has accepted an application dossier in a certain language all other communication not destined to the subject shall be in this language as well. This would facilitate the administrative work of the sponsor and the investigator and would also considerably lower the costs for translations. Consequently, Article 26 first sentence should be amended as follows:

“The language of the application dossier, or parts thereof, as well as of the further communication not destined to the subject shall be determined by the Member State concerned.”

1 EUCOPE’s submission to the European Commission’s proposed revisions to the Clinical Trials Directive is included in the annex of EMIG’s submission.

2 http://www.fpm.org.uk/policypublications/guidingprinciples.

3 Full ICH-3 compliant CSRs contain a listing of the patient-level data, and includes all of the Case Record Forms (CRFs), in section 16. This also contains items such as all Investigator/co Investigator CVs (data protection) and copies of all papers referenced in the report (copyright). Hence our proposal to release sections 1-15 only.

Prepared 16th September 2013