European Union: European Union Negotiations Reach Agreement On New Clinical Trials Regulation

The European Union ("EU") has cleared the way for adoption of a new clinical trials regulation within the EU. On December 20, 2013, the Committee of Permanent Representatives of the European Union endorsed proposed revisions to a draft regulation originally developed by the European Commission and then negotiated between the European Parliament and the Presidency of the Council of the European Union (the "Proposal"). To become law across the EU, the proposed regulation still must receive the formal approval of the European Parliament and of the Council of Ministers. Neither entity is expected to request major revisions at this stage, following the extensive negotiations that have occurred, and the proposed regulation will likely become effective across the EU later in 2014.

The "Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC" would replace an existing Directive that grants individual EU Member States considerable flexibility to craft implementing legislation specific to their country, with a regulation that is binding in its entirety and automatically incorporated into the national laws for all EU Member States. This increased authority and consistency will be channeled towards two goals: establishing a streamlined approval procedure and increasing data transparency for clinical trials conducted across Europe.

Integrated and Streamlined Review

Unified Application Process

The EU's current Directive 2001/20/EC requires that all applications to conduct a clinical trial (each an "Application" submitted by a "Sponsor") be separately submitted to, and approved by, each Member State in which the Sponsor intends to conduct the trial (each an "Implicated Member State"). By contrast, the Proposal charges the European Medicines Agency ("EMA") with establishing, developing and hosting a single web-based portal (the "EU Portal") for submission of all Applications, regardless of the number of Implicated Member States.

The Proposal imposes a consistent set of content requirements for every Application, irrespective of where in the EU the clinical trial will be conducted. Upon submission, the Sponsor must propose, from among the Implicated Member States, one "Reporting Member State" charged with directing and facilitating review of the Application through a new, harmonized process. If the Sponsor's nominated Reporting Member State does not wish to be the Reporting Member State, it has three days after the Application submission to notify the other Implicated Member States through the EU Portal. The Implicated Member States can discuss among themselves which State is willing to assume the position of Reporting Member State; however, if the Implicated Member States cannot agree, the Sponsor's originally proposed Reporting Member State designation stands. The Reporting Member State decision must be made within six days following the Application submission.

Initial Validation

The Proposal also includes new fixed timelines for review of the Application. The Reporting Member State must, within ten days, cursorily review the Application for completeness and compliance and (a) validate the Application, (b) provide the Sponsor with ten days to furnish additional information (which the Reporting Member State will then evaluate within five days), or (c) decline to validate the Application. Notice of validation is provided through the EU Portal to the Sponsor, and triggers commencement of a full, two-part concurrent review.

Part I: Harmonized Review

Once validated, the Reporting Member State will supervise the assessment of the Application. Part I of this assessment typically consists of three phases:

  1. Initial Assessment: Within 26 days of validation, the Reporting Member State will author a Draft Assessment Report to be circulated among all Implicated Member States.
  2. Coordinated Review: Within 12 days of the end of the Initial Assessment phase involving all Implicated Member States, all Implicated Member States will review the Application and Draft Assessment Report, and raise any concerns with respect to the Application (particularly respecting therapeutic benefits, risks to participants and labeling requirements).
  3. Consolidation: Within seven days of completion of the Coordinated Review—that is, within 45 days of the Application's validation—the Reporting Member State will produce Part I of the Assessment Report, which it will distribute through the EU Portal to the Sponsor and Implicated Member States.

Part I of the Assessment Report, once complete, must record all concerns raised during the Coordinated Review, indicate whether and how these concerns have been addressed, and reach a conclusion on the merits of the Application. This conclusion may indicate that the Application is (a) acceptable, (b) acceptable subject to explicitly listed conditions, or (c) unacceptable.

During Coordinated Review or Consolidation, the Reporting Member State may request additional information from the Sponsor and, in such cases, the review deadlines may be extended by up to 31 days as a result. 

Part II: Autonomous Review

In addition to its role in the Coordinated Review, each Implicated Member State must also concurrently complete an assessment of the Application's compliance with that Member State's domestic law and regulation, including the following:

  • Scientific and ethical review of the Application by an independent ethics committee ("IEC") that measures whether the Application complies with Implicated Member State's laws regarding ethical review (this review requirement was removed from prior drafts but restored in the final Proposal);
  • The collection, storage and future use of participants' biological samples;
  • Informed consent arrangements for clinical trial participants; 
  • Compensation and other recruitment arrangements for investigators and participants;
  • The collection and transmission of participants' data;
  • The qualifications and competence of all investigators;
  • The suitability of proposed clinical trial sites; and
  • Arrangements for compensation to participants who suffer injury as a result of their participation in a clinical trial.

In performing this analysis, each Implicated Member State may—like the Reporting Member State in Part I—request additional information and, thus, extend review deadlines by up to 31 days. On completion of its analysis, the Implicated Member State must then conclude—again, as with Part I—that the Application is (a) acceptable, (b) acceptable subject to explicitly listed conditions, or (c) unacceptable.

Final Decision

If both Part I and Part II conclude that the Application is approved or approved with conditions, the clinical trial may be conducted in accordance with conditions, if any, in all Implicated Member States. The Proposal does not address the timeline for when the trial can commence once approval is granted. If Part I of the Assessment Report concludes that the Application is unacceptable, the Application is refused on behalf of all Implicated Member States. If, conversely, Part I of the Assessment Report concludes that the Application is either acceptable or acceptable with conditions, an Implicated Member State may nonetheless refuse to approve the Application with respect to its own jurisdiction if: (a) it disagrees with the conclusion of Part I for one or more enumerated reasons (such as patient safety); or (b) it finds the Application unacceptable in Part II of the Assessment Report. In such case, the clinical trial may only be conducted within the Implicated Member States that approved or approved with conditions; the clinical trial would not be permitted within the Implicated Member States that refused the Application. 

Irrespective of the outcome, extensions granted to submit and process additional information may prolong the review process—from submission of an Application, through satisfaction of additional requests for validation, to receipt of Parts I and II of the Final Assessment Report—to more than 100 days. This extended period represents a significant concession from the European Commission's initially proposed 41-day review period, and has led some industry groups to voice displeasure with the Proposal due to the potential delays allowed in commencing trials.

Increased Data Transparency

The Proposal also contains provisions designed to increase the transparency and accessibility of clinical trial data from trials conducted within the Member States of the EU. These measures first apply to the content submission requirements for new Applications. Specifically, all data supporting the Application to commence a new clinical trial must originate from clinical trials that have been registered and recorded on a publicly and freely accessible database. Registration and recordation includes the clinical trial protocol, the summary of the clinical trial, and the clinical study report, if applicable. An exception is made for supporting clinical trial data generated before the effective date of the Proposal (when implemented); those data, in order to be used to support an Application for a new clinical trial, must have been included in the World Health Organization's registry or a partner clinical trials registry; or the data must have been published in an independent, peer-reviewed scientific publication. Any clinical data that do not comply with these registration or publication requirements will not be considered during evaluation of an Application to conduct a new clinical trial in the EU.

The Proposal also contains provisions related to the transparency of data generated from approved clinical trial Applications within the EU. The EMA must establish and maintain a publicly accessible and searchable database of all approved clinical trial data relating to medicinal products. This database must include:

  • Detailed summaries of clinical trial data from approved Applications, including a summary drafted by the Sponsor in plain language and submitted (except where an exception is granted) within one year of the termination of the clinical trial (e.g., last visit by the last subject or as otherwise defined in the protocol); and
  • For medicinal products for which marketing authorization in the EU has been sought, full clinical study reports that have been submitted to support a marketing authorization, which should be posted within 30 days of the marketing application's authorization, rejection or withdrawal. 

Informed Consent

Informed Consent for Future Uses

Although U.S. Food and Drug Administration ("FDA") regulations and guidance are largely silent on this point, the Proposal explicitly addresses future uses of clinical trial data, allowing Sponsors to ask participants for permission to use their data "outside the protocol of the trial exclusively for scientific purposes." Such permission may be withdrawn at any time, but prior results obtained through permitted use of the data remain valid and useable. 

However, the Proposal also states that these provisions on informed consent for future uses are subject to the applicable data protection legislation. The applicable data protection legislation, Directive 95/46/EC ("1995 Directive"), is currently undergoing reform and the new proposed General Data Protection Regulation ("2013 GDPR") is one step away from approval by the European Parliament. The proposed changes to the 1995 Directive would complicate and limit the secondary uses of data from clinical trials, particularly in terms of the specific consent required for processing health data and the "right to erasure" of any data involving a withdrawn subject. Research institutions and clinical trial sponsors will need to pay close attention to how the provisions of these two new Regulations can be read together in regard to informed consent for future research uses of data collected in clinical trials in the EU. 

Simplified Informed Consent Requirements

The Proposal allows simplified informed consent requirements for randomized cluster trials conducted exclusively in one Member State. The reduced informed consent process allows informed consent to be gained without a face-to-face discussion with a member of the research team. The simplified informed consent process may be used for cluster clinical trials, as long as all of the following are met:

  • The simplified informed consent does not violate any national law in the Implicated Member State;
  • The clinical trial is a low-intervention clinical trial, and if it involves a medicinal product, such product is used in accordance with the terms of the marketing authorization;
  • There are no interventions other than the standard treatment of the concerned subjects; and
  • The protocol describes the scope of information provided to the subjects, the method of providing such information and justifies the reasons for utilizing the simplified informed consent process. 

Informed Consent in Emergency Situations

The Proposal addresses informed consent in emergency situations, such as when a patient suffers a sudden life-threatening medical condition requiring immediate medical intervention, thus bringing EU law largely into line with long-standing FDA regulations on emergency research. The Proposal allows informed consent to be obtained after the intervention in certain emergency situations, if all of the following are met: 

  • The subject and the subject's legal representative are incapable or unavailable to receive all the clinical trial information within the therapeutic window or to provide informed consent prior to the intervention because of a sudden life-threatening or other serious medical condition;
  • The clinical trial is directly related to the cause of the life-threatening or serious medical condition, such that the intervention should have a direct clinically relevant benefit for the subject;
  • The investigator certifies that he or she is unaware of the subject expressing any prior objections to participating in the clinical trial; and
  • The clinical trial poses a minimum risk to, and imposes a minimal burden on the subject, as compared to the standard treatment of the subject's condition. 

Following the emergency intervention, informed consent to continue participation in the clinical trial must be obtained from the subject or the subject's legal representative as soon as possible thereafter. If the subject or the legal representative does not provide consent, he or she must be informed of the right to object to the use of data already obtained from the trial.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
 
In association with
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
 
Email Address
Company Name
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
United States
Worldwide Updates
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement

Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of www.mondaq.com

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.

Disclaimer

Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.

Registration

Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.

Cookies

A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.

Links

This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.

Mail-A-Friend

If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.

Emails

From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

*** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .

Security

This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at enquiries@mondaq.com.

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.