United States: EMA Provides Long-Awaited Guidance Under The Policy On Publication Of Clinical Data

The conduct of non-US clinical trials by North American companies continues to grow at an ever-increasing pace. A significant challenge to US-based companies is remaining current on the laws and regulations in countries in which their trials are being conducted. One such important and highly regulated consideration in any country, including the United States, is the ability to provide meaningful and informative publication of clinical trial results while, at the same time, ensuring privacy rights of the participants in the trial. This article summarizes a portion of the guidance recently provided by the European Medicines Agency ("EMA") on this topic.

In response to growing demands from stakeholders for increased transparency in clinical trial reporting, in 2014, the EMA published the "European Medicines Agency policy on publication of clinical data for medicinal products for human use" (the "Policy").1 EMA's stated purpose for the Policy is "to protect and foster public health," with transparency being key to the delivery of service to patients and society in general.2 Through implementation of the Policy, EMA seeks to achieve transparency by proactively making clinical data available to enable both public scrutiny of data and application of new knowledge in future research.3 With respect to publication of clinical data the Policy is intended to:

  • Avoid duplication of clinical trials, foster innovation, and encourage development of new medicines;
  • Build public trust and confidence in EMA's decision-making processes; and
  • Help academics and researchers to reassess clinical data.4

EMA believes that the Policy will level the playing field by enabling all clinical researchers to benefit from past successes and failures of others and allowing wider use of clinical data by the scientific community in its efforts to gain new knowledge. The stated principles considered by EMA in its development of the Policy are protection of personal data, protection of commercial confidential information, protection of EMA's and the European Commission's decision-making processes, and ensuring investment in pharmaceutical research and development in the future. The Policy applies to all clinical reports contained in initial marketing-authorization applications submitted on or after January 1, 2015, and to all applications requesting to vary an existing marketing authorization for an extension of indication or a line extension submitted on or after July 1, 2015. Both researchers who generate initial clinical data and those who create secondary analysis of clinical data are subject to the Policy.


While the Policy provides detailed requirements regarding clinical data publication, it did not include specific implementation guidance as to requirements to ensure company compliance. The long-awaited implementation guidance, known as "External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use," was published earlier this year in March 2016 (the "Guidance") and provides specific information regarding:

  • Procedural aspects related to the submission of clinical reports;
  • How to identify and redact commercially confidential information in clinical reports; and
  • Anonymising clinical reports.5

This article focuses on the guidance specific to ensuring adequate personal data protection through anonymous reporting.


Chapter 3 of the Guidance addresses anonymisation of clinical reports for the purpose of publication in accordance with EMA Policy 0070 and provides specific direction for achieving anonymous reporting that adequately protects personal data of patients.6 Anonymisation refers to the process of converting data into a form which does not identify an individual and makes it unlikely that identification of the individual can occur. This chapter of the Guidance is not a mandate to follow a specific method of reporting; rather, it is intended to highlight for stakeholders "the process to be followed to ensure that clinical reports submitted to EMA for publication are rendered anonymous prior to publication."7 The stakeholders are referred to by EMA as "Applicant/MAH" which is defined as the persons or organizations submitting clinical reports to EMA in support of applications and the persons or organizations who own intellectual property rights in the clinical reports. Chapter 3 provides:

  • general considerations for achieving anonymisation;
  • advice on application of the general considerations to clinical trial reporting in accordance with the Policy;
  • recommendations on how to best achieve anonymisation; and
  • advice on redaction of personal data of investigators, pharmaceutical company staff, and the Applicant/MAH.

1. General Considerations And Their Application

The first general consideration on how to ensure effective anonymisation outlined in Chapter 3 relates to the variance in the level of risk associated with the possibility of re-identification depending on the context of the specific disclosure. Recognizing that in releases of public data to the world at large there are no effective controls that can be implemented, EMA states that the risk of re-identification in those public data releases must be very low. This low risk tolerance by EMA applies to the context of public data release, as the clinical reports published pursuant to the Guidance will be available online and capable of being downloaded by any registered user.

The second general consideration addresses the concept of anonymisation to remove personal data. Article 2(a) of Regulation (EC) No 45/2001 of the European Parliament and of the Council of 18 December 2000 defines personal data as "any information relating to an identified or identifiable natural person ('data subject'); an identifiable person is one who can be identified, directly or indirectly, in particular by reference to an identification number or to one or more factors specific to his/her physical, physiological, mental, economic, cultural or social identity."8 Clinical reports contained in applications submitted to EMA may contain individual patient information and, therefore, cannot be considered anonymised. The Policy requires the Applicant/ MAH to submit an anonymised report for publication which will be separate and distinct from the scientific evaluation report that accompanies the application.9 The publishable report must be a copy of the scientific evaluation report from which sufficient information has been transformed or removed so that individuals can no longer be identified. The Applicant/MAH is reminded to keep in mind the impact of removal on the scientific usefulness of the report. In addition, the Applicant/MAH is advised to give careful consideration to the complexity of anonymisation in reports of rare disease and small population trials based on the low number of trial participants.

To qualify as anonymised, the personal data must be processed in a manner that ensures the data cannot be used to identify the person through use of "all means likely reasonably to be used by either the controller or a third party."10 The Guidance offers two options. A process that prevents (i) the possibility of singling out an individual, (ii) ability to link records to an individual, and (iii) information being inferred to concern a specific individual, will be considered to meet this threshold and result in the data being anonymous. If all three criteria are not met, the second option is a determination of whether the data has been anonymised based on an evaluation of the identification risks.11

The EMA points out that lack of ability to reverse the methodology or technique used to anonymise is also important. Pseudonymisation is described in the Guidance as a security measure; however, it is not considered to be a measure that is adequate to anonymise because indirect identification of the person remains likely.12 Pseudonymisation must be combined with additional measures, for example, removal and generalization of attributes, deletion of original data, or aggregation of the data at a very high level, in order to effectively anonymise the dataset.

Finally, the Applicant/MAH is instructed to consider future advances in technology that may allow identification. A data controller is required to continuously monitor advances in re-identification techniques and reassess the risk as appropriate.13

2. Recommendations To Achieve Anonymisation

The goal of the Guidance is to assist the Applicant/ MAH in striking the right balance between maximizing scientifically useful information for the benefit of the public and achieving effective anonymisation for the benefit of the individual. The Guidance does not mandate any specific methodology. The choice of methodology and technique is left to the company based on the ultimate purpose of the report and the company's choice of the two options for anonymisation discussed above. EMA acknowledges that, initially, the Applicant/MAH is likely to use a reactive data anonymisation process to anonymise data retrospectively after submission of the clinical report (e.g., redaction). However, as the Applicant/MAH becomes more experienced, a transition should be made to proactive data anonymisation to maximize the clinical usefulness of published data.

The EMA's view is that it is unlikely that a clinical report that maximizes usefulness of the published data will be able to meet the three criteria in the first anonymisation option described earlier. This view is based on recognition that the ability to link multiple records of the same trial participant within the report increases the ability to understand the safety and efficacy profile of the trial product. Inference is also important and the EMA advises that the potential impact of inferred data on the trial participants should be emphasized. Therefore, the EMA suggests that the Applicant/MAH will likely need to choose the option to perform a thorough evaluation of the risk of re-identification to achieve anonymisation.

The Guidance discusses several techniques in great detail, each of which has its own strengths and weaknesses. The Applicant/MAH must identify the most effective technique or combination of techniques based on the specific clinical report and the specific clinical trial data. Detailed discussion of the information and analysis of each of the techniques provided in the Guidance is beyond the scope of this article. However, a brief summary of the techniques is provided.

The simplest method is masking, which ensures that redacted information is irreversibly blocked from the report. EMA recommends masking of pre-specified variables, but not entire sections of the report. EMA also recommends randomisation, which is a series of techniques that remove the link between the data and the trial participant. Randomisation techniques recommended by EMA include noise addition (addition of random data to original microdata) and permutation (changing the order of data arranged in a particular order). Further, generalisation is also a family of techniques that dilutes the attributes of the data by modification of the respective scale or order of magnitude. Recommended generalisation techniques include aggregation, in which a value is replaced by a range, and k-anonymity, which groups a trial participant with other trial participants within the same range.

Applicants/MAHs are reminded that scientific review of the data and marketing authorisation assessment must be completed before anonymisation of the data. The Applicant/MAH's primary focus should be to ensure that "the risk of re-identification is acceptably low and in line with requirements for public disclosure and that the data transformation resulting from the applied anonymisation techniques will not lead to a different interpretation of the study results."14

EMA recommends an anonymisation process that includes the following steps:

  • Identify and remove or protect both direct identifiers and quasi(indirect) identifiers;
  • Identify possible adversaries and likely attackers on the data and evaluate the re-identification risk associated with each;
  • Ensure the anonymised results will produce analysis by third parties similar to the analysis based on the original clinical report prior to anonymisation (the goal is a balance between an acceptable low risk of re-identification and high level of data utility);
  • Determine the risk of re-identification threshold and evaluate the actual risk of re-identification;
  • Identify the most appropriate technique and describe how the risk of re-identification is reduced by this technique; and
  • Document both the process chosen and implemented and the rationale for the choice; specify the option chosen by the Applicant/MAH to achieve anonymity.15

3. Redaction With Respect To Investigators, Company Staff And Applicant/MAH Staff.

The identity of the sponsor and the coordinating investigator of the clinical study must be published, with their contact information and signature being redacted. Personal data of other clinical trial staff will not be published. Further, research site number, name, and the investigator at each research site are not published based on the risk that publication of this information may facilitate identification of trial participants.


Through issuance of the Guidance, EMA is providing instruction on the advancement of the operational implementation of the Policy. The Guidance informs companies of what is required moving forward with respect to publication of clinical trial data. As US-based companies become more active in clinical trials governed by the EMA, knowledge of and compliance with both the Policy and Guidance are crucial. As stated above, an analysis of the entire ninety-one page Guidance document is beyond the scope of one article. Therefore, it is important that any company involved in or considering participation in clinical trial conduct or participation in Europe should ensure its knowledge and understanding of the provisions of the Policy and Guidance.


1. European Medicines Agency, Policy on publication of clinical data for medicinal products for human use (2014), available at http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/10/WC500174796.pdf.

2. Id. at 1.

3. Id. at 4.

4. European Medicines Agency, Clinical data publication, available at http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_ 000555.jsp&mid=WC0b01ac05809f363e.

5. European Medicines Agency, External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use, 31-43 (2016), available at http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2016/03/WC500202621.pdf; European Medicines Agency, Clinical data publication.

6. European Medicines Agency, External guidance, at 31-42.

7. Id. at 32.

8. Official Journal of the European Communities, "Regulation (EC) No. 45/2001 of the European Parliament and of the Council of 18 December 2000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data," Article 2(a), at L 8/4 (2001), available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2001:008:0001:0022:en:PDF.

9. European Medicines Agency, Policy on publication, at 4-7.

10. Official Journal of the European Communities, "Regulation (EC) No. 45/2001, at L8/4; Official Journal of the European Communities "Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data", L 281, § 26 (1995), available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31995L0046:en:HTM.

11. Article 29 Data Protection Working Party: The Working Party on the Protection of Individuals with Regard to the Processing of Personal Data, Opinion 05/2014 on Anonymisation Techniques (2014), available at http://ec.europa.eu/justice/dataprotection/article-29/documentation/opinion-recommendation/files/2014/wp216_en.pdf.

12. Pseudonymisation refers to replacement of one attribute in a record by another.

13. Opinion 05/2014.

14. European Medicines Agency, External guidance, at 38.

15. European Medicines Agency, External guidance, at 41.

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.

In association with
Related Video
Up-coming Events Search
Font Size:
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
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
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.


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.


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.


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.


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.


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.


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.