An information resource for the EU Clinical Trials Regulation

Last updated on 11 June 2024

See history of updates below.

This post is an attempt to provide an information resource for the Clinical Trials Regulation (EU) no 536/2014 (CTR). The information provided is by no means exhaustive.

Click on the ‘+’ sign next to each heading to access the information under each heading.

DateUpdate(s)
11 Jun 20241) Section Is there a comprehensive Q & A document available on the CTR? updated to include link to the latest version of the Q&A Document (Marrch 2024)
2) New section, New CTIS transparency rules from 18 June 2024 added.
1 May 2024In the section About the Clinical Trials Information System (CTIS), link added to EMA webinar of 24 April 2024 entitled CTIS Bitesize Talk: Alternate IMPD-Q and New guidance AxMP.
30 Nov 2023Under the heading Transitional trials i.e. transitioning from Directive 2001/20/EC to transition to Regulation (EU) No. 536/2014 and sub-heading Heads of Medicines Agences, links provided to the latest Best practice guide and cover letter, both Version 3 of November 2023
28 Nov 2023New heading Transitional trials i.e. transitioning from Directive 2001/20/EC to transition to Regulation (EU) No. 536/2014 plus relevant content added.
8 Oct 2023Under the heading About the Clinical Trials Information System (CTIS) a new sub-heading Transparency rules for the EU Clinical Trials Information System (CTIS) was added, with relevant content.
29 Sep 2023In the section entitled Is there a comprehensive Q & A document available on the CTR?, the version of the Q&A document is updated from to Version 6.6 of September 2023.
19 July 2023New section added entitled Guidance for the transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation
7 July 2023New heading Clinical Trials Coordination Group (CTCG) issued documents added with links to
1) Best Practice Guide for sponsors of multinational clinical trials with
different protocol versions approved in different Member States under the
Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014
2) Cover letter template
10 March 2023Table in section entitled New or updated guidelines and other legislation concerning clinical trials updated to add information on the Guideline on computerised systems and electronic data in clinical trials
23 Feb 2023In the section entitled Is there a comprehensive Q & A document available on the CTR?, the version of the Q&A document is updated from Version 6.2 of Sept 2022 to Version 6.4 of Feb 2023.
31 Jan 2023Heading entitled Quick guide for sponsors – Regulation 536/2014 in practice (Eudralex vol. 10) added, plus relevant content.
26 Jan 2023 Section entitled About the Clinical Trials Information System (CTIS) updated to add a link to the webinar entitled CTIS WALk In Clinic of 15 Dec 2022
24 Jan 20231) New section entitled Consultations added, with relevant content.

2) New section entitled New legislation added, with relevant content.
12 Jan 2023Section entitled About the Clinical Trials Information System (CTIS) updated to add a link to the webinar entitled CTIS bitesize talk 23 Nov 22
30 Nov 2022
1) Section entitled About the Clinical Trials Information System (CTIS), sub-section Further Information updated to add a link to a slide from the EMA entitled Getting Started with CTIS, Sposor Quickguide.

2) Section entitled About the Clinical Trials Information System (CTIS) updated to add a link to the webinar entitled Organisation Management System(OMS Troubleshooting Session for CTS, 19 September 2022.
24 Oct 2022Section entitled About the Clinical Trials Information System (CTIS) updated to add a link to the webinar entitled CTIS bitesize talk: Notifications – Part 1, 28 Sept 2022
26 Sept 2022Section entitled Is there a comprehensive Q & A document available on the CTR? updated to add a link to the Q & A Version 6.2 of Sept 2022 (supersedes version 6.1 of May 2022) and provide a brief summary of the updates.
21 Sept 2022Section entitled About the Clinical Trials Information System (CTIS) updated to add links to the following webinars:
i) Organisation Management System (OMS) for CTIS users – 30 June 2022
ii) Organisation Management System (OMS) – 21 July 2022
14 Sept 20221) Section entitled About the Clinical Trials Information System (CTIS) updated to add links to the following webinars:
i)CTIS: Walk-in Clinic – 31 August 2022
ii)CTIS bite size talk: Modifications – 31 May 2022.

2) Section entitled History of updates to this post renamed History of updates and section moved to the beginning of the post.
1 Sept 2022Section entitled About the Clinical Trials Information System (CTIS) updated to add a link to the webinar CTIS Bitesize talk: Deferral rules and Public website – 20 July 2022.

The goal  is to create an environment that is favourable to conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information. The Regulation will require:

  • consistent rules for conducting clinical trials throughout the EU;
  • information on the authorisation, conduct and results of each clinical trial carried out in the EU to be publicly available.

It aims to foster innovation and research, while helping avoid unnecessary duplication of clinical trials or repetition of unsuccessful trials.

The main characteristics of the new CTR are:

  • A streamlined application procedure via a single entry point – an EU portal and database, for all clinical trials conducted in EEA. Registration via the portal will be a prerequisite for the assessment of any application.
  • A single set of documents to be prepared and submitted for the application defined in Annex I of the Regulation.
  • A single authorisation procedure for all clinical trials, allowing a faster and thorough assessment of an application by all Member States concerned and ensuring one single assessment outcome and authorisation per Member State.
  • A harmonised procedure for the assessment of applications for clinical trials, which is divided in two parts:
    • Part I is jointly assessed by all Member States concerned
    • Part II is assessed by each Member State concerned separately;
  • Strictly defined deadlines for the assessment of clinical trial application
  • The involvement of the ethics committees in the assessment procedure in accordance with the national law of the Member state concerned but within the overall timelines defined by the Regulation.
  • Simplified reporting procedures which will spare sponsors from submitting broadly identical information separately to various bodies and different Member States.
  • Clinical trials conducted outside the EU, but referred to in a clinical trial application within the EU, will have to comply with regulatory requirements that are at least equivalent to those applicable in the EU.
  • Strengthened transparency for clinical trials data.
  • A coordination and advisory committee that will serve as a forum for exchanging best practices between Member States.
  • Union controls in Member states and third countries to ensure that clinical trials rules are being properly supervised and enforced.

The expected key benefits of the Regulation include:

  • harmonised electronic submission and assessment process for clinical trials conducted in multiple Member States
  • improved collaboration, information-sharing and decision-making between and within Member States
  • increased transparency of information on clinical trials
  • highest standards of safety for all participants in EU clinical trials.

DateNotes
31 January 2022On 31 January 2022, the Clinical Trials Regulation (CTR) became applicable harmonising the submission, assessment and supervision processes for clinical trials in the European Union (EU). The backbone of the changes brought about by the CTR is the new Clinical Trials Information System (CTIS). CTIS is a single entry point for sponsors and regulators of clinical trials for the submission and assessment of clinical trial data which includes a public searchable database for healthcare professionals, patients and the general public.

More information here from the EMA. Here is a link to the EMA CTR / CTIS go-live press briefing of 25 January 2022.
2 August 2021The European Commission has confirmed that the entry into application of the Clinical Trials Regulation and hence the go-live date for the Clinical Trials Information System (CTIS) will be on 31 January 2022.
31 July 2021The following commission decision was published in the OJEU on 31 July 2021.
Commission Decision (EU) 2021/1240 of 13 July 2021 on the compliance of the EU portal and the EU database for clinical trials of medicinal products for human use with the requirements referred to in Article 82(2) of Regulation (EU) No 536/2014 of the European Parliament and of the Council. 
16 June 2014Although Clinical Trials Regulation (EU) No 536/2014  entered into force on 16 June 2014, the timing of its application depends on confirmation of full functionality of the Clinical Trials Information System (CTIS) through an independent audit.

Currently, sponsors must submit clinical trial applications separately to national competent authorities and ethics committees in each country to gain regulatory approval to run a clinical trial.

CTIS will become the single entry point for clinical trial application submission, authorisation and supervision in the EU, and in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway.

With CTIS, sponsors will be able to apply for clinical trial authorisation in up to 30 EEA countries with a single application. The Clinical Trials Information System will also, together with other EMA IT tools, support the coordinated assessment of safety reporting in the context of clinical trials and therefore contribute to the understanding of the benefits and the risks of medicinal products that are planned to enter or are already on the market of the Union.

When the Regulation becomes applicable, it will repeal the existing EU Clinical Trials Directive No 2001/20/EC and national legislation that was put in place to implement the Directive. It will also apply to trials authorised under the previous legislation if they are still ongoing three years after the Regulation has come into operation.

You can download a guide entitled Clinical Trials Regulation (EU) No 536/2014 in practice (30 January 2023) from this page.

The objective of this document is to provide sponsors and investigators a
quick guide on the rules and procedures of the Clinical Trials Regulation (EU) No 536/2014 with a view to facilitating its implementation. This document should be read in combination with the legislative text. The document has been prepared by the Clinical Trials Coordination and Advisory Group (CTAG) as its members are the National Contact Points defined in the above mentioned Regulation.

The Clinical Trials Regulation (CTR) harmonises the assessment and supervision processes for clinical trials throughout the EU, via a Clinical Trials Information System (CTIS). CTIS will contain the centralised EU portal and database for clinical trials foreseen by the Regulation. The European Medicines Agency (EMA) will set up and maintain CTIS, in collaboration with the Member States and the European Commission. CTIS went live on 31 January 2022 together with the public Clinical Trials website.

CTIS training programme and other resources

The European Medicines Agency (EMA) continues to issue online training modules of the Clinical Trials Information System (CTIS) ahead of its planned launch.

Twenty-three training modules are available as detailed in the table below. You can also access YouTube videos on the modules by visiting YouTube and searching for ‘EMA CTIS training modules’.

Introduction to CTIS
Module Title
1Introduction to the Clinical Trial Regulation 536/2014
2High level overview of CTIS workspaces and common system functionalities
Common functionalities for all registered users
ModuleTitle
3User access management
4Support with workload management
7Management of registered users and role matrix
12Data protection in CTIS
23Transitional trials
Authority workspace
ModuleTitle
6Evaluation of a Clinical Trial application: Selection of reporting member state (RMS) and validation of the clinical trial application
8Evaluation of a Clinical Trial application: assessment and decision making
14Supervise a Clinical Trial: Corrective measures
15Search, view and download a clinical trial and a clinical trial application
16Supervise a clinical trial: Inspection records
17Supervise a clinical trial: Ad hoc assessment
20Assess an Annual Safety Report
21Union Controls in CTIS
Sponsor workspace
Module Title
5Management of a Clinical trial through CTIS
9Search, view and download information on clinical trials and clinical trials applications
10Create, submit and withdraw a clinical trial.
11Respond to requests for information received during the evaluation of a clinical trial application
13Clinical study reports submissions
18How to create and submit an annual safety report and respond to related requests for information
19CTIS for SMEs and academia
Searching CTIS as a public user
ModuleTitle
22Introduction to CTIS for public users
CTIS sponsor handbook

In July 2021, the EMA published Clinical Trial Information System (CTIS) – Sponsor Handbook. This is a a compilation of key guidance, technical information, recommendations and references for getting ready for use of CTIS. You can view the handbook here.

The guidance has been developed by the European Medicines Agency (EMA) in collaboration with some representatives of industry stakeholders.

EMA will be updating this CTIS sponsor handbook with further priority topics as needed.

Transparency rules for the EU Clinical Trials Information System (CTIS)

In October 2023, the EMA has adopted revised transparency rules for the publication of information on clinical trials submitted through CTIS. The simplifications introduced will give access to clinical trial information to stakeholders including patients and healthcare professionals in a faster and more efficient way.

One of the key changes of the revised rules is the removal of the deferral mechanism, which allowed sponsors to delay the publication of certain data and documents for up to seven years after the end of the trial to protect personal data and commercially confidential information (CCI).

Whilst the Agency will endeavour to finalise implementation of the revised transparency rules by the second quarter of 2024, the effective date of completion of the process and application of the new rules will be communicated to CTIS users in due course and prior to the date when they will become applicable.

Source: EMA

Further information
1) EMA website

Information on CTIS training and support is available on the EMA website, here.

2) Sponsor quickguide

Here is a link to a slide from the EMA entitled Getting Started with CTIS, Sposor Quickguide

Webinars
DateTitle
24 Apr 2024CTIS bitesize talk: Alternate IMPD-Q and New Guidance AxMP. View here.
15 Dec 2022CTIS walk in clinic. View here.
23 Nov 2022CTIS bitesize talk 23 Nov 22. View here
28 Sep 2022CTIS bitesize talk: Notifications – Part 1 – View here
19 Sep 2022Organisation Management System(OMS Troubleshooting Session for CTS users – View here
31 Aug 2022Clinical Trials Information System (CTIS): Walk-in Clinic – View here
21 Jul 2022Organisation Management Service (OMS) Trouble Shooting Sessions for CTIS users – View here.
20 Jul 2022CTIS Bitesize talk: Deferral rules and Public website – View here
1 Jul 2022Clinical Trials Information System CTIS webinar: Six months of CTIS and looking forward – View here
30 Jun 2022Organisation Management Service (OMS) for CTIS users – View here
15 Jun 2022CTIS walk in clinic – View here.
2 Jun 2022CTIS walk in clinic – View here.
31 May 2022CTIS bite size talk: Modifications – View here
19 May 2022CTIS walk in clinic – View here.
5 May 2022CTIS walk in clinic – View here.
28 Apr 2022CTIS bitesize talk: Requests for information – View here.
22 Apr 2022CTIS walk in clinic – View here.
28 Mar 2022CTIS walk in clinic – View here.
23 Mar 2022CTIS bitesize talk: Initial clinical trial application – View here.
24 Feb 2022CTIS bitesize talk – User access and role management – The above View here.
26 Oct 2021 Clinical Trials Information System (CTIS) – Virtual Information day – View here.
29 Jul 2021How sponsor organisations can prepare for CTIS – The webinar can be viewed here. You can find more information and presentations on this webinar here

Until the Clinical Trials Regulation (CTR) becomes applicable, all clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials Directive (CTD). The Directive will be repealed on the day of entry into application of the CTR.

The table below details the relevant information on the applicability of the CTD and the CTR.

DateWhich is applicable, CTD or CTR?
Before 31 Jan 2022The CTD will apply to all Clinical Trials Applications (CTAs) submitted before the entry into application date of the CTR.
Any new CTA can only be submitted under the CTD.
31 Jan 2022This is the date on which the CTR will become applicable.

Once the CTR is applicable, for new CTAs submitted between 31 Jan 2022 and 31 Jan 2023, the sponsor can choose to submit either under the Legal Framework of the CTD or the CTR.
31 Jan 2023From this date, all new CTAs can only be submitted under the CTR.

CTAs approved under the CTD prior to this date can continue to be regulated under the Directive, unless the sponsor decides to transition these ongoing applications to the CTR.
31 Jan 2025On this date, the CTD will stop becoming applicable to all CTAs submitted before or after the entry into application of the CTR.

The three year transition period applies to CTAs regulated by the CTD regardless of whether they were submitted before or after the application of the CTR.  By 31 Jan 2025 all CTA must be regulated under CTR.

European Commission

The European Commission has released a set of documents that will be applicable to clinical trials once the CTR is implemented.

Regulation, Directive, Guideline etc.What does it concern?Explanatory notes
Detailed commission guideline adopted on 8 December 2017.Good manufacturing practice for investigational medicinal products, pursuant as per Article 63(1) of the CTRIt is complementary to regulation EU 2017/1569 (see below) on the good manufacturing practice for investigational medicinal products, as per Article 63(1) of the CTR.
Commission Directive EU 2017/1572  of 15 September 2017 Good Manufacturing PracticeThe current GMP Directive 2003/94/EC will be repealed by this Directive on the date of entry into application of the CTR).
The Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017Principles and guidelines for good manufacturing practice for investigational medicinal products for human use, and arrangements for inspections.This regulation supplementing the CTR will apply, as a matter of principle, to all clinical trials as of its entry into application.
During the transition period, EU countries may however continue to apply their national law, adopted in order to transpose Directive 2003/94/EC, to those clinical trials conducted under the CT Directive 2001/20/EC.
Implementing Regulation (EU) 2017/556 of 24 March 2017 Detailed arrangements for the good clinical practice inspection procedures pursuant to the CTR.
The Commission’s GCP Directive 2005/28/EC will apply to clinical trials submitted under the Clinical Trials Directive until the end of the transition period, except the provisions in chapters 5 and 6 related to inspectors and inspection procedures which will be covered by this Regulation (EU) 2017/556 and will apply to all GCP inspections (meaning inspections of CTs conducted under the CTR as well as the CT Directive).
Commission Implementing Regulation (EU) 2022/20
It lays down rules for the application of Regulation (EU) No 536/2014 as regards setting up the rules and procedures for the cooperation of the Member States in safety assessment of clinical trials has been published.
LegislationWhat does it concern?Brief explanatory notes
Commission Delegated Regulation (EU) 2022/2239 of 6 September 2022Amends Regulation (EU) No 536/2014 as regards labelling requirements for unauthorised investigational and unauthorised auxiliary medicinal
products for human use
The regulation came into force on 5 Dec 2022
GuidelineNew/updatedDate
Guideline on computerised systems and electronic data in clinical trials
Final version adopted by the GCP IWG 0n 7 Mar 2023
Date of coming into effect is 6 months after publication
Published on
9 Mar 2023
Annex VI
To procedure for conduction GCP Inspections requested by the CHMP: Record keeping and archiving of documents
UpdatedAdopted on 29 Apr 2022
Annex IV
To procedure for conducting GCP Inspections requested by the CHMP: Sponsor and CRO
UpdatedAdopted on 29 Apr 2022
Annex II
To procedure for conducting GCP inspections requested by the CHMP: Clinical laboratories
UpdatedAdopted on 29 Apr 2022
Annex I
To procedure for conducting GCP inspections requested by the CHMP: Investigator site
=
Updated Adopted on 29 Apr 2022
[DRAFT] Guidance document on how to approach the protection of personal data and commercially confidential information in documents uploaded and published in the Clinical Trial Information System (CTIS) 7 pPril 2022New
Guidance on the management of clinical trials during the COVID-19 (Coronavirus) pandemic

Key changes from v4 (04-02-2021): updated with references to the Clinical Trials Regulation
Updated -Version 5Published date
10 Feb 2022
Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trialsUpdated – Revision 2Effective form 31 Jan 2022
Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trialsUpdated – Revision 2Effective from 31 Jan 2022

Yes there is.

The document is entitled Clinical Trials Regulation (EU) No 536/2014 Questions and Answers You can view the latest update, Version 6.8 of March 2024 here. The updates from the previous Version 6.5 are stated on the first page of the document.

The changes from the previous version 6.7 are detailed on page 1 of the updated document.

This Guidance reflects the agreement reached by CTAG Contact Points and supersedes the chapter 11 of the Q&A on the application of the CTR (version 6.4).

Source: European Commission

Some of the following acronyms will become familiar once you become familiar with the terminology of the CTR.

AcronymIn fullDefinitionCTR reference (if available)
AMSAdditional Member State concernedThis is when an additional member state is added to an already approved clinical trial application.
ARassessment reportFor each clinical trial, an assessment report will be generated. The report will be in two parts, Part I and Part II. Each part refers to the specific documents submitted in a clinical trial application dossier.
AxMPAuxiliary Medicinal Product(s)A medicinal product used for the needs of a clinical trial as described in the protocol, but not as an investigational medicinal product.Art. 2(8)
CTISClinical Trials Information SystemThe Clinical Trials Regulation (CTR) harmonises the assessment and supervision processes for clinical trials throughout the EU, via a Clinical Trials Information System (CTIS)
CTRClinical Trials Regulation No 536/2014Clinical Trials Regulation
MSCMember State concernedMeans the Member State where an application for authorisation of a clinical trial or of a substantial modification has been submitted under Chapters II or III of the CTR respectively.Art. 2(12)
NSMnon-substantial modificationAny change which is not substantial will be a non-substantial modification. A substantial modification is defined below.
RMSreporting member stateFor each clinical trial application,
the sponsor shall propose one of the Member States concerned as reporting Member State.
SMsubstantial modificationMeans any change to any aspect of the clinical trial which is made after notification of a decision referred to in Articles 8, 14, 19, 20 or 23 of the CTR and which is likely to have a substantial impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial.
Art. 2(13)

The list of required documentation and information is set out in Annex I of the CTR.

Part I of the assessment report

The following documents (sections B to J and Q of Annex I) are required for Part I of the assessment report (AR):

  • B. Cover letter
  • C. EU application form
  • D. Protocol
  • E. Investigator’s brochure (IB)
  • F. Documentation relating to compliance with Good Manufacturing Practice (GMP) for the
  • G. Investigational Medicinal Product (IMP). Investigational Medicinal Product Dossier (IMPD)
  • H. Auxiliary Medicinal Product Dossier
  • I. Scientific advice in Paediatric Investigation Plan
  • J. Content of the labelling of the Investigational Medicinal Products
  • Q. Proof of payment of fee (information per member state concerned)
Part II of the assessment report

The following documents (all sections from K to R of Annex, except Q) are required for Part II of the assessment report (AR). This information is required per member state concerned.

  • K. Recruitment arrangements
  • L. Subject information, informed consent and informed consent procedure
  • M. Suitability of the investigator
  • N. suitability of the facilities
  • O. Proof of insurance cover or indemnification
  • P. Financial cover and other arrangements
  • R. Proof that data will be processed in compliance with the union law on data protection

The steps in the authorisation procedure for a clinical trial application are detailed below. They are as per Chapter II of the CTR. All of the steps are performed via the EU portal.

Step in trialLocation in CTRFurther information
Submission of an application dossier and validationArticle 5Validation will confirm the following:
– Whether the CT falls within the scope of the CTR
– Whether the application dossier is complete in line with Annex I of the CTR
Assessment of Parts I and II of the application (done in parallel upon validation of the application)Article 6 – Assessment report – Aspects covered by Part I

Article 7 – Aspects covered by Part II
For CTs with more than one MS, the assessment process for aspects covered by Part I shall include three phases:
(a) an initial assessment phase performed by the reporting Member State
(b) a coordinated review phase performed involving all Member States concerned
(c) a consolidation phase performed by the reporting Member State

The reporting Member State shall draw up an assessment report. Regarding the aspects addressed in Part I of the assessment report, the assessment report shall conclude one of the following:

The conduct of the clinical trial:
-is acceptable
– is acceptable subject to compliance with specific conditions
– is not acceptable

Part I includes assessment of the protocol, investigator’s brochure and investigational
medicinal product dossier (IMPD). Assessment of these documents, within EU-mandated
timelines, is led by the RMS, with MSCs providing comments. The assessment of the above aspects shall constitute Part I of the assessment report.

Part II includes assessment of the subject information and informed consent documents,
the suitability of the investigator and of the trial site, indemnity and data protection. This
assessment is done at national level by each national ethics committee.
The assessment of the above aspects shall constitute Part II of the assessment report.
Decision on the clinical trialArticle 8 – Decision on the clinical trialEach MS shall confirm whether the clinical trial:
– is authorised
– is authorised subject to conditions
– is refused

Comprehensive guidance has been published on Good Lay Summary Practice (GLSP) for EU Clinical trials. The 85 page document was adopted in July 2021 and published on 4 October 2021.

What is the Lay Summary (LS) and is there a legal basis for it?

Article 37 of the Clinical Trials Regulation (EU) No. 536/2014 (CTR) requires trial sponsors to submit a summary (lay summary or LS) that is understandable to laypersons for
each clinical trial with pharmaceuticals into the EU Database, a core element of the
EU Clinical Trials Information System (CTIS).

As stated above, the CTR is the legal basis for the Lay Summary. It is a mandatory requirement and a transparency obligation to all trial participants and the interested public.

What is Good Lay Summary Practice (GLSP) guidance about?

The Good Lay Summary Practice (GLSP”) guidance provides key aspects and detailed recommendations on best practices for how to:

  • Plan
  • develop
  • translate and
  • disseminate (via CTIS) high quality lay language summaries of clinical trial results with medicinal products.
Who developed the GLSP guidance?

The guidance was developed in cooperation with the Roadmap Initiative to Good Lay
Summary Practice and adopted by the Clinical Trials Expert Group (CTEG), a working group of the European Commission representing Ethics Committees and National Competent Authorities (NCA)).

How is the GLSP guidance presented?

The GLSP guidance is presented in two parts:

  • Part 1, a GLSP Quick Guide (pages 6-15) – contains core extracts from the GLSP Handbook and may serve as an overview of the recommendations offered in the Handbook
  • Part 2, a GLSP Handbook.

The handbook is divided into seven sections, including those on on planning, development, translation and dissemination of a Lay Summary.

More about the GLSP guidance

The GLSP guidance :

  • provides recommendations on building Lay Summary (LS) processes with the aim to enable all sponsors to generate and disseminate objective and understandable information on clinical trial results.
  • contains recommendations on how to enable patient engagement all through the LS process although it is acknowledged that sponsors’ resource and infrastructure constraints can limit a routine involvement of patients in the different steps.
  • gives recommendations for LS dissemination aiming to inform trial participants and the general public to ensure fair access to information for all.
  • recognises and addresses the need for specific skills and strategies for LS on paediatric trials and highlights the limited experience available so far.
What are the timelines for the submission of a Lay Summary?

The Lay Summary (LS) must be submitted to the CTIS via the EU Portal no later than 12 months from the protocol-defined end of the clinical trial, 6 months for paediatric studies, and up to 30 months for nontherapeutic Phase 1 trials.

If the lay summary cannot be reported within these timelines for scientific reasons, it shall be submitted as soon as possible. In that case the protocol shall specify when the results are going to be submitted.

Deferral of the publication timelines can be requested for approval by the Member
States concerned either in the initial trial application or as a substantial modification.

Where can you find the details of the content required in the Lay Summary?

The content required in the lay summary is listed in Annex V of the EU CTR and will
accompany a ”Summary of Clinical Trial Results”, the content of which is laid out in
Annex IV.

Substantial modifications are covered by Chapter III of the CTR.

A substantial modification of a clinical trial can concern aspect(s) covered by one of the following:

  • Part I of the assessment report
  • Part II of the assessment report
  • Parts I and II of the assessment report

In all three cases, the steps for authorisation are:

  • Submission of an application
  • Validation of an application
  • Assessment of a substantial modification of an aspect(s) covered by the relevant part(s) of the assessment report
  • Decision on the substantial modification

In all three cases, each Member State concerned shall confirm whether the substantial modification:

  • is authorised
  • it is authorised subject to conditions
  • is refused.

Withdrawal and resubmission are covered under Chapter III of the CTR.

Withdrawal

In line with Article 12 of the CTR:

  • A sponsor may withdraw the application at any time until the reporting date.
  • In such a case, the application may only be withdrawn with respect to all Member States concerned (MSCs).
  • The reasons for the withdrawal shall be communicated through the EU portal.
Resubmission

In line with Article 13 of the CTR:

  • A sponsor may resubmit an application for authorisation to any intended Member State concerned following the refusal to grant an authorisation or the withdrawal of an application,
  • That application shall be deemed to be a new application for authorisation of another clinical trial.

In March 2021, the European Medicines Agency held an SME and academia 2 part training webinar. Here, you can view Day 1 and Day 2 of the webinar.


Presentations from the European Medicines Regulatory Network (EMRN) joint training sessions on the Clinical Trials Regulation (EU) 536/2014 are available.

To support the EU Member States with the implementation of the Clinical Trials Regulation (EU) 536/2014, the following three sections of the EMRN jointly organised training sessions on 9-10 March, 2021:

  • DG SANTE of the European Commission,
  • the European Medicines Agency and the
  • Clinical Trials Facilitation and Coordination Group of the Heads of Medicines Agencies

The aim of the training sessions was to provide an overview of key changes under the Clinical Trials Regulation. The agenda of the training sessions is available here.

There were approximately thirty different presentations during the two days. The presentations have now been made available on the Europa website and should be useful to anyone seeking to improve their knowledge of the key changes under the Clinical Trials Regulation.

A 29 page Q&A on complex clinical trials has been published on the European Commission website. You can download it here.

The Q&A document provides guidance and seeks to support sponsors, clinical trialists and applicants regarding scientific aspects and the planning, set-up, submission for obtaining CT authorisation (CTA), conduct, reporting and transparency, analysis and interpretation of complex clinical trials (CCTs) under the EU Clinical Trials Regulation (EU CTR) as well as their use in submissions for marketing authorisation. It complements and should be used together with relevant EU and ICH guidelines, in particular E6, E8, E9, E10, E16, E19, E11A and E20 (when available).

The following were Adopted at CTCG plenary, June 27 2023:

CTCG Best Practice Guide for sponsors of multinational clinical trials with
different protocol versions approved in different Member States under the
Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014

Cover letter template

Source: HMA

Targeted consultation on the implementation of the Clinical Trials Regulation (EU) No536/2014.

Here is a link to the Factual summary report on the above consultation

This EU survey was launched on 18 July until 9 September 2022 to collect feedback from
sponsors and stakeholders in order to:

  • understand the overarching hurdles that hamper a smooth implementation of the CTR
  • capture how clear the requirements of the CTR are to the stakeholders

The reported experience does not necessarily reflect the current status of CTIS user experience and the CTR implementation. Many of the issues reported have been addressed in the meantime via resolution of the encountered defects and new functionalities in CTIS, alignment of national legislation, additional guidance material for sponsors, as well as targeted modification of the rules of the CTR by a delegated act (i.e. Commission Delegated Regulation (EU) 2022/2039).
.

BfArM

BfArM has also published a Message to sponsors transitioning clinical trials from CTD to CTR/CTIS with further useful information. You can view it here.

Head of Medicines Agencies (HMA)

On the HMA website, on this page, under the heading ‘Transitional trials’, you will find the following documents:

  • Click on ‘Next’ to start the quiz.
  • You will have the opportunity to answer five questions.
  • For questions with multiple answers, you only get a mark if you have selected ALL of the correct answers
  • Click on the ‘Finish’ button once completed.
  • You will then see:
    • The number of questions that you answered correctly
    • Your correct are shown in a box with a dark Green border all round
    • Your incorrect answers are shown in a box with a broken Red border all round
    • The actual correct answers for the quiz are shown underlined in a dark Green border

Results

Next

#1. The CTR entered into force on which date?

Next

#2. Is an authorised medicinal product used as comparator in a clinical trial considered to be an investigational medicinal product?

Next

#3. The addition of another Member state to a clinical trial is considered to be a substantial modification.

Next

#4. The changes to ongoing clinical trials are classified in the Clinical Trials Regulation as which of the following? (There is more than one correct answer.)

Select all that apply:

Next

#5. A substantial modification (SM) to a clinical trial application can only be submitted and assessed after a decision is issued on a previously submitted application for : There is more than one correct answer.

Select all that apply:

Finish

On June 18, the new transparency rules for the European clinical trials database CTIS ( Clinical Trials Information System ) will come into force, along with the update of the CTIS public portal.

Until now, all information provided during the life cycle of the clinical trial was published, except for documents related to quality, financial data and certain information on its supervision.

Under new transparency rules, this clinical trial database managed by the European Medicines Agency (EMA) will only publish some key trial documents and data, simplifying the creation and submission of the requests.

The Spanish Agency for Medicines and Health Products (AEMPS) recommends that promoters take into account these changes, included in the EMA quick guide for users , so that they can adapt their procedures. For all applications submitted on or after June 18, the following must be taken into consideration:

  • It will no longer be possible to delay the publication of data and documents with the deferral mechanism .
  • The data and documents will be published according to the deadlines established for the trial category, phase and age of the population.
  • Only key documents of interest such as the protocol and the final summary of results will be made public.

What will happen to data from clinical trials submitted before 18 June 2024?

Data from clinical trials submitted before June 18, 2024 will be published in accordance with the principles and deadlines established in the new transparency rules. The documents initially presented for said tests will not be made public, but those of the applications that are subsequently sent for them will be made public. Promoters can now apply the principles of the new transparency rules, as outlined in section 4 of the ACT EU Q&A document .

Information session

On June 20, 2024, the EMA will organize an information session on these standards and the new version of the CTIS public portal from 3:30 p.m. to 5 p.m. Participants can submit their questions until June 13. For more information about this session, visit the event website .

For more information about the new transparency rules, consult the ACT EU website , the CTIS website and the AEMPS website.

Source: AEMPS

Image by mcmurryjulie from Pixabay