eNews May 2017

Dear Members, Associate Members, Partners and All,

 

Together with the EUCROF Board, I am very happy to present our second EUCROF Newsletter.

As you will see, the last months have been very rich in activities and initiatives: the first General Assembly held by the new Board in Glasgow at the end of March, numerous meetings with the EMA in which EUCROF plays a significant role, the 4th EUCROF International Conference in Vienna, from the 26th to the 27th February 2018, the launch of the First International Clinical Conference in Kiev. EUCROF continues to provide its training opportunities to members and clients, thanks to our webinars and the intense activities of our Working Groups, with key subject matter experts. Last but not least, we were invited to a Clinical Conference in Algiers and we extended our membership.

 

Thank you all for your contribution to these great achievements.

 

I wish you a happy reading.

Martine Dehlinger-Kremer

Martine Dehlinger-Kremer (MDK), our President, welcomed Members attending the General Assembly and introduced the following agenda:

  • Summary of EUCROF activities 2017
  • Update on the 2018 EUCROF Conference in Vienna
  • Approval of Final 2016 Accounts (Q&A and vote, Bank situation: ING and Caxia Bank)
  • Bylaws 2.0 – translation and finalization
  • CATO Europe – Serbia application to become EUCROF Associated Member: vote
  • Stakeholders Meeting at EMA – Update on EU CT Portals and Database
  • Presentation of a successful initiative of AFCROs: ”Synthesis of the interviews aiming at establishing the directory of French patients’ associations wishing to participate in the ongoing drug developments: an initiative of AFCROs”.
  • EUCROF Working Groups update
  •  EUCROF Objectives for the Future
  • AOB

 

This was an important first General Assembly of the new Executive Board, elected at the Munich GA in November 2016.

The Introductory presentation by Martine Dehlinger-Kremer covered the achievements in 2017 so far. These have included the expansion of membership with the addition of MEDICRO as a new Associate Member with others interested in joining in the near future, for example, Data Matrix (Russia) and OCT (Latvia). Preparatory activities have commenced for the 4th EUCROF International Conference in Vienna, Austria, February 2018. Arrangements have also been made for the next GA which will be in Madrid in November 2017. Furthermore, the Bylaws have now been translated into Dutch as required for their registration in The Netherlands and will be finalised very soon.

EUCROF is also actively supporting its Ukraine Member with the First International Clinical Conference in Ukraine scheduled to take place in November 2017, which will involve the participation of 6 EUCROF members, including providing key note presentations. 

EUCROF has continued its representation at the Authorities with attendance at various meetings at the EMA, which will continue throughout 2017, as well as increasing its visibility at a number of external events in Europe and Africa, all covered later in this eNews edition.

The first eNews was issued to Members and we hoped you all found it an interesting read. However the Board wants to receive feedback on topics Members wish to see presented in this newsletter.  

There was also the first Webinar of the year on March 15th, covering Pharmacovigilance (PV) with 39 attendees, with more webinars to follow.

MDK finished this section of the meeting with a discussion on the initiation of a “strategic plan” for the mandate, which you will hear more about later this year at the General Assembly in Madrid.

For this and each of the agenda topics above there are slides available for reference and further detail and also the minutes of the meeting, all of which are available in the members’ area on the EUCROF website by clicking here.

For further information please contact the Secretary and/or President via email on  or   and/or   or 

 

As our President has announced in the “Introduction” to this eNews, we are pleased that the 4th EUCROF International Conference will take place in Vienna, from 26th to 27th February 2018. The venue will be the Austria Trend Hotel Conference Facility, Olympia Mancini Hall.

As you see below the artwork (which includes the famous Wiener Riesenrad, a giant Ferris wheel) and motto for the conference (“Clinical Research in Europe: Are you ready for the changes”) has recently been published. (Insert Logo and Motto)

Link to Conference page on website.

 

Promotion of the conference has now started and it will be important that all national associations promote the Conference to its membership as this will be key to attracting larger numbers of attendees together with encouraging sponsorship.

The Programme Committee has started its activities too. Search for a key note speaker is on-going and overall we want to achieve a good balance across countries and with CRO speakers not dominating the programme.

 

Your involvement will be key to the success of this conference, so please act now: promote it existence across all of your contacts and book your place on the website. For further details please contact Darina Hrdličková at  (Chair of the Organising Committee) and Michèle Garot,  (Chair of the Programme Committee)

Each of EUCROF’S active Working Groups presented an update of their activities, past and present, at the General Assembly in March. For your information, following is a brief summary for each.

The Clinical Trial Legislation WG responded to a call for comments on the EMA FIH Guidance, which it submitted at the end of February 2017.  It also provided comments to the GCP Renovation Initiative Reflection paper, which were submitted in March 2017.

It should be noted that the Authorities are planning to reopen ICH 8 and E6, plus some new Annexes. Also, new Guidelines will be issued by the European Commission in relation to the new EU Clinical Trial Regulation, which will be the next focus area for the WG. If you wish to know more or to get involved, please contact Dagmar Chase ( );

 

For the Communication WG the main focus will be establishing a clear Communication Plan for the Federation and its Members. This will cover EUCROF’s key target groups, the type of media to use to get EUCROF’s key messages out to the wider audience, and which KPIs to use to monitor progress, including timings with set priorities. The WG also intends to look at enlarging the involvement of the other Working Groups to help increase visibility and awareness of the many important activities being undertaken by so many of EUCROF’s members. 

It is key that national associations make all their Members aware of EUCROF activities and also there is a need for more volunteers to help with EUCROF initiatives.  So if you are interested to hear more, contact Christophe Golenvaux ();

 

The Education & Training WG is chaired by Antoinette Van Dijk (). One of its main areas of focus are the Webinars provided throughout the year. So far, in 2017, there has been one webinar run by our Late Phase WG. The next webinar is planned in May (see Forthcoming Events)

 

The Late Phase WG aims to promote good practice in late Phase Clinical Trials, sharing of knowledge and expertise within the Clinical Trial Community. It plans to undertake various activities in 2017, including two webinars covering Pharmacovigilance and PASS studies. The working group is also currently preparing an article with the Paediatric WG and also a proposal to collaborate with ENCePP. For further details please contact Denis Comet ();

 

The Medical Devices WG now has 9 Members in 6 countries and has become very active in recent years, including monthly TCs, F2F meetings, supporting symposium and EUCROF Webinars.  The WG has been looking at the new Medical Device Regulation within Turkey and now plans to expand its focus on a more European regulatory basis. Contact  Burcu Cehreli ()for more information

 

EUCROF’s President, Martine Dehlinger-Kremer (), leads the Paediatric WG. This WG, too, has 11 members across Europe and is working with EnprEMA on how to communicate between Sponsors and Networks plus is collaborating with PCDO on interaction between CROs and networks. A first meeting took place at EMA on 21 March 2017. ..

As you read in the last edition, the Pan European network IMI2 Call 10 came out in January 2017. The plan is to create a pan-European Paediatric network to gain support on all aspects of a clinical study. The submission occurred on 15 March 2017 and mentions EUCROF, therefore, we are expecting to receive the final document, once issued. The first decision from the EU Commission is expected by 15th May 2017 with the start of initial activities planned for January/February 2018 with potential for some funding support.

Another initiative for the WG is with harmonising Informed Consent with Ethic’s working group of Enpr-EMA. Also a webinar is planned in 2017 plus a presentation at the 1st Kiev Research Forum in November 2017

 

The New Technologies WG is co-chaired by Alan Yeomans () and Yoani Matsakis ().This WG aims to develop an image of technology excellence and expertise, to inform EUCROF Members of advances in technologies, to perform surveys and to increase knowledge of CROs. Currently it has 10 members from 3 countries and one external expert. The WG is very active with TCs occurring every month. Furthermore, the WG looks at expectations of Inspectors in relation with electronic data capture and meets with the EMA to discuss technology involved in clinical trials.

The WG also is a regular contributor to the EUCROF Conference and is planning to prepare a white paper on the use of Electronic TMF, a new leaflet, the analysis of ICH GCP from a technology point of view. In the future, the WG is preparing a webinar on new Data Privacy Regulation, which will be covered at EUCROF 2018 Conference. 

 

The Pharmacovigilance WG has 9 members from across Europe. Its aim is to get visibility plus authoritative and reliable stakeholders in PV connecting with other groups. It holds monthly TCs and F2F meetings (the last was in July 2016) with its next April 2017. Twelve special interest groups have been established to look at different topics.  The WG is preparing a series of position papers to be published to show that outsourcing is a good approach to take in this environment.If you are interested to hear more please contact Nicolas Tsiakkas ().

 

Finally, the activities of two of EUCROF’s Working Groups, Early Phase and Outsourcing Management, are currently on hold, as each require a new Chair.  Both cover very important aspects of our industry, so we truly hope that there is a Member out there with the necessary expertise, time and interest to step forward and take up the baton. If you are interested and wish to hear more please contact Simon Lee at  and Martine Dehlinger-Kremer at .

At the Stakeholders meeting at EMA’s office in London on 14th March, EUCROF was represented by Martine Dehlinger- Kremer, Dagmar Chase and Simon Lee. This was the first of two scheduled meetings in 2017 to discuss the progress of the EU Clinical Trial Portal and Database, which is being developed prior to the implementation of the EU Clinical Trial Regulation in October 2018.

The agenda for the meeting was as follows:-

  • EU Portal and database project status
  • UAT update and process outline
  • User Management and Role Matrix
  • Use Case Review Update – Notifications
  • Documents handling in the workspace
  • EU Application Form Update
  • Transitory Period
  • Safety Reporting Project Update
  • Issues raised by Stakeholders

 

For a summary of the meeting please CLICK here to see the slides.

We will keep you all posted on future developments in this important area, but if you have any questions please don’t hesitate contacting Simon Lee at  .

EUCROF was invited to attend a workshop at the EMA to discuss the forthcoming 'Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products' (EMA/CHMP/SWP/28367/07 Rev. 1).

EUCROF was represented at the meeting by its Vice President, Dr Stefano Marini and by Dr Stuart Mair, a CCRA UK member and Medical Director of Quotient Clinical.

The workshop was set up by various representatives from the EMA including 2 people from the MHRA –David Jones (lead preclinical assessor) and Kirsty Wydenbach (lead medical assessor), who were both primary authors of the guideline. Approximately 80 delegates were present, comprising individuals from CROs, academic translational medicine /clinical pharmacology and Industry.

 

The meeting started with some general presentations, then broke out into three separate work streams or question and answer sessions.

  • Non Clinical Aspects (Jan Willem van der Laan, MEB)
  • Dose selection, escalation and maximal dose. (David Jones, MHRA)
  • Clinical Aspects and monitoring (Kirsty Wydenbach, MHRA)

The main message from the introductory talks was that the guideline was exactly that and was not legally binding. Its primary purpose is to minimise risk to subjects in Early Phase Trials and is applicable to both small molecule and biological IMPs.  Certain aspects of the guideline are clear cut in that a starting dose, dose range and upper dose must be defined but there is leeway in how these are defined, provided a scientific rationale can be provided.

A new guideline was planned following the 2007 EMEA guideline, which was implemented post “TeGenero” the preceding year and had a specific focus on FIH SAD trials. The revised guideline takes on a wider scope and also considers the transition of SAD to MAD and other components of multi –part protocols which have now become standard. The timeline has also been influenced by the trial incident in France last year.

Dose selection, escalation and maximal dose session. The main point for discussion was the new requirement that dose ranging should not exceed the anticipated therapeutic dose range, unless justified. This has come about as a direct consequence of the trial incident last year, in order to define a maximum tolerated dose which was a defined protocol objective.  This means that the dose response curve (pharmacology) is seen as the primary driver of dose setting, rather than the previous approach which was to start with toxicology.

Several US delegates challenged the therapeutic dose range as a flawed concept, as it is at best an estimate and reasoned that it should be standard practice to explore the safety /tolerability range in a controlled environment in HVs to create margins for patient studies where DDIs, organ impairment and accidental OD result in wide variability in exposures. The reply was that subject safety comes first and if they want to exceed the therapeutic dose range they can, if a justification is provided and every IMP will be judged on a case by case basis. They pushed for a low uncertainty/high uncertainty approach, where justification should not be required and the response was that this would be considered.

 

Clinical Aspects

There was significant overlap with the Dose selection aspect, but the main themes were that PK modelling should be based on the highest individual concentrations rather than mean and that sentinel dosing should be included unless justified.

 

Preclinical Aspects

The toxicology approach in terms of defining NOAELs and safety margins has been long established but there should now be a greater emphasis on defining the dose response curve and pharmacology (both invitro and invivo) as the effect on pharmacological processes which affect disease processes is why new medicines are developed.

 

Conclusion

The guideline will be further revised to provide further clarification. 

EUCROF’s Vice President, Dr Stefano Marini, attended and presented at a Round Table on “Access to Innovation & Clinical Research” that Pitch World Fast, organised with the Ministry of Health of Algeria. The presentation discussed the European regulation when it comes to innovative drugs & clinical research, showcasing what regulatory framework enables the EU to give greater & safer access to innovation and how innovation benefits the patients and stakeholders.

This round table was held in Algiers on the 2nd of April and this workshop follows two previously successful ones organised in 2016, also in Algiers, dealing with biotechnology and eHealth.

There were speakers from Singapore, India, Cuba Denmark, Finland, Canada, Spain among other countries and this really enhanced the debate and discussion between the local authorities, the key players and the experts.

 

For more information on the presentation please click here for the slides.

EUCROF continued its involvement in the testing of the EU Portal and Database, an important perquisite to the implementation of the EU Clinical Trial Regulation in 2018. On this occasion, all stakeholders had a reduced number of testers participating due to resource availability and timeframe pressures within the EMA. Overall this did reduce the number of testers from sponsor organisations from the previous 351 to only 26. EUCROF had 3 testers out of this group who were invited directly by the EMA to participate, given their previous detailed contributions in other UATs. So, proportionally, EUCROF, once again, had a strong representation. Overall there were 77 unique testers involved, including 51 Member States and the European Commission.

Testers provided comments on the functionality and features of the system still early in its development, resulting in some useful suggested improvements and required fixes, all of which will be considered for incorporation into the on-going development activities by the EU Portal and Database team at the EMA.

 

Many thanks to the EUCROF testers who participated in UAT5!

We are pleased to welcome two new Associate Members to the EUCROF family, namely CATO from Serbia and MEDICRO from Germany.

EUCROF now has Associate Members in a total of 9 countries: Austria, Bulgaria, Denmark, Germany, Portugal, Serbia, Switzerland, UK and Ukraine. 

There was another successful webinar held in May covering the EU Clinical Trials Regulation 536/2014: Protection of Subjects and Informed Consent. The presenter was Dr. Dagmar Chase, Managing Director of Clinrex GmbH, Munich, Germany, who is also Chair of the EUCROF Clinical Trials Legislation Working Group.


Chapter V of the EU Clinical Trials Regulation 536/2014 covers the important topic of protection of subjects and informed consent in a comprehensive manner. Regarding the informed consent procedure, the Regulation clearly formulates the framework for different (vulnerable) populations, however so called opening clauses provide the national legislators with important flexibility as to the provision of corresponding national rules which aim to mirror the local perception of ethics on these topics.

 

This Webinar provided an overview of Chapter V, pointing out those elements for which one should be alert for local implementation in the different Member States. In addition, the required elements for an informed consent form (ICF) were compared with those set out in ICH-GCP.

This webinar gave participants better awareness of clinical trials designed for individual subject benefit versus those designed for group benefit and of their use in different types of (vulnerable) populations.

 

For more information contact Antoinette Van Dijk ().

The next 2 UATs of the EU Clinical Trial Portal and Database have been planned by the EMA team as part of the UAT strategy. On this occasion, rather than testers participating remotely, the EMA have planned to organise on-site User Acceptance Testing at the EMA facilities in London on the following dates:

- UAT 6 on site testing: Dates to be confirmed (June/July)

- UAT 7 on site testing: Tuesday 29 August to Friday 1 September (4 days)

The intention is to have different subgroups (MS/sponsor) completing collaborative test scenarios, addressing end to end processes in line with the functionalities delivered in each release. It is expected that the testers will participate for the whole scheduled period. Once again the number of testers is limited with only one place guaranteed for each stakeholder organisation.

Following a call to EUCROF Members for testers interested and available for these intensive UATs, 9 testers from 5 countries came forward, offering to participate. Then, in order to be fair to everyone, testers were randomly drawn by the EUCROF Executive Board and 3 potential testers for each UAT put forward to the EU Portal and Database team at the EMA.

However, the EMA has confirmed EUCROF will have all 3 of its testers involved in UAT6 and 2 of its 3 testers involved in UAT7 as follows:-

 

UAT6

  1. Aneta  Wojtczak, Senior Regulatory Officer, PSI Pharma
  2. Sofia Kosmidi, ZEINCRO HELLAS S.A.
  3. Juraj Gaplovsky, PSI Pharma.

 

UAT7

  1. Ingeborg Boddeke, GCP Central,
  2. Lidya Dominguez, Sermes
  3.  Julie Kyrou, Zeincro Hellas S.A. (Reserve)

 

Simon Lee will continue as Focal Point, coordinating the activities of EUCROF testers. If you are interested in becoming a tester, please don’t hesitate to contact Simon immediately at  or .


EUCROF’s next scheduled Webinar is on the 13th June and will cover “Extrapolation approach in paediatric clinical research: chances and bottlenecks”

 

Overview

In the last decades, it has been widely accepted that the development of medicines for use in children should undergo strict qualitative, ethical and procedural rules, in order to appropriately authorise them for paediatric use. 

Thus, considering the vulnerability of this population, all the efforts to minimise unnecessary studies in children have to be made. Moreover, economic burdens and methodological, feasibility and ethical issues strongly impact on the number of children that can be enrolled into a clinical trial and this becomes more complex in the case of rare diseases. For this reason, new methodological strategies have to be explored to exploit the rich source of data that are already available, especially for the adult population.

In this scenario, the extrapolation approach, intended as “extending information and conclusions available from studies in one or more source population, to make inferences for another target population”, is an important tool to adopt when planning a paediatric medicine development programme, possibly allowing for a reduction in new data to be generated for conclusion in paediatric populations.

This approach has been included in the recent ICH-E11 guideline revision and is increasingly adopted in the official paediatric development plans proposed to EMA and FDA.

This webinar will provide an overview of the use of extrapolation of efficacy and safety data in paediatric medicine development, pointing out positive experiences and difficulties. A case-study and several examples will be presented.

After this webinar, participants will have better awareness of the opportunities and the requirements for the extrapolation approach in paediatric medicines development, with a particular insight on the regulatory scenario.

 

Duration

The total duration of the webinar, including Q&A, will be approx. 1.5 hours

 

Presenter

Dr. Lucia Ruggieri

MSc in Paediatric Medicines Development and Evaluation

Researcher at Gianni Benzi Pharmacological Research Foundation

TEDDY Network Scientific Secretariat

Please contact Antoinette Van Dijk ( ) for more information.


We have 2 further currently planned for 2017 as follows:-

  • Informed participation and patient empowerment: a patient-centred approach to improve paediatric clinical research by Mariangela Lupo on Wed, 27th Sep 2017
  • EU Clinical Trial Regulation 536/2014: Safety Reporting OR New Transparency Rules to be presented by Dagmar Chase on Wednesday 11th October 2017;

 

Each of the above will be open to non-members with an associated fee of 90 EUR (EUCROF Members 60 EUR).

The Good Clinical Practice Inspectors Working Group (GCP IWG) will be holding a joint meeting with interested parties on 12 June 2017 from 11.00 until 18.00 at the premises of the European Medicines Agency.

The title of the meeting is: “Meeting with interested parties on topics related to e-source data/ EDC tools in clinical trials”

 

The meeting is to address some of the hot topics in clinical trials, including:

  1. Inspection findings related to e-systems & their vendors  
  2. Risk based software validation
  3. Requirements for a good audit trail
  4. Electronic informed consent

 

Building on the experience of the previous meetings, we would like to explore solutions for some of these topics and therefore balance the time allocated for presentations with discussions and comments sessions.

 

EUCROF has been invited to provide 3 to 4 experts in the field to attend and a call went out to Members last month and is now closed. Final names of EUCROF experts in the field have just been confirmed as follows:-

Yoani Matsakis

Dagmar Chase

Stefanie Broes

Michele Garot

Ana Patacão

Alan Yeomans

 

The proposed list of speakers are:

  • Contractual requirements on the responsibilities of e-systems vendors with regards to GCP by Yoani Matsakis and Dagmar Chase
  • Views on the implementation of a risk based approach to computer systems validation by Yoani Matsakis
  • Methodologies used for system validation (e.g. Agile methodologies) and documentary evidence produced by     Yoani Matsakis and Alan Yeomans.
  • Electronic informed consent by Stefanie Broes


For further information please contact Assia Rosati at  and Martine Dehlinger-Kremer at .

PHARMASICH CRO with the support of the European CRO Federation holds Kiev Clinical Research Forum on 9-10 November 2017 in Kiev, Ukraine.

The Forum is the unique discussing platform for clinical research industry in Eastern Europe.

It will bring together 300 delegates and the speakers from 14 countries, representing the industry, regulatory agencies, academia and non-profit boards and will provide awesome networking opportunities and adequate discussion between speakers and audience.

 

The full programme and other details are available on the conference website:

www.conference-pharmasich.com


If you wish to make a presentation or take part in the panel discussion, please contact us at 

Or, alternatively, we can set up a call to discuss the details.

Martine Dehlinger-Kremer will be attending the Enpr-EMA Annual Workshop in London on 16 May.

 

This will be the ninth annual workshop of the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA) which aims to bring relevant stakeholders together to discuss requirements, barriers and opportunities for high-quality clinical studies in children. Among the highlights of this year’s workshop are the recent efforts to increase cooperation between the European Union and the United States to facilitate global paediatric trials and medicine developments.

 

For further information please contact Martine Dehlinger-Kremer at  .

 

The Pharmaceutical Contract Management Group is holding its annual conference in Copenhagen this June. The venue will be the Radisson Blu Scandinavia Hotel, Copenhagen, Denmark and will be between the 7th and 9th June 2017.

For further details on the conference visit www.pcmg.org.uk or contact  .