Print page Resize text Change font-size Change font-size Change font-size High contrast


Home > Q & A

ENCePP: Questions & Answers

This page provides answers to the most frequently asked questions about ENCePP and its key principles.

You may also be interested in: Frequently asked questions - EU PAS Register

If the answer to your question is not here, please email us at encepp_secretariat@ema.europa.eu

 

Table of contents

 

 

 


Purpose of ENCePP

Q1. What is ENCePP?

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) is a network coordinated by the European Medicines Agency. The members of this network (the ENCePP partners) are public institutions and contract and research organisations (CRO) involved in research in pharmacoepidemiology and pharmacovigilance. Research interests are not restricted to the safety of medicines but may include the benefits and risks of medicines, disease epidemiology and drug utilisation. Participation to ENCePP is voluntary.

Q2. What are the aims of ENCePP?

ENCePP aims to strengthen the monitoring of the benefit-risk balance of medicinal products in Europe by:

  • Facilitating the conduct of high quality, multi-centre, independent post-authorisation studies (PAS) with a focus on observational research;

  • Bringing together expertise and resources in pharmacoepidemiology and pharmacovigilance across Europe and providing a platform for collaborations;

  • Developing and maintaining methodological standards and governance principles for research in pharmacovigilance and pharmacoepidemiology.
Q3. Who are ENCePP's main stakeholders?

ENCePP’s main stakeholders include the research community, regulatory and public health authorities, patients and health care professional associations, and the pharmaceutical industry. The ENCePP website (http://www.encepp.eu) describes the activities of the network and provides access to its documents.

 

Q4. Why was ENCePP created?

ENCePP originates from the European Medicine Agency’s endeavor to enhance scientific and operational expertise in the fields of pharmacoepidemiology and pharmacovigilance across Europe. The project started in 2006 and is a key initiative within the European Risk Management Strategy (ERMS) adopted by Heads of Medicines Agencies, which aims to apply a proactive approach to monitoring of medicines throughout their lifecycle. Instrumental to this was the establishment of a network gathering available expertise and research experience in the fields of pharmacoepidemiology and pharmacovigilance across Europe.

 

Back to top


 

Participation in ENCePP

Q5. Who can be an ENCePP partner?

ENCePP focuses on public and not-for-profit organisations located in one of the EU or EFTA countries. These can be research centres, pharmacovigilance centres, university hospitals, owners of healthcare databases and/or electronic registries. Participation in ENCePP is also open to for-profit organisations such as contract research organisations (CROs), provided they perform studies commissioned by third parties and focussed on pharmacoepidemiology and pharmacovigilance research.

 

Existing European networks (e.g. certain rare diseases, therapeutic fields or adverse drug events) may also join ENCePP if at least one of its members is registered as an ENCePP centre.

 

Pharmaceutical companies cannot be an ENCePP partner, but they are encouraged to make use of the resources offered through the ENCePP networks and to participate in the public review of documents (see Q7).

Q6. What does it mean to be an ENCePP partner?

Being an ENCePP partner means a commitment to

  • adhere to the principles of the ENCePP Code of Conduct and ENCePP Guide on Methodological Standards in Pharmacoepidemiology,

  • register post-authorisation studies (PAS) the ENCePP partners are conducting in the EU PAS Register,

  • participate in the development of research and good practice standards by contributing to, or commenting on, draft proposals prepared by working groups or the ENCePP secretariat and to

  • collaborate with other ENCePP partners, e.g. in multi-centres studies, and share their research experience.

Q7. How can ENCePP help me to conduct a pharmacovigilance or pharmacoepidemiological study?

ENCePP supports the conduct of pharmacovigilance or pharmacoepidemiological studies through a number of deliverables:

  • ENCePP partners have developed research standards in pharmacovigilance and pharmacoepidemiology through written consultation or participation in plenary and working group meetings. The following guidance is available online:

    • The ENCePP Code of Conduct, which provides a set of rules and principles for pharmacoepidemiology and pharmacovigilance studies to promote transparency and scientific independence throughout the research process.

    • The ENCePP Guide on Methodological Standards in Pharmacoepidemiology, which offers a single web resource for methodological English language guidance in pharmacoepidemiology.

    • The ENCePP Checklist for Study Protocols, which is a list of questions on important aspects of study design that stimulates researchers to consider important epidemiological principles when designing a pharmacoepidemiological study and that promotes transparency on study methods.

  • An ENCePP Partners Forum is available where ENCePP partners can discuss research questions and develop protocols.  Anyone seeking to commission a post-authorisation study can submit a request to the ENCePP Secretariat by completing the request form. The request will be shared with researchers via the ENCePP Partners Forum, which is accessible to ENCePP partners only.

  • A publicly available and searchable resource database, an electronic index of self-registered EU research organisations, networks and data sources in the field of pharmacoepidemiology and pharmacovigilance that can be used by researchers and study sponsors seeking to identify organisations and data sets for conducting specific pharmacoepidemiology and pharmacovigilance studies in Europe.
  • A publicly available and searchable register where any pharmacoepidemiological and pharmacovigilance study can be registered by whoever initiates it; this register also serves as the “EU Post-Authorisation Study (PAS) Register” where marketing authorisation holders should register all non-interventional post-authorisation safety studies (PASS) relating to medicines.
  • The ENCePP Seal that recognises studies following the ENCePP principles of standards, transparency and independence.
Q8. What can ENCePP offer to pharmaceutical companies?

ENCePP supports the conduct of high quality industry-funded post-authorisation studies (PAS) by:

  • Supporting the conduct of joint studies by facilitating collaborations; 

  • Providing opportunities to participate, through consultations, in the development of pharmacoepidemiological research standards and methods for the post-authorisation safety surveillance of medicinal products;
  • Developing and maintaining methodological, transparency and governance tools for the planning, design, conduct and reporting of studies according to standards recommended in the EU Good Pharmacovigilance Practices (GVP) and the ENCePP Code of Conduct.
  • Giving access to dedicated tools for the conduct of studies:
    • the ENCePP Resources Database providing a robust network of research centres working in a transparent and independent manner, including data sources;
    • the EU PAS Regsiter developed specifically for the registration of observational studies.

Back to top


 

The ENCePP Code of Conduct

Q9. What is the scope of the Code of Conduct?

The objectives of the ENCePP Code of Conduct are to provide a set of rules and principles for the conduct of pharmacoepidemiology and pharmacovigilance studies. The Code addresses critical areas in the planning, conduct and reporting of studies and the interaction between investigators and study funders with focus on transparency and scientific independence.

The use of the Code is voluntary. However, it is mandatory to declare adherence to the Code for studies seeking the ENCePP Seal by submitting a completed and signed Checklist and Declaration on compliance as part of an application for the seal. ENCePP Seal studies are, therefore, studies that have confirmed their intention to comply with the provisions of the Code in their entirety.

Q10. How would the Code of Conduct apply to ongoing PhEpi and PhV studies?

The Code of Conduct applies to the conduct of a study from its planning stage to final results. Researchers are encouraged to adhere to the principles of the Code for both ongoing and prospectively planned studies, but will be unable to apply for the ENCePP Seal retrospectively if the study has already started (see Q24).

Q11. Does the Code of Conduct only apply to Europe?

The principles within the Code are universally applicable. There are thus no geographical restrictions as regards the use of the Code.

Q12. Can a pharmaceutical company apply the Code of Conduct to internal studies?

The Code of Conduct has been drawn up to address common issues encountered in industry commissioned research. Whilst the principles of the Code are applicable to all pharmacoepidemiological or pharmacovigilance studies, scientific independence (chapter 6 of the Code) cannot be achieved with industry ‘in-house conducted’ or ‘self-funded’ studies which are therefore not eligible for the ENCePP Seal.

Q13. What is the place of the Code of Conduct within existing legislation?

The Code aims to complement existing legislation and associated rules and guidelines by providing a set of rules to which researchers and study funders must adhere in order to achieve   transparency and scientific independence. It does not replace existing relevant legislation (e.g. Regulation (EC) 526/2014 in the case of clinical trials) or regulatory guidance published by the European Medicines Agency (EMA) such as EU Good Pharmacovigilance Practices (GVP) in which the Code is referenced e.g. in GVP Module VIII on post-authorisation safety studies (PASS).

Use of the Code is considered mandatory in certain situations, for example, if the ENCePP Seal has been applied for or if an obligation to adhere to the Code has been agreed in the research contract.

 

Q14. Is compliance with the Code of Conduct monitored?

In line with the principle of trust there is no established monitoring scheme. However, the (primary) lead investigator(s) of an ENCePP Seal study is obliged to inform the ENCePP Secretariat without delay if a study deviates from and/or no longer follows the rules of the Code. The ENCePP Steering Group will investigate concerns (e.g. claims by third parties) that an ENCePP Seal study does not fully comply with the provisions of the Code. Three months after the final study report is available the primary lead investigator is expected to upload a signed study completion notification together with the synopsis of the study findings.

 

Back to top


 

The EU PAS Register

Q15. What studies can be registered in the EU PAS Register?

Registration of clinical trials has been a legal obligation for some time but this is not the case for non-interventional studies. The EU PAS Register as referred to in GVP Module VIII on PASS has been developed in line with ENCePP transparency principles with the aim of filling this gap. The EU PAS Register is open to all pharmacovigilance and pharmacoepidemiology studies for registration, including clinical trials, regardless of whether they are initiated, managed or financed by a marketing authorisation holder, or whether they are conducted by a research centre that is a partner of the ENCePP network or any other research centre, or whether or not they qualify for the ENCePP Seal. Registration of studies is strongly encouraged and can be done at any stage (i.e. from planning to already completed). For a step by step guide how to register a study please refer to the EU PAS Register Guide.

Q16. Can I register a study that is not conducted in Europe?

Yes, the EU PAS Register is open for registration of all pharmacovigilance and pharmacoepidemiology studies, regardless of the country(ies) where they are conducted.

Q17. Who can register a study?

A study may be registered by anybody, typically this would be the (primary) lead investigator or someone on their behalf. In situations where no (primary) lead investigator has been nominated by the sponsor the details of the person in charge of the conduct of the study should be entered in the required fields. The individual who is entering the study details into the EU PAS Register should provide his/her contact details under the contact for scientific or public enquiries.

Q18. What kind of information is included in the EU PAS Register?

The EU PAS Register contains information on the study objectives, the main methodological aspects, administrative details (including study timelines and sources of funding), and associated key documents, including study protocols and study results where available.

Q19. When is registration of a study in the EU PAS Register mandatory?

Registration of non-interventional post-authorisation safety studies (PASS) conducted pursuant to an obligation imposed by a competent authority in accordance with Articles 10 or 10a of Regulation (EC) No 726/2004 or with Articles 21a or 22a of Directive 2001/83/EC is mandatory in line with the provision of GVP Module VIII on PASS. In addition, the registration of studies that wish to qualify for the ENCePP Seal is mandatory.

 

Back to top


 

The ENCePP Seal

Q20. How is the ENCePP Seal attained?

The ENCePP Seal is entirely free of charge and is sought on a voluntary basis by investigators who fulfil certain conditions. The ENCePP Seal places ongoing obligations on the investigators, including adherence to the entirety of the provisions of the ENCePP Code of Conduct. Certain requirements apply before the study starts whilst others relating to study results come into effect at a later stage, including after finalisation of the study. Thus, the ENCePP Seal must be applied for before the study commences (the ENCePP Code of Conduct defines the study start as “the start of data collection as defined in the study protocol”). The application and registration process is facilitated by a step-by-step guide and ready-made forms and checklists. A detailed list of the transparency requirements is provided in the Checklist of the Code of Conduct.

Q21. What is the benefit of getting the ENCePP study seal?

Studies which have been awarded the ENCePP Seal will be immediately recognisable to all stakeholders as being conducted in adherence to the ENCePP Code of Conduct, and by applying these principles of transparency and scientific independence, it will increase trust in the robustness and reliability of the findings.

 

Q22. Can a study conducted solely by a pharmaceutical company gain the ENCePP Seal?

No. Only studies whose lead investigator belongs to an entity that is included in the ENCePP Inventory of Centres and Networks can obtain the ENCePP Seal. Pharmaceutical companies cannot be an ENCePP partner and a study conducted solely by a pharmaceutical company cannot be awarded the ENCePP Seal. However, a study commissioned by a pharmaceutical company for conduct by an ENCePP Centre, is entitled to apply for the ENCePP Seal.

 

See Q&A for ENCePP partnership for further information.

Q23. Can I request the ENCePP Seal for a study that is not conducted in Europe?

To qualify for an ENCePP Seal, a study must be conducted or coordinated by a researcher from an ENCePP partner organisation and, therefore, located in one of the EU or EFTA member states. These restrictions, however, do not apply to other collaborating centres.

Q24. Can I request the ENCePP Seal for a study that has already started or is being completed?

No, as the ENCePP Seal cannot be awarded retrospectively. An application for the ENCePP Seal (i.e. registration of the study in the database and submission of relevant documents) must be done before the study starts. However, the study can still be registered in the EU PAS Register.

Q25. A study has been awarded the ENCePP Seal. Can the Seal be removed?

Given application for the ENCePP Seal is entirely voluntary, investigators can decide they no longer wish to comply with the obligations arising from having the ENCePP Seal and ask for it to be removed. Similarly, if the ENCePP Secretariat is made aware of breaches/deviations to the rules of the Code of Conduct, the concerned study will no longer be entitled to the title ENCePP Seal Study and this information will be made public on the ENCePP website.

 

Arbitration and decisions concerning breaches will be made on a case-by-case basis and may be referred to the ENCePP Steering Group, whose composition is publicly available.

 

Back to top


 

Transparency and Publication of Study Results

Q26. Can the funder of an ENCePP Seal Study participate in the publication of the study results?

Yes, it is possible for the funder to become co-author(s) of publications relating to the study taking account the provisions for the Code regarding the (primary) lead investigator’s right to independently prepare publications (chapter 15) and of other requirements such as those of the International Conference of Medical Journal Editors (ICMJE) regarding author responsibilities and conflicts of interest.

Q27. What are the requirements for publication of the study results?

As a principle, the study results should always be published, whether negative or positive, in the EU PAS Register and preferably in a peer-reviewed journal. Publication should always be timely. For ENCePP Seal studies the final study report should be provided without delay for publication in the EU PAS Register, including an abstract of the study findings in English language within 3 months following the final study report.

Q28. What are the requirements for publication of the study protocol and analysis plan?

The pharmacovigilance legislation requires the protocols and abstracts of results of non-interventional post-authorisation safety studies (PASS) imposed as an obligation by a competent authority in accordance with Articles 10 or 10a of Regulation (EC) No 726/2004 or with Articles 21a or 22a of Directive 2001/83/EC to be published in a publicly available register (the EU PAS Register). It also specifies that the final report of such studies must provide the date of registration in the EU PAS Register. This requirement applies to marketing authorisation holders.

 

For ENCePP Seal studies, a copy of the study protocol needs to be uploaded in the EU PAS Register to be made public after the final study report. Publication of the protocol at an earlier stage is optional and at the discretion of the investigator. A detailed statistical analysis plan has to be included in or annexed to the study protocol.

 

For all other studies, the investigator decides which documents he/she wishes to make publicly available in the EU PAS Register.

Q29. What are the requirements for making available study data?

The ENCePP Code of Conduct states that both the study protocol and the research contract should address rules for access to data. As a principle, data from ENCePP Seal studies should be made available as freely as possible whilst respecting European and national data protection legislation. Detailed information is available in the Implementation Guidance for Sharing of ENCePP Study Data which forms Annex 4 of the Code of Conduct.

Q30. What are the requirements for publication of conflicts of interest?

For ENCePP Seal studies, conflicts of interest must be documented. It is mandatory to make publicly available a conflict of interest declaration in the EU PAS Register (see Annex 5 of the ENCePP Code of Conduct: form for the Declaration of Interests for ENCePP Seal studies). Similarly, the composition of the study steering group (if any) has to be made publicly available.

 

For all other studies, the investigator will decide which documents he/she wishes to make publicly available in the EU PAS Register.

 

Q31. Can published study results be used for academic teaching purposes?

Whilst the Code does not include an explicit reference to the use of study results for the purposes of academic teaching and academic research, the publication of final results (see Q 27) does not exclude academic teaching material and thus the study results may be used for such purposes following publication of the study results in line with the provisions of the Code.

 

Back to top