The success rate in the discovery of novel, safe and effective pharmacotherapies has been declining steadily over the last few decades (Scannell et al., 2012). There are several factors likely accounting for this unfortunate record (DiMasi et al., 2016; Waring et al., 2015; Shih et al., 2018). While some of these factors (e.g. deeper knowledge of disease biology or clinical trial methodology) will take years, if not decades, of continued research to be properly addressed, others can be readily controlled today (Bespalov et al., 2016; Landis et al., 2012). One area requiring immediate attention is research rigor, which is estimated to be lacking in 50–90% of preclinical studies (Freedman et al., 2015).

High risk of failure is an inherent part of developing innovative therapies (DiMasi et al., 2016). However, some risks can be greatly reduced and avoided by adherence to evidence-based rigorous research practices. Indeed, numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor (Begley and Ioannidis, 2015; Landis et al., 2012; Ritskes-Hoitinga and Wever, 2018; Vollert et al., 2020; Volsen and Masson, 2009).

Improving research rigor has biomedical, societal, personal, economic and ethical benefits for academia and industry alike, since the development of novel therapies is often rooted in academic discoveries and requires a highly specialized effort of industry to translate these discoveries into clinically useful applications. Moreover, the simple dichotomy between purely academic research and large industry/big pharma efforts is currently being replaced by networks of biotechs, spin-offs, private and public funders, contract research organizations (CROs), academic institutions engaging in drug discovery projects and manufacturers of research tools. It is therefore important that strategies to increase the robustness and reliability of preclinical research, both in terms of conduct and reporting, involve all these different stakeholders.

To address this challenge in preclinical biomedical research in a collaborative manner, the Enhancing Quality in Preclinical Data (EQIPD; originally called European Quality in Preclinical Data) consortium was formed in 2017 with founding members from 29 institutions across eight different countries (https://quality-preclinical-data.eu). The consortium works closely with a large group of associated collaborators, advisors and stakeholders representing research institutions, publishers, funders, learned societies and professional societies, from more than 100 organizations in Europe and the US.

Supported through the European Union’s Innovative Medicines Initiative (IMI), the EQIPD consortium, among other deliverables, aimed to develop a novel preclinical research quality system that can be applied in both the public and private sectors. Such a quality system should be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions.

EQIPD defines research quality as the extent to which research data are fit for intended use (for related definitions and explanations, see Juran and Godfrey, 1999; Gilis, 2020). Fitness, in this context, is defined by the stakeholders, who can be scientists themselves, but also patients, funders, sponsors, publishers, and collaboration partners (e.g. peers in a multi-site research project).

The EQIPD consortium has developed a quality system that is free for anyone to use. Further, EQIPD is preparing training, support and assessment services for those research units that successfully implement the quality system and would like to seek formal accreditation.

Quality systems usually appear as a response to an existing need (Table 1). For example, the development of the Good Laboratory Practice (GLP) standards, introduced first by the Food and Drug Administration (FDA) in the late 1970s, was triggered by poor research practices that compromised human health, such as mis-identification of control and experimental animals, omitted, non-reported or suppressed scientific findings, data inventions, replacements of animals lost to follow-up, and mis-dosing of animals (Bongiovanni et al., 2020; Marshall, 1983). In the Organisation for Economic Co-operation and Development (OECD) Principles (https://www.oecd.org/chemicalsafety/testing/overview-of-good-laboratory-practice.htm), GLP is defined as 'a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported'.

GLP is a standard approach to quality in the regulated areas of preclinical drug development (which largely relate to non-clinical safety and toxicology studies rather than efficacy; see Appendix 1 Glossary for a definition of regulated research), where trained personnel perform mainly routine analyses, following defined Standard Operating Procedures (SOPs), and deliver data ultimately supporting patient safety.

There have been attempts to develop a quality system based on GLP, that is, taking GLP as the basis and eliminating elements that are seen as excessive for the purposes of non-regulated drug discovery. However, GLP does not provide explicit guidance regarding those aspects of study design, conduct, analysis and reporting that are important to minimize the risk of bias and make research robust. In other words, even if it were made less demanding, conventional GLP cannot address some of today’s key challenges in non-regulated preclinical research.

In contrast, the EQIPD Quality System is a novel system specifically aimed at supporting innovation in preclinical biomedical research. While the direct consequence of installing a quality system will be the generation of research data that are of higher rigor, the ultimate goal is to improve the efficiency of developing novel effective and safe therapies.

EQIPD was started in October 2017 and during the first phase (until June 2018), three work packages of the EQIPD consortium have delivered:

• A systematic review of guidelines for internal validity in the design, conduct and analysis of research involving laboratory animals (Vollert et al., 2020);

• An inventory of current practices and expectations toward quality management in non-regulated preclinical research (based on interviews with 70 consortium members and stakeholders);

• A review and analysis of governance in existing quality management systems (AAALAC International; ASQ Best Quality Practices for Biomedical Research in Drug Development; BBSRC Joint Code of Practice; ISO 9001, ISO 17025, ISO 15189; Janssen discovery quality system; Novartis research quality system; OECD Principles of GLP; RQA – Quality Systems Workbook).

During the second phase (July 2018 - January 2019), a working group was assembled from the EQIPD consortium members (n = 20). Based on the collected information, the working group nominated 75 statements that could define a functional quality system in non-regulated research. After three Delphi feedback rounds and two consensus meetings, these statements were revised, resulting in a final list of 18 core requirements (Table 2; see below for details).

During the third phase (February 2019 – September 2019), a supporting framework was developed (see below) and pilot implementation of the quality system started at four independent research sites.

Based on the feedback from those pilot implementation sites and interactions with the stakeholder group, an updated version of the framework was released for beta-testing in November 2019. The final version of the quality system was released in September 2020.

Table 3 presents five principles on which the EQIPD Quality System is based. These principles delineate in a maximally concise and direct form that the EQIPD Quality System is meant to support scientists in triggering changes in research practices, and that it will help to identify objectives and direction of change but will not prescribe any specific solutions as long as the research processes are kept transparent and traceable.

The EQIPD Quality System will deal with highly diverse research environments and associated challenges. The five principles are, therefore, instrumental in finding answers to specific questions – for example, is this particular practice in line with the EQIPD expectations? or should this particular process be documented?

Flexible: driven by the needs of an individual research unit

Research environments are highly diverse: the needs of researchers at a big pharma company are different from those at a biotech; the needs of CROs are different from those of academic labs, etc. Thus, improving data quality is a challenge that cannot be tackled using a one-size-fits-all solution and flexibility is a critical requirement for future success.

The EQIPD Quality System is flexible: researchers are not confronted with a long and definitive A-to-Z list of what should be done and in what sequence. Instead, implementation of the EQIPD Quality System is characterized by:

• user-specific content – that is the exact nature of the individual elements of the EQIPD Quality System are defined largely by the users and their environment;

• a variable trajectory – that is there are very limited expectations regarding the sequence of introducing the different elements of the EQIPD Quality System; and

• no deadlines or fixed timelines – that is each unit adopts the EQIPD Quality System at its own pace, depending on the existing needs and available resources.

EQIPD has developed tools (for optional use) that help scientists to identify and organize information to address their own customized needs (e.g. related to my research funding source, my national regulations for the use of animals, expectations of my collaboration partners, policies set by my institution, my own commitment to research rigor, etc.). Being unique to a research unit or a researcher, such needs can be very specific to local or personal circumstances (i.e. essential for my success, my funding, my career, for instance because of the requirements of my preferred funder), and as such may be addressed with a higher or lower priority. Based on these factors, each research unit or researcher can determine their sequence of actions (Figure 1). EQIPD tools offer examples and ready-to-use solutions as well as information to develop new user-specific solutions.

Figure 1

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For example, EQIPD has reviewed research quality expectations of several major public funders and pharmaceutical companies. Summaries of these expectations as well as examples of how these expectations can be met are available for downloading from the EQIPD’s online Toolbox (https://eqipd-toolbox.paasp.net).

A system, not just a collection of guidelines and recommendations

Development and implementation of flexible and fit-for-purpose solutions are usually enabled by introducing a continuous improvement process (Deming, 1986). Within the EQIPD environment, the improvement cycle is rooted in the following workflow:

• Understand the rationale for introducing something new or modifying the current work routine (Why - the Need);

• Understand what is needed to achieve it (What - the Challenge);

• Propose a solution for achieving it (How - fit-for-purpose Solution);

• Evaluate the success of the implementation (Assessment).

As an example, a research organization is seeking a collaboration with a biopharmaceutical company (Why). The company informs the research organization about its expectations regarding the raw data record generation, handling, and storage. The research organization recognizes challenges associated with the storage of raw data as defined by the company (What). The EQIPD Toolbox provides information on what is the raw data and what are the best practices in recording and handling the raw data (How). In many cases, the new workflow is applied and has the desired effect. In some cases, there may be deficiencies identified that require remediation such as changes in the protocols, additional communication, educational and training efforts. Evaluation of the success in implementation of new processes concludes the cycle (Assessment).

In addition, the successful use of a new method or procedure often requires training, adequate and timely communication, feedback on incidents and errors, etc. To fully establish the EQIPD Quality System, several corrective or feedback mechanisms have to be included. These mechanisms identify factors affecting the generation, processing and reporting of research data before a study is done (core requirement #15; Table 2; see also Box 1), to analyze and manage the incidents and errors that may occur during the study (core requirement #16; Table 2), and to monitor the performance of the EQIPD Quality System (core requirement #17; Table 2; see also Box 2).

Box 1.

Managing risks to data quality .

Even under the best circumstances, not all recommended practices and protection measures can be applied to a working environment or research study, leaving a potential risk of failure. The EQIPD Quality System recognizes the following main areas where risk assessment should be conducted with risks made transparent and, if appropriate, documented:

1. Alterations from strongly recommended practices (i.e. situations in which the language of the EQIPD guidance includes 'should' and the research unit justifies why it does not or cannot apply). These assessments are done at regular intervals by the Process Owner;

2. Key and support processes that are inherently associated with risks endangering the validity of the results (e.g. risk of unblinding; emergency access to blinding codes). These assessments are done by scientists responsible for a study plan;

3. Changes in the environment inside of the research unit (changes in personnel; facility changes, etc.). These assessments are done or initiated ad hoc by the Process Owner.

4. Changes in the environment outside of the research unit (changes in personnel; facility changes, etc.). These assessments are done or initiated ad hoc by the Process Owner.

Box 1—figure 1

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Box 2.

Self-assessment.

The primary objectives of the self-assessment are to confirm that the research unit has everything in place for proper performance of the fit-for-purpose EQIPD Quality System, and to set the basis for internal or external quality checks/accreditation mechanism.

The Process Owner is responsible for defining the scope and frequency of this self-assessment, which is expected to involve all members of the research unit to ensure that all quality goals in the research unit have been considered and achieved.

As part of the self-assessment, there are spot checks conducted on selected documents (core requirements ## 11, 12, 16, 17; Table 2) and laboratory activities (core requirements ## 6, 7, 8, 9, 10, 13, 14, 15; Table 2). The Process Owner completes a paperless assessment of several solutions being up-to-date (core requirements ## 1, 2, 4, 5; Table 2), reviews and, if necessary, updates documentation (core requirements ## 2, 3, 6, 7, 8; Table 2), and engages the team in the discussion and review of certain processes (core requirements ## 3, 5, 13, 16; Table 2). The self-assessment itself is a core requirement (#17; Table 2) and can be conducted using a template provided in the Toolbox.

Box 2—figure 1

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The ultimate mission of the EQIPD Quality System is to serve the entire community of scientists conducting non-regulated preclinical biomedical research. To achieve this goal, EQIPD’s dissemination strategy initially focusses on early adopters, that is, research groups and scientists who:

1. See the value of higher standards of rigor in research to achieve more robust and reliable results, are willing to learn about and adopt a quality mindset and are prepared to invest effort to set up the EQIPD Quality System;

2. Consider their standards of rigor are already good, but strive to improve them further, and would like to establish the EQIPD Quality System as an independent seal of quality;

3. Can use the EQIPD Quality System to strengthen a grant application, to support decision-making in drug discovery and/or to promote their services (e.g. CROs or academic labs active in the contract research domain) and bolster their reputation;

4. Are motivated by their funders, publishers and collaboration partners to secure high-rigor research standards (e.g. as a condition for funding or collaboration).

Such early adopters are known to be of critical value in every field where a cultural change is under discussion. For instance, academic initiatives have successfully addressed research data management and sharing of best practices by introducing Data Champions that serve as local advocates for good data practices (e.g. https://www.data.cam.ac.uk/intro-data-champions). Peer-to-peer learning eventually supports the dissemination of good practices beyond the early adopters.

The early adopters of the EQIPD Quality System, through their feedback to the EQIPD consortium, will help optimize the balance between the benefits of implementing such a system and any potential adverse consequences (e.g. resources allocated, reduction in conventional indices of scientific productivity). A positive balance will support further dissemination of the EQIPD Quality System and help broader research communities take advantage of the work done by the EQIPD team and the early adopters.

It is a general understanding that not all research units are equally prepared or willing to implement a Quality System, an effort that requires investing time and resources. Tools developed and shared by EQIPD can also be used for other purposes – for example, as a source of information about specific aspects of good research practice, as a guidance for specific types of projects (e.g. industry-academia collaboration), or to enable a specific collaboration project by providing a purpose-fit certification of the current practices being in line with the EQIPD expectations (Table 5).

Since the scientists themselves will be the main users of the EQIPD framework, their leading and proactive role in improving the quality of their own scientific data will define the ways the framework can be used to prepare more and more research units to accept a Quality System as a means for long-term maintenance or research rigor standards.

Even a lean and user-friendly quality system requires effort and resources to be implemented and maintained. This consideration makes it important to emphasize that a decision to start implementing the EQIPD Quality System should be well justified and regularly checked by the Process Owner and discussed with the research team.

Implementation path

There are several ways in which the EQIPD core requirements can be introduced within a research unit in terms of timing and sequence (Figure 2). Whether supported by the (optional) EQIPD tools or not, any of the possible implementation scenarios are acceptable as long as the outcome is the same, that is, a quality system implementing all 18 core requirements.

Figure 2

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The implementation path suggested by EQIPD envisions three phases (Appendix 3 Implementation path):

Phase 1– A short list of cornerstone actions that are the same for all research units to help users understand why things are done, as well as ensuring that efforts triggered by the EQIPD framework have immediate impact (e.g. best practices to support data integrity and traceability).

Phase 2 – Users develop solutions for challenges directly connected to their environment or needs communicated by their funders, publishers and collaboration partners. During this phase, users meet most of the EQIPD core requirements while developing a habit of working toward a quality system.

Phase 3 – Completion of the remaining core requirements enabling formal recognition of a functional quality system.

The implementation is concluded with an important sustainability checkpoint: the Process Owner is expected to estimate the required resources and make them available for maintaining the EQIPD Quality System (core requirement #18; Table 2).

The EQIPD system is a voluntary quality framework that enables research units to fulfill their own quality needs, for example, community guidelines or funder requirements.

Traditional quality systems require either internal (within the organization) or external auditors to check compliance with its system. This in turn requires that organizations employ dedicated and adequately trained quality professionals that understand the specific language in these quality regulations and ensure that the documentation formats correspond to the norm and nomenclature of the certifying organization.

The EQIPD Quality System is conceived as beginning with research scientists and extending to the research environment, and the compliance mechanisms are in line with this approach typically requiring no quality professionals.

On September 30, 2020, the EQIPD Quality System was released for broad deployment and unrestricted use by the research community.

To enable the maintenance and further development of the EQIPD framework beyond the IMI project phase, the EQIPD team is implementing a governance model (Figure 3). The proposed model comprises three closely interacting levels:

• A strategic level represented by the EQIPD Guarantors, a group of the EQIPD project team members responsible for the overall guidance, administration of academic and educational programs, and the dissemination of the EQIPD vision. The EQIPD Guarantors will be supported by an Ethics and Advisory Board, a consultative body composed of current EQIPD consortium members, associate collaborators and advisors as well as key opinion leaders in the field of good research practice.

• An operational level represented by an independent globally acting partner organization, commissioned by the EQIPD Guarantors to provide the operational support and services required for day-to-day business management (including technical support and training for the research units during the implementation and maintenance of the EQIPD Quality System).

• A community level that is represented by the EQIPD Stakeholder group, a diverse group of scientists, funders, quality professionals, manufacturers of research tools, and publishers that provide feedback on practical aspects of the EQIPD Quality System and facilitates connections to a broader biomedical research community.

Figure 3

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The next milestones for the EQIPD team are:

• Launch of an educational platform that will support both the use of the EQIPD Quality System and provide more general training in the field of good research practice;

• Analysis of geographical and cultural differences that may affect the acceptance of the EQIPD Quality System and that may require adaptations in the associated framework;

• Evaluation of the impact of implementation of the EQIPD Quality System on research quality, to inform further development of the EQIPD framework;

• The EQIPD Quality System was developed with the focus on the users and their needs. The EQIPD collaborators will maintain and expand this focus further.

The EQIPD team is actively engaged in discussions with funders (public and private) and publishers to develop instruments and mechanisms that will allow scientists to further benefit from the use of the EQIPD Quality System.

All scientists engaged in biomedical research are invited to join the growing community of the EQIPD Quality System users and supporters (http://www.eqipd.online).

We have not generated any data.

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Author details

1. Anton Bespalov

   PAASP, Heidelberg, Germany

   Contribution

   Conceptualization, Data curation, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing

   Contributed equally with

   René Bernard, Anja Gilis and Björn Gerlach

   For correspondence

   anton.bespalov@paasp.net

   Competing interests

   AB is an employee and/or shareholder at PAASP GmbH, PAASP US LLC, Exciva GmbH, Synventa LLC, Ritec Pharma

   "This ORCID iD identifies the author of this article:" 0000-0003-3730-1395

2. René Bernard

   1. Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany
   2. NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
   3. QUEST Center for Transforming Biomedical Research, Berlin Institute of Health at Charite, Berlin, Germany

   Contribution

   Conceptualization, Data curation, Formal analysis, Supervision, Investigation, Methodology, Project administration, Writing - review and editing

   Contributed equally with

   Anton Bespalov, Anja Gilis and Björn Gerlach

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3265-2372

3. Anja Gilis

   Janssen Pharmaceutica NV, Beerse, Belgium

   Contribution

   Conceptualization, Resources, Data curation, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing

   Contributed equally with

   Anton Bespalov, René Bernard and Björn Gerlach

   Competing interests

   AG are employees of Janssen / Johnson & Johnson and shareholders at Johnson & Johnson

4. Björn Gerlach

   PAASP, Heidelberg, Germany

   Contribution

   Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration

   Contributed equally with

   Anton Bespalov, René Bernard and Anja Gilis

   Competing interests

   BG and CE are employees and shareholders at PAASP GmbH.

   "This ORCID iD identifies the author of this article:" 0000-0002-4900-6302

5. Javier Guillén

   AAALAC International, Pamplona, Spain

   Contribution

   Conceptualization, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing - original draft, Writing - review and editing

   Competing interests

   JG is an employee of AAALAC International that is an EQIPD Associated Collaborator.

   "This ORCID iD identifies the author of this article:" 0000-0001-8188-7587

6. Vincent Castagné

   Porsolt, Le Genest-Saint-Isle, France

   Contribution

   Conceptualization, Data curation, Funding acquisition, Validation, Investigation, Methodology, Writing - review and editing

   Competing interests

   VC and CFC are employees of Porsolt.

   "This ORCID iD identifies the author of this article:" 0000-0002-8728-2922

7. Isabel A Lefevre

   Rare and Neurologic Diseases Research, Sanofi, Chilly-Mazarin, France

   Contribution

   Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing - review and editing

   Competing interests

   IAL and FD are employees of Sanofi.

   "This ORCID iD identifies the author of this article:" 0000-0003-0086-5947

8. Fiona Ducrey

   Integrity and Global Research Practices, Sanofi, Chilly-Mazarin, France

   Contribution

   Conceptualization, Validation, Investigation, Visualization, Methodology, Writing - review and editing

   Competing interests

   IAL and FD are employees of Sanofi.

9. Lee Monk

   Research and Clinical Development Quality, UCB, Slough, United Kingdom

   Contribution

   Conceptualization, Data curation, Validation, Investigation, Visualization, Methodology, Writing - review and editing

   Competing interests

   LM is an employee and shareholder of UCB.

10. Sandrine Bongiovanni

    Quality Assurance, Novartis Institutes for BioMedical Research, Novartis Pharma, Basel, Switzerland

    Contribution

    Conceptualization, Validation, Investigation, Methodology, Writing - review and editing

    Competing interests

    SB is an employee of Novartis Pharma.

    "This ORCID iD identifies the author of this article:" 0000-0002-8655-6514

11. Bruce Altevogt

    Pfizer Inc., Silver Spring, United States

    Contribution

    Conceptualization, Funding acquisition, Investigation, Methodology, Writing - review and editing

    Competing interests

    BA is an employee and shareholder of Pfizer. The views and opinions expressed in this article are those of the individual author and should not be attributed to Pfizer, its directors, officers, employees, affiliates, or any organization with which the author is employed or affiliated.

    "This ORCID iD identifies the author of this article:" 0000-0002-1359-5416

12. María Arroyo-Araujo

    Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-6612-0679

13. Lior Bikovski

    1. School of Behavioral Sciences, Netanya Academic College, Netanya, Israel
    2. The Myers Neuro-Behavioral Core Facility, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Contribution

    Data curation, Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-2275-1609

14. Natasja de Bruin

    Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

    Contribution

    Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-2456-2783

15. Esmeralda Castaños-Vélez

    Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany

    Contribution

    Conceptualization, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-2670-1118

16. Alexander Dityatev

    1. Molecular Neuroplasticity, German Center for Neurodegenerative Diseases, Magdeburg, Germany
    2. Center for Behavioral Brain Sciences, Magdeburg, Germany
    3. Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-0472-0553

17. Christoph H Emmerich

    PAASP, Heidelberg, Germany

    Contribution

    Conceptualization, Data curation, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review and editing

    Competing interests

    BG and CE are employees and shareholders at PAASP GmbH.

    "This ORCID iD identifies the author of this article:" 0000-0002-7594-3973

18. Raafat Fares

    Charles River Laboratories, Safety Assessment, Lyon, France

    Present address

    ERBC Group, Baugy, France

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-3963-381X

19. Chantelle Ferland-Beckham

    Cohen Veterans Bioscience, Boston, United States

    Contribution

    Data curation, Validation, Investigation, Writing - review and editing

    Competing interests

    AB, BA, NdB, UD, CFB, PK, MK, MM, PM, PP, GR, JS, and TS are members of the Preclinical Data Forum (co-chairs - AB and TS), a network financially and organizationally supported by ECNP and Cohen Veterans Bioscience.

20. Christelle Froger-Colléaux

    Porsolt, Le Genest-Saint-Isle, France

    Contribution

    Data curation, Formal analysis, Validation, Investigation, Methodology, Writing - review and editing

    Competing interests

    VC and CFC are employees of Porsolt.

    "This ORCID iD identifies the author of this article:" 0000-0003-0623-8928

21. Valerie Gailus-Durner

    German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

22. Sabine M Hölter

    Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, and Technical University Munich, Munich, Germany

    Contribution

    Validation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-4878-5241

23. Martine CJ Hofmann

    Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

    Contribution

    Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-8280-2036

24. Patricia Kabitzke

    1. PAASP US, Ridgefield, United States
    2. The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, United States

    Contribution

    Conceptualization, Resources, Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    PK is an employee and shareholder at PAASP US LLC.

    "This ORCID iD identifies the author of this article:" 0000-0003-3305-0795

25. Martien JH Kas

    Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands

    Contribution

    Supervision, Funding acquisition, Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-4471-8618

26. Claudia Kurreck

    Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany

    Contribution

    Conceptualization, Data curation, Validation, Investigation, Methodology, Writing - original draft, Writing - review and editing

    Competing interests

    UD and CK receive funding from Volkswagen Foundation

27. Paul Moser

    1. Cerbascience, Toulouse, France
    2. PAASP France, Toulouse, France

    Contribution

    Validation, Investigation, Methodology, Writing - review and editing

    Competing interests

    PM is owner of Cerbascience Consulting

28. Malgorzata Pietraszek

    PAASP, Heidelberg, Germany

    Contribution

    Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - review and editing

    Competing interests

    No competing interests declared

29. Piotr Popik

    Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-0722-1263

30. Heidrun Potschka

    Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University, Munich, Germany

    Contribution

    Supervision, Funding acquisition, Validation, Investigation, Writing - review and editing

    Competing interests

    HP has received during the last three years consulting and speaking fees and/or funding for collaborative projects from Bayer, Roche, Zogenix, and Eisai.

31. Ernesto Prado Montes de Oca

    1. Personalized Medicine Laboratory (LAMPER), Research Center inTechnology and Design Assistance of Jalisco State, National Council of Science andTechnology (CIATEJ-CONACYT), Mexico, Mexico
    2. Scripps Research Translational Institute, La Jolla, United States
    3. Integrative Structural and Computational Biology, Scripps Research, La Jolla, United States

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-0617-4752

32. Leonardo Restivo

    Neuro-BAU, Department of Fundamental Neurosciences, Faculty of Biology and Medicine,University of Lausanne, Lausanne, Switzerland

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

33. Gernot Riedel

    Institute of Medical Sciences, University of Aberdeen, Scotland, United Kingdom

    Contribution

    Supervision, Funding acquisition, Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

34. Merel Ritskes-Hoitinga

    1. SYRCLE, Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands
    2. Department for Clinical Medicine, Aarhus University, Aarhus, Denmark

    Contribution

    Conceptualization, Supervision, Validation, Investigation, Methodology, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-5315-284X

35. Janko Samardzic

    Institute of Pharmacology, Medical Faculty, University of Belgrade, Belgrade, Serbia

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-8464-4924

36. Michael Schunn

    Institute of Science and Technology, Klosterneuburg, Austria

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-4326-5300

37. Claudia Stöger

    German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Contribution

    Validation, Investigation, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-8361-0274

38. Vootele Voikar

    Neuroscience Center and Laboratory Animal Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

    Contribution

    Validation, Methodology, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-4201-8666

39. Jan Vollert

    Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom

    Contribution

    Conceptualization, Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    No competing interests declared

40. Kimberley E Wever

    SYRCLE, Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands

    Contribution

    Conceptualization, Supervision, Funding acquisition, Validation, Investigation, Project administration, Writing - review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-3635-3660

41. Kathleen Wuyts

    Avertim, Brussels, Belgium

    Contribution

    Project administration, Writing - review and editing

    Competing interests

    KW is a consultant of Avertim, Brussels, Belgium, support for this contribution was funded by Janssen Pharmaceutica NV.

42. Malcolm R MacLeod

    Centre for Clinical Brain Sciences, University of Edinburgh, Scotland, United Kingdom

    Contribution

    Conceptualization, Resources, Supervision, Funding acquisition, Validation, Investigation, Methodology, Project administration, Writing - review and editing

    Competing interests

    MM, UD and TS are members of the Advisory Board at PAASP. MM, UD and TS are members of the ARRIVE guidelines working group.

    "This ORCID iD identifies the author of this article:" 0000-0001-9187-9839

43. Ulrich Dirnagl

    1. Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany
    2. NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
    3. QUEST Center for Transforming Biomedical Research, Berlin Institute of Health at Charite, Berlin, Germany

    Contribution

    Conceptualization, Resources, Supervision, Funding acquisition, Validation, Investigation, Methodology, Project administration, Writing - review and editing

    Competing interests

    UD and CK receive funding from Volkswagen Foundation. MM, UD and TS are members of the Advisory Board at PAASP. MM, UD and TS are members of the ARRIVE guidelines working group.

    "This ORCID iD identifies the author of this article:" 0000-0003-0755-6119

44. Thomas Steckler

    Janssen Pharmaceutica NV, Beerse, Belgium

    Contribution

    Conceptualization, Resources, Data curation, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing

    Competing interests

    MM, UD and TS are members of the Advisory Board at PAASP. MM, UD and TS are members of the ARRIVE guidelines working group. TS is an AAALAC ad-hoc specialist. TS and AG are employees of Janssen / Johnson & Johnson and shareholders at Johnson & Johnson.

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