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TOPIC : Improving the preclinical prediction of adverse effects of pharmaceuticals on the nervous system

Topic identifier: IMI2-2017-13-10
Publication date: 30 November 2017

Types of action: IMI2-RIA Research and Innovation action
DeadlineModel:
Opening date:
two-stage
30 November 2017
Deadline:
2nd stage Deadline:
28 February 2018 17:00:00
06 September 2018 17:00:00

Time Zone : (Brussels time)
  Horizon 2020
Topic Description
Specific Challenge:

Neurotoxicity (used in the context of this document as “any adverse effect on the central nervous system (CNS) or peripheral nervous system (PNS)”) is poorly predicted by preclinical studies performed on pharmaceuticals during research and development (R&D) process. As a consequence, adverse effects on nervous system are not uncommon during clinical development and post-marketing. This lack of predictability might have two types of consequences:

  • for human volunteers/patients, this can lead to a risk of adverse effects during clinical trials or even after marketing;
  • for the pharmaceutical industry, this can lead to substantial neurotoxicity-related attrition rates, generally at late stages (clinical phase 2 or 3); according to sources, the figures for this type of attrition are variable, but typically in the range of 5-25%.

Therefore, a better preclinical prediction of adverse effects on nervous system would benefit to human volunteers/patients (by safer drugs) and pharmaceutical industry (by increased productivity).

There is a clear need for a project to deliver on: (i) increased knowledge on mechanisms of neurotoxicity (e.g. establish adverse outcome pathway for each type of neurotoxicity); (ii) better understanding of factors that favour neurotoxicity (pharmacological targets and pathways, physico-chemical properties, pharmacokinetics); (iii) implementing new-found knowledge to improve the current preclinical toolbox, through a combination of high throughput, predictive in silico, in vitro and in vivo models, including safety biomarkers, where appropriate (iiii) combine these tools in an integrated risk assessment approach for better decision-points throughout R&D process, and better protection of human volunteers and patients.

Scope:

The objective of the project is to improve the preclinical predictivity of adverse effects of pharmaceuticals on the central and peripheral nervous systems through increasing our knowledge on mechanisms of neurotoxicity and improving the experimental toolbox. The results would be an integrated prediction/evaluation approach that would include a combination of in silico, in vitro and in vivo models, including safety biomarkers (for peripheral neuropathies). This toolbox would increase the preclinical prediction of adverse effects of drugs throughout all aspects: identification of hazards, characterisation of mechanisms of toxicity, prediction of clinical consequences and possible follow-up in trials with safety biomarkers, and integrated risk-assessment approach for proper decision-making process.

Expected Impact:

At the level of R&D, regulatory, clinical and healthcare practice the impact would be (i) safer drugs for human volunteers/patients (ii) shortened development timelines, through reduced attrition, reduced testing, and shortened development plans:

  • improved subjects/patients safety during clinical trials and after marketing authorisation;
  • reduced attrition, especially at late stages of R&D (during clinical trials), for safety reasons related to neurotoxic effects;
  • reduced post-marketing events necessitating labelling changes;
  • reduced post-marketing events resulting in drug withdrawal;
  • greater R&D productivity/shorter timelines;
  • lower development costs.

In terms of ethics/animal welfare/3Rs, innovation and integration of new knowledge the impact would be:

  • replacement: whenever possible animal models would be replaced by in silico/in vitro models, provided they have at least the same level of prediction;
  • refinement and reduction: relevant biomarkers or any other appropriate endpoints would enrich current in vivo animal experiment and help (i) earlier detection and longitudinal follow-up of toxicities before inappropriate animal suffering (ii) decision-making process.

In terms of improving European citizens' health and wellbeing (volunteers and patients), the impact would be:

  • lower risk of neurotoxic events during clinical trials, whatever the clinical indication (relating to nervous system or not);
  • improved monitoring and risk minimisation procedures during clinical trials;
  • drugs with a better risk/benefit ratio.
  • In terms of industrial competitiveness the applicants should indicate how they will strengthen the competitiveness and industrial leadership of Europe by, for example, engaging suitable SMEs.
Topic conditions and documents

Please read carefully all provisions below before the preparation of your application.

The IMI2 13th Call for proposals topic text as well as the Call Conditions are available here.

 The budget breakdown for this Call is given at the end of the Call topics text, in the Call Condtions section, as well as the following information:

1.   Eligible countries: described in article 10(2) of the Rules for participation in Horizon 2020 and in article 1 of the Commission Delegated Regulation related to IMI JU.

2.   Eligibility and admissibility conditions: described in the IMI2 Manual for evaluation, submission and grant award. See also the Commission Delegated Regulation related to IMI JU.

Proposal page limits and layout: Please refer to Part B of the proposal template in the submission tool below.

3.   Evaluation:
Submission and evaluation process, including evaluation criteria and procedure, scoring and threshold are described in the IMI2 Manual for submission, evaluation and grant award. See also the proposal templates for your specific action in section 5, below.

4.   Indicative time for evaluation and grant agreement:
Notification of outcomes of stage 1 evaluations: maximum 5 months from deadline for submitting proposals.
Notification of outcomes of stage 2 evaluations: maximum 5 months from deadline for submitting full proposals.

Signature of grant agreements: maximum 3 months from the date of informing successful applicants.

5.   Proposal templates, evaluation forms and model grant agreements (MGA), clinical trials template:

IMI2 Research and Innovation Action (IMI2-RIA) and Innovation Action (IMI2-IA):

Proposal templates are available after entering the submission tool.

Standard evaluation form RIA 

IMI2 Model Grant Agreement
:
Members of consortium are required to conclude a consortium agreement prior to the signature of the grant agreement.

Clinical trial template:
The Clinical Trial template is compulsory at stage 2 only !

IMI2 Coordination and Support Action (IMI2-CSA):

Proposal templates are available after entering the submission tool.

Standard evaluation form CSA

IMI2 Model Grant Agreement
:
Members of consortium are required to conclude a consortium agreement prior to the signature of the grant agreement.

Clinical trial template:
The Clinical Trial template is compulsory at stage 2 only !

6.   Open access must be granted to all scientific publications resulting from Horizon 2020 actions.

Where relevant, proposals should also provide information on how the participants will manage the research data generated and/or collected during the project, such as details on what types of data the project will generate, whether and how this data will be exploited or made accessible for verification and re-use, and how it will be curated and preserved.

Open access to research data
The Open Research Data Pilot has been extended to cover all Horizon 2020 topics for which the submission is opened on 26 July 2016 or later. Projects funded under this topic will therefore by default provide open access to the research data they generate, except if they decide to opt-out under the conditions described in Annex L of the H2020 main Work Programme. Projects can opt-out at any stage, that is both before and after the grant signature.

Note that the evaluation phase proposals will not be evaluated more favourably because they plan to open or share their data, and will not be penalised for opting out.

Open research data sharing applies to the data needed to validate the results presented in scientific publications. Additionally, projects can choose to make other data available open access and need to describe their approach in a Data Management Plan.

Projects need to create a Data Management Plan (DMP), except if they opt-out of making their research data open access. A first version of the DMP must be provided as an early deliverable within six months of the project and should be updated during the project as appropriate. The Commission already provides guidance documents, including a template for DMPs. See the Online Manual.

Eligibility of costs: costs related to data management and data sharing are eligible for reimbursement during the project duration.

The legal requirements for projects participating in this pilot are in the article 29.3 of the Model Grant Agreement.

7. Additional documents:

Summary of the most relevant provisions for participating in IMI2 actions

IMI2 - 2nd Amendment to the Annual Work Plan 2017

IMI2 Regulators Guidance tool for researchers

IMI JU derogation to H2020 Rules for Participation  

Horizon 2020 Rules for Participation 

Horizon 2020 Regulation of Establishment

Horizon 2020 Specific Programme

 

Members of consortium are required to conclude a consortium agreement prior to the signature of the grant agreement.

Additional documents

  • IMI2 Call 13 stage 1 - Flash Call Info Report en

Submission Service

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