Introduction

The ERA-Net E-Rare has successfully implemented ten Joint Transnational Calls for rare disease research projects since 2006. This effort continues in the framework of the European Joint Programme on Rare Diseases (EJP RD) that has been established to further help in coordinating the research efforts of European, Associated and non-European countries in the field of rare diseases and implement the objectives of the International Rare Disease Research Consortium (IRDiRC).

Aim of the Call

The call for demonstration projects aims to show the usability and capability of the innovative statistical methodologies for clinical trials in rare diseases, which have not been demonstrated on existing data for specific rare disease clinical trials yet. Necessary for a successful demonstration project is the collection of sufficient data from a rare disease clinical trial and related information to enable demonstration of the practicability, performance and opportunities of the innovative methodologies applied to these already acquired data. Trials are often performed with standard classical methodologies not specific for rare diseases resulting in a loss of power to show positive effects. The demonstration projects should use one of the following nine innovative statistical methodologies:

1. Uncertainty evaluation (bias assessment)
2. Primary outcome variable (surrogate)
3. Primary outcome variable (co-primary)
4. Use of external information (historical control)
5. Use of external information (extrapolation)
6. Use of external information (dose response profiles)
7. Use of external information (single arm trials – threshold crossing)
8. n-of-1 trials
9. Rigorous use of longitudinal information, linked to an existing clinical trials dataset for a specific rare disease.

The details of data needed to demonstrate the above listed methodological topics are described in section "4.3 Further information".

Projects may concern a group of rare diseases or a single rare disease following the European definition of a rare disease i.e. a disease affecting not more than five in 10.000 persons in either the European Community, EC associated states or Canada.

Consortium Make-up

Submission of demonstration projects is limited to partners from institutions beneficiaries of the EJP RD. This includes Linked Third Parties or, parties bound by the Network Agreement with the beneficiary institution (and thus being able to integrate EJP RD project as Linked Third Party at later stage). In addition, each proposal must include one of the methodological experts matching the expertise for methodologies identified under section 4.3 Table 1 of the Call Text.

IMPORTANT: The applicants are asked to NOT to engage with any statistical experts and elaborate statistics plan until the preparation of full proposal.

The list of eligible methodology experts that will accompany the projects (and were identified in advance by the Task Force Group as the best experts to fulfil the objectives of this call) will be provided only on the 31st of March 2020 to avoid any potential Conflict of Interest and privilege any proposal over the other (please see further instructions below). A partnership with one of these experts is mandatory to efficiently prepare the full proposal.

Each full proposal must nominate a project consortium coordinator among the project partner principal investigators. In the case that one PI participates in more than one proposal, he/she should not be coordinating more than 2 projects. Each consortium partner will be represented by a single principal investigator. Each consortium partner will be represented by a single principal investigator. Each proposal is limited to 10 partners including a maximum of two participants from the same country.

Specific case of European Reference Networks:

At present, all 24 ERNs are involved in the EJP RD through their coordinating institution or (in exceptional cases) through one of the ERN member institutions. In order to accommodate the participation of specific members of each ERN it was agreed that they should be attached to the main ERN beneficiary as Linked Third Parties (LTP). Each identified LTP must be enumerated in the EJP RD Grant Agreement and their tasks and budget should be described. The legal connection between the main ERN beneficiary and its LTP(s) is ensured by the Network Agreement signed within each ERN and independent on their participation in the EJP RD. Similarly the bilater agreement signed between ERN coordinating institution and the Affiliated Partners of an ERN counts as legal document.

In case new (not yet identified as main beneficiary or its LTP in the GA of the EJP RD) ERN entities (including Affiliated Partners) that will participate and will be granted in the demonstration projects, it will be mandatory to amend the EJP RD Grant Agreement and identify them as LTPs with respective budget. Thus, it is mandatory that the Network Agreement or bilater agreement (for Affiliated Partners) is signed within each participating ERN.

Budget

Maximum number of funded projects: 6
Maximum amount of funding for each project: 220,000€

Duration

The maximum duration of the project is 24 months.

Deadlines

There will be a two-stage submission

• Deadline for submission of 1-pager: March 15th 2020
• Deadline for submission of full proposals: May 15th 2020

Web

http://www.ejprarediseases.org/index.php/joint-transnational-calls-2/